bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retroperitoneal leiomyosarcoma in a female patient with a germline splicing variant RAD51D c.904-2A > T: a case report
Authors: Futagawa Mashu , Yamamoto Hideki , Kochi Mariko , Urakawa Yusaku , Sogawa Reimi , Kato Fumino , Okazawa-Sakai Mika , Ennishi Daisuke , Shinozaki Katsunori , Inoue Hirofumi , Yanai Hiroyuki , Hirasawa Akira 
Published: November 2021

Abstract
Background
RAD51D (RAD51 paralog D) is an intermediate cancer susceptibility gene for primary ovarian cancer, including fallopian tube and peritoneal carcinomas and breast cancer. Although gynecological non-epithelial tumors such as uterine sarcomas are associated with genomic instability, including BRCA impairment, there is no clear evidence of the relationship between RAD51D variants and the risk of sarcoma development.

Case presentation
A Japanese woman in her 50s underwent multiple surgical resections and several regimens of chemotherapy for tumors that originated in the retroperitoneum and recurred in the peritoneum over a clinical course of approximately 4 years. The peritoneal tumor was histologically diagnosed as a leiomyosarcoma and was genetically identified to show a splice variant of RAD51D c.904-2A > T [NM_002878] through tumor profiling performed as a part of cancer precision medicine. The confirmatory genetic test performed after genetic counseling revealed that the RAD51D splicing variant detected in her tumor was of germline origin. In silico analyses supported the possible pathogenicity of the detected splice variant of RAD51D with a predicted attenuation in mRNA transcription and truncated protein production due to frameshifting, which was attributed to a single-nucleotide alteration in the splicing acceptor site at the 3′-end of intron 9 of RAD51D. Considering her unfavorable clinical outcome, which showed a highly aggressive phenotype of leiomyosarcoma with altered RAD51D, this case provided novel evidence for the relationship of a RAD51D splicing variant with malignant tumor development or progression. We report the findings of this rare case with possible involvement of the germline variant of RAD51D c.904-2A > T as a potential predisposing factor for malignant tumors, including leiomyosarcoma.

Conclusions
We present the findings of a case of leiomyosarcoma in the peritoneum of a female patient with a novel germline splicing variant of RAD51D as potential evidence for the pathogenicity of the variant and its involvement in the risk of sarcoma etiology and/or development. To the best of our knowledge, this is the first case report describing a leiomyosarcoma carrying a germline RAD51D splicing variant and elucidating its pathogenicity on the basis of computational prediction of the impairment of normal transcription and the presumed loss of functional protein production.
A multicenter randomized placebo-controlled trial of intravenous thyroxine for heart-eligible brain-dead organ donors
Authors: Dhar Rajat , Klinkenberg Dean , Marklin Gary 
Published: November 2021

Abstract
Background
Brain death frequently induces hemodynamic instability and cardiac stunning. Impairments in cardiac performance are major contributors to hearts from otherwise eligible organ donors not being transplanted. Deficiencies in pituitary hormones (including thyroid-stimulating hormone) may contribute to hemodynamic instability, and replacement of thyroid hormone has been proposed as a means of improving stability and increasing hearts available for transplantation. Intravenous thyroxine is commonly used in donor management. However, small controlled trials have not been able to demonstrate efficacy.

Methods
This multicenter study will involve organ procurement organizations (OPOs) across the country. A total of 800 heart-eligible brain-dead organ donors who require vasopressor support will be randomly assigned to intravenous thyroxine for at least 12 h or saline placebo. The primary study hypotheses are that thyroxine treatment will result in a higher proportion of hearts transplanted and that these hearts will have non-inferior function to hearts not treated with thyroxine. Additional outcome measures are the time to achieve hemodynamic stability (weaning off vasopressors) and improvement in cardiac ejection fraction on echocardiography.

Discussion
This will be the largest randomized controlled study to evaluate the efficacy of thyroid hormone treatment in organ donor management. By collaborating across multiple OPOs, it will be able to enroll an adequate number of donors and be powered to definitively answer the critical question of whether intravenous thyroxine treatment increases hearts transplanted and/or provides hemodynamic benefits for donor management.

Trial registration
ClinicalTrials.govNCT04415658. Registered on June 4, 2020
Metacognitive therapy and work-focused interventions for patients on sick leave due to anxiety and depression: study protocol for a randomised controlled wait-list trial
Authors: Sandin Kenneth , Gjengedal Ragne G. H. , Osnes Kåre , Hannisdal Marit , Berge Torkil , Leversen Jonas S. R. , Røv Lars G. , Reme Silje Endresen , Lagerveld Suzanne , Blonk Roland , Nordahl Hans M. , Shields Gemma , Wells Adrian , Hjemdal Odin 
Published: November 2021

Abstract
Background
Common mental disorders such as depression and anxiety are major contributors to the global burden of disease. Affected individuals suffer reduced quality of life, impaired functioning and reduced capacity to work. Maintaining employment is an important determinant for health and wellbeing, and the economic impact of depression and anxiety is a significant societal expense. Treatments providing effective symptom reduction and helping patients return to work (RTW) would thus have substantial public health benefits. The present study will explore the effectiveness of metacognitive therapy (MCT) and work-focused interventions on reducing symptoms and increasing RTW rates for patients on sick leave due to depression and anxiety.

Methods
The study is a randomised controlled wait-list trial (RCT; N = 240). The intervention group will receive protocol-based MCT and work-focused interventions immediately after inclusion. The control condition is a wait-list control group. All patients will receive up to 12 weekly sessions. The study context is a Norwegian outpatient clinic part of a national programme aimed at reducing sick leave. The co-primary outcomes are change in RTW and symptoms of depression and anxiety at the end of treatment. In addition to self-report, sick leave will also be collected from national registries from 2 years prior to intervention to 4 years after intervention. Symptoms of depression and anxiety will be collected by self-report at pre- and post-treatment and at 6 and 12 months follow-up after treatment. A cost-effectiveness analysis will use total cost and quality-adjusted life-years as the secondary outcomes.

Discussion
There is broad consensus on the importance of identifying treatment that effectively reduces depression and anxiety symptoms and aids RTW. This study is an important contribution to the field as it is the first RCT on MCT and work-focused interventions for patients on sick leave due to anxiety and depression.

Trial registration
ClinicalTrials.gov NCT03301922. Registered on October 4, 2017.
Phylogenetic analysis of the Neotropical Albitarsis Complex based on mitogenome data
Authors: Bourke Brian P. , Justi Silvia A. , Caicedo-Quiroga Laura , Pecor David B. , Wilkerson Richard C. , Linton Yvonne-Marie 
Published: November 2021

Abstract
Background
Some of the most important malaria vectors in South America belong to the Albitarsis Complex (Culicidae; Anophelinae; Anopheles). Understanding the origin, nature, and geographical distribution of species diversity in this important complex has important implications for vector incrimination, control, and management, and for modelling future responses to climate change, deforestation, and human population expansion. This study attempts to further explore species diversity and evolutionary history in the Albitarsis Complex by undertaking a characterization and phylogenetic analysis of the mitogenome of all 10 putative taxa in the Albitarsis Complex.

Methods
Mitogenome assembly and annotation allowed for feature comparison among Albitarsis Complex and Anopheles species. Selection analysis was conducted across all 13 protein-coding genes. Maximum likelihood and Bayesian inference methods were used to construct gene and species trees, respectively. Bayesian methods were also used to jointly estimate species delimitation and species trees.

Results
Gene composition and order were conserved across species within the complex. Unique signatures of positive selection were detected in two species—Anopheles janconnae and An. albitarsis G—which may have played a role in the recent and rapid diversification of the complex. The COI gene phylogeny does not fully recover the mitogenome phylogeny, and a multispecies coalescent-based phylogeny shows that considerable uncertainty exists through much of the mitogenome species tree. The origin of divergence in the complex dates to the Pliocene/Pleistocene boundary, and divergence within the distinct northern South American clade is estimated at approximately 1 million years ago. Neither the phylogenetic trees nor the delimitation approach rejected the 10-species hypothesis, although the analyses could not exclude the possibility that four putative species with scant a priori support (An. albitarsis G, An. albitarsis H, An. albitarsis I, and An. albitarsis J), represent population-level, rather than species-level, splits.

Conclusion
The lack of resolution in much of the species tree and the limitations of the delimitation analysis warrant future studies on the complex using genome-wide data and the inclusion of additional specimens, particularly from two putative species, An. albitarsis I and An. albitarsis J.

Graphical Abstract
The interrelationship and accumulation of cardiometabolic risk factors amongst young adults in the United Arab Emirates: The UAE Healthy Future Study
Authors: Mezhal Fatima , Oulhaj Abderrahim , Abdulle Abdishakur , AlJunaibi Abdulla , Alnaeemi Abdulla , Ahmad Amar , Leinberger-Jabari Andrea , Al Dhaheri Ayesha S. , Tuzcu E. Murat , AlZaabi Eiman , Al-Maskari Fatma , Alanouti Fatme , Alameri Fayza , Alsafar Habiba , Alblooshi Hamad , Alkaabi Juma , Wareth Laila Abdel , Aljaber Mai , Kazim Marina , Weitzman Micheal , Al-Houqani Mohammad , Ali Mohammad Hag , Oumeziane Naima , El-Shahawy Omar , Al-Rifai Rami H. , Scherman Scott , Shah Syed M. , Loney Tom , Almahmeed Wael , Idaghdour Youssef , Ahmed Luai A. , Ali Raghib 
Published: November 2021

Abstract
Introduction
Similar to other non-communicable diseases (NCDs), people who develop cardiovascular disease (CVD) typically have more than one risk factor. The clustering of cardiovascular risk factors begins in youth, early adulthood, and middle age. The presence of multiple risk factors simultaneously has been shown to increase the risk for atherosclerosis development in young and middle-aged adults and risk of CVD in middle age.

Objective
This study aimed to address the interrelationship of CVD risk factors and their accumulation in a large sample of young adults in the United Arab Emirates (UAE).

Methods
Baseline data was drawn from the UAE Healthy Future Study (UAEHFS), a volunteer-based multicenter study that recruits Emirati nationals. Data of participants aged 18 to 40 years was used for cross-sectional analysis. Demographic and health information was collected through self-reported questionnaires. Anthropometric data and blood pressure were measured, and blood samples were collected.

Results
A total of 5126 participants were included in the analysis. Comorbidity analyses showed that dyslipidemia and obesity co-existed with other cardiometabolic risk factors (CRFs) more than 70% and 50% of the time, respectively. Multivariate logistic regression analysis of the risk factors with age and gender showed that all risk factors were highly associated with each other. The strongest relationship was found with obesity; it was associated with four-fold increase in the odds of having central obesity [adjusted OR 4.70 (95% CI (4.04–5.46)], and almost three-fold increase odds of having abnormal glycemic status [AOR 2.98 (95% (CI 2.49–3.55))], hypertension (AOR 3.03 (95% CI (2.61–3.52))] and dyslipidemia [AOR 2.71 (95% CI (2.32–3.15)]. Forty percent of the population accumulated more than 2 risk factors, and the burden increased with age.

Conclusion
In this young population, cardiometabolic risk factors are highly prevalent and are associated with each other, therefore creating a heavy burden of risk factors. This forecasts an increase in the burden of CVD in the UAE. The robust longitudinal design of the UAEHFS will enable researchers to understand how risk factors cluster before disease develops. This knowledge will offer a novel approach to design group-specific preventive measures for CVD development.
Transient congenital hyperinsulinism and hemolytic disease of a newborn despite rhesus D prophylaxis: a case report
Authors: Riis Sandra Simony Tornoe , Joergensen Marianne Hoerby , Rasmussen Kristina Fruerlund , Husby Steffen , Hasselby Jane Preuss , Borgwardt Lise , Brusgaard Klaus , Fagerberg Christina Ringmann , Christesen Henrik Thybo 
Published: November 2021

Abstract
Background
In neonates, rhesus D alloimmunization despite anti-D immunoglobulin prophylaxis is rare and often unexplained. Rhesus D alloimmunization can lead to hemolytic disease of the newborn with anemia and unconjugated hyperbilirubinemia. In past reports, transient congenital hyperinsulinism has been described as a rare complication of rhesus D alloimmunization. Our case report illustrates that rhesus D alloimmunization can result in a pseudosyndrome with severe congenital hyperinsulinism, anemia, and conjugated hyperbilirubinemia, despite correctly administered anti-D immunoglobulin prophylaxis.

Case presentation
We report of a 36-year-old, Caucasian gravida 1, para 1 mother with A RhD negative blood type who received routine antenatal anti-D immunoglobulin prophylaxis. Her full term newborn boy presented with severe congenital hyperinsulinism, anemia, and conjugated hyperbilirubinemia up to 295 µmol/L (ref. < 9), accounting for 64% of the total bilirubin. Syndromic congenital hyperinsulinism was suspected. Examinations showed a positive direct antiglobulin test, initially interpreted as caused by irregular antibodies; diffuse congenital hyperinsulinism by 18F-DOPA positron emission tomography/computed tomography scan; normal genetic analyses for congenital hyperinsulinism; mildly elevated liver enzymes; delayed, but present bile excretion by Tc99m-hepatobiliary iminodiacetic acid scintigraphy; and cholestasis and mild fibrosis by liver biopsy. The maternal anti-D titer was 1:16,000 day 20 postpartum. Y-chromosome material in the mother’s blood could not be identified. This could, however, not exclude late intrapartum fetomaternal hemorrhage as the cause of immunization. No causative genetic findings were deetrmined by trio whole exome sequencing. The child went into clinical remission after 5.5 months.

Conclusion
Our case demonstrates that rhesus D alloimmunization may present as a pseudosyndrome with transient congenital hyperinsulinism, anemia, and inspissated bile syndrome with conjugated hyperbilirubinaemia, despite anti-D immunoglobulin prophylaxis, possibly due to late fetomaternal hemorrhage.
Interferon-induced sarcoidosis with uveitis as the initial symptom: a case report and review of the literature
Authors: Kato Ai , Ishihara Mami , Mizuki Nobuhisa 
Published: November 2021

AbstractBackgroundIn recent years, numerous studies have reported the development or exacerbation of sarcoidosis due to interferon therapy. However, ocular lesions rarely present as initial symptoms. Herein, we describe a rare case of interferon-α-induced sarcoidosis with uveitis as the initial symptom, and present a review of the relevant literature.Case presentationThis case involved a 62-year-old-Japanese woman with a history of a combination treatment of pegylated interferon-α-2a, ribavirin, and simeprevir, after which she developed granulomatous panuveitis. She was subsequently diagnosed with sarcoidosis following histological examination of skin biopsy specimens. In addition to reporting this case, we performed a literature review of 27 cases (24 case reports) of histopathologically diagnosed interferon-α-induced sarcoidosis published between January 2009 and November 2018.ConclusionsAmong the reviewed cases, 23 (85.1%) cases developed skin lesions and 19 (70.1%) had lung lesions. Only three cases (11.1%) had accompanying eye lesions. Interferon-α therapy was discontinued in 16 cases (52.9%), and the majority exhibited improvement after systemic corticosteroid treatment. There are few reported cases of interferon-α-induced sarcoidosis with uveitis as the initial symptom. However, if uveitis develops during or after interferon-α treatment, it might represent an initial symptom of interferon-α-induced sarcoidosis, as observed in the present case.
Nitrification mainly driven by ammonia-oxidizing bacteria and nitrite-oxidizing bacteria in an anammox-inoculated wastewater treatment system
Authors: Lu Jing , Hong Yiguo , Wei Ying , Gu Ji-Dong , Wu Jiapeng , Wang Yu , Ye Fei , Lin Jih-Gaw 
Published: November 2021

AbstractAnaerobic ammonium oxidation (anammox) process has been acknowledged as an environmentally friendly and time-saving technique capable of achieving efficient nitrogen removal. However, the community of nitrification process in anammox-inoculated wastewater treatment plants (WWTPs) has not been elucidated. In this study, ammonia oxidation (AO) and nitrite oxidation (NO) rates were analyzed with the incubation of activated sludge from Xinfeng WWTPs (Taiwan, China), and the community composition of nitrification communities were investigated by high-throughput sequencing. Results showed that both AO and NO had strong activity in the activated sludge. The average rates of AO and NO in sample A were 6.51 µmol L−1 h−1 and 6.52 µmol L−1 h−1, respectively, while the rates in sample B were 14.48 µmol L−1 h−1 and 14.59 µmol L−1 h−1, respectively. The abundance of the nitrite-oxidizing bacteria (NOB) Nitrospira was 0.89–4.95 × 1011 copies/g in both samples A and B, the abundance of ammonia-oxidizing bacteria (AOB) was 1.01–9.74 × 109 copies/g. In contrast, the abundance of ammonia-oxidizing archaea (AOA) was much lower than AOB, only with 1.28–1.53 × 105 copies/g in samples A and B. The AOA community was dominated by Nitrosotenuis, Nitrosocosmicus, and Nitrososphaera, while the AOB community mainly consisted of Nitrosomonas and Nitrosococcus. The dominant species of Nitrospira were Candidatus Nitrospira defluvii, Candidatus Nitrospira Ecomare2 and Nitrospira inopinata. In summary, the strong nitrification activity was mainly catalyzed by AOB and Nitrospira, maintaining high efficiency in nitrogen removal in the anammox-inoculated WWTPs by providing the substrates required for denitrification and anammox processes.
A systematic review of GWAS identified SNPs associated with outcomes of medications for opioid use disorder
Authors: Chawar Caroul , Hillmer Alannah , Sanger Stephanie , D’Elia Alessia , Panesar Balpreet , Guan Lucy , Xie Dave Xiaofei , Bansal Nandini , Abdullah Aamna , Kapczinski Flavio , Pare Guillaume , Thabane Lehana , Samaan Zainab 
Published: November 2021

Abstract
Background
Patients with opioid use disorder (OUD) display an interindividual variability in their response to medications for opioid use disorder (MOUD). A genetic basis may explain the variability in this response. However, no consensus has been reached regarding which genetic variants significantly contribute to MOUD outcomes.

Objectives
This systematic review aims to summarize genome-wide significant findings on MOUD outcomes and critically appraise the quality of the studies involved.

Methods
Databases searched from inception until August 21st, 2020 include: MEDLINE, Web of Science, EMBASE, CINAHL and Pre-CINAHL, GWAS Catalog and GWAS Central. The included studies had to be GWASs that assessed MOUD in an OUD population. All studies were screened in duplicate. The quality of the included studies was scored and assessed using the Q-Genie tool. Quantitative analysis, as planned in the protocol, was not feasible, so the studies were analyzed qualitatively.

Results
Our search identified 7292 studies. Five studies meeting the eligibility criteria were included. However, only three studies reported results that met our significance threshold of p ≤ 1.0 × 10–7. In total, 43 genetic variants were identified. Variants corresponding to CNIH3 were reported to be associated with daily heroin injection in Europeans, OPRM1, TRIB2, and ZNF146 with methadone dose in African Americans, EYS with methadone dose in Europeans, and SPON1 and intergenic regions in chromosomes 9 and 3 with plasma concentrations of S-methadone, R-methadone, and R-EDDP, respectively, in Han Chinese.

Limitations
The limitations of this study include not being able to synthesize the data in a quantitative way and a conservative eligibility and data collection model.

Conclusion
The results from this systematic review will aid in highlighting significant genetic variants that can be replicated in future OUD pharmacogenetics research to ascertain their role in patient-specific MOUD outcomes.
Systematic review registration number CRD42020169121.
Are coveralls required as personal protective equipment during the management of COVID-19 patients?
Authors: Jung Jongtak , Song Kyoung-Ho , Jeong Hyeonju , Ham Sin Young , Kim Eu Suk , Kim Hong Bin 
Published: November 2021

Abstract
Objectives
Few studies have investigated the contamination of personal protective equipment (PPE) during the management of patients with severe-to-critical coronavirus disease (COVID-19). This study aimed to determine the necessity of coveralls and foot covers for body protection during the management of COVID-19 patients.

Methods
PPE samples were collected from the coveralls of physicians exiting a room after the management of a patient with severe-to-critical COVID-19 within 14 days after the patient’s symptom onset. The surface of coveralls was categorized into coverall-only parts (frontal surface of the head, anterior neck, dorsal surface of the foot cover, and back and hip) and gown-covered parts (the anterior side of the forearm and the abdomen). Sampling of the high-contact surfaces in the patient’s environment was performed. We attempted to identify significant differences in contamination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between the coverall-only and gown-covered parts.

Results
A total of 105 swabs from PPEs and 28 swabs from patient rooms were collected. Of the PPE swabs, only three (2.8%) swabs from the gown-covered parts were contaminated with SARS-CoV-2. However, 23 of the 28 sites (82.1%) from patient rooms were contaminated. There was a significant difference in the contamination of PPE between the coverall-only and gown-covered parts (0.0 vs 10.0%, p = 0.022).

Conclusions
Coverall contamination rarely occurred while managing severe-to-critical COVID-19 patients housed in negative pressure rooms in the early stages of the illness. Long-sleeved gowns may be used in the management of COVID-19 patients.