bluuebunny/crossref_metadata_2025 huggingface dataset:
Provider attitudes about childhood tuberculosis prevention in Lesotho: a qualitative study
Authors: Hirsch-Moverman Yael , Mantell Joanne E. , Lebelo Limakatso , Howard Andrea A. , Hesseling Anneke C. , Nachman Sharon , Frederix Koen , Maama Llang Bridget , El-Sadr Wafaa M.
Published: May 2020

Background

The World Health Organization estimated that 1.12 million children developed tuberculosis (TB) in 2018, and at least 200,000 children died from TB. Implementation of effective child contact management is an important strategy to prevent childhood TB but these practices often are not prioritized or implemented, particularly in low- and middle-income countries. This study aimed to explore attitudes of healthcare providers toward TB prevention and perceived facilitators and challenges to child contact management in Lesotho, a high TB burden country. Qualitative data were collected via group and individual in-depth interviews with 12 healthcare providers at five health facilities in one district and analyzed using a thematic framework.

Results

Healthcare providers in our study were interested and committed to improve child TB contact management and identified facilitators and challenges to a successful childhood TB prevention program. Facilitators included: provider understanding of the importance of TB prevention and enhanced provider training on child TB contact management, with a particular focus on ruling out TB in children and addressing side effects. Challenges identified by providers were at multiple levels -- structural, clinic, and individual and included: [1] access to care, [2] supply-chain issues, [3] identification and screening of child contacts, and [4] adherence to isoniazid preventive therapy.

Conclusions

Given the significant burden of TB morbidity and mortality in young children and the recent requirement by the WHO to report IPT initiation in child contacts, prioritization of child TB contact management is imperative and should include enhanced provider training on childhood TB and mentorship as well as strategies to eliminate challenges. Strategies that enable more efficient child TB contact management delivery include creating standardized tools that facilitate the implementation, tracking, and monitoring of child TB contact management coupled with guidance and mentorship from the district health management team. To tackle access to care challenges, we propose delivering intensive community health education, conducting community screening more efficiently using standardized tools, and facilitating access to services in the community.
Clinical signs, MRI findings and outcome in dogs with peripheral vestibular disease: a retrospective study
Authors: Orlandi Rocio , Gutierrez-Quintana Rodrigo , Carletti Beatrice , Cooper Camilla , Brocal Josep , Silva Sara , Gonçalves Rita
Published: May 2020

Background

Vestibular dysfunction is relatively common in dogs, with a prevalence of 0.08% reported in primary veterinary care in the UK. There are several studies investigating how to differentiate between peripheral and central vestibular disease but only limited information regarding the possible underlying causes for peripheral vestibular dysfunction in dogs. This study therefore aimed to describe the clinical signs, magnetic resonance imaging findings (MRI), underlying causes and outcome in a large population of dogs diagnosed with peripheral vestibular disease.

Results

One hundred eighty-eight patients were included in the study with a median age of 6.9 years (range 3 months to 14.6 years). Neurological abnormalities included head tilt (n = 185), ataxia (n = 123), facial paralysis (n = 103), nystagmus (n = 97), positional strabismus (n = 93) and Horner syndrome (n = 7). The most prevalent diagnosis was idiopathic vestibular disease (n = 128), followed by otitis media and/or interna (n = 49), hypothyroidism (n = 7), suspected congenital vestibular disease (n = 2), neoplasia (n = 1) and cholesteatoma (n = 1). Long-term follow-up revealed persistence of head tilt (n = 50), facial paresis (n = 41) and ataxia (n = 6) in some cases. Recurrence of clinical signs was observed in 26 dogs. Increasing age was associated with a mild increased chance of diagnosis of idiopathic vestibular syndrome rather than otitis media and/or interna (P = 0.022, OR = 0.866; CI 0.765–0.980). History of previous vestibular episodes (P = 0.017, OR = 3.533; CI 1.251–9.981) was associated with an increased likelihood of resolution of the clinical signs whilst contrast enhancement of cranial nerves VII and/or VIII on MRI (P = 0.018, OR = 0.432; CI 0.251–0.868) was associated with a decreased chance of resolution of the clinical signs.

Conclusions

Idiopathic vestibular disease is the most common cause of peripheral vestibular dysfunction in dogs and it is associated with advanced age. Incomplete recovery from peripheral vestibular disease is common, especially in dogs presenting with cranial nerve enhancement on MRI but less so if there is previous history of vestibular episodes.
Long term N-acetylcysteine administration rescues liver steatosis via endoplasmic reticulum stress with unfolded protein response in mice
Authors: Tsai Ching-Chou , Chen Yu-Jen , Yu Hong-Ren , Huang Li-Tung , Tain You-Lin , Lin I-Chun , Sheen Jiunn-Ming , Wang Pei-Wen , Tiao Mao-Meng
Published: May 2020

Background

Fat accumulation in the liver contributes to the development of non-alcoholic fatty liver disease (NAFLD). N-acetylcysteine (NAC) is an antioxidant, acting both directly and indirectly via upregulation of cellular antioxidants. We examined the mechanisms of liver steatosis after 12 months high fat (HF) diet and tested the ability of NAC to rescue liver steatosis.

Methods

Seven-week-old C57BL/6 (B6) male mice were administered HF diet for 12 months (HF group). Two other groups received HF diet for 12 months accompanied by NAC for 12 months (HFD + NAC(1–12)) or 6 months (HFD + NAC(1–6)). The control group was fed regular diet for 12 months (CD group).

Results

Liver steatosis was more pronounced in the HF group than in the CD group after 12 month feeding. NAC intake for 6 or 12 months decreased liver steatosis in comparison with HF diet (p < 0.05). Furthermore, NAC treatment also reduced cellular apoptosis and caspase-3 expression. In the unfolded protein response (UPR) pathway, the expression of ECHS1, HSP60, and HSP70 was decreased in the HFD group (p < 0.05) and rescued by NAC therapy. With regards to the endoplasmic reticulum (ER) stress, Phospho-PERK (p-PERK) and ATF4 expression was decreased in the HF group, and only the HFD + NAC(1–12), but not HFD + NAC(1–6) group, showed significant improvement.

Conclusion

HF diet for 12 months induces significant liver steatosis via altered ER stress and UPR pathway activity, as well as liver apoptosis. NAC treatment rescues the liver steatosis and apoptosis induced by HF diet.
Retraction Note: The fatty liver index (FLI) and incident hypertension: a longitudinal study among Chinese population
Authors: Zhou Kena , Cen Jie
Published: May 2020

An amendment to this paper has been published and can be accessed via the original article.
Ernst Haeckel, Nikolai Miklucho-Maclay and the racial controversy over the Papuans
Authors: Levit Georgy S. , Hossfeld Uwe
Published: May 2020

Background

The “German Darwin” Ernst Haeckel (1834–1919) was a key figure during the first “Darwinian revolution“, a time when the foundations of the modern evolutionary theory were laid. It was Haeckel, who crucially contributed to the visualization of the Darwinian theory by designing “genealogical-trees” illustrating the evolution of various species, including humans. Although the idea of explaining human evolution by natural selection belongs to Darwin, Haeckel was the first who attempted to create a new exact anthropology based on the Darwinian method.

Discussion

Trying to immediately reconstruct human evolution proceeding from the description of modern populations led Haeckel to the views which, from the contemporary perspective, are definitely racist. Haeckel created racial anthropology intending to prove human origins from a lower organism, but without the intention of establishing a discriminatory racial praxis. Although hierarchical in its outcome, the Haeckelian method did not presuppose the necessity of a racial hierarchy of currently living humans. It is crucial to grasp in what sense Haeckel’s theoretical explorations in human evolution were racist, and in what sense they were not. Our argument flows as follows. One of Haeckel’s pupils was the Russian ethnographer, anthropologist and zoologist Nikolai Nikolajewitsch Miklucho-Maclay (1846–1888). Maclay and Haeckel worked closely together for several years; they traveled jointly and Maclay had enough time to learn the major methodological principles of Haeckel’s research. Yet in contrast to Haeckel, Maclay is regarded as one of the first scientific anti-racists, who came to anti-racist views using empirical field studies in Papua-New Guinea.

Conclusions

We claim that while conducting these studies Maclay applied scientific principles to a significant extent acquired from Haeckel. The paper contributes to the view that Haeckel’s theoretical racism did not follow the Darwinian method he used.
Inter-examiner reliability of radiographic measurements from Open-mouth lateral bending cervical radiographs
Authors: Hariharan Karthik V. , Terhorst Lauren , Maxwell Matthew D. , Bise Christopher G. , Timko Michael G. , Schneider Michael J.
Published: May 2020

Background

Following head and neck trauma, the involvement of the cranio-cervical junction (CCJ) and its contribution to a patients transition to chronic pain, is poorly understood. The detection of hypermobility in this region is dependent on clinical examination and static imaging modalities such as x-ray, CT and MRI. Sagittal plane hypermobility of the CCJ is evaluated using saggital view, flexion-extension cervical radiographs. Frontal plane hypermobility is typically assessed using lateral bending and open mouth cervical radiographs. Unfortunately there is no established reliability surrounding the use of these measures. This study explores the reliability of radiographic measurements of lateral-bending open-mouth cervical radiographs.

Methods

Cervical open-mouth lateral-bending X-ray images were collected from 56 different patients between 18 and 60 years of age patients following cervical spine injury. These images were interpreted by two musculoskeletal radiologists and two clinicians (physiatrist and chiropractor), using a standard set of measurements. Measurements included qualitative and quantitative assessments of the amount of asymmetry noted between various osseous landmarks. Reliability statistics were calculated for levels of agreement using kappa coefficients (κ) and Intraclass Correlation Coefficients (ICC) for dichotomous and continuous variables, respectively.

Results

Reliability (κ) for qualitative assessments were moderate to substantial for asymmetry of neutral C2 spinous position, dens-lateral mass spacing, and “step off” between the lateral borders of the articular pillars of C2 and C1 lateral mass (κ range = .47–.78). ICC values for the quantitative measurements of dens-lateral mass spacing and “step off” between the lateral borders of the C2 articular pillars and C1 lateral mass were moderate to excellent (ICC range = .56–.97).

Conclusions

The qualitative and quantitative measurements used in this study demonstrated good to excellent inter-examiner reliability. Correlation with clinical findings is necessary to establish the utility of these measurements in clinical practice.
The G2-to-M transition from a phosphatase perspective: a new vision of the meiotic division
Authors: Lemonnier Tom , Dupré Aude , Jessus Catherine
Published: May 2020

Cell division is orchestrated by the phosphorylation and dephosphorylation of thousands of proteins. These post-translational modifications underlie the molecular cascades converging to the activation of the universal mitotic kinase, Cdk1, and entry into cell division. They also govern the structural events that sustain the mechanics of cell division. While the role of protein kinases in mitosis has been well documented by decades of investigations, little was known regarding the control of protein phosphatases until the recent years. However, the regulation of phosphatase activities is as essential as kinases in controlling the activation of Cdk1 to enter M-phase. The regulation and the function of phosphatases result from post-translational modifications but also from the combinatorial association between conserved catalytic subunits and regulatory subunits that drive their substrate specificity, their cellular localization and their activity. It now appears that sequential dephosphorylations orchestrated by a network of phosphatase activities trigger Cdk1 activation and then order the structural events necessary for the timely execution of cell division. This review discusses a series of recent works describing the important roles played by protein phosphatases for the proper regulation of meiotic division. Many breakthroughs in the field of cell cycle research came from studies on oocyte meiotic divisions. Indeed, the meiotic division shares most of the molecular regulators with mitosis. The natural arrests of oocytes in G2 and in M-phase, the giant size of these cells, the variety of model species allowing either biochemical or imaging as well as genetics approaches explain why the process of meiosis has served as an historical model to decipher signalling pathways involved in the G2-to-M transition. The review especially highlights how the phosphatase PP2A-B55δ critically orchestrates the timing of meiosis resumption in amphibian oocytes. By opposing the kinase PKA, PP2A-B55δ controls the release of the G2 arrest through the dephosphorylation of their substrate, Arpp19. Few hours later, the inhibition of PP2A-B55δ by Arpp19 releases its opposing kinase, Cdk1, and triggers M-phase. In coordination with a variety of phosphatases and kinases, the PP2A-B55δ/Arpp19 duo therefore emerges as the key effector of the G2-to-M transition.
Effects of de-implementation strategies aimed at reducing low-value nursing procedures: a systematic review and meta-analysis
Authors: Rietbergen Tessa , Spoon Denise , Brunsveld-Reinders Anja H. , Schoones Jan W. , Huis Anita , Heinen Maud , Persoon Anke , van Dijk Monique , Vermeulen Hester , Ista Erwin , van Bodegom-Vos Leti
Published: May 2020

Background

In the last decade, there is an increasing focus on detecting and compiling lists of low-value nursing procedures. However, less is known about effective de-implementation strategies for these procedures. Therefore, the aim of this systematic review was to summarize the evidence of effective strategies to de-implement low-value nursing procedures.

Methods

PubMed, Embase, Emcare, CINAHL, PsycINFO, Cochrane Central Register of Controlled Trials, Web of Science, and Google Scholar were searched till January 2020. Additionally, reference lists and citations of the included studies were searched. Studies were included that described de-implementation of low-value nursing procedures, i.e., procedures, test, or drug orders by nurses or nurse practitioners. PRISMA guideline was followed, and the ‘Cochrane Effective Practice and Organisation of Care’ (EPOC) taxonomy was used to categorize de-implementation strategies. A meta-analysis was performed for the volume of low-value nursing procedures in controlled studies, and Mantel–Haenszel risk ratios (95% CI) were calculated using a random effects model.

Results

Twenty-seven studies were included in this review. Studies used a (cluster) randomized design (n = 10), controlled before-after design (n = 5), and an uncontrolled before-after design (n = 12). Low-value nursing procedures performed by nurses and/or nurse specialists that were found in this study were restraint use (n = 20), inappropriate antibiotic prescribing (n = 3), indwelling or unnecessary urinary catheters use (n = 2), ordering unnecessary liver function tests (n = 1), and unnecessary antipsychotic prescribing (n = 1). Fourteen studies showed a significant reduction in low-value nursing procedures. Thirteen of these 14 studies included an educational component within their de-implementation strategy. Twelve controlled studies were included in the meta-analysis. Subgroup analyses for study design showed no statistically significant subgroup effect for the volume of low-value nursing procedures (p = 0.20).

Conclusions

The majority of the studies with a positive significant effect used a de-implementation strategy with an educational component. Unfortunately, no conclusions can be drawn about which strategy is most effective for reducing low-value nursing care due to a high level of heterogeneity and a lack of studies. We recommend that future studies better report the effects of de-implementation strategies and perform a process evaluation to determine to which extent the strategy has been used.

Trial registration

The review is registered in Prospero (CRD42018105100).
Right heart failure before LVAD implantation predicts right heart failure after LVAD implantation – is it that easy?
Authors: Wagner Tobias , Bernhardt Alexander M. , Magnussen Christina , Reichenspurner Hermann , Blankenberg Stefan , Grahn Hanno
Published: May 2020

Background

Right heart failure (RHF) after left ventricular assist device (LVAD) implantation is common and associated with worse outcome. Prediction of RHF remains challenging. Our study aims to assess predictors of RHF focusing on clinical manifestations.

Methods

We retrospectively analyzed clinical, echocardiographic and hemodynamic parameters of 112 patients undergoing LVAD implantation. Pre-operative, early (ERHF, day 7 and 14) and late postoperative RHF (LRHF, after 1, 3, 6 and 12 months) were assessed.

Results

In the total study population (87.5% men, mean age 55 years), early RHF was frequent (47% on day 7 and 30% on day 14). Prevalence of late RHF and death from RHF was high after 3, 6 and 12 months (23, 24 and 17%). Pre-existing RHF was only associated with early RHF and persistent, but not for new onset late RHF. Early RHF was associated with lower INTERMACS level (p < 0.001), higher pulmonary vascular resistance (p = 0.046) and CVP/PAWP quotient (p = 0.011), higher bilirubin (p = 0.038) and creatinine (p = 0.013). LRHF was associated with creatinine (p = 0.006), urea (p = 0.012) and load adaption index (p = 0.007). Binary logistic regression models identified no single risk factors. Comparing the predictive value of regression models with a model of three clinical findings (INTERMACS level, age and pre-operative RHF) did not reveal differences in RHF.

Conclusions

RHF before LVAD implantation enhances the risk of early RHF and persistent late RHF, but not for new onset late RHF, supporting the hypothesis of differences in the etiology. Echocardiographic or hemodynamic parameters did not show a predictive value for new onset late RHF. Similar predictive value of clinical findings and statistic models of risk factors suggest that a clinical evaluation is equally matched to predict RHF.
Efficacy and safety of Bujing Yishi tablet for glaucoma with controlled IOP: study protocol for a multi-centre randomized controlled trial
Authors: Liu Hongji , Li Xiang , Zhang Zongduan , Zeng Jieping , Dai Yan , Wang Chao , Xie Zhao , Cheng Lin , Cui Linru
Published: May 2020

Background

As an irreversible, intractable disease with vision loss, glaucoma leads to permanent and progressive damage of visual function. Lowering high intraocular pressure (HIOP) is the first choice for treating glaucoma; however, the control of HIOP is not enough to prevent progressive vison loss. Currently, the therapies to treat glaucoma with controlled IOP (GPCI) are unsatisfactory. Chinese medicine is effective for improving visual function in patients with GPCI. Bujing Yishi tablets (BJYSP) have been the standard preparation for treating GPCI in our hospital for decades. However, no rigorous randomized controlled clinical studies have investigated its effects and safety.

Methods

This study will be a 6-month, multicenter, stratified trial following a prospective, randomized, open-label, blinded endpoint (PROBE) protocol. A total of 216 eligible GPCI patients aged 18–75 years will be stratified according to the early, moderate, and advanced stages of glaucoma. After stratifying, the participants will be randomly assigned to the BJYSP group or control group at a ratio of 1:1. Following randomization, participants in the BJYSP group and control group will receive BJYSP and mecobalamin tablets, respectively, for the same 6-month period. The primary outcomes will include the best-corrected visual acuity (BCVA), visual field assessment, visual evoked potential (VEP) test, and Heidelberg retina tomography II (HRT II); the secondary outcomes will include intraocular pressure (IOP) and Traditional Chinese medicine (TCM) clinical symptom scales. The primary and secondary outcomes will be measured at baseline and 8, 16, and 24 weeks thereafter. Safety assessments will also be evaluated at baseline and 12 and 24 weeks thereafter.

Discussion

This study will be a standardized, scientific, clinical trial designed to evaluate the therapeutic effects and safety of BJYSP as a novel therapeutic strategy for improving visual function in patients with GPCI.

Trial registration

Chinese Clinical Trial Registry, ChiCTR1800016431. Registered on 1 June 2018.
Efficacy of a training programme to support the application of the guideline evidence-based health information: study protocol of a randomised controlled trial
Authors: Lühnen Julia , Berger-Höger Birte , Haastert Burkhard , Hinneburg Jana , Kasper Jürgen , Steckelberg Anke
Published: May 2020

Background

The evidence-based guideline entitled guideline evidence-based health information emerged from the German Network for Evidence-based Medicine (DNEbM) and was published in February 2017. The guideline addresses providers of health information and its goal is to improve the quality of health information. In addition, we explored the competences of providers of health information and developed a training programme.

The aim of this study is to evaluate the efficacy of a training programme addressing providers of health information to support the application of the guideline evidence-based health information. We expected the intervention to improve the quality of health information in comparison to the provision of the guideline on its own.

Methods/design

The trial uses a superiority randomised control group design with 10 months’ follow-up. Twenty-six providers of health information (groups with up to ten members) will be enrolled to compare the intervention (guideline and training programme) with usual care (a publicly available guideline). The 5-day training programme comprises an evidence-based medicine training module and a module to prepare the application of the guideline. The primary outcome parameter is the quality of the health information. Quality is operationalised as the extent of adherence to the guideline’s recommendations. Each provider will prepare a single health information item informing a health-related decision on a topic freely chosen before randomisation. The quality of this information will be rated using the Mapping Health Information Quality (MAPPinfo) Checklist. An accompanying process evaluation will then be conducted.

Discussion

The study results should show whether the efficacy of the intervention justifies implementation of the training programme to enhance health information developers’ competences in evidence-based medicine and to ensure high-quality evidence-based health information (EBHI) in the long term.

Trial registration

ISRCTN registry, ID: ISRCTN96941060. Registered on 7 March 2019.
Update to the AWED (Applying Wolbachia to Eliminate Dengue) trial study protocol: a cluster randomised controlled trial in Yogyakarta, Indonesia
Authors: Anders Katherine L. , Indriani Citra , Ahmad Riris Andono , Tantowijoyo Warsito , Arguni Eggi , Andari Bekti , Jewell Nicholas P. , Dufault Suzanne M. , Ryan Peter A. , Tanamas Stephanie K. , Rancès Edwige , O’Neill Scott L. , Simmons Cameron P. , Utarini Adi
Published: May 2020

Background

The AWED (Applying Wolbachia to Eliminate Dengue) trial is a parallel, two-arm, non-blinded cluster randomised controlled trial that is under way in Yogyakarta, Indonesia, with the aim of measuring the efficacy of Wolbachia-infected Aedes aegypti deployments in reducing dengue incidence in an endemic setting. Enrolment began in January 2018 and is ongoing. The original study protocol was published in April 2018. Here, we describe amendments that have been made to the study protocol since commencement of the trial.

Methods

The key protocol amendments are (1) a revised study duration with planned end of participant enrolment in August 2020, (2) the addition of new secondary objectives (i) to estimate serotype-specific efficacy of the Wolbachia intervention and (ii) to compare Ae. aegypti abundance in intervention versus untreated clusters, (3) an additional exposure classification for the per-protocol analysis where the Wolbachia exposure index is calculated using only the cluster-level Wolbachia prevalence in the participant’s cluster of residence, (4) power re-estimation using a multinomial sampling method that better accounts for randomness in sampling, and (5) the addition of two trial stopping rules to address the potential for persistently low rates of virologically confirmed dengue case enrolment and Wolbachia contamination into untreated clusters. Additional minor changes to the protocol are also described.

Discussion

The findings from this study will provide the first experimental evidence for the efficacy of Wolbachia in reducing dengue incidence. Enrolment in the trial will conclude this year (2020) and results will be reported shortly thereafter.

Trial registration

ClinicalTrials.gov, identifier: NCT03055585. Registered on 14 February 2017. Last updated 22 March 2020.
Force production during the sustained phase of Rugby scrums: a systematic literature review
Authors: Martin Eric , Beckham George
Published: May 2020

Background

Since World Rugby changed the laws regarding scrums in the 2013–2014 season, the sustained push phase of the scrum has increased in tactical importance. Therefore, the purpose of this systematic literature review was to examine the biomechanical demands during the sustained push phase of individual, unit, and full pack scrummaging.

Methods

Pubmed, EBSCO (specifically and simultaneously searching Academic Search Premier, CINAHL, and SPORTDiscus), and Google Scholar were searched for any research that presented force production in a live or simulated rugby scrum. Study quality was appraised using the National Institute of Health’s Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Recorded scrum forces, positioning of players including joint angles, and testing procedures were extracted and narratively synthesized.

Results

Twenty six studies were included in the review. 50% of included studies were rated good, 31% fair, and 19% poor. Major limitations included not reporting any effect size, statistical power, or reliability. Reported group mean values for average sustained forces against a machine generally ranged from 1000 to 2000 N in individual scrums and 4000–8000 N for full packs of male rugby players older than high school age. Individuals seem to optimize their force generation when their shoulders are set against scrum machine pads at approximately 40% of body height, with feet parallel, and with knee and hip angles around 120°. A 10% difference in pack force seems to be necessary for one pack to drive another back in the scrum, but little data exist to quantify differences in force production between winning and losing packs during live scrums. Data collection within studies was not standardized, making comparisons difficult. There is a lack of data in live scrums, and the current research indicates that machine scrums may not replicate many of the demands of live scrums. There is a lack of data for female rugby players.

Conclusions

This review indicates an optimal individual body position for players to strive to achieve during scrummaging, consisting of a low body height (40% of stature) and large extended hip and knee angles (120° each).
Therapeutic strategies against hDOT1L as a potential drug target in MLL-rearranged leukemias
Authors: Banday Shahid , Farooq Zeenat , Ganai Shabir Ahmad , Altaf Mohammad
Published: May 2020

Therapeutic intervention of proteins participating in chromatin-mediated signaling with small-molecules is a novel option to reprogram expression networks for restraining disease states. Protein methyltransferases form the prominent family of such proteins regulating gene expression via epigenetic mechanisms thereby representing novel targets for pharmacological intervention. Disruptor of telomeric silencing, hDot1L is the only non-SET domain containing histone methyltransferase that methylates histone H3 at lysine 79. H3K79 methylation mediated by hDot1L plays a crucial role in mixed lineage leukemia (MLL) pathosis. MLL fusion protein mediated mistargeting of DOT1L to aberrant gene locations results in ectopic H3K79 methylation culminating in aberrant expression of leukemogenic genes like HOXA9 and MEIS1. hDOT1L has thus been proposed as a potential target for therapeutic intervention in MLL. This review presents the general overview of hDOT1L and its functional role in distinct biological processes. Furthermore, we discuss various therapeutic strategies against hDOT1L as a promising drug target to vanquish therapeutically challenging MLL.
Impact of sex and gender on COVID-19 outcomes in Europe
Authors: Gebhard Catherine , Regitz-Zagrosek Vera , Neuhauser Hannelore K. , Morgan Rosemary , Klein Sabra L.
Published: May 2020

Background

Emerging evidence from China suggests that coronavirus disease 2019 (COVID-19) is deadlier for infected men than women with a 2.8% fatality rate being reported in Chinese men versus 1.7% in women. Further, sex-disaggregated data for COVID-19 in several European countries show a similar number of cases between the sexes, but more severe outcomes in aged men. Case fatality is highest in men with pre-existing cardiovascular conditions. The mechanisms accounting for the reduced case fatality rate in women are currently unclear but may offer potential to develop novel risk stratification tools and therapeutic options for women and men.

Content

The present review summarizes latest clinical and epidemiological evidence for gender and sex differences in COVID-19 from Europe and China. We discuss potential sex-specific mechanisms modulating the course of disease, such as hormone-regulated expression of genes encoding for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) entry receptors angiotensin converting enzyme (ACE) 2 receptor and TMPRSS2 as well as sex hormone-driven innate and adaptive immune responses and immunoaging. Finally, we elucidate the impact of gender-specific lifestyle, health behavior, psychological stress, and socioeconomic conditions on COVID-19 and discuss sex specific aspects of antiviral therapies.

Conclusion

The sex and gender disparities observed in COVID-19 vulnerability emphasize the need to better understand the impact of sex and gender on incidence and case fatality of the disease and to tailor treatment according to sex and gender. The ongoing and planned prophylactic and therapeutic treatment studies must include prospective sex- and gender-sensitive analyses.
Microenvironment characterization and multi-omics signatures related to prognosis and immunotherapy response of hepatocellular carcinoma
Authors: Liu Furong , Qin Lu , Liao Zhibin , Song Jia , Yuan Chaoyi , Liu Yachong , Wang Yu , Xu Heze , Zhang Qiaofeng , Pei Youliang , Zhang Hongwei , Pan Yonglong , Chen Xiaoping , Zhang Zhanguo , Zhang Wanguang , Zhang Bixiang
Published: May 2020

Background

Immune cell infiltration in the tumor microenvironment (TME) affects tumor initiation, patients’ prognosis and immunotherapy strategies. However, their roles and interactions with genomics and molecular processes in hepatocellular carcinoma (HCC) still have not been systematically evaluated.

Methods

We performed unsupervised clustering of total 1000 HCC samples including discovery and validation group from available public datasets. Immune heterogeneity of each subtype was explored by multi-dimension analysis. And a support vector machine (SVM) model based on multi-omics signatures was trained and tested. Finally, we performed immunohistochemistry to verify the immune role of signatures.

Results

We defined three immune subtypes in HCC, with diverse clinical, molecular, and genomic characteristics. Cluster1 had worse prognosis, better anti-tumor characteristics and highest immune scores, but also accompanied by immunosuppression and T cell dysfunction. Meanwhile, a better anti-PD1/CTLA4 immunotherapeutic response was predicted in cluster1. Cluster2 was enriched in TAM-M2 and stromal cells, indicating immunosuppression. Cluster3, with better prognosis, had lowest CD8 T cell but highest immune resting cells. Further, based on genomic signatures, we developed an SVM classifier to identify the patient’s immunological status, which was divided into Type A and Type B, in which Type A had poorer prognosis, higher T cell dysfunction despite higher T cell infiltration, and had better immunotherapeutic response. At the same time, MMP9 may be a potential predictor of the immune characteristics and immunotherapeutic response in HCC.

Conclusions

Our work demonstrated 3 immune clusters with different features. More importantly, multi-omics signatures, such as MMP9 was identified based on three clusters to help us recognize patients with different prognosis and responses to immunotherapy in HCC. This study could further reveal the immune status of HCC and provide potential predictors for immune checkpoint treatment response.
Heart failure supported by veno-arterial extracorporeal membrane oxygenation (ECMO): a systematic review of pre-clinical models
Authors:   on behalf of the European Extracorporeal Life Support Organisation (EuroELSO) Innovations Workgroup & the National Health Medical Research Council Australia Centre of Research Excellence for Advanced Cardio-respiratory Therapies Improving Organ Support (NHMRC CREACTIONS), Heinsar Silver , Rozencwajg Sacha , Suen Jacky , Bassi Gianluigi Li , Malfertheiner Maximilian , Vercaemst Leen , Broman Lars Mikael , Schmidt Matthieu , Combes Alain , Rätsep Indrek , Fraser John F. , Millar Jonathan E.
Published: May 2020

Objectives

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly being used to treat patients with refractory severe heart failure. Large animal models are developed to help understand physiology and build translational research projects. In order to better understand those experimental models, we conducted a systematic literature review of animal models combining heart failure and VA-ECMO.

Studies selection

A systematic review was performed using Medline via PubMed, EMBASE, and Web of Science, from January 1996 to January 2019. Animal models combining experimental acute heart failure and ECMO were included. Clinical studies, abstracts, and studies not employing VA-ECMO were excluded.

Data extraction

Following variables were extracted, relating to four key features: (1) study design, (2) animals and their peri-experimental care, (3) heart failure models and characteristics, and (4) ECMO characteristics and management.

Results

Nineteen models of heart failure and VA-ECMO were included in this review. All were performed in large animals, the majority (n = 13) in pigs. Acute myocardial infarction (n = 11) with left anterior descending coronary ligation (n = 9) was the commonest mean of inducing heart failure. Most models employed peripheral VA-ECMO (n = 14) with limited reporting.

Conclusion

Among models that combined severe heart failure and VA-ECMO, there is a large heterogeneity in both design and reporting, as well as methods employed for heart failure. There is a need for standardization of reporting and minimum dataset to ensure translational research achieve high-quality standards.
iStent inject trabecular microbypass stent implantation with cataract extraction in open-angle glaucoma: early clinical experience
Authors: Ferguson Tanner J. , Dockter Zachary , Bleeker Adam , Karpuk Kayla L. , Schweitzer Justin , Ibach Mitch J. , Berdahl John P.
Published: May 2020

Background

Retrospective, consecutive case series to evaluate the implantation of two second-generation trabecular microbypass stents in combination with cataract surgery in a real-world, clinical setting.

Methods

The series included 56 eyes implanted with the iStent inject device with phacoemulsification. The series consisted of eyes with primary open-angle glaucoma (n = 52) and pseudoexfoliative glaucoma (n = 4). Primary outcome measures included intraocular pressure (IOP) and number of glaucoma medications. Safety outcomes included the need for secondary surgical intervention and the incidence of IOP spikes ≥10 mmHg and ≥ 15 mmHg.

Results

IOP was reduced by 21% to 14.7 ± 2.9 mmHg (p < 0.01) at 6 months postoperative from 18.7 ± 5.8 mmHg at baseline. Preoperatively, the mean number of glaucoma medications was 1.5 ± 0.9 and reduced by 39% to 0.9 ± 1.2 (p < 0.01) at 6 months. At 6 months, 68% of eyes had an IOP ≤15 mmHg, increased from 30% at baseline. 55% of eyes were medication-free at 6 months, up from 18% at baseline. There were no severe postoperative complications. No eyes underwent an additional glaucoma procedure.

Conclusions

Implantation of the iStent inject device with concomitant cataract surgery effectively provides a sustained reduction in IOP with a markedly improved medication burden out to 6 months postoperative. The safety profile is excellent.
Physical modeling and arbitrary Lagrangian–Eulerian finite element analysis of indentation of a sensitive clay by a flat-ended axisymmetrical indenter
Authors: Abou-Samra Ghassan , Ewane Mireille Sandrine , Silvestri Vincenzo
Published: May 2020

Because indentation tests which are used in several engineering fields allow obtaining material strength parameters in a fast, reliable and reproducible manner, the present study was initiated with the aim of finding out whether such tests could also be used in geotechnical engineering. Experimental results are obtained from undrained indentation tests performed with a rigid flat-tipped, cylindrical indenter on Champlain clay specimens in order to deduce values of elastic moduli and yield stresses. These values are compared to those deduced from unconfined compression tests. Results of an Arbitrary Lagrangian–Eulerian (ALE) based finite element analysis that simulates such test are also presented. It is assumed that the clay behaves as a linear-elastic, perfectly plastic material obeying von-Mises yield criterion. A frictionless contact interface is chosen to realistically model interactions on the indenter-clay, clay-platen and clay-ring interfaces. The paper presents distributions of contact pressures beneath the indenter and along lateral and lower boundaries. Typical contours of von Mises deviator stress and equivalent plastic strain corresponding to different indentation depths in the clay specimen are presented. It is also shown that the presence of hairline cracks on the clay along the perimeter of the indenter and the limited thickness of the sample affect the deduced values of Young’s modulus and yield stress.
Quantification of three-dimensional facial asymmetry for diagnosis and postoperative evaluation of orthognathic surgery
Authors: Cao Hua-Lian , Kang Moon-Ho , Lee Jin-Yong , Park Won-Jong , Choung Han-Wool , Choung Pill-Hoon
Published: May 2020

Background

To evaluate the facial asymmetry, three-dimensional computed tomography (3D-CT) has been used widely. This study proposed a method to quantify facial asymmetry based on 3D-CT.

Methods

The normal standard group consisted of twenty-five male subjects who had a balanced face and normal occlusion. Five anatomical landmarks were selected as reference points and ten anatomical landmarks were selected as measurement points to evaluate facial asymmetry. The formula of facial asymmetry index was designed by using the distances between the landmarks. The index value on a specific landmark indicated zero when the landmarks were located on the three-dimensional symmetric position. As the asymmetry of landmarks increased, the value of facial asymmetry index increased. For ten anatomical landmarks, the mean value of facial asymmetry index on each landmark was obtained in the normal standard group. Facial asymmetry index was applied to the patients who had undergone orthognathic surgery. Preoperative facial asymmetry and postoperative improvement were evaluated.

Results

The reference facial asymmetry index on each landmark in the normal standard group was from 1.77 to 3.38. A polygonal chart was drawn to visualize the degree of asymmetry. In three patients who had undergone orthognathic surgery, it was checked that the method of facial asymmetry index showed the preoperative facial asymmetry and the postoperative improvement well.

Conclusions

The current new facial asymmetry index could efficiently quantify the degree of facial asymmetry from 3D-CT. This method could be used as an evaluation standard for facial asymmetry analysis.
The assessment of procedural skills in physiotherapy education: a measurement study using the Rasch model
Authors: Sattelmayer Karl Martin , Jagadamma Kavi C. , Sattelmayer Franziska , Hilfiker Roger , Baer Gillian
Published: May 2020

Background

Procedural skills are a key element in the training of future physiotherapists. Procedural skills relate to the acquisition of appropriate motor skills, which allow the safe application of clinical procedures to patients. In order to evaluate procedural skills in physiotherapy education validated assessment instruments are required. Recently the assessment of procedural skills in physiotherapy education (APSPT) tool was developed. The overall aim of this study was to establish the structural validity of the APSPT. In order to do this the following objectives were examined: i) the fit of the items of APSPT to the Rasch-model, ii) the fit of the overall score to the Rasch model, iii) the difficulty of each test item and iv) whether the difficulty levels of the individual test items cover the whole capacity spectrum of students in pre-registration physiotherapy education.

Methods

For this observational cross-sectional measurement properties study a convenience sample of 69 undergraduate pre-registration physiotherapy students of the HES-SO Valais-Wallis was recruited. Participants were instructed to perform a task procedure on a simulated patient. The performance was evaluated with the APSPT. A conditional maximum likelihood approach was used to estimate the parameters of a partial credit model for polytomous item responses. Item fit, ordering of thresholds, targeting and goodness of fit to the Rasch model was assessed.

Results

Item fit statistics showed that 25 items of the APSPT showed adequate fit to the Rasch model. Disordering of item thresholds did not occur and the targeting of the APSPT was adequate to measure the abilities of the included participants. Undimensionality and subgroup homogeneity were confirmed.

Conclusion

This study presented evidence for the structural validity of the APSPT. Undimensionality of the APSPT was confirmed and therefore presents evidence that the latent dimension of procedural skills in physiotherapy education consists of several subcategories. However, the results should be interpreted with caution given the small sample size.
Mandible lymphoma: an aggressive osteolytic lesion
Authors: Oliveira Camila S. , de Lima Matheus H. A. , D’Almeida Costa Felipe , da Cruz Perez Danyel Elias , da Silveira da Rocha Talita Maira Bueno , Alves Fabio Abreu
Published: May 2020

Background

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-hodgkin’s lymphoma. In oral cavity represents approximately 2% of all malignancies.

Case presentation

This report describes a rare mandibular involvement of DLBCL. A 56 year-old man was referred for evaluation of left mandible pain. In the anamnesis, the patient informed to be treating tooth pain in lasting 6 months. On oral evaluation, an intense mobility of the left mandibular second molar and a swelling in posterior left mandible were observed. Computed tomography showed a large osteolytic lesion affecting both mandibular body and ramus. An incisional biopsy was performed and according to histopathological and imumnohistochemical features, DLBCL was diagnosed. The treatment consisted of 8 cycles of R-CHOP and adjuvant radiotherapy. He is asymptomatic after 6 years.

Conclusion

This case showed a rare bone presentation of DLBCL and such tumor should be considered as differential diagnosis of osteolytic lesion of the mandible.
Methanol fixation for scanning electron microscopy of plants
Authors: Kim Ki Woo
Published: May 2020

Plant specimens for scanning electron microscopy (SEM) are commonly treated using standard protocols. Conventional fixatives consist of toxic chemicals such as glutaraldehyde, paraformaldehyde, and osmium tetroxide. In 1996, methanol fixation was reported as a rapid alternative to the standard protocols. If specimens are immersed in methanol for 30 s or longer and critical-point dried, they appear to be comparable in preservation quality to those treated with the chemical fixatives. A modified version that consists of methanol fixation and ethanol dehydration was effective at preserving the tissue morphology and dimensions. These solvent-based fixation and dehydration protocols are regarded as rapid and simple alternatives to standard protocols for SEM of plants.