bluuebunny/crossref_metadata_2025 huggingface dataset:
Syphilitic Outer Retinopathy: A Case Report and Review of the Literature
Authors: Amaral Claudia , Joy Leilani , Jimenez Hiram , Cruz-Inñigo Yousef J. , Ulloa-Padilla Jan P. , Oliver Armando L.
Published: June 2021

Purpose:

This work presents a case of syphilitic outer retinopathy with findings similar to those of acute zonal occult outer retinopathy (AZOOR). We also discuss the clinical characteristics, treatment, and prognosis of this entity.

Methods:

A case report and systematic literature review are presented.

Results:

A 56-year-old woman presented with acute vision loss, localized photopsia, a central scotoma, and retinal findings that were all consistent with AZOOR. A further workup led to a diagnosis of syphilis. Oral prednisone and intravenous penicillin resulted in the resolution of the posterior uveitis and the restoration of visual acuity. However, the central scotoma remained at the 3-year follow-up visit.

Conclusions:

Syphilitic outer retinopathy is a distinct entity characterized by the disruption of the ellipsoid zone visible on optical coherence tomography and a corresponding increase in fundus hyperautofluorescence in the affected areas. Although some patients may present with a demarcation line, as is seen with AZOOR, the fundus is oftentimes unremarkable or may show only subtle retinal pigment epithelium changes. Uveitis resolution and visual acuity restoration may be expected following treatment; however, visual field disturbances may persist.
Hill Repair—Why It Is Still Relevant and Should Be Taught
Authors: Dharampal Navjit , Aye Ralph W.
Published: June 2021

The Hill repair for gastroesophageal reflux disease, though effective, durable, and in some regards a superior repair, has unfortunately seen less widespread adoption in the laparoscopic era relative to Nissen and Toupet fundoplications. Some purported objections to the Hill repair include conceptual and technical barriers, need for intraoperative manometry, and lack of clear-cut advantages. However, it has proven to be remarkably durable at 20 years and beyond relative to other repairs, with a low side-effect profile; there are also unique applications of the Hill repair and Hill sutures which broaden one’s armamentarium for managing the spectrum of patients with reflux disease. Lastly, understanding its anatomic components strengthens the surgeon’s knowledge of the anatomy and function of the gastroesophageal junction and antireflux repairs.
Arthroscopy versus mini-arthrotomy approach for matrix-induced autologous chondrocyte implantation in the knee: a systematic review
Authors: Migliorini Filippo , Eschweiler Jörg , Spiezia Filippo , van de Wall Bryan J. M. , Knobe Matthias , Tingart Markus , Maffulli Nicola
Published: June 2021

Background

Matrix-induced autologous chondrocyte implantation (mACI) can be performed in a full arthroscopic or mini-open fashion. A systematic review was conducted to investigate whether arthroscopy provides better surgical outcomes compared with the mini-open approach for mACI in the knee at midterm follow-up.

Methods

This systematic review was conducted following the PRISMA guidelines. The literature search was performed in May 2021. All the prospective studies reporting outcomes after mACI chondral defects of the knee were accessed. Only studies that clearly stated the surgical approach (arthroscopic or mini-open) were included. Only studies reporting a follow-up longer than 12 months were eligible. Studies reporting data from combined surgeries were not eligible, nor were those combining mACI with less committed cells (e.g., mesenchymal stem cells).

Results

Sixteen studies were included, and 770 patients were retrieved: 421 in the arthroscopy group, 349 in the mini-open. The mean follow-up was 44.3 (12–60) months. No difference between the two groups was found in terms of mean duration of symptoms, age, body mass index (BMI), gender, defect size (P > 0.1). No difference was found in terms of Tegner Score (P = 0.3), Lysholm Score (P = 0.2), and International Knee Documentation Committee (IKDC) Score (P = 0.1). No difference was found in the rate of failures (P = 0.2) and revisions (P = 0.06).

Conclusion

Arthroscopy and mini-arthrotomy approaches for mACI in knee achieve similar outcomes at midterm follow-up.

Level of evidence

II, systematic review of prospective studies.
Saving lives through life-threatening measures? The COVID-19 paradox of infection prevention in long-term care facilities
Authors: Thiel Ansgar , Altmeier Dorothee , Frahsa Annika , Eschweiler Gerhard W. , Nieß Andreas , Sudeck Gorden ,   on behalf of the BaSAlt study team
Published: June 2021

The current SARS Cov-2 infection control measures have paradoxical effects. On the one hand, the lockdown measures help to protect vulnerable populations in particular. On the other hand, these measures inevitably have the effect that those who are to be protected not only become socially isolated and are exposed to enormous psychological stress, but also break down physically due to inactivity. Thus, the activation that is omitted in the lockdown is not compensated by external reference groups, which also indicates that important conditions for healthy ageing are not given in long-term care facilities.
Behavioral features in Prader-Willi syndrome (PWS): consensus paper from the International PWS Clinical Trial Consortium
Authors: Schwartz Lauren , Caixàs Assumpta , Dimitropoulos Anastasia , Dykens Elisabeth , Duis Jessica , Einfeld Stewart , Gallagher Louise , Holland Anthony , Rice Lauren , Roof Elizabeth , Salehi Parisa , Strong Theresa , Taylor Bonnie , Woodcock Kate
Published: June 2021

Prader-Willi syndrome (PWS) is a rare neurodevelopmental genetic disorder associated with a characteristic behavioral phenotype that includes severe hyperphagia and a variety of other behavioral challenges such as temper outbursts and anxiety. These behaviors have a significant and dramatic impact on the daily functioning and quality of life for the person with PWS and their families. To date, effective therapies addressing these behavioral challenges have proven elusive, but several potential treatments are on the horizon. However, a limiting factor for treatment studies in PWS is the lack of consensus in the field regarding how to best define and measure the complex and interrelated behavioral features of this syndrome. The International PWS Clinical Trials Consortium (PWS-CTC, www.pwsctc.org) includes expert PWS scientists, clinicians, and patient advocacy organization representatives focused on facilitating clinical trials in this rare disease. To address the above gap in the field, members of the PWS-CTC “Behavior Outcomes Working Group” sought to develop a unified understanding of the key behavioral features in PWS and build a consensus regarding their definition and description. The primary focus of this paper is to present consensus definitions and descriptions of key phenotypic PWS behaviors including hyperphagia, temper outbursts, anxiety, obsessive–compulsive behaviors, rigidity, and social cognition deficits. Patient vignettes are provided to illustrate the interrelatedness and impact of these behaviors. We also review some available assessment tools as well as new instruments in development which may be useful in measuring these behavioral features in PWS.
The impact of diabetes and osteoarthritis on the occurrence of stroke, acute myocardial infarction, and heart failure among older adults with non-valvular atrial fibrillation in Hawaii: a retrospective observational cohort study
Authors: Matsunaga Masako , Chen John J. , Jijiwa Mayumi , Lim Eunjung
Published: June 2021

Background

To date, little is known about cardiovascular disease risks among older adults with non-valvular atrial fibrillation by their association with diabetes and osteoarthritis status, based on longitudinal data with substantial amounts of non-white individuals. The objective of this study was to examine the risks for three cardiovascular diseases: stroke, acute myocardial infarction (AMI), and heart failure (HF), by diabetes and osteoarthritis status among older adults with non-valvular atrial fibrillation in Hawaii.

Methods

We conducted a retrospective observational cohort study for older adults (65 years and older) with non-valvular atrial fibrillation using the Hawaii Medicare data 2009–2017. Their risks for the three cardiovascular diseases by diabetes and osteoarthritis status (diabetes, osteoarthritis, diabetes and osteoarthritis, and without diabetes and osteoarthritis) were examined by multivariable Cox proportional hazard regression models.

Results

The analysis included 19,588 beneficiaries followed up for a maximum of 3288 days (diabetes: n = 4659, osteoarthritis: n = 1978, diabetes and osteoarthritis: n = 1230, without diabetes and osteoarthritis: n = 11,721).  Among them, those diagnosed with the cardiovascular diseases were identified (stroke: diabetes n = 837, osteoarthritis n = 315, diabetes and osteoarthritis n = 184, without diabetes and osteoarthritis n = 1630)(AMI: diabetes n = 438, osteoarthritis n = 128, diabetes and osteoarthritis n = 118, without diabetes and osteoarthritis n = 603)(HF: diabetes n = 2254, osteoarthritis n = 764, diabetes and osteoarthritis n = 581, without diabetes and osteoarthritis n = 4272). After adjusting for age, sex, race/ethnicity, and other potential confounders, those with diabetes and osteoarthritis had higher risks for HF (hazard ratio: 1.21 95% confidence interval: 1.10–1.33) than those without diabetes and osteoarthritis. They also had higher risks than those with osteoarthritis for HF. Those with diabetes had higher risks for all three cardiovascular diseases than the other three groups.

Conclusions

Variation in cardiovascular disease risks for older adults with non-valvular atrial fibrillation in Hawaii exists with diabetes and osteoarthritis status.
Depletion of EREG enhances the osteo/dentinogenic differentiation ability of dental pulp stem cells via the p38 MAPK and Erk pathways in an inflammatory microenvironment
Authors: Ran Ran , Yang Haoqing , Cao Yangyang , Yan Wanhao , Jin Luyuan , Zheng Ying
Published: June 2021

Background

Epiregulin (EREG) is an important component of EGF and was demonstrated to promote the osteo/dentinogenic differentiation of stem cells from dental apical papilla (SCAPs). Whether EREG can stimulate the osteo/dentinogenic differentiation of dental pulp stem cells (DPSCs) in inflammatory environment is not clear. The purpose of the present study is to investigate the role of EREG on the osteo/dentinogenic differentiation ability of DPSCs in inflammatory environment.

Methods

DPSCs were isolated from human third molars. Short hairpin RNAs (shRNAs) were used to knock down EREG expression in DPSCs. Recombinant human EREG (rhEREG) protein was used in the rescue experiment. TNF-α was employed to mimic the inflammatory environment in vitro. Alkaline phosphatase (ALP) staining, Alizarin red staining, quantitative calcium analysis, and real-time RT-PCR were performed to detect osteo/dentinogenic differentiation markers and related signalling pathways under normal and inflammatory conditions.

Results

EREG depletion promoted the ALP activity and mineralization ability of DPSCs. The expression of BSP, DMP-1, and DSPP was also enhanced. Moreover, 50 ng/mL rhEREG treatment decreased the osteo/dentinogenic differentiation potential of DPSCs, while treatment with 10 ng/mL TNF-α for 4 h increased the expression of EREG in DPSCs. Conversely, EREG knockdown rescued the impaired osteo/dentinogenic differentiation ability caused by TNF-α treatment. Further mechanistic studies showed that EREG depletion activated the p38 MAPK and Erk signalling pathways in DPSCs under normal and inflammatory conditions.

Conclusions

Our results demonstrated that EREG could inhibit the osteo/dentinogenic differentiation potential of DPSCs via the p38 MAPK and Erk signalling pathways. Under inflammatory environment, EREG depletion enhanced osteo/dentinogenic differentiation potential of DPSCs by improving the expression of p-p38 MAPK and p-Erk.
Assessment of an electronic patient record system on discharge prescribing errors in a Tertiary University Hospital
Authors: O’Shea Michael Patrick , Kennedy Cormac , Relihan Eileen , Harkin Kieran , Hennessy Martina , Barry Michael
Published: June 2021

Background

Prescribing error represent a significant source of preventable harm to patients. Prescribing errors at discharge, including omission of pre-admission medications (PAM), are particularly harmful as they frequently propagate following discharge. This study assesses the impact of an educational intervention and introduction of an electronic patient record (EPR) in the same centre on omission of PAM at discharge using a pragmatic design. A survey of newly qualified doctors is used to contextualise findings.

Methods

Discharge prescriptions and discharge summaries were reviewed at discharge, and compared to admission medicine lists, using a paper-based chart system. Discrepancies were noted, using Health Information and Quality Authority guidelines for discharge prescribing. An educational intervention was conducted. Further review of discharge prescriptions and discharge summaries took place. Following introduction of an EPR, review of discharge summaries and discharge prescriptions was repeated. A survey was administered to recently qualified doctors (interns), and analysed using descriptive statistics and thematic analysis.

Results

Omission of PAM as prescribed or discontinued items at discharge occurs frequently. An educational intervention did not significantly change prescribing error rates (U = 1255.5, p = 0.206). EPR introduction did significantly reduce omission of PAM on discharge prescribing (U = 694, p < 0.001), however there was also a reduction in the rate of deliberate discontinuation of PAM at discharge (U = 1237.5, p = 0.007). Survey results demonstrated that multiple sources are required to develop a discharge prescription. Time pressure, access to documentation and lack of admission medicine reconciliation are frequently cited causes of discharge prescribing error.

Conclusion

This study verified passive educational interventions alone do not improve discharge prescribing. Introduction of EPR improved discharge prescribing, but negatively impacted deliberate discontinuation of PAM at discharge. This is attributable to reduced access to key sources of information used in formulating discharge prescriptions, and separation of the discontinuation function from the prescribing function on the EPR discharge application.
The use of ondansetron for the treatment of nausea in dogs with vestibular syndrome
Authors: Foth S. , Meller S. , Kenward H. , Elliott J. , Pelligand L. , Volk H. A.
Published: June 2021

Background

Vestibular syndrome is often accompanied by nausea. Drugs currently approved for its treatment have been developed to stop vomiting but not nausea. The efficacy of 5-HT3 receptor antagonists to reduce nausea has been described for chemotherapy, but not for nausea secondary to vestibular disorders.

Methods

Sixteen dogs with vestibular syndrome-associated nausea were included in the open-label, multicentre study. The intensity of nausea-like behaviour was analysed before ondansetron administration (0.5 mg/kg i.v.) and 2 h afterwards, using a validated 5-point-scale. The occurrence and frequency of salivation, lip licking, restlessness, vocalisation, lethargy, and vomiting were assessed.

Results

All dogs initially showed signs of nausea, whereas only 31% showed vomitus. The intensity of nausea was significantly reduced in all dogs (p ≤ 0.0001) 2 h after ondansetron administration, including the clinical signs of nausea analysed in 11 dogs (salivation [p = 0.0078], lip licking [p = 0.0078], restlessness [p = 0.0039], and lethargy [p = 0.0078]) except for vocalisation (p > 0.9999).

Conclusions

The results provide preliminary evidence of the potential benefit of ondansetron in the treatment of nausea, which was present in all examined dogs. Vomiting was only observed in 5 dogs indicating that nausea can occur separately and should not be perceived only as a preceding stimulation of the vomiting centre.
Droplet digital PCR allows vector copy number assessment and monitoring of experimental CAR T cells in murine xenograft models or approved CD19 CAR T cell-treated patients
Authors: Haderbache Rafik , Warda Walid , Hervouet Eric , da Rocha Mathieu Neto , Trad Rim , Allain Vincent , Nicod Clementine , Thieblemeont Catherine , Boissel Nicolas , Varlet Pauline , Agha Ibrahim Yakoub , Bouquet Lucie , Guiot Melanie , Venet Fabienne , Sujobert Pierre , Roussel Xavier , Rouzaire Paul-Oliver , Caillot Denis , Casasnovas Olivier , Bories Jean Christophe , Bachy Emmanuel , Caillat-Zucman Sophie , Deschamps Marina , Ferrand Christophe
Published: June 2021

Background

Genetically engineered chimeric antigen receptor (CAR) T lymphocytes are promising therapeutic tools for cancer. Four CAR T cell drugs, including tisagenlecleucel (tisa-cel) and axicabtagene-ciloleucel (axi-cel), all targeting CD19, are currently approved for treating B cell malignancies. Flow cytometry (FC) remains the standard for monitoring CAR T cells using a recombinant biotinylated target protein. Nevertheless, there is a need for additional tools, and the challenge is to develop an easy, relevant, highly sensitive, reproducible, and inexpensive detection method. Molecular tools can meet this need to specifically monitor long-term persistent CAR T cells.

Methods

Based on 2 experimental CAR T cell constructs, IL-1RAP and CS1, we designed 2 quantitative digital droplet (ddPCR) PCR assays. By targeting the 4.1BB/CD3z (28BBz) or 28/CD3z (28z) junction area, we demonstrated that PCR assays can be applied to approved CD19 CAR T drugs. Both 28z and 28BBz ddPCR assays allow determination of the average vector copy number (VCN) per cell. We confirmed that the VCN is dependent on the multiplicity of infection and verified that the VCN of our experimental or GMP-like IL-1RAP CAR T cells met the requirement (< 5 VCN/cell) for delivery to the clinical department, similar to approved axi-cel or tisa-cel drugs.

Results

28BBz and 28z ddPCR assays applied to 2 tumoral (acute myeloid leukemia (AML) or multiple myeloma (MM) xenograft humanized NSG mouse models allowed us to quantify the early expansion (up to day 30) of CAR T cells after injection. Interestingly, following initial expansion, when circulating CAR T cells were challenged with the tumor, we noted a second expansion phase. Investigation of the bone marrow, spleen and lung showed that CAR T cells disseminated more within these tissues in mice previously injected with leukemic cell lines. Finally, circulating CAR T cell ddPCR monitoring of R/R acute lymphoid leukemia or diffuse large B cell lymphoma (n = 10 for tisa-cel and n = 7 for axi-cel) patients treated with both approved CAR T cells allowed detection of early expansion, which was highly correlated with FC, as well as long-term persistence (up to 450 days), while FC failed to detect these events.

Conclusion

Overall, we designed and validated 2 ddPCR assays allowing routine or preclinical monitoring of early- and long-term circulating approved or experimental CAR T cells, including our own IL-1RAP CAR T cells, which will be evaluated in an upcoming phase I clinical trial.
A review of research-supported group treatments for drug use disorders
Authors: López Gabriela , Orchowski Lindsay M. , Reddy Madhavi K. , Nargiso Jessica , Johnson Jennifer E.
Published: June 2021

This paper reviews methodologically rigorous studies examining group treatments for interview-diagnosed drug use disorders. A total of 50 studies reporting on the efficacy of group drug use disorder treatments for adults met inclusion criteria. Studies examining group treatment for cocaine, methamphetamine, marijuana, opioid, mixed substance, and substance use disorder with co-occurring psychiatric conditions are discussed. The current review showed that cognitive behavioral therapy (CBT) group therapy and contingency management (CM) groups appear to be more effective at reducing cocaine use than treatment as usual (TAU) groups. CM also appeared to be effective at reducing methamphetamine use relative to standard group treatment. Relapse prevention support groups, motivational interviewing, and social support groups were all effective at reducing marijuana use relative to a delayed treatment control. Group therapy or group CBT plus pharmacotherapy are more effective at decreasing opioid use than pharmacotherapy alone. An HIV harm reduction program has also been shown to be effective for reducing illicit opioid use. Effective treatments for mixed substance use disorder include group CBT, CM, and women’s recovery group. Behavioral skills group, group behavioral therapy plus CM, Seeking Safety, Dialectical behavior therapy groups, and CM were more effective at decreasing substance use and psychiatric symptoms relative to TAU, but group psychoeducation and group CBT were not. Given how often group formats are utilized to treat drug use disorders, the present review underscores the need to understand the extent to which evidence-based group therapies for drug use disorders are applied in treatment settings.
Pivoting in the pandemic: a qualitative study of child and adolescent psychiatrists in the times of COVID-19
Authors: DiGiovanni Madeline , Weller Indigo , Martin Andrés
Published: June 2021

Objectives

We examined the personal and professional impacts of the COVID-19 pandemic on the development, practice, and shifting values of child and adolescent psychiatrists (CAP), in order to inform how the field may move forward post-pandemic.

Methods

We conducted individual semi-structured interviews of child and adolescent psychiatrists (n = 24) practicing in the United States. Participants were selected as a diverse purposive sample of active members of the American Academy of Child and Adolescent Psychiatry (AACAP). We analyzed anonymized transcripts through iterative coding using thematic analysis aided by NVivo software.

Results

We identified three main thematic domains within participants’ response to the pandemic, which have engendered a reevaluation of and a recommitment to the aims of each clinician and the field of CAP more broadly. These domains, paired with representative questions, include: (1) Unsettling, or “who have we been?” (identifying discontents such as daily inefficiencies and intraprofessional loss of trust); (2) Adaptation, or “who are we now?” (exploring affordances and limitations of virtual work, and the evolution of personal and professional identity); and (3) Reimagination, or “who will we become?” (renewing a commitment to psychiatry as advocacy). Even as we identified a collective agreement toward the need for implementing change, just what needs to change, and how that change will be realized, remain contested.

Conclusion

These three thematic domains, augmented by a national confrontation with race and equity, have engendered a field-wide reckoning with known inequities. They have reinvigorated collective responses and calls to action. The divergent mindsets to change and leadership have provided an aperture for what values and practices the field might instill in its next generation of practitioners.
USP1-dependent RPS16 protein stability drives growth and metastasis of human hepatocellular carcinoma cells
Authors: Liao Yuning , Shao Zhenlong , Liu Yuan , Xia Xiaohong , Deng Yuanfei , Yu Cuifu , Sun Wenshuang , Kong Weiyao , He Xiaoyue , Liu Fang , Guo Zhiqiang , Chen Guoxing , Tang Daolin , Gan Huoye , Liu Jinbao , Huang Hongbiao
Published: June 2021

Background

Hepatocellular carcinoma (HCC) remains a medical challenge due to its high proliferation and metastasis. Although deubiquitinating enzymes (DUBs) play a key role in regulating protein degradation, their pathological roles in HCC have not been fully elucidated.

Methods

By using biomass spectrometry, co-immunoprecipitation, western blotting and immunofluorescence assays, we identify ribosomal protein S16 (RPS16) as a key substrate of ubiquitin-specific peptidase 1 (USP1). The role of USP1-RPS16 axis in the progression of HCC was evaluated in cell cultures, in xenograft mouse models, and in clinical observations.

Results

We show that USP1 interacts with RPS16. The depletion of USP1 increases the level of K48-linked ubiquitinated-RPS16, leading to proteasome-dependent RPS16 degradation. In contrast, overexpression of USP1-WT instead of USP1-C90A (DUB inactivation mutant) reduces the level of K48-linked ubiquitinated RPS16, thereby stabilizing RPS16. Consequently, USP1 depletion mimics RPS16 deficiency with respect to the inhibition of growth and metastasis, whereas transfection-enforced re-expression of RPS16 restores oncogenic-like activity in USP1-deficient HCC cells. Importantly, the high expression of USP1 and RPS16 in liver tissue is a prognostic factor for poor survival of HCC patients.

Conclusions

These findings reveal a previously unrecognized role for the activation of USP1-RPS16 pathway in driving HCC, which may be further developed as a novel strategy for cancer treatment.
A rare ovarian hilus cell tumour accompanying bilateral serous cystadenomas: report of a case
Authors: Malakzai Haider Ali , Abdul-Ghafar Jamshid , Ibrahimkhil Abdul Sami , Haidary Ahmed Maseh
Published: June 2021

Background

Hilus cell tumours is considered an uncommon branch of androgen producing neoplasms that accounts for < 5% of all ovarian tumours. They are mostly benign and have characteristic gross and microscopic features. Here we present the first case of a hilus cell tumour in association with bilateral serous cystadenomas.

Case presentation

A 65-year-old lady with no symptoms of virilization, presented with postmenopausal dysfunctional uterine bleeding and radiological investigations revealing bilateral ovarian cysts that required a total abdominal hysterectomy with bilateral salpingo-oophorectomy. Gross and microscopic evaluation confirmed the diagnosis of hilus cell tumour associated with bilateral serous cystadenomas.

Conclusions

This was the first case of hilus cell tumour in association with bilateral serous cystadenomas of the ovaries. Although, majority of hilus cell tumours that have been reported in the literature were benign, further studies are required to determine the behavior of the disease.
The impact of improved water supply on cholera and diarrhoeal diseases in Uvira, Democratic Republic of the Congo: a protocol for a pragmatic stepped-wedge cluster randomised trial and economic evaluation
Authors: Gallandat Karin , Jeandron Aurélie , Ross Ian , Mufitini Saidi Jaime , Bashige Rumedeka Baron , Lumami Kapepula Vercus , Cousens Simon , Allen Elizabeth , MacDougall Amy , Cumming Oliver
Published: June 2021

Introduction

Diarrhoeal disease remains a leading cause of mortality and morbidity worldwide. Cholera alone is estimated to cause 95,000 deaths per year, most of which occur in endemic settings with inadequate water access. Whilst a global strategy to eliminate cholera by 2030 calls for investment in improved drinking water services, there is limited rigorous evidence for the impact of improved water supply on endemic cholera transmission in low-income urban settings. Our protocol is designed to deliver a pragmatic health impact evaluation of a large-scale water supply intervention in Uvira (Democratic Republic of the Congo), a cholera transmission hotspot.

Methods/design

A stepped-wedge cluster randomised trial (SW-CRT) was designed to evaluate the impact of a large-scale drinking water supply intervention on cholera incidence among the 280,000 inhabitants of Uvira. The city was divided into 16 clusters, where new community and household taps will be installed following a randomised sequence over a transition period of up to 8 weeks in each cluster. The primary trial outcomes are the monthly incidence of “confirmed” cholera cases (patients testing positive by rapid detection kit) and of “suspected” cholera cases (patients admitted to the cholera treatment centre). Concurrent process and economic evaluations will provide further information on the context, costs, and efficiency of the intervention.

Discussion

In this protocol, we describe a pragmatic approach to conducting rigorous research to assess the impacts of a complex water supply intervention on severe diarrhoeal disease and cholera in an unstable, low-resource setting representative of cholera-affected areas. In particular, we discuss a series of pre-identified risks and linked mitigation strategies as well as the value of combining different data collection methods and preparation of multiple analysis scenarios to account for possible deviations from the protocol. The study described here has the potential to provide robust evidence to support more effective cholera control in challenging, high-burden settings.

Trial registration

This trial is registered on clinicaltrials.gov (NCT02928341, 10th October 2016) and has received ethics approval from the London School of Hygiene and Tropical Medicine (8913, 10603) and from the Ethics Committee from the School of Public Health, University of Kinshasa, Democratic Republic of the Congo (ESP/CE/088/2015).
Soil, senescence and exudate utilisation: characterisation of the Paragon var. spring bread wheat root microbiome
Authors: Prudence Samuel MM. , Newitt† Jake T. , Worsley Sarah F. , Macey Michael C. , Murrell J. Colin , Lehtovirta-Morley Laura E. , Hutchings Matthew I.
Published: June 2021

Background

Conventional methods of agricultural pest control and crop fertilisation are unsustainable. To meet growing demand, we must find ecologically responsible means to control disease and promote crop yields. The root-associated microbiome can aid plants with disease suppression, abiotic stress relief, and nutrient bioavailability. The aim of the present work was to profile the community of bacteria, fungi, and archaea associated with the wheat rhizosphere and root endosphere in different conditions. We also aimed to use 13CO2 stable isotope probing (SIP) to identify microbes within the root compartments that were capable of utilising host-derived carbon.

Results

Metabarcoding revealed that community composition shifted significantly for bacteria, fungi, and archaea across compartments. This shift was most pronounced for bacteria and fungi, while we observed weaker selection on the ammonia oxidising archaea-dominated archaeal community. Across multiple soil types we found that soil inoculum was a significant driver of endosphere community composition, however, several bacterial families were identified as core enriched taxa in all soil conditions. The most abundant of these were Streptomycetaceae and Burkholderiaceae. Moreover, as the plants senesce, both families were reduced in abundance, indicating that input from the living plant was required to maintain their abundance in the endosphere. Stable isotope probing showed that bacterial taxa within the Burkholderiaceae family, among other core enriched taxa such as Pseudomonadaceae, were able to use root exudates, but Streptomycetaceae were not.

Conclusions

The consistent enrichment of Streptomycetaceae and Burkholderiaceae within the endosphere, and their reduced abundance after developmental senescence, indicated a significant role for these families within the wheat root microbiome. While Streptomycetaceae did not utilise root exudates in the rhizosphere, we provide evidence that Pseudomonadaceae and Burkholderiaceae family taxa are recruited to the wheat root community via root exudates. This deeper understanding crop microbiome formation will enable researchers to characterise these interactions further, and possibly contribute to ecologically responsible methods for yield improvement and biocontrol in the future.
The association of standardized patient educators (ASPE) gynecological teaching associate (GTA) and male urogenital teaching associate (MUTA) standards of best practice
Authors: Hopkins Holly , Weaks Chelsea , Webster Tim , Elcin Melih
Published: June 2021

Gynecological Teaching Associates (GTAs) and Male Urogenital Teaching Associates (MUTAs) instruct healthcare professional learners to perform accurate and respectful breast, speculum, bimanual vaginal, rectal, urogenital, and prostate examinations. During such sessions, the GTA/MUTA uses their own body to instruct while providing real-time feedback. While GTAs/MUTAs fall under the broader umbrella of Standardized Patient methodology, the specificity of their role indicates need for establishment of Standards of Best Practice (SOBP) for GTA/MUTA programs. On behalf of the Association of Standardized Patient Educators (ASPE), the Delphi process was utilized to reach international consensus identifying the Practices that comprise the ASPE GTA/MUTA SOBP. The original ASPE SOBP was used as the foundation for the iterative series of three surveys. Results were presented at the ASPE 2019 conference for additional feedback. Fifteen participants from four countries completed the Delphi process. Four of the original ASPE SOBP Domains were validated for GTA/MUTA programs: Safe Work Environment, Instructional Session Development, Training GTAs/MUTAs, and Program Management. Principles and Practices were shaped, and in some instances created, to best fit the distinct needs of GTA/MUTA programs. The ASPE GTA/MUTA SOBP apply to programs that engage GTAs/MUTAs in formative instructional sessions with learners. Programs that incorporate GTAs/MUTAs in simulation roles or in summative assessment are encouraged to reference the ASPE SOBP in conjunction with this document. The SOBP are aspirational and should be used to shape Practices within the program’s local context. The ASPE GTA/MUTA SOBP will continue to evolve as our knowledge-base and practice develop.
Persistent cognitive impairment associated with cerebrospinal fluid anti-SARS-CoV-2 antibodies six months after mild COVID-19
Authors: Borsche Max , Reichel Dirk , Fellbrich Anja , Lixenfeld Anne S. , Rahmöller Johann , Vollstedt Eva-Juliane , Föh Bandik , Balck Alexander , Klein Christine , Ehlers Marc , Moser Andreas
Published: June 2021

Neurological long-term sequelae are increasingly considered an important challenge in the recent COVID-19 pandemic. However, most evidence for neurological symptoms after SARS-CoV-2 infection and central nervous system invasion of the virus stems from individuals severely affected in the acute phase of the disease. Here, we report long-lasting cognitive impairment along with persistent cerebrospinal fluid anti-SARS-CoV-2 antibodies in a female patient with unremarkable standard examination 6 months after mild COVID-19, supporting the implementation of neuropsychological testing and specific cerebrospinal fluid investigation also in patients with a relatively mild acute disease phase.
Integrating machine learning and blockchain to develop a system to veto the forgeries and provide efficient results in education sector
Authors: Shah Dhruvil , Patel Devarsh , Adesara Jainish , Hingu Pruthvi , Shah Manan
Published: June 2021

Although the education sector is improving more quickly than ever with the help of advancing technologies, there are still many areas yet to be discovered, and there will always be room for further enhancements. Two of the most disruptive technologies, machine learning (ML) and blockchain, have helped replace conventional approaches used in the education sector with highly technical and effective methods. In this study, a system is proposed that combines these two radiant technologies and helps resolve problems such as forgeries of educational records and fake degrees. The idea here is that if these technologies can be merged and a system can be developed that uses blockchain to store student data and ML to accurately predict the future job roles for students after graduation, the problems of further counterfeiting and insecurity in the student achievements can be avoided. Further, ML models will be used to train and predict valid data. This system will provide the university with an official decentralized database of student records who have graduated from there. In addition, this system provides employers with a platform where the educational records of the employees can be verified. Students can share their educational information in their e-portfolios on platforms such as LinkedIn, which is a platform for managing professional profiles. This allows students, companies, and other industries to find approval for student data more easily.
Occupational and Personal Consequences of the COVID-19 Pandemic on US Oncologist Burnout and Well-Being: A Study From the ASCO Clinician Well-Being Task Force
Authors: Hlubocky Fay J. , Back Anthony L. , Shanafelt Tait D. , Gallagher Colleen M. , Burke John M. , Kamal Arif H. , Paice Judith A. , Page Ray D. , Spence Rebecca , McGinnis Molly , McFarland Daniel C. , Srivastava Piyush
Published: June 2021

INTRODUCTION:

The COVID-19 pandemic is an unprecedented global crisis profoundly affecting oncology care delivery.

PURPOSE:

This study will describe the occupational and personal consequences of the COVID-19 pandemic on oncologist well-being and patient care.

MATERIALS AND METHODS:

Four virtual focus groups were conducted with US ASCO member oncologists (September-November 2020). Inquiry and subsequent discussions centered on self-reported accounts of professional and personal COVID-19 experiences affecting well-being, and oncologist recommendations for well-being interventions that the cancer organization and professional societies (ASCO) might implement were explored. Qualitative interviews were analyzed using Framework Analysis.

RESULTS:

Twenty-five oncologists were interviewed: median age 44 years (range: 35-69 years), 52% female, 52% racial or ethnic minority, 76% medical oncologists, 64% married, and an average of 51.5 patients seen per week (range: 20-120). Five thematic consequences emerged: (1) impact of pre-COVID-19 burnout, (2) occupational or professional limitations and adaptations, (3) personal implications, (4) concern for the future of cancer care and the workforce, and (5) recommendations for physician well-being interventions. Underlying oncologist burnout exacerbated stressors associated with disruptions in care, education, research, financial practice health, and telemedicine. Many feared delays in cancer screening, diagnosis, and treatment. Oncologists noted personal and familial stressors related to COVID-19 exposure fears and loss of social support. Many participants strongly considered working part-time or taking early retirement. Yet, opportunities arose to facilitate personal growth and rise above pandemic adversity, fostering greater resilience. Recommendations for organizational well-being interventions included psychologic or peer support resources, flexible time-off, and ASCO and state oncology societies involvement to develop care guidelines, well-being resources, and mental health advocacy.

CONCLUSION:

Our study suggests that the COVID-19 pandemic has adversely affected oncologist burnout, fulfillment, practice health, cancer care, and workforce. It illuminates where professional organizations could play a significant role in oncologist well-being.
The Facilitatory Effects of Adjuvant Pharmaceutics to Prolong the Duration of Local Anesthetic for Peripheral Nerve Block: A Systematic Review and Network Meta-analysis
Authors: Xuan Chengluan , Yan Wen , Wang Dan , Li Cong , Ma Haichun , Mueller Ariel , Wang Jingping
Published: June 2021

BACKGROUND:

Peripheral nerve block (PNB) with perineural local anesthetic is used for anesthesia or analgesia with many benefits. To extend these benefits, various adjuvant drugs have been used to prolong the duration of analgesia. We aimed to evaluate the effectiveness of various adjuvants at prolonging the duration of sensory and motor blockade for PNB.

METHODS:

A network meta-analysis of placebo-controlled and active randomized controlled trials was performed comparing 10 adjuvants. Embase, PubMed, Web of Science, and Cochrane library were searched, with articles before May 21, 2020 included. Two authors independently selected studies and extracted data. The primary outcomes were sensory block (SB) and motor block (MB) time, and the secondary outcome was time of first analgesia rescue (FAR). Effect size measures were described as mean differences (MD) with 95% confidence intervals (CIs). Confidence in evidence was assessed using Confidence in Network Meta-Analysis (CINeMA). The study protocol was preregistered with the prospectively registered systematic reviews in health and social care international database (PROSPERO), as number CRD42020187866.

RESULTS:

Overall 16,364 citations were identified, of which 53 studies were included with data for 3649 patients. In network meta-analyses, 4 of 7 included treatment strategies were associated with more efficacious analgesia compared with placebo therapy, including dexamethasone (SB time: 5.73 hours, 95% CI, 4.16–7.30; MB time: 4.20 hours, 95% CI, 2.51–5.89; time of FAR: 8.71 hours, 95% CI, 6.63–10.79), dexmedetomidine (SB time: 4.51 hours, 95% CI, 3.52–5.50; MB time: 4.04 hours, 95% CI, 2.98–5.11; time of FAR: 5.25 hours, 95% CI, 4.08–6.43), fentanyl (SB time: 3.59 hours, 95% CI, 0.11–7.06; MB time: 4.42 hours, 95% CI, 0.78–8.06), and clonidine (SB time: 2.75 hours, 95% CI, 1.46–4.04; MB time: 2.93 hours, 95% CI, 1.69–4.16; time of FAR: 3.35 hours, 95% CI, 1.82–4.87). In a subgroup analysis, addition of dexamethasone to ropivacaine significantly increased the time of FAR when compared to dexmedetomidine (time of FAR: 5.23 hours, 95% CI, 2.92–7.54) or clonidine (time of FAR: 6.61 hours, 95% CI, 4.29–8.92) with ropivacaine.

CONCLUSIONS:

These findings provide evidence for the consideration of dexmedetomidine, dexamethasone, and clonidine as adjuvants to prolong the duration of PNB. The addition of dexamethasone to ropivacaine has a longer time of FAR compared with clonidine or dexmedetomidine.
Affective Dynamics of Excitable Speech in Milo Rau’s Breiviks Erklärung and Mitleid
Authors: Walter-Jochum Robert
Published: June 2021

Robert Walter-Jochum reflects on the successes and failures of Milo Rau’s stage explorations of hate speech, investigating what Judith Butler terms “restaging and resignifying.” Walter-Jochum references two of Rau’s performances: Breivik’s Statement and Compassion: The History of the Machine Gun. Both pieces highlight the hypocrisy and similarities of rhetoric from right-wing terrorists and liberals with seemingly good intentions. Breivik’s Statement restages hate speech with an actor of color inverting the meaning of the speech, while Compassion restages a woman of color refugee reflecting on her childhood, while a white woman contemplates her time volunteering in the Congo. Walter-Jochum dissects each monologue, analyzing deeper meaning in Rau’s projects.
A genomic exploration of the early evolution of extant cats and their sabre-toothed relatives
Authors: Westbury Michael V , Barnett Ross , Sandoval-Velasco Marcela , Gower Graham , Vieira Filipe Garrett , de Manuel Marc , Hansen Anders J , Yamaguchi Nobuyuki , Werdelin Lars , Marques-Bonet Tomas , Gilbert M Thomas P , Lorenzen Eline D
Published: June 2021

Background: The evolutionary relationships of Felidae during their Early–Middle Miocene radiation is contentious. Although the early common ancestors have been subsumed under the grade-group Pseudaelurus, this group is thought to be paraphyletic, including the early ancestors of both modern cats and extinct sabretooths.

Methods: Here, we sequenced a draft nuclear genome of Smilodon populator, dated to 13,182 ± 90 cal BP, making this the oldest palaeogenome from South America to date, a region known to be problematic for ancient DNA preservation. We analysed this genome, together with genomes from other extinct and extant cats to investigate their phylogenetic relationships.

Results: We confirm a deep divergence (~20.65 Ma) within sabre-toothed cats. Through the analysis of both simulated and empirical data, we show a lack of gene flow between Smilodon and contemporary Felidae.

Conclusions: Given that some species traditionally assigned to Pseudaelurus originated in the Early Miocene ~20 Ma, this indicates that some species of Pseudaelurus may be younger than the lineages they purportedly gave rise to, further supporting the hypothesis that Pseudaelurus was paraphyletic.
English for IT-Specialists
Authors:   Sevastopol State University, Braslavskaya Elena , Pavlova Tatyana ,   Sevastopol State University
Published: June 2021

The course is designed in the e-learning environment LMS MOODLE AND INTENDED FOR REMOTE SUPPORT of the 2d-year students' INDEPENDENT WORK IN THE DISCIPLINE «ENGLISH language» of the institute of radio electronics and information security and the Institute of Information Technology and Management in technical systems in Sevsu. The aim of the course is the bachelor training, who can speak foreign language in various situations of interpersonal and professional communication at the level of at least B1+ according to the international scale EVALUATION; IMPROVING THE INITIAL FOREIGN LANGUAGE level reached at previous levels of education; mastering of the necessary and sufficient level of competence FOR SOLVING SOCIO-COMMUNICATIVE TASKS IN VARIOUS spheres OF PROFESSIONAL AND SCIENTIFIC ACTIVITIES WHEN COMMUNICATING WITH FOREIGN PARTNERS; FURTHER SELF-EDUCATION.
TOPICAL ISSUES OF PROFESSIONAL AND PSYCHOLOGICAL SUITABILY IN THE SYSTEM OF THE MIA OF THE REPUBLIC OF TAJIKISTAN
Authors: Latifzoda Somon
Published: June 2021

This article discusses the main problems and issues of professional and psychological suitability in the system of the Ministry of Internal Affairs of the Republic of Tajikistan. The analysis of the existing scientific literature was carried out, and also the author's recommendations were formulated to improve the professional training and professional suitability of the employees of the Ministry of Internal Affairs. Along with the professional training of police officers, their psychological qualities also play a decisive role in ensuring efficiency in operational-search activities.

The quality and effectiveness of the implementation of operational-search activities, then its level directly depends on the psychological characteristics of the operative and his professional training. It should be noted that scientifically grounded conclusions about the professional and psychological suitability of employees can only be achieved with the help of high-quality and correct psychological diagnostics, that is, using psychometric methods.

The basis for the survey of professional and psychological suitability, the procedure, procedure, conditions and terms of the survey, cases of re-examination are determined by regulatory legal acts.

Consequently, the research and scientifically grounded measures to determine professional suitability in the internal affairs bodies of the Republic of Tajikistan are relevant, and the scientifically grounded results obtained as a result of our research can be used to further improve the professional and psychological selection to the law enforcement agencies of the country.