bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perspectives of drug treatment and mental health professionals towards treatment provision for substance use disorders with coexisting mental health problems in England
Authors: Houghton Ben , Bailey Alexis , Kouimtsidis Christos , Duka Theodora , Notley Caitlin 
Published: November 2021

Background Opioid-related deaths are at record levels in the UK and contribute to over half of all drug-related deaths. The prevalence of psychiatric disorders within people who uses substances is known to be considerably higher than the general population, yet only 4% of people accessing treatment are thought to receive integrated care for coexisting conditions. This study aimed to explore perspectives on treatment for people with substance use disorders and coexisting psychiatric problems. Methods Face-to-face semi-structured interviews with community drug workers, specialist nurses, prescribing administration worker and one clinical psychologist were conducted. Deductive analysis of three preconceived themes (i.e. reasons for substance use, treatment provision, the role of medication) was conducted. Results There was agreement between drug treatment professionals and mental health professionals for the complexities for being in treatment for people who use substances. An expectancy of prolonged periods of abstinence from drug and alcohol use before psychological treatment would be initiated leading to relapse was reported. Individual judgements of practitioners, stigmatisation and fear of people who use substances and organisational barriers often meant psychological help was unavailable which contributed to a reliance on medication, against national clinical guidance which was known by only one interviewee. Conclusion The UK drug treatment and mental health services should review the pathways to ensure that national guidelines are followed so that people who use substances are not excluded from accessing psychological therapies. Data from the coronavirus pandemic indicates heightened psychiatric problems, where illicit drug use may escalate as a means of self-medication leading to further increases in drug-related deaths.
A multisite randomized controlled trial of two group education programs for fatigue in multiple sclerosis: Very long term (5–6 year) follow-up at one site
Authors: Norton Julia , Joos Sandra , Cameron Michelle H , Hugos Cinda L 
Published: November 2021

Background A multicomponent group MS fatigue self-management program reduced fatigue impact compared to a rigorous control 12 months after enrollment. Objectives Assess and compare changes between groups in fatigue impact and behavior changes implemented 5–6 years after enrollment. Methods The Modified Fatigue Impact Scale (MFIS) and a behavior change questionnaire were administered 5–6 years after enrollment. Results There were no significant changes in mean MFIS scores within or between groups from baseline to 5–6 years later. Behavior changes were of similar frequency in both groups. Conclusion Fatigue impact was stable and behavior changes were similar between groups 5–6 years after a fatigue self-management program.
Selexipag for the treatment of chronic thromboembolic pulmonary hypertension
Authors: Ogo Takeshi , Shimokawahara Hiroto , Kinoshita Hideyuki , Sakao Seiichiro , Abe Kohtaro , Matoba Satoaki , Motoki Hirohiko , Takama Noriaki , Ako Junya , Ikeda Yasuhiro , Joho Shuji , Maki Hisataka , Saeki Takahiro , Sugano Teruyasu , Tsujino Ichizo , Yoshioka Koichiro , Shiota Naoki , Tanaka Shinichi , Yamamoto Chieko , Tanabe Nobuhiro , Tatsumi Koichiro ,   for the Study Group
Published: November 2021

BackgroundTreatment options for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) remain limited. Selexipag, an oral selective IP prostacyclin receptor agonist approved for pulmonary arterial hypertension, is a potential treatment option for CTEPH.MethodsIn this multicentre, randomised, double-blind, placebo-controlled study, 78 Japanese patients with inoperable CTEPH or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy and/or balloon pulmonary angioplasty were randomly assigned to receive placebo or selexipag. The primary end-point was the change in pulmonary vascular resistance (PVR) from baseline to week 20. Secondary end-points were changes in other haemodynamic parameters: 6-min walk distance (6MWD), Borg dyspnoea scale score, World Health Organization (WHO) functional class, EuroQol five-dimension five-level tool and N-terminal pro-brain natriuretic peptide.ResultsThe change in PVR was −98.2±111.3 dyn·s·cm−5and −4.6±163.6 dyn·s·cm−5in the selexipag and placebo groups, respectively (mean difference −93.5 dyn·s·cm−5; 95% CI −156.8 to −30.3; p=0.006). The changes in cardiac index (p<0.001) and Borg dyspnoea scale score (p=0.036) were also significantly improved over placebo. 6MWD and WHO functional class were not significantly improved. The common adverse events in the selexipag group corresponded to those generally observed following administration of a prostacyclin analogue.ConclusionSelexipag significantly improved PVR and other haemodynamic variables in patients with CTEPH, although exercise capacity remained unchanged. Further large-scale investigation is necessary to prove the role of selexipag in CTEPH.
Urinary metabotype of severe asthma evidences decreased carnitine metabolism independent of oral corticosteroid treatment in the U-BIOPRED study
Authors: Reinke Stacey N. , Naz Shama , Chaleckis Romanas , Gallart-Ayala Hector , Kolmert Johan , Kermani Nazanin Z. , Tiotiu Angelica , Broadhurst David I. , Lundqvist Anders , Olsson Henric , Ström Marika , Wheelock Åsa M. , Gómez Cristina , Ericsson Magnus , Sousa Ana R. , Riley John H. , Bates Stewart , Scholfield James , Loza Matthew , Baribaud Frédéric , Bakke Per S. , Caruso Massimo , Chanez Pascal , Fowler Stephen J. , Geiser Thomas , Howarth Peter , Horváth Ildikó , Krug Norbert , Montuschi Paolo , Behndig Annelie , Singer Florian , Musial Jacek , Shaw Dominick E. , Dahlén Barbro , Hu Sile , Lasky-Su Jessica , Sterk Peter J. , Chung Kian Fan , Djukanovic Ratko , Dahlén Sven-Erik , Adcock Ian M. , Wheelock Craig E. 
Published: November 2021

IntroductionAsthma is a heterogeneous disease with poorly defined phenotypes. Patients with severe asthma often receive multiple treatments including oral corticosteroids (OCS). Treatment may modify the observed metabotype, rendering it challenging to investigate underlying disease mechanisms. Here, we aimed to identify dysregulated metabolic processes in relation to asthma severity and medication.MethodsBaseline urine was collected prospectively from healthy participants (n=100), patients with mild-to-moderate asthma (n=87) and patients with severe asthma (n=418) in the cross-sectional U-BIOPRED cohort; 12–18-month longitudinal samples were collected from patients with severe asthma (n=305). Metabolomics data were acquired using high-resolution mass spectrometry and analysed using univariate and multivariate methods.ResultsA total of 90 metabolites were identified, with 40 significantly altered (p<0.05, false discovery rate <0.05) in severe asthma and 23 by OCS use. Multivariate modelling showed that observed metabotypes in healthy participants and patients with mild-to-moderate asthma differed significantly from those in patients with severe asthma (p=2.6×10−20), OCS-treated asthmatic patients differed significantly from non-treated patients (p=9.5×10−4), and longitudinal metabotypes demonstrated temporal stability. Carnitine levels evidenced the strongest OCS-independent decrease in severe asthma. Reduced carnitine levels were associated with mitochondrial dysfunctionviadecreases in pathway enrichment scores of fatty acid metabolism and reduced expression of the carnitine transporter SLC22A5 in sputum and bronchial brushings.ConclusionsThis is the first large-scale study to delineate disease- and OCS-associated metabolic differences in asthma. The widespread associations with different therapies upon the observed metabotypes demonstrate the need to evaluate potential modulating effects on a treatment- and metabolite-specific basis. Altered carnitine metabolism is a potentially actionable therapeutic target that is independent of OCS treatment, highlighting the role of mitochondrial dysfunction in severe asthma.
Lung transplantation for acute respiratory distress syndrome: a retrospective European cohort study
Authors: Gottlieb Jens , Lepper Philipp M. , Berastegui Cristina , Montull Beatriz , Wald Alexandra , Parmar Jasvir , Magnusson Jesper M. , Schönrath Felix , Laisaar Tanel , Michel Sebastian , Larsson Hillevi , Vos Robin , Haneya Assad , Sandhaus Tim , Verschuuren Erik , le Pavec Jérôme , Tikkanen Jussi , Hoetzenecker Konrad 
Published: November 2021

BackgroundThe published experience of lung transplantation in acute respiratory distress syndrome (ARDS) is limited. The aim of this study was to investigate the contemporary results of lung transplantation attempts in ARDS in major European centres.MethodsWe conducted a retrospective multicentre cohort study of all patients listed for lung transplantation between 2011 and 2019. We surveyed 68 centres in 22 European countries. All patients admitted to the waitlist for lung transplantation with a diagnosis of “ARDS/pneumonia” were included. Patients without extracorporeal membrane oxygenation (ECMO) or mechanical ventilation were excluded. Patients were followed until 1 October 2020 or death. Multivariable analysis for 1-year survival after listing and lung transplantation was performed.Results55 centres (81%) with a total transplant activity of 12 438 lung transplants during the 9-year period gave feedback. 40 patients with a median age of 35 years were identified. Patients were listed for lung transplantation in 18 different centres in 10 countries. 31 patients underwent lung transplantation (0.25% of all indications) and nine patients died on the waitlist. 90% of transplanted patients were on ECMO in combination with mechanical ventilation before lung transplantation. On multivariable analysis, transplantation during 2015–2019 was independently associated with better 1-year survival after lung transplantation (OR 10.493, 95% CI 1.977–55.705; p=0.006). 16 survivors out of 23 patients with known status (70%) returned to work after lung transplantation.ConclusionsLung transplantation in highly selected ARDS patients is feasible and outcome has improved in the modern era. The selection process remains ethically and technically challenging.
Dexamethasone in hospitalised COVID-19 patients not on intensive respiratory support
Authors: Crothers Kristina , DeFaccio Rian , Tate Janet , Alba Patrick R. , Goetz Matthew Bidwell , Jones Barbara , King Joseph T. , Marconi Vincent , Ohl Michael E. , Rentsch Christopher T. , Rodriguez-Barradas Maria C. , Shahrir Shahida , Justice Amy C. , Akgün Kathleen M. ,   for the Veterans Aging Cohort Study Clinical COVID-19 Working Group
Published: November 2021

BackgroundDexamethasone decreases mortality in coronavirus disease 2019 (COVID-19) patients on intensive respiratory support (IRS) but is of uncertain benefit if less severely ill. We determined whether early (within 48 h) dexamethasone was associated with mortality in patients hospitalised with COVID-19 not on IRS.MethodsWe included patients admitted to US Veterans Affairs hospitals between 7 June 2020 and 31 May 2021 within 14 days after a positive test for severe acute respiratory syndrome coronavirus 2. Exclusions included recent prior corticosteroids and IRS within 48 h. We used inverse probability of treatment weighting (IPTW) to balance exposed and unexposed groups, and Cox proportional hazards models to determine 90-day all-cause mortality.ResultsOf 19 973 total patients (95% men, median age 71 years, 27% black), 15 404 (77%) were without IRS within 48 h. Of these, 3514 out of 9450 (34%) patients on no oxygen received dexamethasone and 1042 (11%) died; 4472 out of 5954 (75%) patients on low-flow nasal cannula (NC) only received dexamethasone and 857 (14%) died. In IPTW stratified models, patients on no oxygen who received dexamethasone experienced 76% increased risk for 90-day mortality (hazard ratio (HR) 1.76, 95% CI 1.47–2.12); there was no association with mortality among patients on NC only (HR 1.08, 95% CI 0.86–1.36).ConclusionsIn patients hospitalised with COVID-19, early initiation of dexamethasone was common and was associated with no mortality benefit among those on no oxygen or NC only in the first 48 h; instead, we found evidence of potential harm. These real-world findings do not support the use of early dexamethasone in hospitalised COVID-19 patients without IRS.
Randomized quantile residuals for diagnosing zero-inflated generalized linear mixed models with applications to microbiome count data
Authors: Bai Wei , Dong Mei , Li Longhai , Feng Cindy , Xu Wei 
Published: November 2021

AbstractBackgroundFor differential abundance analysis, zero-inflated generalized linear models, typically zero-inflated NB models, have been increasingly used to model microbiome and other sequencing count data. A common assumption in estimating the false discovery rate is that thepvalues are uniformly distributed under the null hypothesis, which demands that the postulated model fit the count data adequately. Mis-specification of the distribution of the count data may lead to excess false discoveries. Therefore, model checking is critical to control the FDR at a nominal level in differential abundance analysis. Increasing studies show that the method of randomized quantile residual (RQR) performs well in diagnosing count regression models. However, the performance of RQR in diagnosing zero-inflated GLMMs for sequencing count data has not been extensively investigated in the literature.ResultsWe conduct large-scale simulation studies to investigate the performance of the RQRs for zero-inflated GLMMs. The simulation studies show that the type I error rates of the GOF tests with RQRs are very close to the nominal level; in addition, the scatter-plots and Q–Q plots of RQRs are useful in discerning the good and bad models. We also apply the RQRs to diagnose six GLMMs to a real microbiome dataset. The results show that the OTU counts at the genus level of this dataset (after a truncation treatment) can be modelled well by zero-inflated and zero-modified NB models.ConclusionRQR is an excellent tool for diagnosing GLMMs for zero-inflated count data, particularly the sequencing count data arising in microbiome studies. In the supplementary materials, we provided two generic R functions, called and , for calculating the RQRs given fitting outputs of the R package .
Alternative splicing level related to intron size and organism complexity
Authors: Yang Pengcheng , Wang Depin , Kang Le 
Published: November 2021

Abstract
Background
Alternative splicing is the process of selecting different combinations of splice sites to produce variably spliced mRNAs. However, the relationships between alternative splicing prevalence and level (ASP/L) and variations of intron size and organism complexity (OC) remain vague. Here, we developed a robust protocol to analyze the relationships between ASP/L and variations of intron size and OC. Approximately 8 Tb raw RNA-Seq data from 37 eumetazoan species were divided into three sets of species based on variations in intron size and OC.

Results
We found a strong positive correlation between ASP/L and OC, but no correlation between ASP/L and intron size across species. Surprisingly, ASP/L displayed a positive correlation with mean intron size of genes within individual genomes. Moreover, our results revealed that four ASP/L-related pathways contributed to the differences in ASP/L that were associated with OC. In particular, the spliceosome pathway displayed distinct genomic features, such as the highest gene expression level, conservation level, and fraction of disordered regions. Interestingly, lower or no obvious correlations were observed among these genomic features.

Conclusions
The positive correlation between ASP/L and OC ubiquitously exists in eukaryotes, and this correlation is not affected by the mean intron size of these species. ASP/L-related splicing factors may play an important role in the evolution of OC.
Comparison of the effects of open vs. closed skill exercise on the acute and chronic BDNF, IGF-1 and IL-6 response in older healthy adults
Authors: Behrendt Tom , Kirschnick Franziska , Kröger Lasse , Beileke Phillip , Rezepin Maxim , Brigadski Tanja , Leßmann Volkmar , Schega Lutz 
Published: November 2021

AbstractBackgroundAccumulating evidence shows that physical exercise has a positive effect on the release of neurotrophic factors and myokines. However, evidence regarding the optimal type of physical exercise for these release is still lacking. The aim of this study was to assess the acute and chronic effects of open-skill exercise (OSE) compared to closed-skill exercise (CSE) on serum and plasma levels of brain derived neurotrophic factor (BDNFS, BDNFP), and serum levels of insulin like growth factor 1 (IGF-1), and interleukin 6 (IL-6) in healthy older adults.MethodsTo investigate acute effects, thirty-eight participants were randomly assigned to either an intervention (badminton (aOSE) and bicycling (aCSE), n  = 24, 65.83 ± 5.98 years) or control group (reading (CG), n  = 14, 67.07 ± 2.37 years). Blood samples were taken immediately before and 5 min after each condition. During each condition, heart rate was monitored. The mean heart rate of aOSE and aCSE were equivalent (65 ± 5% of heart rate reserve). In a subsequent 12-week training-intervention, twenty-two participants were randomly assigned to either a sport-games (cOSE, n  = 6, 64.50 ± 6.32) or a strength-endurance training (cCSE, n  = 9, 64.89 ± 3.51) group to assess for chronic effects. Training intensity for both groups was adjusted to a subjective perceived exertion using the CR-10 scale (value 7). Blood samples were taken within one day after the training-intervention.ResultsBDNFS, BDNFP, IGF-1, and IL-6 levels increased after a single exercise session of 30 min. After 12 weeks of training BDNFSand IL-6 levels were elevated, whereas IGF-1 levels were reduced in both groups. However, only in the cOSE group these changes were significant. We could not find any significant differences between the exercise types.ConclusionOur results indicate that both exercise types are efficient to acutely increase BDNFS, BDNFP, IGF-1 and IL-6 serum levels in healthy older adults. Additionally, our results tend to support that OSE is more effective for improving basal BDNFSlevels after 12 weeks of training.
Genome-wide identification and expression profiling of invertase gene family for abiotic stresses tolerance in Poncirus trifoliata
Authors: Dahro Bachar , Wang Yue , Alhag Ahmed , Li Chunlong , Guo Dayong , Liu Ji-Hong 
Published: November 2021

Abstract
Background
Sucrose (Suc) hydrolysis is directly associated with plants tolerance to multiple abiotic stresses. Invertase (INV) enzymes irreversibly catalyze Suc degradation to produce glucose (Glc) and fructose (Frc). However, genome-wide identification and function of individual members of the INV gene family in Poncirus trifoliata or its Citrus relatives in response to abiotic stresses are not fully understood.

Results
In this report, fourteen non-redundant PtrINV family members were identified in P. trifoliata including seven alkaline/neutral INV genes (PtrA/NINV1–7), two vacuolar INV genes (PtrVINV1–2), and five cell wall INV isoforms (PtrCWINV1–5). A comprehensive analysis based on the biochemical characteristics, the chromosomal location, the exon–intron structures and the evolutionary relationships demonstrated the conservation and the divergence of PtrINVs. In addition, expression analysis of INV genes during several abiotic stresses in various tissues indicated the central role of A/NINV7 among INV family members in response to abiotic stresses. Furthermore, our data demonstrated that high accumulation of Suc, Glc, Frc and total sugar contents were directly correlated with the elevated activities of soluble INV enzymes in the cold-tolerant P. trifoliata, C. ichangensis and C. sinensis, demonstrating the potential role of soluble INV enzymes for the cold tolerance of Citrus.

Conclusions
This work offered a framework for understanding the physiological role of INV genes and laid a foundation for future functional studies of these genes in response to abiotic stresses.
Human granulocytic anaplasmosis combined with rhabdomyolysis: a case report
Authors: Cho Jeong Min , Chang Jeonghyun , Kim Dong-Min , Kwak Yee Gyung , Cho Chong Rae , Song Je Eun 
Published: November 2021

AbstractBackgroundHuman granulocytic anaplasmosis (HGA) is a systemic inflammatory response caused by the rickettsial bacteriumAnaplasma phagocytophilum. Rhabdomyolysis and acute kidney injury (AKI) are rare complications of HGA. Here, we report a case of HGA concurrent with rhabdomyolysis and AKI in an elderly patient.Case presentationAn 84-year old woman with a medical history of hypertension was hospitalised after two days of fever, dizziness, whole body pain, and general weakness. Laboratory investigations showed severe thrombocytopenia, leukopenia, impaired renal function, and elevated cardiac enzyme and myoglobin levels. On the day after admission, peripheral blood smear revealed morula inclusions in neutrophils, a suggestive finding of HGA. Real-time polymerase chain reaction (PCR) results indicated the presence ofA. phagocytophilum. Antibiotics were de-escalated to doxycycline monotherapy. After 10 days of antibiotic treatment, laboratory tests showed complete recovery from HGA complicated with rhabdomyolysis and AKI.ConclusionsHGA can lead to serious complications in patients with associated risk factors. Therefore, in patients with HGA accompanied by rhabdomyolysis, management with antibiotics and hydration should be initiated immediately, and not delayed until diagnostic confirmation.
Personal exposure to particulate matter and heart rate variability among informal electronic waste workers at Agbogbloshie: a longitudinal study
Authors: Amoabeng Nti Afua A. , Robins Thomas G. , Mensah John Arko , Dwomoh Duah , Kwarteng Lawrencia , Takyi Sylvia A. , Acquah Augustine , Basu Niladri , Batterman Stuart , Fobil Julius N. 
Published: November 2021

Abstract
Background
Informal electronic waste recycling activities are major contributors to ambient air pollution, yet studies assessing the effects or relationship between direct/continuous exposure of informal e-waste workers to particulate matter and cardiovascular function are rare.

Methods
Repeated measurements of fractions of PM2.5, PM10–2.5, and PM10 in personal air of informal e-waste workers, (n = 142) and a comparable group (n = 65) were taken over a period of 20 months (March 2017 to November, 2018). Concurrently, 5-min resting electrocardiogram was performed on each participant to assess resting heart rate variability indices. Linear mixed-effects models were used to assess the association between PM fractions and cardiac function.

Results
SDNN, RMSSD, LF, HF and LH/HF ratio were all associated with PM. Significant associations were observed for PM2.5 and Mean NN (p = 0.039), PM10 and SDNN (p = 0.035) and PM 10–2.5 and LH/HF (p = 0.039). A 10 μg/m3 increase in the concentrations of PM 2.5, PM10–2.5, and PM10 in personal air was associated with reduced HRV indices and increased resting HR. A 10 μg/m3 per interquartile (IQR) increase in PM10–2.5 and PM10, decreased SDNN by 11% [(95% CI: − 0.002- 0.000); (p = 0.187)] and 34% [(95% CI: − 0.002-0.001); (p = 0.035)] respectively. However, PM2.5 increased SDNN by 34% (95% CI: − 1.32-0.64); (p = 0.493). Also, 10 μg/m3 increase in PM2.5, PM10–2.5 and PM10 decreased RMSSD by 27% [(− 1.34–0.79); (p = 0.620)], 11% [(− 1.73, 0.95); (p = 0.846)] and 0.57% [(− 1.56–0.46); (p = 0.255%)].

Conclusion
Informal e-waste workers are at increased risk of developing cardiovascular disease from cardiac autonomic dysfunction as seen in reduced HRV and increased heart rate.