bluuebunny/crossref_metadata_2025_split huggingface dataset:
The nosological status of unipolar mania and hypomania within UK Biobank according to objective and subjective measures of diurnal rest and activity
Authors: Sangha Natasha , Lyall Laura , Wyse Cathy , Cullen Breda , Whalley Heather C. , Smith Daniel J. 
Published: June 2022

AbstractBackgroundThere is uncertainty whether unipolar mania is a discrete sub‐type of bipolar disorder. Disrupted rest/activity rhythms are a key feature of bipolar disorder (BD) but have not been well characterised in unipolar mania/hypomania (UM). We compared subjective and objective rest/activity patterns, demographic and mental health outcomes across BD, UM and control groups.MethodsUK residents aged 37–73 years were recruited into UK Biobank from 2006 to 2010. BD, UM and control groups were identified via a mental health questionnaire. Demographic, mental health and subjective sleep outcomes were self‐reported. Accelerometery data were available for a subset of participants, and objective measures of sleep and activity were derived.ResultsA greater proportion of males met UM criteria, and more females were in the BD group. Both BD and UM groups had poor mental health outcomes vs. controls. Objectively measured activity differed between all three groups: UM had highest levels of activity and BD lowest. The UM group had shorter sleep duration compared to controls. Subjective rest/activity measures showed that both mood disorder groups (compared to controls) had later chronotype preference, more disturbed sleep and increased difficulty getting up in the morning. However, the UM group were more likely to report an early chronotype compared to BD and control groups.ConclusionsBD and UM share features in common, but key differences support the proposition that UM may be a distinct and more clinically homogenous disorder. UM was characterised by a higher proportion of males, early chronotype, increased activity and shorter sleep duration.
Facing difficult but unavoidable choices: Donor blood safety and the deferral of men who have sex with men
Authors: Pierik Roland , Verweij Marcel , van de Laar Thijs , Zaaijer Hans 
Published: June 2022

AbstractBlood service organizations employ various ways to ensure transfusion blood safety, including the testing of all donations for transfusion‐transmissible infections (TTI) and the exclusion of donors who are at increased risk of a recent infection. As some TTIs are more common among men who have sex with men (MSM), many jurisdictions (temporarily) defer the donation of blood by sexually active MSM. This boils down to a categorical exclusion of a large group solely on the basis of their sexual orientation, which is seen as unduly discriminatory and stigmatizing. Blood service organizations in the U.K. and the Netherlands have recently changed their deferral policies for MSM. The problem of the MSM deferral involves a conflict between fundamental rights: the right of MSM to equal treatment and the right to health of the recipients of blood and blood products. We distinguish and discuss three broad alternative options to the current categorical deferral of MSM donations: (1) completely abandoning donor selection on the basis of sexual behavior, (2) individual risk assessment of the sexual activities of each potential donor, and (3) individual risk assessment of the sexual activities of MSM only. The new U.K. policy falls within the second category, and the new Dutch policy is in the third category. We argue that each approach comes with moral costs but that the most reasonable option is different from the policies of both the U.K. and the Netherlands.
Haematological variables and risk of future venous thromboembolism in the British Regional Heart Study on men. Combined D‐dimer and APTT as a predictive test for thromboembolism?
Authors: Wannamethee S. Goya , Papacosta Olia , Lennon Lucy , Whincup Peter H. , Rumley Ann , Lowe Gordon D. O. 
Published: June 2022

SummaryWe examined the associations between haematological and inflammatory variables with future venous thromboembolism (VTE), in 3494 men aged 60–79 years, with no previous history of VTE or myocardial infarction, who were not receiving oral anticoagulants. After a mean follow‐up period of 18 years, there were 149 confirmed cases of fatal or non‐fatal VTE (deep vein thrombosis and/or pulmonary embolism). Among classical cardiovascular risk factors, only obesity and cigarette smoking were associated with VTE risk. After adjustment for age, obesity and smoking, VTE risk was associated with coagulation factor VIII, factor IX, von Willebrand factor (VWF), activated partial thromboplastin time (APTT), and fibrin D‐dimer. Hazard ratios (95% CI) for top to bottom quarters (bottom to top for APTT), were respectively 2.17 (1.37, 3.44), 2.15 (1.30, 3.53), 2.02 (1.27, 3.22), 2.43 (1.47, 4.02) and 3.62 (2.18, 6.08). The 11% of men with both the shortest APTT and highest D‐dimer combined had a 5.02 (2.37, 10.62) higher risk of VTE. VTE risk was not associated with fibrinogen, factor VII or activated protein C resistance; full blood count variables or with inflammatory markers, plasma viscosity, C‐reactive protein or interleukin‐6. The combination of D‐dimer and APTT merits evaluation as an adjunct to VTE risk prediction scores.
Impaired humoral and cellular response to primary COVID‐19 vaccination in patients less than 2 years after allogeneic bone marrow transplant
Authors: Murray Sam M. , Barbanti Maria , Campbell Cori , Brown Anthony , Chen Lucia , Dhanapal Jay , Tseu Bing , Pervaiz Omer , Peters Louis , Springett Sally , Danby Robert , Adele Sandra , Phillips Eloise , Malone Tom , Amini Ali , Stafford Lizzie , Deeks Alexandra S. , Dunachie Susanna , Klenerman Paul , Peniket Andrew , Barnes Eleanor , Kesavan Murali 
Published: June 2022

SummaryAllogeneic haematopoietic stem cell transplant (HSCT) recipients remain at high risk of adverse outcomes from coronavirus disease 2019 (COVID‐19) and emerging variants. The optimal prophylactic vaccine strategy for this cohort is not defined. T cell‐mediated immunity is a critical component of graft‐versus‐tumour effect and in determining vaccine immunogenicity. Using validated anti‐spike (S) immunoglobulin G (IgG) and S‐specific interferon‐gamma enzyme‐linked immunospot (IFNγ‐ELIspot) assays we analysed response to a two‐dose vaccination schedule (either BNT162b2 or ChAdOx1) in 33 HSCT recipients at ≤2 years from transplant, alongside vaccine‐matched healthy controls (HCs). After two vaccines, infection‐naïve HSCT recipients had a significantly lower rate of seroconversion compared to infection‐naïve HCs (25/32 HSCT vs. 39/39 HCs no responders) and had lower S‐specific T‐cell responses. The HSCT recipients who received BNT162b2 had a higher rate of seroconversion compared to ChAdOx1 (89% vs. 74%) and significantly higher anti‐S IgG titres (p = 0.022). S‐specific T‐cell responses were seen after one vaccine in HCs and HSCT recipients. However, two vaccines enhanced S‐specific T‐cell responses in HCs but not in the majority of HSCT recipients. These data demonstrate limited immunogenicity of two‐dose vaccination strategies in HSCT recipients, bolstering evidence of the need for additional boosters and/or alternative prophylactic measures in this group.
CD73 facilitates invadopodia formation and boosts malignancy of head and neck squamous cell carcinoma via the MAPK signaling pathway
Authors: Xue Feifei , Wang Tianxiao , Shi Hao , Feng Hongjie , Feng Guanying , Wang Ruixia , Yao Yao , Yuan Hua 
Published: June 2022

AbstractElevated adenosine generated by CD73 (ecto‐5′‐nucleotidase; NT5E) could boost immunosuppressive responses and promote immune evasion in the tumor microenvironment. However, despite the immune response, CD73 could also promote tumor progression in a variety of cancers, and the nonimmunologic role and corresponding molecular mechanism of CD73 involved in head and neck squamous cell carcinoma (HNSCC) progression are not well characterized. Here, we demonstrated that CD73/NT5E is overexpressed in HNSCC tissues and predicts poor prognosis. Suppression of CD73 inhibited the proliferation, migration, and invasion of HNSCC cell lines (CAL27 and HN4) in vitro and in vivo. Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) predicted that CD73 may be involved in invadopodia formation and MAPK signaling activation. As expected, knockdown of CD73 inhibited the MAPK signaling pathway, and the suppressive effect of CD73 knockdown on proliferation, migration, invasion, and invadopodia formation was reversed by a MAPK signaling activator. Our results suggest that CD73 could promote the proliferation, migration, invasion, and invadopodia formation of HNSCC via the MAPK signaling pathway and provide new mechanistic insights into the nonimmunological role of CD73 in HNSCC.
Long noncoding RNA OVAAL enhances nucleotide synthesis through pyruvate carboxylase to promote 5‐fluorouracil resistance in gastric cancer
Authors: Tan Jia‐nan , Zhou Sheng‐ning , Zhang Wei , Yang Bin , Zhong Guang‐yu , Huang Jing , Hu Hai , Han Fang‐hai , Luo Man‐Li 
Published: June 2022

Abstract5‐Fluorouracil (5‐FU) is widely used in gastric cancer treatment, yet 5‐FU resistance remains an important clinical challenge. We established a model based on five long noncoding RNAs (lncRNA) to effectively assess the prognosis of gastric cancer patients; among them, lncRNA OVAAL was markedly upregulated in gastric cancer and associated with poor prognosis and 5‐FU resistance. In vitro and in vivo assays confirmed that OVAAL promoted proliferation and 5‐FU resistance of gastric cancer cells. Mechanistically, OVAAL bound with pyruvate carboxylase (PC) and stabilized PC from HSC70/CHIP‐mediated ubiquitination and degradation. OVAAL knockdown reduced intracellular levels of oxaloacetate and aspartate, and the subsequent pyrimidine synthesis, which could be rescued by PC overexpression. Moreover, OVAAL knockdown increased sensitivity to 5‐FU treatment, which could be reversed by PC overexpression or repletion of oxaloacetate, aspartate, or uridine. OVAAL overexpression enhanced pyrimidine synthesis to promote proliferation and 5‐FU resistance of gastric cancer cells, which could be abolished by PC knockdown. Thus, OVAAL promoted gastric cancer cell proliferation and induced 5‐FU resistance by enhancing pyrimidine biosynthesis to antagonize 5‐FU induced thymidylate synthase dysfunction. Targeting OVAAL‐mediated nucleotide metabolic reprograming would be a promising strategy to overcome chemoresistance in gastric cancer.
Safety and effectiveness of eculizumab in Japanese patients with generalized myasthenia gravis: Analysis of 1‐year postmarketing surveillance
Authors: Murai Hiroyuki , Suzuki Shigeaki , Fukamizu Yuji , Osawa Takehiko , Kikui Hidekazu , Utsugisawa Kimiaki 
Published: June 2022

AbstractIntroductionEculizumab, a terminal complement protein C5 inhibitor, is approved in Japan for the treatment of patients with anti‐acetylcholine receptor antibody‐positive (AChR Ab+) generalized myasthenia gravis (gMG) that is difficult to control with plasmapheresis or high‐dose intravenous immunoglobulin therapy.MethodsThis analysis of mandatory postmarketing surveillance in Japan assessed the safety and effectiveness of eculizumab in patients with AChR Ab+ gMG who had completed case‐report forms at 26 wk after eculizumab initiation up to the cutoff date of April 2021. Changes from baseline were assessed for Myasthenia Gravis‐Activities of Daily Living (MG‐ADL) and Quantitative Myasthenia Gravis (QMG) total scores overall, and MG‐ADL scores in patient subgroups according to sex, age at diagnosis and baseline, and baseline disease severity. The change in concomitant corticosteroid use was also evaluated.ResultsData were available for 134 adults (67.2% female; mean age 51.9 y); the effectiveness‐analysis set comprised 126 patients. After 26 wk, 78% of patients were continuing eculizumab treatment. Adverse drug reactions were reported by 49 patients (37%) (most frequently headache [n = 10]). Improvements in MG‐ADL scores were seen regardless of sex; age at diagnosis (<50/≥50 y); baseline age (18 to <40/≥40 to <65/≥65 y); Myasthenia Gravis Foundation of America disease classification (IIa/IIb/IIIa/IIIb/IVa/IVb/V); or baseline MG‐ADL score (<6/≥6). Of patients receiving corticosteroids, the proportion receiving low doses (average ≤5 mg/d) increased from 7.0% before eculizumab initiation to 26.4% by Week 52.ConclusionEculizumab was well tolerated and effective in treating AChR Ab+ gMG across a broad spectrum of adult Japanese patients with difficult‐to‐control gMG.
A single centre 20‐year retrospective cohort study: Percutaneous endoscopic colostomy
Authors: Farkas Nicholas , Kenny Ross , Conroy Michael , Harris Holly , Anele Chukwuemeka , Simson Jay , Levy Bruce 
Published: June 2022

AbstractAimPercutaneous endoscopic colostomy (PEC) represents an important intervention in specific patients. Limited data currently exist. We present the largest recorded study of patients undergoing PEC.MethodsRetrospective analysis of consultant logbooks highlighted all patients from 1997 to 2020. Two independent reviewers assessed records. Parameters measured were age, sex, indication, number of sites, complications, mortality and survival. Three subgroups were identified: recurrent sigmoid volvulus (RSV), pseudo‐obstruction and neurogenic. ANOVA, chi‐squared and Fischer's exact tests were utilized; Kaplan–Meier curves estimated survival and the log‐rank test was applied. A p value of <0.05 was considered statistically significant.ResultsNinety‐six PEC insertions were done on 91 patients (five reinsertions). There were 66 men (69%) and the mean age was 73.1 years (interquartile range 23). The indications were RSV n = 72, pseudo‐obstruction n = 13, neurogenic n = 11. The 30‐day complication rate was overall n = 27 (28%), RSV n = 23, pseudo‐obstruction n = 4. Nine patients leaked (9.9%) (eight RSV, one pseudo‐obstruction), of whom five died. 90‐day mortality was 14.6% (14 patients), 18.5% (13/72) for RSV, 7.7% (1/13) for pseudo‐obstruction. Overall recurrence following PEC was 10.4%. The median follow‐up was 25 months (interquartile range 4.6–62.2 months). At 3, 5 and 10 years survival was 46%, 34% and 26% for RSV, 70%, 55% and 15% for pseudo‐obstruction and 91%, 91% and 81% for neurogenic respectively.ConclusionRecurrent sigmoid volvulus and pseudo‐obstruction patients undergoing PEC compared to neurogenic patients have poorer outcomes with higher complication rates and shorter life expectancy. We advocate that high volume specialist units undertake PEC. The significant associated risks of PEC require careful consideration when determining patient suitability. Utilizing risk stratification scores may help guide shared decision making between patients, relatives and clinicians.
Ano‐rectovaginal fistula after obstetrical anal sphincter injury: Diverting stoma does not improve the surgical results
Authors: Venara Aurélien , Trilling Bertrand , Ngoma Marie , Brochard Charlène , Duchalais Emilie , Siproudhis Laurent , Faucheron Jean‐Luc , de Parades Vincent , Alves Arnaud , Cotte Eddy , Ouaissi Mehdi , Bridoux Valérie , Corbière Lisa , Heraud Jeanne , Ortega‐Deballon Pablo , Abo‐Alhassan Fawaz , Hamel Jean‐Francois 
Published: June 2022

AbstractAimAno‐rectovaginal fistulas (ARVF) are challenging for the surgeon. Most of the series mix aetiologies, leading to confusion with respect to the conclusion. The aim of this study was to assess the factors associated with the success of ARVF management following obstetrical anal sphincter injury (OASIS).MethodsThis retrospective multicentric study included all the patients undergoing surgery for ARVF identified by the hospital codes. Patients for whom the aetiology of ARVF was not OASIS were excluded. The major outcome measure was the success of the procedure.ResultsSixty patients with treated ARVF due to OASIS were identified. The success of overall management was 91.7%. Female patients underwent a mean of 2.5 (±1.7) procedures. A diverting stoma was formed in 29 patients (48.3%) of which 26 were closed at the end of the management period (89.7%). Of the 148 surgical procedures, only 55 were successful (37.2%). The order of the procedures (OR = 1.38; 95% CI: 0.75–2.51) or the diverting stoma (OR = 1.46; 95% CI: 0.31–6.91) were not significantly associated with the success of the surgery. However, Martius flap (OR = 4.13; 95% CI: 1.1–15.54) and Musset procedures (OR = 5.79; 95% CI: 1.77–18.87) produced better results than the endorectal advancement flap (ERAF). The other procedures did not show a significant correlation with management success.ConclusionA diverting stoma is not mandatory in the management of ARVF due to OASIS to improve the success of the surgical procedure. While the Martius flap procedure offers better results, the ERAF procedure may be preferred as a primary intervention in the absence of sphincter injury as it is less invasive. In cases of residual sphincter injury, the Musset procedure is most likely to be the best option.
Comorbid diseases among bullous pemphigoid patients in Germany: new insights from a case‐control study
Authors: Martin Eva , Mauer Isabell , Malzahn Uwe , Heuschmann Peter Ulrich , Goebeler Matthias , Benoit Sandrine 
Published: June 2022

SummaryBackground and objectivesBullous pemphigoid (BP) is associated with neuropsychiatric disorders. Other comorbid diseases are discussed controversially. We evaluated the prevalence of comorbidity in BP patients in a representative area of Germany.Patients and methodsMedical files of all BP patients treated at the Department of Dermatology, University Hospital Würzburg, Germany, between June 2002 and May 2013 were retrospectively reviewed. Bullous pemphigoid was diagnosed based on established criteria. For each patient, two controls were individually matched. Records were evaluated for age, sex, laboratory values, concomitant medication and comorbidity. Conditional logistic regression, multivariable regression analysis and complex regression models were performed to compare results.Results300 BP patients were identified and compared to 583 controls. Bullous pemphigoid was associated with neuropsychiatric disorders as well as laboratory abnormalities including leukocytosis and eosinophilia. Importantly, a highly significant association of BP with anemia (OR 2.127; 95 % CI 1.532–2.953) and renal impairment (OR 2.218; 95 % CI 1.643–2.993) was identified. No association was found with malignancy and arterial hypertension.ConclusionsOur data revealed an increased frequency of anemia and renal impairment in BP patients. In accordance with previous studies the strong association for neuropsychiatric disorders was confirmed (p < 0.0005).
Ivermectin impacts on dung beetle diversity and their ecological functions in two distinct Brazilian ecosystems
Authors: Correa César M. A. , Ferreira Kleyton R. , Abot Alfredo R. , Louzada Julio , Vaz‐de‐Mello Fernando Z. 
Published: June 2022

Abstract
The indiscriminate use of Ivermectin is becoming a frequent scenario in Brazil, one of the largest beef cattle herds in the world, and the second‐highest commercial production, despite this product having harmful effects on non‐target organisms. Among these organisms, dung beetles are essential for the maintenance of ecosystem functioning in introduced pastures.
This study evaluated the effects of Ivermectin on dung beetle assemblage attributes (species richness, abundance, species composition, functional groups and indicator species) as well as their ecological functions (dung removal and soil bioturbation) in introduced pastures with different priorities for livestock intensification in Brazil; Amazon (high) and Pantanal (low).
We found a negative response of dung beetle assemblages to Ivermectin in both Brazilian ecosystems, where these negative effects were more pronounced in the Pantanal. Tunneler beetles are the functional group most negatively affected in both ecosystems. Finally, the Ivermectin reduces the ecological functions performed by dung beetles, with a dung removal reduction of ca. 50% and 70% in the Amazon and Pantanal, respectively.
The most negative impacts in the Brazilian Pantanal reflect the long‐term consequences due to a long history of Ivermectin use than in the Amazon. However, these results also indicate a drastic future for dung beetles in Amazonian pastures.
Thus, a sustainable cattle production system reducing Ivermectin use will be important for conserving dung beetles on introduced Brazilian pastures and the ecological functions that these insects provide in livestock‐dominated landscapes.
Place cells in the claustrum remap under NMDA receptor control
Authors: Rizzello Emanuela , Martin Seán K. , Rouine Jennifer , Callaghan Charlotte , Mathiasen Mathias L. , O'Mara Shane M. 
Published: June 2022

AbstractPlace cells are cells that exhibit location‐dependent responses; they have mostly been studied in the hippocampus. Place cells have also been reported in the rat claustrum, an underexplored paracortical region with extensive corto‐cortical connectivity. It has been hypothesised that claustral neuronal responses are anchored to cortical visual inputs. We show rat claustral place cells remap when visual inputs are eliminated from the environment, and that this remapping is NMDA‐receptor‐dependent. Eliminating visual input decreases claustral delta‐band oscillatory activity, increases theta‐band oscillatory activity, and increases simultaneously recorded visual cortical activity. We conclude that, like the hippocampus, claustral place field remapping might be mediated by NMDA receptor activity, and is modulated by visual cortical inputs.
TheDay‐in‐the‐Lifemethod for assessing infant caregiving in rural Pakistan
Authors: O'Donnell Karen J. , Gallis John A. , Turner Elizabeth L. , Hagaman Ashley K. , Scherer Elissa , Sikander Siham , Maselko Joanna 
Published: June 2022

AbstractObjectiveThis manuscript describes the Day‐in‐the‐Life (DIL) method for assessing child caregiving activities, its implementation, and findings regarding family members' roles and associations with maternal depression symptoms.BackgroundInfant caregiving activities are most commonly performed by the mother, although there is increasing acknowledgement of others' contribution. Few methods exist to measure the diverse caregiving activities that mothers and others perform.MethodMethod development occurred within the Bachpan Cohort Study in rural Pakistan (N = 1154 maternal–child dyads) when the child was 3 months old. The DIL was designed as a semi‐structured interview in which the mother describes her child's day from their perspective. Regression analyses were then used to explore the correlation between the DIL and depression symptoms, using the Patient Health Questionnaire‐9 (PHQ‐9) measure.ResultsThe DIL method was easy to administer and displayed excellent interrater agreement. The findings indicated that instrumental caregiving was mostly provided by the mother alone, others in the household tended to contribute more to infant social interactions, and there was more support from others when the mother was less able to provide care (e.g., when ill). Depression symptoms were higher among women who experienced less contribution from family members when the mother was less able to provide care.ConclusionsThe DIL can be deployed to measure infant caregiving activities and associations with maternal mental health.ImplicationsThis method is promising for researchers interested in disentangling the contribution of multiple family members toward child caregiving and its impacts on maternal and child health.