bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aspiration and severe exacerbations in COPD: a prospective study
Authors: Cvejic Lydia , Guiney Nadine , Nicholson Tiffany , Lau Kenneth K. , Finlay Paul , Hamza Kais , Osadnik Christian , Leong Paul , MacDonald Martin , King Paul T. , Bardin Philip G. 
Published: October 2020

RationaleSwallow may be compromised in COPD leading to aspiration and adverse respiratory consequences. However, prevalence and consequences of detectable aspiration in stable COPD are not known.ObjectivesWe tested the hypothesis that a significant number of patients with stable COPD will have detectable aspiration during swallow (prandial aspiration) and that they would experience more frequent severe acute exacerbations of COPD (AECOPD) over the subsequent 12 months.MethodsPatients (n=151) with verified and stable COPD of all severities were recruited at a tertiary care hospital. Videofluoroscopy was conducted to evaluate aspiration using Rosenbek's scale for penetration–aspiration during 100-mL cup drinking. AECOPD was documented as moderate (antibiotics and/or corticosteroid treatment) or severe (emergency department admission or hospitalisation) over the ensuing 12 months.Measurements and main resultsAspiration was observed in 30 out of 151 patients (19.9%, 18 males, 12 females; mean age 72.4 years). Patients with aspiration had more overall AECOPD events (3.03versus2 per patient; p=0.022) and severe AECOPD episodes (0.87versus0.39; p=0.032). Severe AECOPD occurred in more patients with aspiration (50% of patientsversus18.2%; OR 4.5, CI 1.9–10.5; p=0.001) and with silent aspiration (36.7%versus18.2%; OR 2.6, CI 1.1–6.2; p=0.045). Aspiration was related to a shorter exacerbation-free period during the 12-month follow-up period (p=0.038).ConclusionsPrandial aspiration is detectable in a subset of patients with COPD and was predictive of subsequent severe AECOPD. Studies to examine if the association is causal are essential to direct strategies aimed at prevention of aspiration and AECOPD.
NBZIMM: negative binomial and zero-inflated mixed models, with application to microbiome/metagenomics data analysis
Authors: Zhang Xinyan , Yi Nengjun 
Published: October 2020

AbstractBackgroundMicrobiome/metagenomic data have specific characteristics, including varying total sequence reads, over-dispersion, and zero-inflation, which require tailored analytic tools. Many microbiome/metagenomic studies follow a longitudinal design to collect samples, which further complicates the analysis methods needed. A flexible and efficient R package is needed for analyzing processed multilevel or longitudinal microbiome/metagenomic data.ResultsNBZIMM is a freely available R package that provides functions for setting up and fitting negative binomial mixed models, zero-inflated negative binomial mixed models, and zero-inflated Gaussian mixed models. It also provides functions to summarize the results from fitted models, both numerically and graphically. The main functions are built on top of the commonly used R packages nlme and MASS, allowing us to incorporate the well-developed analytic procedures into the framework for analyzing over-dispersed and zero-inflated count or proportion data with multilevel structures (e.g., longitudinal studies). The statistical methods and their implementations in NBZIMM particularly address the data characteristics and the complex designs in microbiome/metagenomic studies. The package is freely available from the public GitHub repositoryhttps://github.com/nyiuab/NBZIMM.ConclusionThe NBZIMM package provides useful tools for complex microbiome/metagenomics data analysis.
Illuminating the dark side of the human transcriptome with long read transcript sequencing
Authors: Kuo Richard I. , Cheng Yuanyuan , Zhang Runxuan , Brown John W. S. , Smith Jacqueline , Archibald Alan L. , Burt David W. 
Published: October 2020

Abstract

Background
The human transcriptome annotation is regarded as one of the most complete of any eukaryotic species. However, limitations in sequencing technologies have biased the annotation toward multi-exonic protein coding genes. Accurate high-throughput long read transcript sequencing can now provide additional evidence for rare transcripts and genes such as mono-exonic and non-coding genes that were previously either undetectable or impossible to differentiate from sequencing noise.

Results
We developed the Transcriptome Annotation by Modular Algorithms (TAMA) software to leverage the power of long read transcript sequencing and address the issues with current data processing pipelines. TAMA achieved high sensitivity and precision for gene and transcript model predictions in both reference guided and unguided approaches in our benchmark tests using simulated Pacific Biosciences (PacBio) and Nanopore sequencing data and real PacBio datasets. By analyzing PacBio Sequel II Iso-Seq sequencing data of the Universal Human Reference RNA (UHRR) using TAMA and other commonly used tools, we found that the convention of using alignment identity to measure error correction performance does not reflect actual gain in accuracy of predicted transcript models. In addition, inter-read error correction can cause major changes to read mapping, resulting in potentially over 6 K erroneous gene model predictions in the Iso-Seq based human genome annotation. Using TAMA’s genome assembly based error correction and gene feature evidence, we predicted 2566 putative novel non-coding genes and 1557 putative novel protein coding gene models.

Conclusions
Long read transcript sequencing data has the power to identify novel genes within the highly annotated human genome. The use of parameter tuning and extensive output information of the TAMA software package allows for in depth exploration of eukaryotic transcriptomes. We have found long read data based evidence for thousands of unannotated genes within the human genome. More development in sequencing library preparation and data processing are required for differentiating sequencing noise from real genes in long read RNA sequencing data.
Bupivacaine suppresses the progression of gastric cancer through regulating circ_0000376/miR-145-5p axis
Authors: Ju Changqiao , Zhou Jia , Miao Hui , Chen Xin , Zhang Qingyu 
Published: October 2020

Abstract

Background
Local anesthetic Bupivacaine commonly used in gastric cancer resection operation has been reported to suppress the progression of gastric cancer. However, the specific mechanism by which Bupivacaine functions is largely unexplored.

Methods
The viability and metastasis of gastric cancer cells were assessed by Cell counting kit-8 (CCK8) assay and transwell migration and invasion assays. The apoptosis was evaluated by caspase-3 activity detection assay and flow cytometry. The glycolysis was analyzed through detecting the extracellular acidification rate (ECAR) via Seahorse XF 96 Extracellular Flux Analyzer and the expression of glucose transporter type 1 (GLUT1) and lactic dehydrogenase A (LDHA) via Western blot assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the expression of circular RNA 0000376 (circ_0000376) and microRNA-145-5p (miR-145-5p). The interaction between circ_0000376 and miR-145-5p was predicted using Circular RNA Interactome database and validated by dual-luciferase reporter assay.

Results
Bupivacaine restrained the viability, metastasis and glycolytic process while promoted the apoptosis of gastric cancer cells. Bupivacaine decreased the level of circ_0000376 while enhanced the abundance of miR-145-5p in gastric cancer cells. Circ_0000376 accelerated the malignant behaviors of gastric cancer cells. MiR-145-5p directly interacted with circ_0000376 in gastric cancer cells, and miR-145-5p was negatively regulated by circ_0000376. The addition of circ_0000376 or the interference of miR-145-5p partly reversed Bupivacaine-mediated influences in gastric cancer cells.

Conclusion
Bupivacaine exerted an anti-tumor role to suppress the progression of gastric cancer through reducing the abundance of circ_0000376 and up-regulating miR-145-5p.
Beyond the scope and the glue: update on evaluation and management of gastric varices
Authors: Philips Cyriac Abby , Ahamed Rizwan , Rajesh Sasidharan , George Tom , Mohanan Meera , Augustine Philip 
Published: October 2020

Abstract
Gastric varices are encountered less frequently than esophageal varices. Nonetheless, gastric variceal bleeding is more severe and associated with worse outcomes. Conventionally, gastric varices have been described based on the location and extent and endoscopic treatments offered based on these descriptions. With improved understanding of portal hypertension and the dynamic physiology of collateral circulation, gastric variceal classification has been refined to include inflow and outflow based hemodynamic pathways. These have led to an improvement in the management of gastric variceal disease through newer modalities of treatment such as endoscopic ultrasound-guided glue-coiling combination therapy and the emergence of highly effective endovascular treatments such as shunt and variceal complex embolization with or without transjugular intrahepatic portosystemic shunt (TIPS) placement in patients who are deemed ‘difficult’ to manage the traditional way. Furthermore, the decisions regarding TIPS and additional endovascular procedures in patients with gastric variceal bleeding have changed after the emergence of ‘portal hypertension theories’ of proximity, throughput, and recruitment. The hemodynamic classification, grounded on novel theories and its cognizance, can help in identifying patients at baseline, in whom conventional treatment could fail. In this exhaustive review, we discuss the conventional and hemodynamic diagnosis of gastric varices concerning new classifications; explore and illustrate new ‘portal hypertension theories’ of gastric variceal disease and corresponding management and shed light on current evidence-based treatments through a ‘new’ algorithmic approach, established on hemodynamic physiology of gastric varices.
Fitness effects for Ace insecticide resistance mutations are determined by ambient temperature
Authors: Langmüller Anna Maria , Nolte Viola , Galagedara Ruwansha , Poupardin Rodolphe , Dolezal Marlies , Schlötterer Christian 
Published: October 2020

AbstractBackgroundInsect pest control programs often use periods of insecticide treatment with intermittent breaks, to prevent fixing of mutations conferring insecticide resistance. Such mutations are typically costly in an insecticide-free environment, and their frequency is determined by the balance between insecticide treatment and cost of resistance.Ace, a key gene in neuronal signaling, is a prominent target of many insecticides and across several species, three amino acid replacements (I161V, G265A, and F330Y) provide resistance against several insecticides. Because temperature disturbs neuronal signaling homeostasis, we reasoned that the cost of insecticide resistance could be modulated by ambient temperature.ResultsExperimental evolution of a naturalDrosophila simulanspopulation at hot and cold temperature regimes uncovered a surprisingly strong effect of ambient temperature. In the cold temperature regime, the resistance mutations were strongly counter selected (s = − 0.055), but in a hot environment, the fitness costs of resistance mutations were reduced by almost 50% (s = − 0.031). We attribute this unexpected observation to the advantage of the reduced enzymatic activity of resistance mutations in hot environments.ConclusionWe show that fitness costs of insecticide resistance genes are temperature-dependent and suggest that the duration of insecticide-free periods need to be adjusted for different climatic regions to reflect these costs. We suggest that such environment-dependent fitness effects may be more common than previously assumed and pose a major challenge for modeling climate change.
Engineering T cells with hypoxia-inducible chimeric antigen receptor (HiCAR) for selective tumor killing
Authors: Liao Qibin , He Huan , Mao Yunyu , Ding Xiangqing , Zhang Xiaoyan , Xu Jianqing 
Published: October 2020

Abstract
Chimeric antigen receptor-modified T cells (CAR-T cells) have shown good effects in the treatment of hematologic cancers; however, they may cause on-target off-tumor toxicity because of minimal expression of tumor-associated antigens (TAAs) on normal tissues, particularly in the context of treating solid tumors. Hypoxia is a common hallmark of solid tumors because of the Warburg effect. To minimize side effects, we designed a hypoxia-inducible CAR (HiCAR), which is driven by a hypoxia response element (HRE), and consists of a conventional CAR and an oxygen-dependent degradation domain (ODD) that is actively degraded under normoxia but stabilized under hypoxia. HiCAR-T cells showed enhanced cytotoxicity against tumor cells under hypoxia compared to normoxia in vitro and antitumor efficacy comparable to that of conventional CAR-T cells in vivo. Overall, our study demonstrates the potential of the HiCAR for improving the safety of CAR-T cells to promote the clinical application of CAR-T immunotherapy.
The influence of primary care physicians’ mental health knowledge, attitudes and self-efficacy on referrals to specialised services: findings from a longitudinal pilot trial
Authors: Spagnolo Jessica , Vasiliadis Helen-Maria , Berbiche Djamal , Champagne François , Leduc Nicole , Melki Wahid , Saeed Khalid , Charfi Fatma 
Published: October 2020

Background
Training based on the Mental Health Gap Action Programme (mhGAP) is being increasingly adopted by countries to enhance non-specialists’ mental health capacities. However, the influence of these enhanced capacities on referral rates to specialised mental health services remains unknown.

Aims
We rely on findings from a longitudinal pilot trial to assess the influence of mental health knowledge, attitudes and self-efficacy on self-reported referrals from primary to specialised mental health services before, immediately after and 18 months after primary care physicians (PCPs) participated in an mhGAP-based training in the Greater Tunis area of Tunisia.

Method
Participants included PCPs who completed questionnaires before (n = 112), immediately after (n = 88) and 18 months after (n = 59) training. Multivariable analyses with linear mixed models accounting for the correlation among participants were performed with the SAS version 9.4 PROC MIXED procedure. The significance level was α < 0.05.

Results
Data show a significant interaction between time and mental health attitudes on referrals to specialised mental health services per week. Higher scores on the attitude scale were associated with more referrals to specialised services before and 18 months after training, compared with immediately after training.

Conclusion
Findings indicate that, in parallel to mental health training, considering structural/organisational supports to bring about a sustainable change in the influence of PCPs’ mental health attitudes on referrals is important. Our results will inform the scale-up of an initiative to further integrate mental health into primary care settings across Tunisia, and potentially other countries with similar profiles interested in further developing task-sharing initiatives.
Fatal accident inquiries into 83 deaths in Scottish prison custody: 2010–2013
Authors: Bird Sheila M. 
Published: October 2020

Background
The only non-legal reference in Lord Cullen's Review of fatal accident inquiry (FAI) Legislation in Scotland (2009) was my audit of FAIs into 97 deaths in prison custody in Scotland, 1999–2003: recommending that waiting time from prisoner death to end of FAI should be less than 1 year for 90% of FAIs, and epidemiological rules for FAIs to have a written determination versus formal findings.

Aims
Audit of FAIs into 83 deaths in Scottish prison custody in the period 2010–2013.

Method
Assessement of waiting times from prisoner death to end of FAI; dissemination of written determinations; self-inflicted death rate per 1000 prisoner-years; cause of natural deaths; and yellow card submissions. Detailed cross-checking was nec37essary between Scottish Prison Service and courts’ websites and the Scottish Fatalities Investigation Unit.

Results
Of 83 FAIs into deaths in Scottish prison custody, 2010–2013, 37 (45%) were long-awaited (ongoing >2 years after the prisoner's death); 16 (19%, 95% CI 11–28%) beyond 3 years. Of 37 long-awaited FAIs, 27 made written determinations but only 12 of these (44%) were published. Self-inflicted deaths numbered 36: 1.1 per 1000 prisoner-years (95% CI 0.75–1.48). Of 47 deaths from natural causes, cardiovascular disease accounted for 23 (49%, 95% CI 34–63%); liver disease was implicated in 10 of 47. To support pharmacovigilance, submissions were made to Medicines and Healthcare Regulatory Agency for eight deaths (10%, 95% CI 4–19%).

Conclusions
FAIs into prisoner deaths in Scotland are too long-awaited given that four (5%) identified precautions that could have prevented death.
A Pilot Study of Gut-Brain Signaling After Octreotide Therapy for Unintentional Weight Loss After Esophagectomy
Authors: Murphy Conor F , Stratford Nicholas , Docherty Neil G , Moran Brendan , Elliott Jessie A , Healy Marie-Louise , McMorrow Jason P , Ravi Narayanasamy , Goldstone Anthony P , Reynolds John V , le Roux Carel W 
Published: October 2020

Abstract

Background
Recurrence-free patients after esophageal cancer surgery face long-term nutritional consequences, occurring in the context of an exaggerated postprandial gut hormone response. Acute gut hormone suppression influences brain reward signaling and eating behavior. This study aimed to suppress gut hormone secretion and characterize reward responses and eating behavior among postesophagectomy patients with unintentional weight loss.

Methods
This pilot study prospectively studied postoperative patients with 10% or greater body weight loss (BWL) beyond 1 year who were candidates for clinical treatment with long-acting octreotide (LAR). Before and after 4 weeks of treatment, gut hormone secretion, food cue reactivity (functional magnetic resonance imaging), eating motivation (progressive ratio task), ad libitum food intake, body composition, and symptom burden were assessed.

Results
Eight patients (7 male, age: mean ± SD 62.8 ± 9.4 years, postoperative BWL: 15.5 ± 5.8%) participated. Octreotide LAR did not significantly suppress total postprandial plasma glucagon-like peptide-1 response at 4 weeks (P = .08). Postprandial symptom burden improved after treatment (Sigstad score median [range]: 12 [2-28] vs 8 [3-18], P = .04) but weight remained stable (pre: 68.6 ± 12.8 kg vs post: 69.2 ± 13.4 kg, P = .13). There was no significant change in brain reward system responses, during evaluation of high-energy or low-energy food pictures, nor their appeal rating. Moreover, treatment did not alter motivation to eat (P = .41) nor ad libitum food intake(P = .46).

Conclusion
The protocol used made it feasible to characterize the gut-brain axis and eating behavior in this cohort. Inadequate suppression of gut hormone responses 4 weeks after octreotide LAR administration may explain the lack of gut-brain pathway alterations. A higher dose or shorter interdose interval may be required to optimize the intervention.
Body Composition is Associated With Islet Function After Pancreatectomy and Islet Autotransplantation for Pancreatitis
Authors: Harindhanavudhi Tasma , Yang Yi , Hodges James S , Pruett Timothy L , Kirchner Varvara , Beilman Gregory J , Bellin Melena D 
Published: October 2020

Abstract

Context
Body composition in total pancreatectomy with islet autotransplantation (TPIAT) has never been studied.

Objective
Determine whether presurgical body composition is associated with islet function and insulin sensitivity after TPIAT.

Methods
In 88 adults undergoing TPIAT (median age 41.0 years, IQR 32.8-48.0), beta-cell function and insulin sensitivity were assessed using mixed meal tolerance test and frequent sample intravenous glucose tolerance test before surgery and 12 and 18 months afterward. Body composition was measured by dual x-ray absorptiometry. Analyses used linear and logistic regression.

Results
Before surgery, 8 individuals (9.1%) were underweight, 40 (45.5%) normal weight, 20 (22.7%) overweight, and 20 (22.7%) obese. Overweight/obese patients had higher area under the curve C-peptide and lower insulin sensitivity index. Baseline body weight was positively associated with first-phase insulin secretion (AIRg) at 12 months (average 38.5 [SE 17.1] mU/L/min higher per extra kg; P = 0.03) and 18 months (38.3 [18.5]; P = 0.04), while baseline lean mass was inversely associated with AIRg at 12 months (−0.05 [0.02] per extra kg; P = 0.01) and 18 months (−0.05 [0.02]; P = 0.03). Percent gynoid fat was inversely associated with disposition index at 18 months (−206.0 [97.2] per extra percent; P = 0.04). Percent body fat and percent gynoid fat were associated with glucose effectiveness index at 18 months (1.9 × 10-3 [0.9 × 10-3] per extra percent; P = 0.04 and −1.96 × 10-3 [0.8 × 10-3]; P = 0.02, respectively). Insulin independence was not significantly associated with body weight or composition.

Conclusions
Half of these chronic pancreatitis patients were overweight/obese; underweight was uncommon. Preoperative body weight and composition were associated with islet function but not insulin independence after TPIAT.
Testosterone Use in Adolescent Males: Current Practice and Unmet Needs
Authors: Vogiatzi Maria , Tursi James P , Jaffe Jonathan S , Hobson Sue , Rogol Alan D 
Published: October 2020

AbstractTestosterone replacement therapy (TRT) is routinely prescribed in adolescent males with constitutional delay of growth and puberty (CDGP) or hypogonadism. With many new testosterone (T) formulations entering the market targeted for adults, we review current evidence and TRT options for adolescents and identify areas of unmet needs. We searched PubMed for articles (in English) on testosterone therapy, androgens, adolescence, and puberty in humans. The results indicate that short-term use of  T enanthate (TE) or oral  T undecanoate is safe and effective in inducing puberty and increasing growth in males with CDGP. Reassuring evidence is emerging on the use of transdermal  T to induce and maintain puberty. The long-term safety and efficacy of TRT for puberty completion and maintenance have not been established. Current  TRT regimens are based on consensus and expert opinion, but evidence-based guidelines are lacking. Limited guidance exists on when and how  T should be administered and optimal strategies for monitoring therapy once it is initiated. Only  TE and  T pellets are US Food and Drug Administration approved for use in adolescent males in the United States. Despite the introduction of a wide variety of new  T formulations, they are designed for adults, and their metered doses are difficult to titrate in adolescents. In conclusion, TRT in adolescent males is hindered by lack of long-term safety and efficacy data and limited options approved for use in this population. Additional research is needed to identify the route, dose, duration, and optimal timing for TRT in adolescents requiring androgen therapy.
Synthesis and Reduction of a Cyclic (Alkyl)(amino)bromoborane to Generate a Thermally Labile Cyclic (Alkyl)(amino)boryl Anion
Authors: Kisu Haruki , Kosai Tomoyuki , Iwamoto Takeaki , Yamashita Makoto 
Published: October 2020

Abstract
A cyclic (alkyl)(amino)bromoborane (CAABBr) was synthesized by a reaction of the corresponding hydroborane with bromine in the presence of triethylamine. Reduction of the resulting CAABBr with Li powder and 4,4′-di-tert-butylbiphenyl (DBB) generated a thermally labile cyclic (alkyl)(amino)boryllithium (CAABLi) which was characterized by NMR spectroscopy. Quenching of the mixture reduced by Li/DBB with methanol-d1 or MeOTf at low temperature gave a deuterioborane or methylborane, supporting the generation of CAABLi.