bluuebunny/crossref_metadata_2025 huggingface dataset:
Initial tacrolimus weight-based dosing strategy in allogeneic hematopoietic stem-cell transplantation
Authors: Soskind Rose , Xiang Elaine , Lewis Tyler , Al-Homsi A. Samer , Papadopoulos John , Cirrone Frank
Published: September 2020

Tacrolimus is a mainstay medication for graft-versus-host disease (GVHD) prophylaxis in combination with other immunosuppressive agents. Achieving therapeutic tacrolimus levels is vital in preventing acute GVHD (aGVHD), while supratherapeutic levels may increase risk of toxicity and relapse. We performed a single center retrospective chart review including all adult patients post-allogeneic hematopoietic stem-cell transplantation who received initial tacrolimus continuous intravenous infusion for GVHD prophylaxis between June 1, 2017 and December 31, 2019. The primary outcome was the percent of patients with an initial therapeutic tacrolimus level, defined as 5–12 ng/mL, after empiric weight-based dosing at 0.02 mg/kg/day. Secondary outcomes included evidence of tacrolimus toxicity within seven days of initiation, incidence of aGVHD by day 100, and relapse after six months. An initial therapeutic level was achieved in 47% of patients with a median initial level of 12.4 ng/mL. Fifty-two percent of patients had supratherapeutic levels. No significant nephrotoxicity, hepatotoxicity, or neurotoxicity occurred within a week of starting tacrolimus or at neutrophil engraftment. Grade II-IV aGVHD by day 100 was observed in 22% of patients, and relapse after six months was found in 16% of patients. These results have led to consideration of an empiric 20% dose reduction to 0.016 mg/kg/day or an expanded initial tacrolimus target of 5–15 ng/mL as there was low aGVHD incidence and no increased risk of toxicity.
Postpartum Depression: A Metaphorical Analysis
Authors: Beck Cheryl Tatano
Published: September 2020

Background:

The reported incidence of postpartum depression in healthy women without a history of depression was 12%, and the prevalence was 17%. A silent health crisis in America is the undiagnosed and untreated mental health of women related to childbirth. Unfamiliar with medical terminology, persons may communicate more effectively by means of metaphors to describe what they are experiencing.

Aims:

To examine the language women used to describe their experiences of postpartum depression with metaphors that can provide a valuable source of insight for psychiatric nurses and other clinicians.

Methods:

Secondary qualitative data analysis of three primary datasets of postpartum depression was conducted. Metaphor identification procedure was the approach used to analyze the texts for metaphorical expressions.

Results:

Eleven metaphors were identified that women used to help explain their postpartum depression: being hit by a ton of bricks, being a tightrope walker, living in a nightmare, feeling trapped, being in the middle of the sea, feeling like an alien, being a loner, being a basket case, having cobwebs in the brain, feeling like garbage, and hitting rock bottom.

Conclusions:

These 11 metaphors provide a new voice for women’s experiences of postpartum depression. As a result, they provide rich insights for psychiatric nurses and other clinicians to help identify women struggling with postpartum depression.
Three alternative versions of the theory for a Timoshenko–Ehrenfest beam on a Winkler–Pasternak foundation
Authors: Tonzani Giulio Maria , Elishakoff Isaac
Published: September 2020

This paper analyzes the free vibration frequencies of a beam on a Winkler–Pasternak foundation via the original Timoshenko–Ehrenfest theory, a truncated version of the Timoshenko–Ehrenfest equation, and a new model based on slope inertia. We give a detailed comparison between the three models in the context of six different sets of boundary conditions. In particular, we analyze the most common combinations of boundary conditions deriving from three typical end constraints, namely the simply supported end, clamped end, and free end. An interesting intermingling phenomenon is presented for a simply-supported (S-S) beam together with proof of the ‘non-existence’ of zero frequencies for free-free (F-F) and simply supported-free (S-F) beams on a Winkler–Pasternak foundation.
Quality factor of circular microdiaphragm with surface effects in contact with liquids
Authors: Zhang RM , Zhou SS , Li AQ
Published: September 2020

This paper reports an investigation of the influences of surface effects and residual stress on the quality factor of a circular microdiaphragm in contact with liquids on one side. Acoustic radiation, as the main source of energy dissipation, can decrease the quality factor of a circular microdiaphragm. An approximate solution for the natural frequency can be obtained based on the Rayleigh–Ritz energy method. The results show that the influence of surface effects on the quality factor is obvious, in particular for thinner microdiaphragms. A stiffened surface decreases the quality factor, while a softened surface increases it. Furthermore, the quality factor increases with increases in the normalized tension parameter k for both stiffened and softened surfaces. If k is greater than 30, the influence of the surface effects on the quality factor must be considered. The results can provide effective guidance for the determination of dimensions and selection of material parameters in designing microdiaphragm resonant sensors.
Tobacco Use Among the Youth in India: Evidence From Global Adult Tobacco Survey-2 (2016-2017)
Authors: Grover Shekhar , Anand Tanu , Kishore Jugal , Tripathy Jaya Prasad , Sinha Dhirendra N
Published: September 2020

Background:

Worldwide, tobacco use is a serious public health concern affecting the youth. A vast majority of tobacco users start using tobacco well before the age of 18 years which has enormous psychosocial and health effects.

Objectives:

To estimate the prevalence of individual forms of tobacco usage among youth aged 15 to 24 years and to assess the association of sociodemographic factors with tobacco use.

Methods:

The source of data was a cross-sectional GATS-2 survey in India (analysed using SPSSv17.0) which used a multistage, geographically stratified cluster sampling method. Bivariate analysis was done for evaluation of the possible association of tobacco use with sociodemographic factors. Multivariable logistic regression analysis was conducted to determine the relative strength of association between those factors and tobacco use.

Results:

There were 13 329 respondents (44.9% males and 55.1% females) aged 15 to 24 years. Overall, 11.9% of respondents were using tobacco. The prevalence of smoke and smokeless tobacco usage was 5% and 10.9%, respectively, whereas 2% of respondents reported dual usage. The odds of using any form of tobacco were significantly higher among respondents aged 20 to 24 years (odds ratio [OR]: 2 [1.76-2.77]) who were primarily residing in rural areas (adjusted odds ratio [aOR]: 1.36 [1.2-1.54]) and were unmarried (aOR: 1.56 [1.37-1.88]). The odds of using any form of tobacco were significantly lower among females (aOR: 0.21 [0.19-0.24]), literate individuals (aOR: 0.33 [0.29-0.37]), and those who were unemployed/students/homemakers (aOR: 0.44 [0.39-0.50]).

Conclusions:

The overall tobacco usage of 11.9% among young people in the age group of 15 to 24 years is a matter of concern. The study identified several sociodemographic factors significantly associated with tobacco use, implying the need for designing interventions considering social vulnerabilities of youth.
The spatial heterogeneity and dynamics of tourism-flow spillover effect: The role of high-speed train in China
Authors: Zhou Bo , Wen Zhihong , Sutherland Ian , Lee Seul Ki
Published: September 2020

The existing literature has not fully explored the spatial heterogeneity and dynamics of spillover effects of tourism-flow patterns, and this article makes contributions to addressing this issue. Using spatial autoregressive models and comparing the results for the non-high-speed train (HST) era (2002–2006) and those for the HST era (2011–2015) of China, this article finds that in the HST era, the spillover effect of tourism flows from neighboring regions has changed from positive to negative. Moreover, in the HST era, the cities with HST services have significantly positive effects on for a particular city, while those cities without HST have negative effects. These results reveal the spatial heterogeneity and dynamics of the tourism-flow spillover. After evaluating the variation of other factors which potentially contribute to the change of spillover patterns, this study identifies that the HST service plays an important role in such changes. Finally, this article uses geographically weighted regressions to explore the spatial heterogeneity in an elaborative way.
Using mixed methods in health services research: A review of the literature and case study
Authors: de Haan Maarten , van Eijk-Hustings Yvonne , Vrijhoef Hubertus JM
Published: September 2020

Objective

To provide an overview of the challenges of conducting mixed methods research (MMR) in the context of health services research (HSR) and to discuss a case study example of the triangulation procedures used in a MMR study on task-shifting in the Netherlands.

Method

A narrative literature review of publications between January 2000 and February 2020 on the use of mixed methods in the context of HSR and a description of the triangulation procedures in an HSR study with a MMR design on task shifting in the Netherlands.

Results

The narrative review identified eight challenges. Those related to publishing and appraisal of MMR within HSR were most frequently reported (e.g. ‘lack of MMR examples’, ‘lack of recognition’ and ‘triangulation issues’). Also, practical problems for conducting MMR within HSR were identified (e.g. ‘lack or resources’, ‘teamwork’ and ‘lack of quality criteria’). Methodological challenges (e.g. ‘sampling’ and ‘paradigm wars’) were less frequently reported as a challenge.

Conclusion

While increasing in popularity, there remain a range of challenges for the design, conduct and reporting of MMR designs in HSR. Using a triangulation protocol can potentially help address some of these challenges.
One-Year Outcomes of Heparin-Bonded Stent-Graft Therapy for Real-World Femoropopliteal Lesions and the Association of Patency With the Prothrombotic State Based on the Prospective, Observational, Multicenter Viabahn Stent-Graft Placement for Femoropopliteal Diseases Requiring Endovascular Therapy (VANQUISH) Study
Authors: Iida Osamu , Takahara Mitsuyoshi , Soga Yoshimitsu , Yamaoka Terutoshi , Nanto Shinsuke , Kuratani Toru , Sakata Yasushi , Mano Toshiaki
Published: September 2020

Purpose:

To evaluate the real-world primary patency of heparin-bonded stent-graft therapy for femoropopliteal (FP) occlusive disease and identify any clinical factors, including the prothrombotic state, associated with the loss of patency.

Materials and Methods:

This multicenter study prospectively enrolled 424 limbs of 371 patients (mean age 75±8 years; 247 men) scheduled for Viabahn stent-graft placement in the FP segment. A full-coverage strategy using only a Viabahn stent-graft was preferred, but “spot stenting” with the Viabahn was also allowed. The prothrombotic state was assessed by measuring platelet reactivity. Vascular morphology was evaluated using intravascular ultrasound (IVUS). Primary patency was estimated using the Kaplan-Meier method in the subgroup of patients having full lesion stent-graft coverage (n=343 limbs, 81.1%). The secondary outcomes were major amputation, surgical reconstruction, target lesion revascularization (TLR), and thrombotic occlusion. Regression analyses were used to explore associations of baseline and clinical variables with loss of patency; the results are given as the odds ratio (OR) and 95% confidence interval (CI).

Results:

The 1-year primary patency estimate was 80.3% (95% CI 75.5% to 85.1%) in the full-coverage group. There were 7 surgical reconstructions, 46 TLRs, 21 acute thrombotic occlusions, and 1 major amputation during the 1-year follow-up in the full-coverage group. Only angiography- and IVUS-determined vessel diameters were significantly associated with loss of patency, with crude ORs of 0.64 (95% CI 0.45 to 0.89, p=0.009) and 0.67 (95% CI 0.51 to 0.90, p=0.009), respectively, per 1-mm increase, whereas other variables, including the prothrombotic state (p=0.74), were not. Multivariable analysis demonstrated that only IVUS-determined vessel diameter was independently associated with loss of patency (adjusted OR per 1-mm increase 0.72, 95% CI 0.52 to 1.00, p=0.049).

Conclusion:

FP stent-graft placement achieved acceptable patency at 1 year in a real-world setting. A smaller vessel size was significantly associated with loss of patency, whereas the prothrombotic state was not.
Comparing distributions of ordinal data
Authors: Jenkins Stephen P.
Published: September 2020

To compare distributions of ordinal data such as individuals’ responses on Likert-type scale variables summarizing subjective well-being, we should not apply the toolbox of methods developed for cardinal variables such as income. Instead, we should use an analogous toolbox that accounts for the ordinal nature of the responses. In this article, I review these methods and introduce a new command, ineqord, for undertaking distributional comparisons. As the empirical illustrations demonstrate, ineqord can be used for dominance checks as well as for estimation of indices of polarization and inequality.
Global robust super-twisting algorithm with adaptive switching gains for a hybrid robot
Authors: Gao Guoqin , Zhang Songyun , Ye Mengyang
Published: September 2020

To improve the robustness performance of dynamic sliding mode control to the time-varying uncertainties without the upper bound information in a hybrid robot system, a global robust super-twisting algorithm with adaptive switching gains is proposed. The main contributions are as follows: (1) for the problem that the robustness of the sliding mode control system is not guaranteed in the reaching phase, a global robust sliding surface is designed to eliminate the reaching phase of the sliding mode control; (2) for the chattering problem existing in the sliding phase of the sliding mode control system due to the conservative selection of switching gains, based on a reconstructive super-twisting sliding mode control and the equivalent principle, a fast-adaptive law is designed to effectively reduce the chattering while the global robustness is ensured. The stability of the proposed algorithm is proved by Lyapunov stability theorem. The simulation and experiment on the hybrid robot prototype system are implemented to verify the effectiveness of the proposed control method.
The use of barbed sutures in the Pulvertaft weave: a biomechanical study
Authors: Xing Fu Hap Daniel , Rung Wong Yoke , Rajaratnam Vaikunthan
Published: September 2020

The use of barbed sutures in tendon repair and reconstruction is advantageous because it allows for a knotless suturing technique. In this biomechanical study, we compared barbed sutures with conventional sutures in tendon transfers using the Pulvertaft weave technique in a human cadaveric model. Thirty human cadaveric finger flexor tendons were transected and divided into three groups of ten tendons, which were then reconstructed by the Pulvertaft weave technique using 3-0 Prolene (Ethicon, Inc., Somerville, NJ, USA), 3-0 Ethilon (Ethicon, Inc., Somerville, NJ, USA) or 3-0 V-Loc (Covidien Deutschland GmbH, Neustadt, Germany) sutures. Biomechanical testing showed that repairs in the V-Loc group had significantly greater ultimate tensile strength and stiffness than conventional sutures. The time taken to complete the weave and the length of sutures used were also the least in the V-Loc group. Our study has shown that the barbed suture has a better biomechanical performance than conventional suture types when used in the Pulvertaft weave technique.
Study of Components and Mechanism of Juechuang Against Platelet Aggregation Based on Network Pharmacology
Authors: Xie Zhou-Tao , Liu Bo , Xiong Yi-yi , Yang Yan-Fang , Wu He-Zhen
Published: September 2020

Juechuang, a traditional Chinese herbal medicine, is originated from Rostellularia procumbens (L.) Nees. Many studies have shown that the ethyl acetate extract from Juechaung may inhibit platelet aggregation. However, the antiplatelet aggregation mechanism of Juechuang requires more systematic research. In this article, network pharmacology was used to explore the antiplatelet aggregation components and its antiplatelet aggregation mechanism. Different components were evaluated and screened by pharmacokinetic characteristics. The potential targets of active ingredients were predicted by a reverse pharmacophore matching method, and the targets were screened according to targets related to antiplatelet aggregation in the GeneCards database. Thus, an interaction network of component-target-pathway of Juechuang was generated using Cytoscape 3.2.1. software. Furthermore, the binding energy of relevant active components with key targets was calculated using a Lamarck genetic algorithm in the molecular docking calculations. Finally, the study identified 28 potentially active ingredients in Juechuang, providing further evidence that the active ingredients act on 277 targets, and 38 protein targets related to antiplatelet aggregation were screened. Through the Kyoto encyclopedia of genes and genome pathway enrichment analysis, we found that the mechanism of antiplatelet aggregation may be related to the Ras signaling pathway, platelet activation signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, etc. Via molecular docking of 2 targets, non-receptor tyrosine kinases(SRC) and MAPK were selected for molecular docking. By comparing the molecular docking results of Chinensinaphthol, Taiwanin E, Tuberculatin, Cycloeucalenol, and Justicidin B to the control drug, we found that those test molecules combined with targets and lead to high binding activity. These molecular docking results were also consistent with the literature values, and they helped identify the active ingredients and assured the reliability of the network analysis. This study may further provide a reference for the systematic study of the pharmacodynamic effect and the antiplatelet aggregation mechanism of Juechuang.
A novel program of self-administration of medications within an acute inpatient rehabilitation unit
Authors: Meng Kwok Kah , Chao Wee Tze , San San Tay
Published: September 2020

Introduction:

Self-administration of medications (SAM) is a critical component of independent living in the face of chronic illnesses. The current local practice, where nurses manage all aspects of inpatient medication administration, has significant limitations in promoting this important activity post-discharge. Inpatient SAM is considered novel in Singapore. In this paper, we aim to describe the process of establishing a SAM program in a local rehabilitation inpatient ward.

Materials and methods:

In 2016, a multidisciplinary workgroup was formed in a local general hospital to develop a SAM protocol to empower participants to better self-manage their medications post-discharge through a series of graduated assessments and targeted education. The program started as a pilot in April 2017, and was eventually expanded to all rehabilitation wards within the hospital. Medication errors and near-misses were tracked, and surveys targeting participating patients and staff were given at the end of each encounter.

Results:

As of 31 December 2019, 160 patients were enrolled into the SAM program. Of these, 75, 63 and 22 patients were in SAM 1, SAM 2 and SAM 3 (tiers representing differing independence levels), respectively, at discharge. There were no medication errors. One near-miss was reported. The program was well-received by both patients and staff.

Conclusions:

We present a novel and viable protocol for the inpatient selection and assessment of patients, with the aim of supporting safe SAM post-discharge through educational empowerment and early identification of barriers with interventions.
Introducing the UCDP Candidate Events Dataset
Authors: Hegre Håvard , Croicu Mihai , Eck Kristine , Högbladh Stina
Published: September 2020

This article presents a new, monthly updated dataset on organized violence—the Uppsala Conflict Data Program Candidate Events Dataset. It contains recent observations of candidate events, a majority of which are eventually included in the Uppsala Conflict Data Program Georeferenced Event Dataset as part of its annual update after a careful vetting process. We describe the definitions, sources and procedures employed to code the candidate events, and a set of issues that emerge when coding data on organized violence in near-real time. Together, the Uppsala Conflict Data Program Candidate and Georeferenced Event Datasets minimize an inherent trade-off between update speed and quality control. Having monthly updated conflict data is advantageous for users needing near-real time monitoring of violent situations and aiming to anticipate future developments. To demonstrate this, we show that including them in a conflict forecasting system yields distinct improvements in terms of predictive performance: Average precision increases by 20–40% relative to using the Uppsala Conflict Data Program Georeferenced Event Dataset only. We also show that to ensure quality and consistency, revisiting the initial coding making use of sources that become available later is absolutely necessary.
Accuracy of Peripheral Arterial Disease Registers in UK General Practice: Case-Control Study
Authors: Kyle Daniel , Boylan Luke , Wilson Lesley , Haining Shona , Oates Crispian , Sims Andrew , Guri Ina , Allen John , Wilkes Scott , Stansby Gerry
Published: September 2020

Background:

Approximately 20% of the UK population aged 55 to 75 years have evidence of peripheral arterial disease (PAD). PAD affects quality of life and life expectancy if not appropriately diagnosed and managed. At risk patients require accurate diagnosis to ensure optimal treatment to slow disease progression and minimize adverse outcomes.

Aim:

To assess the accuracy of general practice (GP) registration of the diagnosis of peripheral arterial disease (PAD).

Design and Setting:

An observational analytic case-control study. As part of a National Institute for Health Research–funded (ISRCTN13301188) project assessing novel diagnostic methods set in GP practice.

Methods:

A total of 125 patients registered as having PAD and 125 age- and sex-matched controls were recruited from 15 general practices across North East England. The register was then assessed for accuracy of diagnosis. Duplex vascular ultrasound scanning (DUS) undertaken by vascular scientists was used as the gold standard reference for PAD.

Results:

The PAD register had a sensitivity of 86% (95% CI 77%-92%) and specificity of 74% (95% CI 67%-81%) when compared with DUS. The positive predictive value, however, was 69.6% (95% CI 63%-75%) and negative predictive value 88.8% (95% CI 82%-92%). The overall diagnostic effectiveness of the PAD register was 79.2% (95% CI 73%-84%).

Conclusion:

This analysis indicates that while PAD is detected with reasonable sensitivity in primary care, many patients registered with a diagnosis of PAD lacked DUS-proven disease. Improved approaches to the objective diagnosis of PAD may improve diagnosis and management of PAD in primary care.
Effect of periarticular multimodal injection versus femoral nerve block on in-hospital rehabilitation after total knee arthroplasty in Chinese population: A prospective randomized control trial study
Authors: Yeung Ip Hoi , Kan Yeung Yip , Cheong Lo Kim , Andy Tse Choi Yeung , Ho Wong Kwok
Published: September 2020

Introduction:

Total knee arthroplasty has been adopted to be the most successful treatment for advanced knee osteoarthritis. The adoption of multimodal periarticular analgesic (MPI) has been shown to have satisfactory pain control after surgery. However, there is relatively lack of data investigating whether this mode of pain control is effective in enhancing rehabilitation.

Method:

This is a prospective randomized control trial from July 2017 to June 2018, including 82 patients, in which 43 of them had MPI injection and 39 of them had no MPI injection. Primary outcome measures included the number of days required to perform straight leg raise, length of hospital stay, and Insall knee score upon discharge. Secondary outcome measures included total dose of patient-controlled analgesia (PCA) consumption postoperatively and visual analog scale (VAS) at rest and on motion during postoperative days 1–4.

Result:

The MPI group performed significantly better than the femoral nerve block (FNB) group in terms of early functional outcome, namely the number of days required to perform straight leg raising and length of hospital stay. The total postoperative PCA consumption and VAS score on motion during postoperative day 1 were also significantly better for MPI group. There was no difference in Insall knee score upon discharge between these two groups.

Conclusion:

Compared to FNB, MPI depicts a faster inpatient rehabilitation, accounted by its quadriceps-sparing, and better pain relief especially in the early postoperative period.
Comparison Between Surgical and Nonsurgical Treatment for Primary Patellar Dislocations in Adolescents: A Systematic Review and Meta-analysis of Comparative Studies
Authors: Zhang Kaibo , Jiang Hua , Li Jian , Fu Weili
Published: September 2020

Background:

Whether surgical or nonsurgical management is more appropriate for primary patellar dislocations (PPDs) in adolescents (younger than 18 years) remains controversial.

Purpose:

To compare the clinical outcomes of surgical versus nonsurgical treatment for adolescents and children with PPDs.

Study Design:

Systematic review; Level of evidence, 3.

Methods:

There were 2 reviewers who independently searched the PubMed, Embase, Ovid, and Cochrane databases for English-language studies of randomized controlled trials (RCTs), quasi-RCTs, and observational studies comparing surgical with nonsurgical treatment for PPDs. The primary outcomes were redislocations, the Kujala score, and the Knee injury and Osteoarthritis Outcome Score (KOOS), and the secondary outcome was subsequent surgery.

Results:

A total of 6 studies were included in our systematic review and meta-analysis. Among patients younger than 18 years, surgery was associated with a lower redislocation rate compared with nonsurgical treatment within 5 years of treatment (risk ratio [RR], 0.58 [95% CI, 0.37-0.91]; P = .02; I 2 = 47%) but not beyond 5 years (RR, 0.80 [95% CI, 0.59-1.07]; P = .14; I 2 = 34%). However, surgery resulted in worse Kujala and KOOS scores compared with nonsurgical treatment. Yet, the treatment difference between the 2 groups tended to decrease over time.

Conclusion:

The available evidence suggests that for adolescents with PPDs, surgery was superior to nonsurgical treatment in the short term to reduce the redislocation rate but resulted in poorer outcomes of knee function based on the Kujala and KOOS scores. However, the superiority of either surgical or nonsurgical treatment in adolescents did not appear to persist in the long term.
Wikipedia: A Medical Student Educational Project to Edit Wikipedia in Preparation for Practicing Evidence-Based Pain Medicine
Authors: Kantarovich Diana , Vollbrecht Hanna B , Cruz Sebastian A , Castillo Hector , Lee Cody S , Kushner Josef , Leng Jim X , Morgan Vince K , Hellman Kevin M
Published: September 2020

Objective:

Wikipedia is commonly used to acquire information about various medical conditions such as chronic pain. Ideally, better online pain management content could reduce the burden of opioid use disorders. Our goal was to improve the quality of the content available on Wikipedia to make it more accurate and applicable to medical students and the general public while training medical students to practice evidence-based medicine and critically assess their sources of information.

Methods:

An elective class in Neuroscience, Pain, and Opioids composed of 10 medical students met biweekly to discuss landmark and practice-changing research articles in the fields of acute pain, chronic pain, and opioid management. The professor chose Wikipedia articles relevant to this course. Three independent viewers analyzed the quality of citations, anecdotal medical content, and content value for both patients and medical professionals. As part of their coursework, students then edited the Wikipedia articles.

Results:

Although some of the Wikipedia pain topic content (6.7% ± 2.0) was anecdotal, financially biased, or inconsistent with Western Medical Practice content, overall articles included primarily high-quality citations (85.6% ± 3.1). On a 0-5 Likert scale, students felt content would be moderately helpful for both medical students/professionals (3.4 ± 0.2) and laypersons (3.5 ± 0.2). Editing and adding citations was feasible, but novel material was often reverted.

Conclusion:

A significant amount of pain medicine content was relevant and amenable to student editing. Therefore, future use of this tactic could provide a unique opportunity to integrate evidence-based medicine into the medical curriculum and have a direct impact on the widely available medical information. Future refinement in the editorial process may also further improve online information.
Neuroimmunological effects of early life experiences
Authors: Brydges Nichola M. , Reddaway Jack
Published: September 2020

Exposure to adverse experiences during development increases the risk of psychiatric illness later in life. Growing evidence suggests a role for the neuroimmune system in this relationship. There is now substantial evidence that the immune system is critical for normal brain development and behaviour, and responds to environmental perturbations experienced early in life. Severe or chronic stress results in dysregulated neuroimmune function, concomitant with abnormal brain morphology and function. Positive experiences including environmental enrichment and exercise exert the opposite effect, promoting normal brain and immune function even in the face of early life stress. The neuroimmune system may therefore provide a viable target for prevention and treatment of psychiatric illness. This review will briefly summarise the neuroimmune system in brain development and function, and review the effects of stress and positive environmental experiences during development on neuroimmune function. There are also significant sex differences in how the neuroimmune system responds to environmental experiences early in life, which we will briefly review.
Microbial Spectrum and Antibacterial Susceptibility of Endophthalmitis Cultures in a Tertiary Referral Center in the Midwestern United States: An Analysis From 295 Patients
Authors: Gemayel Michael , Neiweem Ashley , Aebi Brent , Bracha Peter , Ciulla Thomas
Published: September 2020

Purpose:

This work evaluates the microbial spectrum and antibiotic susceptibility pattern of endophthalmitis cases in a large tertiary referral center in the Midwestern United States.

Methods:

This retrospective case series included patients with clinically diagnosed endophthalmitis between April 14, 2006 and April 14, 2016, in whom ocular samples were submitted to the Microbiology Department at Indiana University. The patients were assessed by 11 vitreoretinal surgeons from 6 different sites in Indianapolis, including Indiana University and private practices, who receive patients from urban, suburban, and rural agricultural areas. Submitted specimens were cultured with the following media: blood agar, chocolate agar, MacConkey agar, and thioglycolate broth.

Results:

A total of 327 specimens from 295 patients were analyzed, with 96 (32.5%) samples from 90 (30.5%) patients meeting the criteria of confirmed growth. Of these 96 positive specimens, 83 (86.5%) organisms were identified as bacterial, and 13 (13.5%) were identified as fungal. Coagulase-negative Staphylococcus was the most common isolate (37.5%). Fifty gram-positive isolates and 10 gram-negative isolates underwent susceptibility testing. All 40 of the gram-positive isolates tested for vancomycin sensitivity were susceptible, whereas all 7 of the gram-negative isolates tested for ceftazidime sensitivity were susceptible.

Conclusions:

Empiric treatment with vancomycin and ceftazidime remains appropriate in most cases of endophthalmitis in the Midwestern United States, with 100% susceptibility of bacterial organisms tested with these antibiotics in this series. The high fungal culture rates in this study highlight the utility of obtaining vitreous cultures and potential need for antifungal agents in suspicious cases.
Practical guide to genetic screening for inherited eye diseases
Authors: Méjécase Cécile , Malka Samantha , Guan Zeyu , Slater Amy , Arno Gavin , Moosajee Mariya
Published: September 2020

Genetic eye diseases affect around one in 1000 people worldwide for which the molecular aetiology remains unknown in the majority. The identification of disease-causing gene variant(s) allows a better understanding of the disorder and its inheritance. There is now an approved retinal gene therapy for autosomal recessive RPE65-retinopathy, and numerous ocular gene/mutation-targeted clinical trials underway, highlighting the importance of establishing a genetic diagnosis so patients can fully access the latest research developments and treatment options. In this review, we will provide a practical guide to managing patients with these conditions including an overview of inheritance patterns, required pre- and post-test genetic counselling, different types of cytogenetic and genetic testing available, with a focus on next generation sequencing using targeted gene panels, whole exome and genome sequencing. We will expand on the pros and cons of each modality, variant interpretation and options for family planning for the patient and their family. With the advent of genomic medicine, genetic screening will soon become mainstream within all ophthalmology subspecialties for prevention of disease and provision of precision therapeutics.
Covid, racism and Black Lives Matter: A deadly constellation
Authors: Music Graham
Published: September 2020

This paper looks at how people from Black and Minority Ethnic groups have been disproportionately affected by COVID. The paper links this with both psycho-social factors and childhood stress and trauma. It looks at the effects of unconscious racism on the minds and physiology of those affected. The relationship between the impact of stress, trauma, racism and Adverse Childhood Experiences (ACEs) is discussed, and how ACEs are linked with very poor later physical and mental health outcomes. The article suggests that these issues are highly over determined but that for change to occur we need interventions at a range of levels, from the macro-political, psychosocial, individual and economic, including unconscious implicit biases.
Numerical prediction of settlement due to the Pohang earthquake
Authors: Park Sung-Sik , Doan Nhat-Phi , Nong Zhenzhen
Published: September 2020

On 15 November 2017, an earthquake with a magnitude of 5.4 caused geotechnical damage over a wide area of Pohang, South Korea. In this study, the UBCSAND constitutive effective stress model is calibrated by cyclic direct simple shear (CDSS) tests conducted on a type of sand from liquefied paddy fields at Pohang under confining stresses of 100 and 200 kPa. The calibrated UBCSAND model is then used to assess the liquefaction and calculate the ground settlement based on standard penetration test (SPT) data near the epicenter of the Pohang earthquake. The liquefaction characteristics from the UBCSAND model matched those from laboratory tests. According to the numerical results, liquefaction mostly occurred within the uppermost 10 m, and ground surface settlement from excess pore water pressure dissipation varied from 3.86 to 10.95 cm. These settlements were higher than the surface displacement estimated by satellite image analysis with interferometric synthetic aperture radar (InSAR) and lower than the ground subsidence observed solely by visiting the sites.
Noncanonical effector functions of the T-memory–like T-PLL cell are shaped by cooperative TCL1A and TCR signaling
Authors: Oberbeck S. , Schrader A. , Warner K. , Jungherz D. , Crispatzu G. , von Jan J. , Chmielewski M. , Ianevski A. , Diebner H. H. , Mayer P. , Kondo Ados A. , Wahnschaffe L. , Braun T. , Müller T. A. , Wagle P. , Bouska A. , Neumann T. , Pützer S. , Varghese L. , Pflug N. , Thelen M. , Makalowski J. , Riet N. , Göx H. J. M. , Rappl G. , Altmüller J. , Kotrová M. , Persigehl T. , Hopfinger G. , Hansmann M. L. , Schlößer H. , Stilgenbauer S. , Dürig J. , Mougiakakos D. , von Bergwelt-Baildon M. , Roeder I. , Hartmann S. , Hallek M. , Moriggl R. , Brüggemann M. , Aittokallio T. , Iqbal J. , Newrzela S. , Abken H. , Herling M.
Published: September 2020

T-cell prolymphocytic leukemia (T-PLL) is a poor-prognostic neoplasm. Differentiation stage and immune-effector functions of the underlying tumor cell are insufficiently characterized. Constitutive activation of the T-cell leukemia 1A (TCL1A) oncogene distinguishes the (pre)leukemic cell from regular postthymic T cells. We assessed activation-response patterns of the T-PLL lymphocyte and interrogated the modulatory impact by TCL1A. Immunophenotypic and gene expression profiles revealed a unique spectrum of memory-type differentiation of T-PLL with predominant central-memory stages and frequent noncanonical patterns. Virtually all T-PLL expressed a T-cell receptor (TCR) and/or CD28-coreceptor without overrepresentation of specific TCR clonotypes. The highly activated leukemic cells also revealed losses of negative-regulatory TCR coreceptors (eg, CTLA4). TCR stimulation of T-PLL cells evoked higher-than-normal cell-cycle transition and profiles of cytokine release that resembled those of normal memory T cells. More activated phenotypes and higher TCL1A correlated with inferior clinical outcomes. TCL1A was linked to the marked resistance of T-PLL to activation- and FAS-induced cell death. Enforced TCL1A enhanced phospho-activation of TCR kinases, second-messenger generation, and JAK/STAT or NFAT transcriptional responses. This reduced the input thresholds for IL-2 secretion in a sensitizer-like fashion. Mice of TCL1A-initiated protracted T-PLL development resembled such features. When equipped with epitope-defined TCRs or chimeric antigen receptors, these Lckpr-hTCL1Atg T cells gained a leukemogenic growth advantage in scenarios of receptor stimulation. Overall, we propose a model of T-PLL pathogenesis in which TCL1A enhances TCR signals and drives the accumulation of death-resistant memory-type cells that use amplified low-level stimulatory input, and whose loss of negative coregulators additionally maintains their activated state. Treatment rationales are provided by combined interception in TCR and survival signaling.
Mutational landscape of gray zone lymphoma
Authors: Sarkozy Clémentine , Hung Stacy S. , Chavez Elizabeth A. , Duns Gerben , Takata Katsuyoshi , Chong Lauren C. , Aoki Tomohiro , Jiang Aixiang , Miyata-Takata Tomoko , Telenius Adèle , Slack Graham W. , Molina Thierry Jo , Ben-Neriah Susana , Farinha Pedro , Dartigues Peggy , Damotte Diane , Mottok Anja , Salles Gilles A. , Casasnovas Rene-Olivier , Savage Kerry J. , Laurent Camille , Scott David W. , Traverse-Glehen Alexandra , Steidl Christian
Published: September 2020

The mutational landscape of gray zone lymphoma (GZL) has not yet been established, and differences from related entities are largely unknown. Here, we studied coding sequence mutations of 50 Epstein-Barr virus (EBV)-negative GZLs and 20 polymorphic EBV+ diffuse large B-cell lymphoma (DLBCL) not otherwise specified (poly-EBV-L) in comparison with classical Hodgkin lymphoma (cHL), primary mediastinal large B-cell lymphoma (PMBCL), and DLBCL. Exomes of 21 GZL and 7 poly-EBV-L cases, along with paired constitutional DNA, were analyzed as a discovery cohort, followed by targeted sequencing of 217 genes in an extension cohort of 29 GZL and 13 poly-EBV-L cases. GZL cases with thymic niche involvement (anterior mediastinal mass) exhibited a mutation profile closely resembling cHL and PMBCL, with SOCS1 (45%), B2M (45%), TNFAIP3 (35%), GNA13 (35%), LRRN3 (32%), and NFKBIA (29%) being the most recurrently mutated genes. In contrast, GZL cases without thymic niche involvement (n = 18) had a significantly distinct pattern that was enriched in mutations related to apoptosis defects (TP53 [39%], BCL2 [28%], BIRC6 [22%]) and depleted in GNA13, XPO1, or NF-κB signaling pathway mutations (TNFAIP3, NFKBIE, IKBKB, NFKBIA). They also exhibited more BCL2/BCL6 rearrangements compared with thymic GZL. Poly-EBV-L cases presented a distinct mutational profile, including STAT3 mutations and a significantly lower coding mutation load in comparison with EBV− GZL. Our study highlights characteristic mutational patterns in GZL associated with presentation in the thymic niche, suggesting a common cell of origin and disease evolution overlapping with related anterior mediastinal lymphomas.
Human GATA2 mutations and hematologic disease: how many paths to pathogenesis?
Authors: Bresnick Emery H. , Jung Mabel M. , Katsumura Koichi R.
Published: September 2020

The surge of human genetic information, enabled by increasingly facile and economically feasible genomic technologies, has accelerated discoveries on the relationship of germline genetic variation to hematologic diseases. For example, germline variation in GATA2, encoding a vital transcriptional regulator of multilineage hematopoiesis, creates a predisposition to bone marrow failure and acute myeloid leukemia termed GATA2 deficiency syndrome. More than 300 GATA2 variants representing missense, truncating, and noncoding enhancer mutations have been documented. Although these variants can diminish GATA2 expression and/or function, the functional ramifications of many variants are unknown. Studies using genetic rescue and knockin mouse systems have established that GATA2 mutations differentially affect molecular processes in distinct target genes and within a single target cell. Considering that target genes for a transcription factor can differ in sensitivity to altered levels of the factor, and transcriptional mechanisms are often cell type specific, the context-dependent consequences of GATA2 mutations in experimental systems portend the complex phenotypes and interindividual variation of GATA2 deficiency syndrome. This review documents GATA2 human genetics and the state of efforts to traverse from physiological insights to pathogenic mechanisms.
Hypoxia induces the translocation of glucose transporter 1 to the plasma membrane in vascular endothelial cells
Authors: Mamun Abdullah Al , Hayashi Hisaki , Yamamura Aya , Nayeem Md Junayed , Sato Motohiko
Published: September 2020

Glucose uptake and adenosine triphosphate (ATP) generation are important for the survival and growth of endothelial cells. An increase of glucose uptake under hypoxia was previously shown to be associated with the increased expression of glucose transporters (GLUTs). However, the regulation of GLUT trafficking to the cell surface has not been examined in detail. Here, we report the characterization of GLUT1 translocation to the plasma membrane during hypoxia in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were exposed to hypoxia (1% O2) for 12 h, which significantly induced GLUT1 expression and translocation to the plasma membrane. GLUT1 translocation was associated with a decrease of intracellular ATP by hypoxia. Decreasing ATP levels with antimycin-A and 2-deoxyglucose induced GLUT1 translocation under normoxia. The induction of hypoxia-inducible factor-1α under normoxia did not influence the cell surface expression of GLUT1 or cellular ATP concentration. Interestingly, the translocation of GLUT1 induced by hypoxia was inhibited by the ATP-sensitive potassium (KATP) channel inhibitor glibenclamide, while the mitochondrial KATP channel inhibitor 5-HD did not influence GLUT1 translocation during hypoxia. These observations indicate that a decrease of intracellular ATP triggers GLUT1 translocation to the plasma membrane and is mediated by KATP channels, which would contribute to glucose uptake in HUVECs during hypoxia.
Theoretical characterisation of strand cross-correlation in ChIP-seq
Authors: Anzawa Hayato , Yamagata Hitoshi , Kinoshita Kengo
Published: September 2020

Background

Strand cross-correlation profiles are used for both peak calling pre-analysis and quality control (QC) in chromatin immunoprecipitation followed by sequencing (ChIP-seq) analysis. Despite its potential for robust and accurate assessments of signal-to-noise ratio (S/N) because of its peak calling independence, it remains unclear what aspects of quality such strand cross-correlation profiles actually measure.

Results

We introduced a simple model to simulate the mapped read-density of ChIP-seq and then derived the theoretical maximum and minimum of cross-correlation coefficients between strands. The results suggest that the maximum coefficient of typical ChIP-seq samples is directly proportional to the number of total mapped reads and the square of the ratio of signal reads, and inversely proportional to the number of peaks and the length of read-enriched regions. Simulation analysis supported our results and evaluation using 790 ChIP-seq data obtained from the public database demonstrated high consistency between calculated cross-correlation coefficients and estimated coefficients based on the theoretical relations and peak calling results. In addition, we found that the mappability-bias-correction improved sensitivity, enabling differentiation of maximum coefficients from the noise level. Based on these insights, we proposed virtual S/N (VSN), a novel peak call-free metric for S/N assessment. We also developed PyMaSC, a tool to calculate strand cross-correlation and VSN efficiently. VSN achieved most consistent S/N estimation for various ChIP targets and sequencing read depths. Furthermore, we demonstrated that a combination of VSN and pre-existing peak calling results enable the estimation of the numbers of detectable peaks for posterior experiments and assess peak calling results.

Conclusions

We present the first theoretical insights into the strand cross-correlation, and the results reveal the potential and the limitations of strand cross-correlation analysis. Our quality assessment framework using VSN provides peak call-independent QC and will help in the evaluation of peak call analysis in ChIP-seq experiments.
Intermittent hypoxia reduces infarct size in rats with acute myocardial infarction: a systematic review and meta-analysis
Authors: Hu Ke , Deng Wei , Yang Jing , Wei Yu , Wen Chaolin , Li Xingsheng , Chen Qingwei , Ke Dazhi , Li Guiqiong
Published: September 2020

Background

To determine whether intermittent hypoxia (IH) can reduce the infarct size (IS) after acute myocardial infarction (AMI) in rats.

Methods

Articles were identified in PubMed, EMBASE and the Web of Science and were included if they evaluated the effect of IH on the changes in the infarcted area after AMI in rats.

Results

A preliminary search identified 3633 articles and 29 data sets from 23 articles (12 in vivo, 16 in vitro). The IS decreased after AMI in IH rats both in vitro (SMD -1.46, 95% CI [− 2.37, − 0.55]; I2 = 85.6%,P = 0.000) and in vivo (SMD -1.43, 95% CI [− 2.05, − 0.82], I2 = 73.6%,P = 0.000). Sensitivity analysis indicated that IH had a strong protective effect against myocardial infarction, and the hypoxia concentration was significantly correlated with the change in IS after AMI.

Conclusion

IH can reduce IS after AMI in rats. This effect of IH may be related to the dose of hypoxia, and the oxygen concentration may be one of the most important influencing factors.