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Κυριακή 28 Οκτωβρίου 2018

Increased 90-Day Mortality in Spontaneously Breathing Patients With Paraquat Poisoning: In Addition to Disease Severity, Lung Strain May Play a Role

Objectives: 1) To evaluate the prognostic roles of quantitative CT and pulmonary function tests and 2) to assess the association of dynamic strain and ventilation heterogeneity during unassisted spontaneous breathing with 90-day survival in patients with paraquat poisoning. Design: Prospective study. Setting: A university hospital ICU. Patients: One-hundred spontaneously breathing patients with paraquat poisoning without mechanical ventilation. Interventions: A standardized treatment protocol. Measurements and Main Results: Blood samples were collected to measure the plasma paraquat concentration upon arrival. CT scans at suspended inspiration and pulmonary function tests were performed at day 5. The weight of the poorly aerated lung compartment as a percentage of total lung weight (%Wpoor) was exponentially transformed, generating a new variable, Exp(%Wpoor/15). The functional residual capacity that was determined by helium dilution was used to calculate the dynamic strain (tidal volume/functional residual capacity by helium dilution method). Respiratory system reactance at 5 Hz was used as a marker of ventilation heterogeneity. Exp(%Wpoor/15) (adjusted hazard ratio, 2.58; 95% CI, 2.021–3.296; p

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Acute Phase Response in Critically Ill Elderly Burn Patients

Objectives: Survival of elderly burn patients remains unacceptably poor. The acute phase, defined as the first 96 hours after burn, includes the resuscitation period and influences subsequent outcomes and survival. The aim of this study was to determine if the acute phase response post burn injury is significantly different in elderly patients compared with adult patients and to identify elements contributing to adverse outcomes. Design: Cohort study. Setting: Tertiary burn center. Patients: Adult (

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Clinical spectrum of severe chronic central serous chorioretinopathy and outcome of photodynamic therapy

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Incidence of and risk factors for secondary ocular hypertension in moderate to severe infectious ulcerative keratitis

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Clinical features, management and outcomes of severe ischaemic stroke in tertiary hospitals in China: protocol for a prospective multicentre registry-based observational study

Introduction

Severe ischaemic stroke is a devastating condition with high mortality and morbidity; however, there is insufficient evidence on its management. The aim of this study is to investigate causes, risk factors, clinical course, management and outcomes of severe ischaemic stroke in a real-world setting in tertiary hospitals in China.

Methods and analysis

This is a prospective, multicentre, registry-based observational study. We will recruit 2500 patients with acute ischaemic stroke from nine tertiary hospitals in Western China. Patients with acute ischaemic stroke admitted to the Department of Neurology within 30 days of stroke onset will be included. Patients will be visited within 24 hours after admission, on day 3, day 7 and at discharge, to collect data on their clinical state, blood biomarkers and brain imaging. Severe stroke is defined as severe neurological deficits (National Institute of Health Stroke Scale (NIHSS) ≥15 or in coma) on admission or clinical worsening (NIHSS increased by ≥4 scores) during hospitalisation. Patients will be followed up by structured telephone interviews at 3 months and 1 year after stroke onset. In-hospital outcomes include symptomatic haemorrhagic transformation and brain oedema by day 7 of admission, and survival status (death or survival) by discharge; follow-up outcomes will include survival status and functional outcome (assessed by modified Rankin Scale) at 3 months and 1 year. The current study will improve our knowledge about the development of severe ischaemic stroke at acute phase and factors influencing its outcomes, which will eventually facilitate optimisation of individualised interventions for its prevention and treatment.

Ethics and dissemination

Ethics approval is obtained from The Biomedical Research Ethics Committee of West China Hospital, Sichuan University (Reference No. 2017(130)). We will present our findings at the national and international conferences and peer-reviewed journals in stroke and neurology.

Trial registration number

NCT03222024; Pre-results.



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Acute cholecystitis and gallbladder perforation leading to massive haemoperitoneum in a patient taking rivaroxaban

We present the case of an 80-year old man taking rivaroxaban for atrial fibrillation who sustained massive intra-abdominal bleeding in the setting of acute cholecystitis. CT scan on admission revealed evidence of active bleeding into the gallbladder lumen and gallbladder perforation. Immediate resuscitation was commenced with intravenous fluids, antibiotics and blood products. Despite attempts to correct coagulopathy, the patient's haemodynamic status deteriorated and an emergency laparotomy was performed, with open cholecystectomy, washout and haemostasis. The patient had a largely uneventful recovery and was discharged on day 11 of admission. Patients with coagulopathies, whether pharmacological or due to underlying disease processes, are at very high risk of severe haemorrhagic complications and subsequent morbidity. As such, prompt recognition and operative management of haemorrhagic perforated cholecystitis is of crucial importance.



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Infection of a tophaceous nodule of the wirst and hand

Tophaceous gout occurs years after recurrent attacks of acute inflammatory arthritis. The urate deposits are incriminated in the inflammatory process; however, their infection is exceptional. We report the observation of an infected gouty tophus of the pinky and the wrist of a 40-year-old man, presented as an excruciating inflammatory pain with buff-yellow swelling of the fifth right finger and wrist in a febrile context. As a matter of fact, the evolution was favourable after surgical excision and antibiotic therapy. The infection of a tophus is an exceptional complication of the gout. In daily practice, this diagnosis is really a difficult challenge for the clinician. The systematic bacteriological examination of the tophi with cutaneous fistulation is necessary to introduce prematurely an adapted treatment.



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Rare extraspinal cause of acute lumbar radiculopathy

A 60-year-old man presented to an outpatient pain management clinic with antalgic gait and left lower extremity (LLE) radiculopathy from an unknown aetiology. A lumbar MRI revealed minimal disc protrusion at L3 and a partially visualised left-sided kidney abnormality. Abdominal and pelvic CT demonstrated severe hydronephrosis of the left kidney compressing the left psoas major. The patient was immediately referred to an outside hospital for nephrology workup, and following nephrostomy tube, his radicular pain resolved. He remained asymptomatic at 4 weeks follow-up. We found two cases of postsurgical, retroperitoneal fluid collection that caused lumbar radiculopathy, but none associated with hydronephrosis. To our knowledge, this is the first case in the literature to report hydronephrosis as the potential aetiology of lumbar radiculopathy, which highlights an important clinical reminder: to consider extraspinal aetiologies in all patients who present with lumbar radiculopathy, when clinical symptoms, examination findings and diagnostic studies present with unusual characteristics.



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Coexisting polyarticular septic arthritis, gout and pseudogout

A case of a 67-year-old man with coexisting polyarticular septic arthritis due to group G Streptococcus, gout and pseudogout is presented. Septic arthritis of the left knee joint was further complicated by the development of an adjacent osteomyelitis. Appropriate management led to a full clinical recovery. Atypical clinical presentations in elderly, need for a sampling of more than one joint in polyarthritis and a summary of similar cases in literature is discussed.



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Rare vascular complication of acute meningococcal meningitis in a child

Description 

A 5-year-old boy presented with fever for 4 days and acute-onset weakness of the right upper and lower limb for 1  day. There was no history of headache, seizures, vomiting and altered sensorium, rash or bleeding from any site. On examination, he had normal mentation, neck stiffness, Kernig's sign, right-sided upper motor neuron facial palsy and right hemiparesis. The rest of the systemic examination was unremarkable. A clinical diagnosis of acute meningitis with left Middle Cerebral Artery (MCA) territory stroke was made.

Cerebrospinal fluid examination revealed 980 cells/µL (90% polymorphonuclear leucocytes and 10% lymphocytes), glucose 47 mg/dL, proteins 110 mg/dL and Neisseria meningitides antigen was positive; however, no organism could be isolated on microscopy and culture. He was unimmunised for meningococcal vaccine. Blood culture was sterile. Detailed stroke and immune deficiency work-up was negative. MRI of the brain showed altered signal changes in left frontal lobe, anterior limb of the internal capsule,...



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Unique retroinnominate course of the left brachiocephalic vein

Description  

A 4-year-old girl diagnosed with tetralogy of Fallot on transthoracic echocardiogram, was referred for a CT angiography (CTA) for preoperative anatomical assessment of the primary cardiac defect and associated cardiovascular anomalies. Review of CTA images revealed a unique anomalous course of the left brachiocephalic vein (*) where it was seen crossing the midline above the arch, anterior to the left common carotid artery (LCCA) and left subclavian artery (LSCA) but coursing posterior to the innominate artery, before joining the right brachiocephalic vein (RBCV) to form the right superior vena cava (RSVC) (figure 1A–D).

Figure 1

Volume rendered and axial maximum intensity projection images of CT angiography  (A–D) depicts the left brachiocephalic vein (*) traversing anterior to the left subclavian artery and left common carotid artery and posterior to the innominate artery, before joining the right brachiocephalic vein. LCCA, left common carotid artery; LSCA, left subclavian artery; RBCV, right...



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Remediating doctors performance to restore patient safety: a realist review protocol

Introduction

Underperformance by doctors poses a risk to patient safety. Remediation is an intervention designed to remedy underperformance and return a doctor to safe practice. Remediation is widely used across healthcare systems globally, and has clear implications for both patient safety and doctor retention. Yet, there is a poor evidence base to inform remediation programmes. In particular, there is a lack of understanding as to why and how a remedial intervention may work to change a doctor's practice. The aim of this research is to identify why, how, in what contexts, for whom and to what extent remediation programmes for practising doctors work to support patient safety.

Methods and analysis

Realist review is an approach to evidence synthesis that seeks to develop programme theories about how an intervention works to produce its effects. The initial search strategy will involve: database and grey literature searching, citation searching and contacting authors. The evidence search will be extended as the review progresses and becomes more focused on the development of specific aspects of the programme theory. The development of the programme theory will involve input from a stakeholder group consisting of professional experts in the remediation process and patient representatives. Evidence synthesis will use a realist logic of analysis to interrogate data in order to develop and refine the initial programme theory into a more definitive realist programme theory of how remediation works. The study will follow and be reported according to Realist And Meta-narrative Evidence Syntheses—Evolving Standards (RAMESES).

Ethics and dissemination

Ethical approval is not required. Our dissemination strategy will include input from our stakeholder group. Customised outputs will be developed using the knowledge-to-action cycle framework, and will be targeted to: policy-makers; education providers and regulators, the National Health Service, doctors and academics.

PROSPERO registration number

CRD42018088779.



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Can socioeconomic health differences be explained by physical activity at work and during leisure time? Rationale and protocol of the active worker individual participant meta-analysis

Introduction

Socioeconomic health differences have often been described, but remain insufficiently understood. Recent evidence suggests that workers who are high (compared with low) physically active at work are less healthy. Moreover, workers who are highly physically active at work are predominantly physically inactive during leisure time. These observations suggest that workers with a lower socioeconomic status may be exposed to negative health consequences of occupational physical activity and may only benefit to a limited extent from health benefits of leisure-time physical activity. Physical activity may therefore be an important driver of socioeconomic health differences. We describe the rationale and protocol of the active worker study, an individual participant data meta-analysis aimed at exploring socioeconomic health differences by differential doses of physical activity at work and leisure time.

Methods and analysis

Using database and scoping searches (we searched in PubMed, Embase, CINAHL, PsycINFO and Evidence-Based Medicine Reviews from database inception to 14 September 2017), we have identified 49 published and unpublished prospective studies in which the association of occupational and leisure-time physical activity with cardiovascular or all-cause mortality was assessed. Principal investigators of these studies will be invited to participate in the active worker consortium, after which data will be retrieved. After data merging and harmonising, we will perform multilevel survival analysis assessing the combined association of occupational and leisure-time physical activity with mortality. We will also test the mediating effect of physical activity on the association of socioeconomic status and mortality (ie, socioeconomic health differences).

Discussion

The Medical Ethical Committee of the VU University Medical Center has declared, according to Dutch legislation, that the 'Dutch Medical Research Involving Human Subjects Act' does not apply to the current study. As such, no ethics approval is required. We intent to publish outcomes of the active worker Study in scientific peer-reviewed journals.

PROSPERO registration number

CRD42018085228.



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Using patient-reported outcome measures (PROMs) to promote quality of care in the management of patients with established kidney disease requiring treatment with haemodialysis in the UK (PROM-HD): a qualitative study protocol

Introduction

Patients undergoing haemodialysis (HD) for end-stage kidney disease often report a poor quality of life (QoL) and identify that improving QoL has a higher priority for them than improvements in long-term survival. Research suggests that regular collection and usage of patient-reported outcome measures (PROMs) in patients with chronic conditions may reduce hospitalisation, improve QoL and overall survival. In the UK, despite increased use within research settings, PROMs have not been introduced into the routine clinical care for patients undergoing HD.

We report the protocol for 'Using patient reported outcome measures (PROMs) to promote quality of care in the management of patients with established kidney disease requiring treatment with haemodialysis in the UK—PROM-HD'. The study aim is to investigate the methodological basis for the use of routine PROMs assessment, particularly using electronic formats (ePROMs) within clinical and research settings, to maximise the potential of PROM use in the management of the care of this patient group.

Methods and analysis

The project will use qualitative methodology to explore, by thematic analysis, the views, perceptions and experiences of patients receiving HD and members of the HD multidisciplinary team regarding the collection and use of PROMs in routine clinical care, particularly ePROMs. This will involve interviews with up to 30 patients or until saturation is achieved and three focus group sessions with approximately 18 members of the clinical team delivering care to this patient group, which will be interpreted broadly to include both professional and non-professional staff.



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Efficacy of compound Lactobacillus acidophilus tablets combined with quadruple therapy for Helicobacter pylori eradication and its correlation with pH value in the stomach: a study protocol of a randomised, assessor-blinded, single-centre study

Introduction

Helicobacter pylori (Hp) is an important pathogenic factor for chronic gastritis, peptic ulcer, gastric cancer, gastric mucosa-associated lymphoid tissue lymphoma and other diseases. In China, the Hp infection rate is high, but the eradication rate is decreasing. A large number of literatures have shown that the addition of Lactobacillus acidophilus can improve the Hp eradication rate and reduce the side effects of antibiotic treatments. At present, the exact mechanism and curative effect of L. acidophilus in the eradication of Hp have not yet been determined, and the conclusions obtained from relevant meta-analyses at home and abroad are different. Thus, it is very necessary and urgent to further complete a high-quality, clinical, randomised controlled trial research. If this study is successful, it can provide a new idea and a plan for Hp eradication therapy.

Methods and analysis

This study is a prospective, randomised controlled, single-blinded, parallel-design trial. We will randomly assign 526 adult patients (≥18 years but <70 years) with Hp confirmed positive by the kit for 14C-urea breath test. Eligible subjects were randomly divided into two groups (group A and group B), with 263 subjects in each group. Group A is a quadruple therapy group, while group B is an L. acidophilus tablets combined with quadruple therapy group. All patients were examined by gastroscopy, and 50 patients in each group will be placed under gastric pH monitor. The Hp eradication rate is the primary outcome. The secondary outcomes include gastric pH situation and adverse drug reactions.

Ethics and dissemination

The study protocol has been approved by the Clinical Research Ethics Committees of Chongqing University Cancer Hospital and Chongqing Cancer Hospital (2018[012]). The results from this trial will be submitted for publication in peer-reviewed journals and will be presented at national and international conferences.

Trial registration number

ChiCTR17014185; Pre-results.



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Molecular diagnosis of inherited peripheral neuropathies by targeted next-generation sequencing: molecular spectrum delineation

Purpose

Inherited peripheral neuropathies (IPN) represent a large heterogenous group of hereditary diseases with more than 100 causative genes reported to date. In this context, targeted next-generation sequencing (NGS) offers the opportunity to screen all these genes with high efficiency in order to unravel the genetic basis of the disease. Here, we compare the diagnostic yield of targeted NGS with our previous gene by gene Sanger sequencing strategy. We also describe several novel likely pathogenic variants.

Design and participants

We have completed the targeted NGS of 81 IPN genes in a cohort of 123 unrelated patients affected with diverse forms of IPNs, mostly Charcot-Marie-Tooth disease (CMT): 23% CMT1, 52% CMT2, 9% distal hereditary motor neuropathy, 7% hereditary sensory and autonomic neuropathy and 6.5% intermediate CMT.

Results

We have solved the molecular diagnosis in 49 of 123 patients (~40%). Among the identified variants, 26 variants were already reported in the literature. In our cohort, the most frequently mutated genes are respectively: MFN2, SH3TC2, GDAP1, NEFL, GAN, KIF5A and AARS. Panel-based NGS was more efficient in familial cases than in sporadic cases (diagnostic yield 49%vs19%, respectively). NGS-based search for copy number variations, allowed the identification of three duplications in three patients and raised the diagnostic yield to 41%. This yield is two times higher than the one obtained previously by gene Sanger sequencing screening. The impact of panel-based NGS screening is particularly important for demyelinating CMT (CMT1) subtypes, for which the success rate reached 87% (36% only for axonal CMT2).

Conclusion

NGS allowed to identify causal mutations in a shorter and cost-effective time. Actually, targeted NGS is a well-suited strategy for efficient molecular diagnosis of IPNs. However, NGS leads to the identification of numerous variants of unknown significance, which interpretation requires interdisciplinary collaborations between molecular geneticists, clinicians and (neuro)pathologists.



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Use of an electronic patient-reported outcome measure in the management of patients with advanced chronic kidney disease: the RePROM pilot trial protocol

Introduction

Chronic kidney disease (CKD) affects up to 16% of adults in the UK. Patient quality of life is particularly reduced in end-stage renal disease and is strongly associated with increased hospitalisation and mortality. Thus, accurate and responsive healthcare is a key priority. Electronic patient-reported outcome measures (ePROMs) are online questionnaires which ask patients to self-rate their health status. Evidence in oncology suggests that the use of ePROM data within routine care, alongside clinical information, may enhance symptom management and improve patient outcomes. However, National Health Service (NHS)-based ePROM research in CKD is lacking. This pilot trial will assess the feasibility of undertaking a full-scale randomised controlled trial (RCT) in patients with CKD within the NHS.

Methods and analysis

The renal ePROM pilot trial is an investigator-led single-centre, open-label, two-arm randomised controlled pilot trial of 66 participants ≥18 years with advanced CKD. Participants will be randomised to receive either usual care or usual care supplemented with an ePROM intervention. Participants within the intervention arm will be asked to submit monthly self-reports of their health status using the ePROM system. The system will provide tailored information to patients in response to each report and notify the clinical team of patient deterioration. The renal clinical team will monitor for ePROM notifications and will respond with appropriate action, in line with standard clinical practice. Measures of study feasibility, participant quality of life and CKD severity will be completed at 3 monthly intervals. Health economic outcomes will be assessed. Clinicians will record treatment decision-making. Acceptability and feasibility of the protocol will be assessed alongside outcome measure and intervention compliance rates. Qualitative process evaluation will be conducted.

Ethics and dissemination

The findings will inform the design of a full-scale RCT and the results will be submitted for publication in peer-reviewed journals. The study has ethical approval.

Trial registration numbers

ISRCTN12669006; Pre-results.



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Two-year effectiveness of a stepped-care depression prevention intervention and predictors of incident depression in primary care patients with diabetes type 2 and/or coronary heart disease and subthreshold depression: data from the Step-Dep cluster randomised controlled trial

Introduction

Major depressive disorders (MDD), diabetes mellitus type 2 (DM2) and coronary heart disease (CHD) are leading contributors to the global burden of disease and often co-occur.

Objectives

To evaluate the 2-year effectiveness of a stepped-care intervention to prevent MDD compared with usual care and to develop a prediction model for incident depression in patients with DM2 and/or CHD with subthreshold depression.

Methods

Data of 236 Dutch primary care patients with DM2/CHD with subthreshold depression (Patient Health Questionnaire 9 (PHQ-9) score ≥6, no current MDD according to the Mini International Neuropsychiatric Interview (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria)) who participated in the Step-Dep trial were used. A PHQ-9 score of ≥10 at minimally one measurement during follow-up (at 3, 6, 9, 12 and 24 months) was used to determine the cumulative incidence of MDD. Potential demographic and psychological predictors were measured at baseline via web-based self-reported questionnaires and evaluated using a multivariable logistic regression model. Model performance was assessed with the Hosmer-Lemeshow test, Nagelkerke's R2 explained variance and area under the receiver operating characteristic curve (AUC). Bootstrapping techniques were used to internally validate our model.

Results

192 patients (81%) were available at 2-year follow-up. The cumulative incidence of MDD was 97/192 (51%). There was no statistically significant overall treatment effect over 24 months of the intervention (OR 1.37; 95% CI 0.52 to 3.55). Baseline levels of anxiety, depression, the presence of >3 chronic diseases and stressful life events predicted the incidence of MDD (AUC 0.80, IQR 0.79–0.80; Nagelkerke's R2 0.34, IQR 0.33–0.36).

Conclusion

A model with 4 factors predicted depression incidence during 2-year follow-up in patients with DM2/CHD accurately, based on the AUC. The Step-Dep intervention did not influence the incidence of MDD. Future depression prevention programmes should target patients with these 4 predictors present, and aim to reduce both anxiety and depressive symptoms.

Trial registration number

NTR3715.



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Clinical, endoscopic, and histologic characteristics of lymphocytic esophagitis: a systematic review

Abstract

Objective

Lymphocytic esophagitis (LyE) is a novel, yet poorly described, clinicopathologic entity. The aim of this systematic review was to characterize the demographic, clinical, endoscopic, and histologic features of LyE in observational studies of adult and pediatric patients.

Design

We searched the Embase, MEDLINE, and SCOPUS databases for relevant studies in 2018. Two authors reviewed and extracted data from studies that met the inclusion and exclusion criteria.

Results

We identified 20 studies for analysis of demographic, clinical, and endoscopic features of LyE. The mean age ranged from 9 to 67 years. When pooled, there were 231 (52.7%) patients with LyE that were female. The most common presenting symptom was dysphagia reported in 191 (48.8%) patients. On endoscopy, most patients with LyE tended to have abnormal findings (69.0%), which included erosive esophagitis, multiple esophageal rings, linear furrows, and narrow-caliber esophagus. In the 31 studies used to assess the histologic definition, the cut-off number of intraepithelial lymphocytes (IELs) was reported in 16 (51.6%) studies, peripapillary IEL specification in 18 (58.1%) studies, and presence of spongiosis in 6 (19.4%) studies.

Conclusion

We identified a spectrum of demographic, clinical, and endoscopic findings characteristic of patients with LyE. A consensus on the diagnostic criteria of LyE is required.



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Chronic Myeloid Leukemia: Beyond BCR-ABL1

Abstract

Purpose of review

In this review, we emphasize up-to-date practical cytogenetic and molecular aspects of chronic myeloid leukemia (CML) and summarize current knowledge on tyrosine kinase inhibitor (TKI) resistance and treatment response monitoring of CML.

Recent findings

The introduction of TKIs has changed the natural course of CML and markedly improved patient survival. Over the past decades, many research efforts were devoted to elucidating the leukemogenic mechanisms of BCR-ABL1 and developing novel TKIs. More recent studies have attempted to answer new questions that have emerged in the TKI era, such as the cytogenetic and molecular bases of treatment failure and disease progression, the clinical impact of genetic aberrations in Philadelphia chromosome (Ph)-positive and Ph-negative cells, and the biological significance of Ph secondarily acquired during therapy of other hematological neoplasms.

Summary

Recent progresses in the understanding of the cytogenetic and molecular mechanisms underlying therapeutic failure and disease progression have improved the risk stratification of CML and will be helpful in the design of novel therapeutic strategies.



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High tibial osteotomy technique for knee osteoarthritis [Letters]



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Should health care dollars be used to house the homeless? [News]



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Warnings on every cigarette: extending health messaging to the consumption experience [Commentary]



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Is it weight loss or exercise that matters in osteoarthritis? [Letters]



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Oral curcumin in elective abdominal aortic aneurysm repair: a multicentre randomized controlled trial [Research]

BACKGROUND:

Curcumin, a popular herbal supplement from the plant turmeric, has prevented ischemic reperfusion and toxin-induced injury in many animal studies and a single-centre randomized human trial. We sought to test whether perioperative oral curcumin (compared with placebo) affects the inflammatory response and risk of postrepair complications after elective abdominal aortic aneurysm repair in humans.

METHODS:

We conducted a parallel-group, randomized, placebo-controlled trial of patients from 10 hospitals in Canada who were scheduled to undergo elective repair of an unruptured abdominal aortic aneurysm (November 2011 to November 2014). Patients in the treatment group received perioperative oral curcumin (2000-mg doses 8 times over 4 d). Patients, health care providers and local research staff were unaware of the treatment assignment. The primary outcomes were median concentrations of 4 bio markers indicating injury and inflammation (postoperative urine interleukin-18 and perioperative rise in serum creatinine, plasma N-terminal pro–B-type natriuretic peptide and plasma high-sensitivity C-reactive protein).

RESULTS:

Baseline characteristics were similar in the 2 groups (606 patients overall; median age 76 yr). More than 85% of patients in each group took more than 80% of their scheduled capsules. Neither curcumin nor placebo significantly affected any of the 4 biomarkers (p > 0.05 for all comparisons). Regarding the secondary outcomes, there was a higher risk of acute kidney injury with curcumin than with placebo (17% v. 10%, p = 0.01), but no between-group difference in the median length of hospital stay (5 v. 5 days, p > 0.9) or the risk of clinical events (9% v. 9%, p = 0.9).

INTERPRETATION:

Curcumin had no beneficial effects when used in elective abdominal aortic aneurysm repair. These findings emphasize the importance of testing turmeric and curcumin before espousing their health benefits, as is currently done in the popular media.

Trial registration:

ClinicalTrials.gov, no. NCT01225094.



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Take turmeric with a grain of salt [Editorial]



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Exposure to rabies during pregnancy [Practice]



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The authors respond to "High tibial osteotomy technique for knee osteoarthritis" [Letters]



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Reactivation of hepatitis B virus associated with immunosuppression therapy [Practice]



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CMA quits global medical body over plagiarism row [News]



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Career conundrum [Humanities]



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Even resilient doctors report high levels of burnout, finds CMA survey [News]



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Cognitive Training Focused on Consequences May Promote Healthier Habits

Interventions aimed at reducing unhealthy behaviors often focus on retraining people's mental associations, but a series of studies suggests that showing people the consequences of the behaviors may be more effective. The findings are published in Psychological Science, a journal of the Association for Psychological Science.

The research specifically focuses on "approach-avoidance" training in which participants learn to approach some targets (e.g., nutritious foods) and avoid other ones (e.g., junk foods). Repeated exposure to these pairings is supposed to reinforce their mental associations in ways that increase positive behaviors and reduce negative behaviors. However, studies have not consistently shown an effect of this type of training.

Psychological scientist Pieter Van Dessel and colleagues hypothesized that this training may work when it actually alters people's beliefs about the consequences that follow when they approach or avoid certain foods.

"Our findings show that targeting these adaptive inferences can be effective in changing unhealthy eating behavior," says Van Dessel, a researcher at Ghent University. "This is important because it is often difficult to change these types of automatic behavior."

Van Dessel and coauthors Sean Hughes and Jan De Houwer tested their hypothesis in three online studies and one lab-based study, with a combined total of 1,547 participants. In all four studies, the participants completed a series of computer-based trials in which they saw a digital avatar standing near an open refrigerator. In each trial, the refrigerator contained a particular food and a color cue indicated whether the participants should move the avatar toward the food or away from it.

Some participants also saw a bar that indicated the avatar's health, which reflected the consequences of the participants' decisions. If they chose to approach the healthy food (or avoid the unhealthy food), the avatar's health bar filled up and the avatar appeared healthier while exclaiming "I feel healthy." Choosing to approach the unhealthy food (or avoid the healthy food), on the other hand, depleted the health bar and the avatar appeared less healthy, exclaiming "I feel sick."

Another group of participants saw these outcomes and were explicitly told to try to make their avatar as healthy as possible.

The results were consistent across the studies: Participants who had the explicit mission of maximizing their avatar's health showed the most positive automatic evaluations of the healthy food, gave the most positive ratings to the healthy food, and were most likely to choose a coupon for the healthy food compared with participants who saw the consequences of their choices but had no goal and those who did not see the consequences at all and only performed the typical approach-avoidance training.

Participants who were given a health-related goal also seemed to internalize the relationship between the foods and their consequences – compared with the other groups, they were most likely to approach the healthy food and avoid the unhealthy food when they were given free rein to choose foods without any consequences.

These effects also extended to actual eating behavior. In one version of the experiment, participants followed the avatar task with a supposedly unrelated task that involved rating the sensory characteristics of snack foods, such as candy and potato chips. The results showed that participants who had worked to maximize their avatar's health in the first task ate smaller quantities of the snacks compared with their peers.

In another experiment, participants who had the goal of boosting their avatar's health reported less unhealthy eating the next day and a greater intention to eat healthy foods.

Van Dessel was intrigued to find that the results of the inference training were so robust:

"After one instance of inference training, on one occasion, in one specific context, we found effects on participants' actual snacking behavior and self-reported food consumption a day after the training," he says. "This is striking because this quick training needs to go against an entire learning history of many years, in which people might have learned that eating unhealthy foods has positive effects for them."

The findings suggest that when trainees have a goal that requires that they learn the consequences of certain behaviors, it enhances the overall effectiveness of approach-avoidance training. Future research will help to illuminate whether changing certain aspects of the task, such as making it more personally relevant or including more trials, will strengthen the effects.

The researchers are now expanding on these findings, investigating whether consequence-based training can help to reduce other unwanted behaviors (such as smoking and alcohol use), and even increase certain positive behaviors (such as environmentally friendly behaviors).

Van Dessel was supported by a postdoctoral fellowship from the Scientific Research Foundation, Flanders (FWO-Vlaanderen). J. De Houwer was supported by Methusalem Grant BOF16/MET_V/002 from Ghent University.

All data and materials have been made publicly available via the Open Science Framework, as have the design and analysis plans. The complete Open Practices Disclosure for this article is available online. This article has received the badges for Open Data, Open Materials, and Preregistration.



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Primary spinal T cell/histiocyte-rich large B cell lymphoma (THRLBCL)—a rare diagnosis at a rare site

Abstract

T cell/histiocyte-rich large B cell lymphoma (THRLBCL) is an unusual variant of diffuse large B cell lymphoma with poor prognosis. We describe a case of THRLBCL with an uncommon isolated spinal involvement. A 37-year-old male came to the neurosurgery outpatient department with weakness of both upper and lower limbs. Histopathology and immunohistochemistry revealed features consistent with THRLBCL. The patient was treated with D5-D6 laminectomy followed by six cycles of chemotherapy (CHOP; cyclophosphamide, hydroxydaunorubicin, oncovin, prednisolone) and was disease free for 5 years until he had relapse of disease at the same location in 2016 for which he is receiving palliative radiation therapy. Isolated spinal involvement as the first or only manifestation of THRLBCL is very rare and has been described very occasionally in the literature. It is important to correctly diagnose this entity and differentiate it from its mimics because of different prognostic and therapeutic implications.



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Grounds for Trust: Essential Epistemic Opacity and Computational Reliabilism

Abstract

Several philosophical issues in connection with computer simulations rely on the assumption that results of simulations are trustworthy. Examples of these include the debate on the experimental role of computer simulations (Parker in Synthese 169(3):483–496, 2009; Morrison in Philos Stud 143(1):33–57, 2009), the nature of computer data (Barberousse and Vorms, in: Durán, Arnold (eds) Computer simulations and the changing face of scientific experimentation, Cambridge Scholars Publishing, Barcelona, 2013; Humphreys, in: Durán, Arnold (eds) Computer simulations and the changing face of scientific experimentation, Cambridge Scholars Publishing, Barcelona, 2013), and the explanatory power of computer simulations (Krohs in Int Stud Philos Sci 22(3):277–292, 2008; Durán in Int Stud Philos Sci 31(1):27–45, 2017). The aim of this article is to show that these authors are right in assuming that results of computer simulations are to be trusted when computer simulations are reliable processes. After a short reconstruction of the problem of epistemic opacity, the article elaborates extensively on computational reliabilism, a specified form of process reliabilism with computer simulations located at the center. The article ends with a discussion of four sources for computational reliabilism, namely, verification and validation, robustness analysis for computer simulations, a history of (un)successful implementations, and the role of expert knowledge in simulations.



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Focal adhesion kinase activation limits efficacy of Dasatinib in c‐Myc driven hepatocellular carcinoma

Cancer Medicine, EarlyView.


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A randomised controlled trial of an advance care planning intervention for patients with incurable cancer

A randomised controlled trial of an advance care planning intervention for patients with incurable cancer

A randomised controlled trial of an advance care planning intervention for patients with incurable cancer, Published online: 29 October 2018; doi:10.1038/s41416-018-0303-7

A randomised controlled trial of an advance care planning intervention for patients with incurable cancer

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A randomised controlled trial of an advance care planning intervention for patients with incurable cancer



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The electrodiagnosis of Guillain-Barré syndrome subtypes: where do we stand?

In 2012 we reviewed the criteria employed for the electrodiagnosis of Guillain-Barré syndrome (GBS) cautioning about their inadequacy and advocating the development of more reliable criteria sets (Uncini and Kuwabara, 2012). This was timely because since the 1990s the electrodiagnosis of GBS have become more complicated because besides acute inflammatory demyelinating polyradiculoneuropathy (AIDP), two primary axonal subtypes: acute motor axonal neuropathy (AMAN) and acute motor and sensory axonal neuropathy (AMSAN), associated with antecedent Campylobacter jejuni infection and autoantibodies against gangliosides were recognized.

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Your guide to improving your EMS agency's safety culture (eBook)

Learn about the biggest drivers of transforming a fear-based culture into a Just Culture

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A Plate Competition Assay As a Quick Preliminary Assessment of Disease Suppression

Presented is a protocol for a plate competition assay to identify whether a specific compost is likely to contain bacteria and fungi that suppress growth of Rhizoctonia solani.

https://ift.tt/2RlhE0e

Morphology-Based Distinction Between Healthy and Pathological Cells Utilizing Fourier Transforms and Self-Organizing Maps

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Here, we provide a workflow that allows the identification of healthy and pathological cells based on their 3-dimensional shape. We describe the process of using 2D projection outlines based on the 3D surfaces to train a Self-Organizing Map that will provide objective clustering of the investigated cell populations.

https://ift.tt/2Q2guq4

Conducting Multiple Imaging Modes with One Fluorescence Microscope

Here we present a practical guide of building an integrated microscopy system, which merges conventional epi-fluorescent imaging, single-molecule detection-based super-resolution imaging, and multi-color single-molecule detection, including single-molecule fluorescence resonance energy transfer imaging, into one set-up in a cost-efficient way.

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Expression of EMT regulators TWIST, SLUG, and SNAIL in follicular thyroid tumours may relate to widely invasive, poorly differentiated, and distant metastasis

Histopathology, Volume 0, Issue ja, -Not available-.


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Metal‐Organic Framework Encapsulation Preserves the Bioactivity of Protein Therapeutics

Advanced Healthcare Materials, EarlyView.


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CC Nerd-The Case of the Subjective Truth

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A recent post examining the utility of cricoid pressure and how to interpret non-inferiority trials stimulated discussion on Bayesian analysis and the question of whether a formal quantitative analysis is necessary or if an informal qualitative assessment is adequate. A recent reanalysis of the EOLIA trial published in JAMA by Goligher et al1 allows us to […]

EMCrit Project by Rory Spiegel.



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Newborn Metabolic Profile Associated with Hyperbilirubinemia With and Without Kernicterus

Clinical and Translational Science, EarlyView.


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Facile Engineering of Long‐Term Culturable Ex Vivo Vascularized Tissues Using Biologically Derived Matrices

Advanced Healthcare Materials, EarlyView.


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Dual Polymerizations: Untapped Potential for Biomaterials

Advanced Healthcare Materials, EarlyView.


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Electrocardiographic Effects of a Supratherapeutic Dose of WCK 2349, a benzoquinolizine fluoroquinolone

Clinical and Translational Science, Volume 0, Issue ja, -Not available-.


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Randomized placebo‐controlled trial of droperidol and ondansetron for adult emergency department patients with nausea

Academic Emergency Medicine, Volume 0, Issue ja, -Not available-.


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Lung‐Protective Ventilation for Acute Respiratory Distress Syndrome

Academic Emergency Medicine, Volume 0, Issue ja, -Not available-.


https://ift.tt/2z8cCwK

A case report of infantile cystic nephroblastoma

Nephroblastoma (NB) is a malignant embryonal neoplasm derived from nephrogenic blastemal cells. NB usually forms a solid mass, but in extremely rare cases, it may show cystic changes.

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Cover Image

Hepatology, Volume 68, Issue 5, November 2018.


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CD2‐Associated Protein Contributes to Hepatitis C, Virus Propagation and Steatosis by Disrupting Insulin Signaling

Hepatology, Volume 68, Issue 5, Page 1710-1725, November 2018.


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Table of contents

Hepatology, Volume 68, Issue 5, November 2018.


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Notices

Hepatology, Volume 68, Issue 5, November 2018.


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Masthead

Hepatology, Volume 68, Issue 5, November 2018.


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Instructions to Authors

Hepatology, Volume 68, Issue 5, November 2018.


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Potential Clinical Targets in Hepatopulmonary Syndrome: Lessons From Experimental Models

Hepatology, Volume 68, Issue 5, Page 2016-2028, November 2018.


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Hepatology Highlights

Hepatology, Volume 68, Issue 5, Page 1665-1667, November 2018.


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Intrahepatic T‐Cell Receptor β Immune Repertoire Is Essential for Liver Regeneration

Hepatology, Volume 68, Issue 5, Page 1977-1990, November 2018.


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10‐year recurrence rates for breast cancer subtypes in the Netherlands: A large population‐based study

International Journal of Cancer, Volume 0, Issue ja, -Not available-.


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Strongyloidosis Hyperinfection Syndrome in an HIV-Infected Patient: A Rare Manifestation of Immune Reconstitution Inflammatory Syndrome

Parasitic infections such as Strongyloides stercoralis and HIV have been reported to coexist, particularly in resource-limited settings such as India. In an immunocompromised host, S. stercoralis can progress to strongyloidiasis hyperinfection syndrome (SHS). However, SHS is not common in patients with advanced HIV disease. Immune reconstitution inflammatory syndrome (IRIS) developing after initiation of antiretroviral therapy (ART) can target multiple pathogens including S. stercoralis. The authors present here a 46-year-old HIV-infected female who was recently diagnosed with HIV-1 infection, started ART, and developed SHS. Her upper GI endoscopy revealed severe gastroduodenitis, and X-ray chest showed extensive bilateral pneumonitis. We could identify S. stercoralis in induced sputum and duodenal biopsy. We could also identify gut inflammation to restrict invading parasites. After receiving antihelminthic therapy, she showed improvement, a course of events that fit the diagnosis of unmasking S. stercoralis IRIS.

https://ift.tt/2JpeKF6

Cancers, Vol. 10, Pages 405: In Vivo Evaluation of a New Recombinant Hyaluronidase to Improve Gene Electro-Transfer Protocols for DNA-Based Drug Delivery against Cancer

Cancers, Vol. 10, Pages 405: In Vivo Evaluation of a New Recombinant Hyaluronidase to Improve Gene Electro-Transfer Protocols for DNA-Based Drug Delivery against Cancer

Cancers doi: 10.3390/cancers10110405

Authors: Robertis Pasquet Loiacono Bellard Messina Vaccaro Pasquale Fazio Rols Teissie Golzio Signori

Cancer vaccines based on plasmid DNA represent a good therapeutic perspective, despite their low potency. Animal-derived hyaluronidases (Hyals) are employed in oncological clinical practice. Hyal has been also demonstrated to be a good enhancer of intramuscular Gene Electro-Transfer (GET) efficiency in anti-cancer preclinical protocols, with increased transfected cells and higher expression of the encoded genes. Nevertheless, the use of animal-derived Hyals results limited respect to their potentialities, since such preparations could be affected by low purity, variable potency and uncertain safety. To improve the delivery of intramuscular GET-based protocols in mouse, we investigated a new recombinant Hyal, the rHyal-sk, to assess in vivo safety and activity of this treatment at cellular and biochemical levels. We evaluated the cellular events and the inflammation chemical mediators involved at different time points after rHyal-sk administration plus GET. Our results demonstrated the in vivo safety and efficacy of rHyal-sk when injected once intramuscularly in association with GET, with no toxicity, good plasmid in-take ability, useful inflammatory response activation, and low immunogenicity. Following these findings, we would recommend the use of the new rHyal-sk for the delivery of DNA-based vaccines and immunotherapy, as well as into clinical practice, for tumor disease treatments.



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Simultaneous monitoring of Ca2+ responses and salivary secretion in live animals reveals a threshold intracellular Ca2+ concentration for salivation

Experimental Physiology, Volume 0, Issue ja, -Not available-.


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AutoTube: a novel software for the automated morphometric analysis of vascular networks in tissues

Abstract

Due to their involvement in many physiologic and pathologic processes, there is a great interest in identifying new molecular pathways that mediate the formation and function of blood and lymphatic vessels. Vascular research increasingly involves the image-based analysis and quantification of vessel networks in tissue whole-mounts or of tube-like structures formed by cultured endothelial cells in vitro. While both types of experiments deliver important mechanistic insights into (lymph)angiogenic processes, the manual analysis and quantification of such experiments are typically labour-intensive and affected by inter-experimenter variability. To bypass these problems, we developed AutoTube, a new software that quantifies parameters like the area covered by vessels, vessel width, skeleton length and branching or crossing points of vascular networks in tissues and in in vitro assays. AutoTube is freely downloadable, comprises an intuitive graphical user interface and helps to perform otherwise highly time-consuming image analyses in a rapid, automated and reproducible manner. By analysing lymphatic and blood vascular networks in whole-mounts prepared from different tissues or from gene-targeted mice with known vascular abnormalities, we demonstrate the ability of AutoTube to determine vascular parameters in close agreement to the manual analyses and to identify statistically significant differences in vascular morphology in tissues and in vascular networks formed in in vitro assays.



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Issue Information

Chemical Biology &Drug Design, Volume 92, Issue 5, Page 1819-1821, November 2018.


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N‐Pyridin‐2‐yl Benzamide Analogues as Allosteric Activators of Glucokinase: Design, Synthesis, In Vitro, In Silico and In Vivo Evaluation

Chemical Biology &Drug Design, Volume 0, Issue ja, -Not available-.


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Cover Image

Chemical Biology &Drug Design, Volume 92, Issue 5, Page i-i, November 2018.


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A Rare Culprit of Spontaneous Abortion, Latent Tuberculosis Complicated by Disseminated Peritoneal TB

This is a case of a 38-year-old female with latent TB complicated by disseminated peritoneal TB with associated spontaneous abortion, who was initially thought to have an ovarian neoplasm, prompting extensive workup. Laparoscopy with biopsy later confirmed the patient's condition; she was initiated on the appropriate therapy and had a full recovery.

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Upregulation of AKR1C1 and AKR1C3 expression in OPSCC with integrated HPV16 and HPV‐negative tumors is an indicator of poor prognosis

International Journal of Cancer, Volume 0, Issue ja, -Not available-.


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Cost‐effectiveness of Breast Cancer Screening Programme for Women in Rural China

International Journal of Cancer, Volume 0, Issue ja, -Not available-.


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Cancer‐associated fibroblasts (CAFs) promote the lymph node metastasis of esophageal squamous cell carcinoma

International Journal of Cancer, Volume 0, Issue ja, -Not available-.


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Inflammation‐induced overexpression of microRNA‐223‐3p regulates odontoblastic differentiation of human dental pulp stem cells by targeting SMAD3

International Endodontic Journal, Volume 0, Issue ja, -Not available-.


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