bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID‐19 and emergency care for adults experiencing homelessness
Authors: Miller Jean‐Philippe , Phillips Georgina , Hutton Jennie , Mackelprang Jessica L , O'Reilly Gerard M , Mitchell Rob D , Smith Cathie , Mitra Biswadev 
Published: September 2020

AbstractHomeless individuals face many barriers to accessing healthcare, and EDs are often their primary entry point to the healthcare system. The COVID‐19 pandemic has the potential to exacerbate existing social inequities and health disparities, including barriers to accessing social services and healthcare. Addressing the complex social and chronic health issues associated with homelessness can be challenging within the acute care environment. This perspective reflects upon the delivery of emergency healthcare to patients experiencing homelessness, and highlights strategies for optimising health outcomes during and beyond the pandemic.
Prognostic effect of a novel long noncoding RNA signature and comparison with clinical staging systems for patients with hepatitis B virus‐related hepatocellular carcinoma after hepatectomy
Authors: Wu Hao , Liu Tian Tian , Feng Yue Min , Xie Xiao Yu , Su Xiao Nan , Qi Jian Ni , Zhu Qiang , Qin Cheng Yong 
Published: September 2020

ObjectivesWe aimed to establish a novel prognostic long noncoding RNA (lncRNA) signature for hepatitis B virus‐related hepatocellular carcinoma (HBV‐HCC) patients after hepatectomy and to validate its prognostic efficacy compared with other clinical staging systems.MethodsExpression data of 374 HCC samples were retrieved from The Cancer Genome Atlas (TCGA) database. Cox regression analyses were performed to develop the lncRNA model. The expression levels of lncRNAs were detected by qualitative real‐time polymerase chain reaction (qRT‐PCR) in HBV‐HCC. Then the qRT‐PCR‐based signature and nomogram were constructed and compared with those of other clinical staging systems in a clinical cohort and qRT‐PCR, RNA fluorescent in situ hybridization and comprehensive bioinformatics analyses were conducted.ResultsThe signature containing five lncRNAs was constructed through TCGA. This model showed the highest predictive efficacy in patients with HBV‐HCC. Compared with normal liver tissues, all lncRNAs were highly expressed in HBV‐HCC. A four‐lncRNA signature containing LINC01116, DDX11‐AS1, LUCAT1 and FIRRE was developed based on the qRT‐PCR data in a clinical HBV‐HCC patient cohort. A Kaplan‐Meier analysis indicated that the low‐risk group had significantly longer overall survival than the high‐risk group. Additionally, the qRT‐PCR‐based four‐lncRNA formula was an independent prognostic factor and had better predictive efficacy for survival (area under the receiver operating characteristic curve 0.875) compared with other clinical staging systems in HBV‐HCC. The lncRNA‐mRNA co‐expression and enrichment analyses revealed the potential regulatory mechanisms of the lncRNA identified.ConclusionThe four‐lncRNA model may be an effective prognostic signature and provides potential prognostic biomarkers and therapeutic targets for HBV‐HCC.
Revealing formate production from carbon monoxide in wild type and mutants of Rnf‐ and Ech‐containing acetogens, Acetobacterium woodii and Thermoanaerobacter kivui
Authors: Schwarz Fabian M. , Ciurus Sarah , Jain Surbhi , Baum Christoph , Wiechmann Anja , Basen Mirko , Müller Volker 
Published: September 2020

SummaryAcetogenic bacteria have gained much attraction in recent years as they can produce different biofuels and biochemicals from H2 plus CO2 or even CO alone, therefore opening a promising alternative route for the production of biofuels from renewable sources compared to existing sugar‐based routes. However, CO metabolism still raises questions concerning the biochemistry and bioenergetics in many acetogens. In this study, we focused on the two acetogenic bacteria Acetobacterium woodii and Thermoanaerobacter kivui which, so far, are the only identified acetogens harbouring a H2‐dependent CO2 reductase and furthermore belong to different classes of ‘Rnf’‐ and ‘Ech‐acetogens’. Both strains catalysed the conversion of CO into the bulk chemical acetate and formate. Formate production was stimulated by uncoupling the energy metabolism from the Wood–Ljungdahl pathway, and specific rates of 1.44 and 1.34 mmol g−1 h−1 for A. woodii ∆rnf and T. kivui wild type were reached. The demonstrated CO‐based formate production rates are, to the best of our knowledge, among the highest rates ever reported. Using mutants of ∆hdcr, ∆cooS, ∆hydBA, ∆rnf and ∆ech2 with deficiencies in key enzyme activities of the central metabolism enabled us to postulate two different CO utilization pathways in these two model organisms.
The treatment journey for patients with axial spondyloarthritis in North Africa and the Middle East: From diagnosis to management
Authors: El Zorkany Bassel , Ali Yaser Mustafa , Namas Rajaie , Bedaiwi Mohamed , Husain Waleed , Ahmed Haytham Mohamed , Ziade Zoghbi Nelly 
Published: September 2020

AbstractThe management of axial spondyloarthritis (axSpA) is challenging worldwide, and the particular challenges shared by North Africa and the Middle East are mainly related to early diagnosis and standardized management. We believe there are several reasons for these challenges, including: (a) limited awareness of the disease manifestations and prevalence in the region among physicians; (b) the concept of nonradiographic axSpA, while accepted with some difficulty by the rheumatology community, may not be well understood by the referring primary care physicians; (c) access to, and training in magnetic resonance imaging varies greatly between countries in the North Africa and Middle East region, and this may have a large impact on early diagnosis; (d) country‐specific treatment guidelines are unavailable; and (e) economic and cultural factors influence patients’ attempts to seek and continue treatment. In this review, we will discuss the prevalence of axSpA in North Africa and the Middle East, as well as the challenges to diagnose and treat patients in this region. As rheumatologists practicing in North Africa and the Middle East, we also provide suggestions to assist physicians, other healthcare professionals, and researchers in facilitating early, accurate diagnosis and treatment of axSpA.
Going further with model verification and deep learning
Authors: Christin Sylvain , Hervet Éric , Lecomte Nicolas 
Published: September 2020

Abstract

In our recent review paper aiming to introduce deep learning to ecologists, we presented a workflow describing the steps required to create a deep learning model. This figure did not present some of the following steps of model use such as model verification.

By ensuring model adequacy, model verification is an important step after model creation in order to answer ecological questions.

Adding model verification to a deep learning model development workflow can raise some new issues such as detecting the difference among the multiple datasets or what to do when model verification fails. In the spirit of our previous review, we identify some questions users trying to verify their deep learning model can have and try to find, for each, a solution to help them navigate the steps of deep learning model testing.

We provide an additional cheat sheet to quickly help answer common questions regarding using model verification and deep learning. We hope these resources help stimulate further synthesis and coherence in the use of deep learning models in ecology.
Phenological stages and degree days of oil palm crosses grown under irrigation in tropical conditions
Authors: Suresh Kancherla , Behera Sanjib Kumar , Manorama Kamireddy , Mathur Ravi K. 
Published: September 2020

AbstractStudies on phenology and growing degree days (GDD) of four oil palm crosses, that is, Palode, Deli × Nigeria, United Plantations and Deli × Ghana were conducted in India under tropical conditions. Observations were recorded in adult oil palms over a period of 1.5 years from visual opening of spear leaf to development of female flower till harvest. Biologische Bundesantalt, Bundessortenamt and Chemische Industrie (BBCH) General Scale was used for conducting various phenological growth stages. The GDD from development of spear leaf to maturity in the different crosses varied between 6,320.2 and 6,937.3. The degree days and duration from development of spear leaf to maturity were less in the crosses of United Plantations. The time taken for spear leaf unfolding to maturity and flower opening to maturity in the different crosses, respectively, varied from 447.9 to 485.2 days and 145.8 to 153.7 days. The study gives an insight in evaluating thermal time for achieving various phenophases in oil palm and genotypic variations of time taken in attaining the different phenophases that have been documented. Climatic and yield prediction models can also be evolved through these studies.
Coronavirus: A possible cause of reduced male fertility
Authors: Huang Chuan , Ji Xiren , Zhou Wenjun , Huang Zhenghui , Peng Xiangjie , Fan Liqing , Lin Ge , Zhu Wenbing 
Published: September 2020

AbstractIn lately December 2019, a novel coronavirus (SARS‐CoV‐2) outbreak occurred in Wuhan, PR China. It is a high contagious virus that has threatened human health worldwide. SARS‐CoV‐2 infection, termed COVID‐19, causes rapidly developing lung lesions that can lead to multiple organ failure in a short period. Whenever a novel virus emerges, reproductive risk assessments should be performed after infection. In this review, we show that male fertility might be damaged by coronavirus associated with (i) direct cytopathic effects derived from viral replication and viral dissemination in the testis; and (ii) indirect damage to male fertility derived from immunopathology. In this review, we briefly describe the impaired fertility of humans and animals infected with coronaviruses to deduce the impact of the new coronavirus on male fertility. Together with information related to other coronaviruses, we extrapolate this knowledge to the new coronavirus SARS‐CoV‐2, which may have a significant impact on our understanding of the pathophysiology of this new virus.
European academy of andrology guidelines on Klinefelter Syndrome Endorsing Organization: European Society of Endocrinology
Authors: Zitzmann Michael , Aksglaede Lise , Corona Giovanni , Isidori Andrea M. , Juul Anders , T'Sjoen Guy , Kliesch Sabine , D'Hauwers Kathleen , Toppari Jorma , Słowikowska‐Hilczer Jolanta , Tüttelmann Frank , Ferlin Alberto 
Published: September 2020

AbstractBackgroundKnowledge about Klinefelter syndrome (KS) has increased substantially since its first description almost 80 years ago. A variety of treatment options concerning the spectrum of symptoms associated with KS exists, also regarding aspects beyond testicular dysfunction. Nevertheless, the diagnostic rate is still low in relation to prevalence and no international guidelines are available for KS.ObjectiveTo create the first European Academy of Andrology (EAA) guidelines on KS.MethodsAn expert group of academicians appointed by the EAA generated a consensus guideline according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system.ResultsClinical features are highly variable among patients with KS, although common characteristics are severely attenuated spermatogenesis and Leydig cell impairment, resulting in azoospermia and hypergonadotropic hypogonadism. In addition, various manifestations of neurocognitive and psychosocial phenotypes have been described as well as an increased prevalence of adverse cardiovascular, metabolic and bone‐related conditions which might explain the increased morbidity/mortality in KS. Moreover, compared to the general male population, a higher prevalence of dental, coagulation and autoimmune disorders is likely to exist in patients with KS. Both genetic and epigenetic effects due to the supernumerary X chromosome as well as testosterone deficiency contribute to this pathological pattern. The majority of patients with KS is diagnosed during adulthood, but symptoms can already become obvious during infancy, childhood or adolescence. The paediatric and juvenile patients with KS require specific attention regarding their development and fertility.ConclusionThese guidelines provide recommendations and suggestions to care for patients with KS in various developmental stages ranging from childhood and adolescence to adulthood. This advice is based on recent research data and respective evaluations as well as validations performed by a group of experts.
Fertility outcomes and predictors for successful sperm retrieval and pregnancy in 327 azoospermic men with a history of cryptorchidism who underwent microdissection testicular sperm extraction
Authors: Çayan Selahittin , Orhan İrfan , Altay Barış , Aşcı Ramazan , Akbay Erdem , Ayas Bülent , Yaman Önder 
Published: September 2020

AbstractBackgroundAlthough few studies have reported fertility outcomes, no study has reported risk factors that might predict sperm retrieval and pregnancy in azoospermic men with a history of cryptorchidism in a large series.ObjectivesTo investigate fertility outcomes and predictors for successful sperm retrieval and pregnancy in azoospermic men with a history of cryptorchidism who underwent microdissection testicular sperm extraction (mTESE).Materials and methodsThis retrospective observational study included 327 azoospermic men with a history of cryptorchidism who underwent mTESE. Fertility outcomes including sperm retrieval, fertilization rate, number of transferred embryos, pregnancy, miscarriage, and live birth rates were recorded.ResultsSperm retrieval was observed in 172 (52.6%) of the patients. The mean fertilization, pregnancy, and live birth rates were 55.2%±20.5, 53.5%, and 44.8%, respectively. The sperm retrieval rate was significantly higher at the orchidopexy age of ≤ 9.5 years (70.8%) than the orchidopexy age of > 9.5 years (42.1%) (P = .000). Patients with total testicular volume of ≥ 13.75 mL had significantly higher sperm retrieval rate (65.2%) than the patients with total testicular volume of < 13.75 mL (45.5%) (P = .001). Patients with total testosterone level of ≥ 300.5 ng/dL had significantly higher sperm retrieval rate (65.6%) than the patients with total testosterone level of < 300.5 ng/dL (40.3%) (P = .000). Patients with follicle‐stimulating hormone (FSH) level of ≤ 17.25 mIU/ml had significantly higher sperm retrieval rate (72.3%) than the patients with FSH level of > 17.25 mIU/mL (44.4%) (P = .000). Younger male and female ages, and higher fertilization rates were the parameters that might predict pregnancy.ConclusionsInfertile azoospermic men with a history of cryptorchidism have high sperm retrieval rate with mTESE. Patients who had orchidopexy at the age of ≤ 9.5 years, and having total testicular volumes of ≥ 13.75 mL with total testosterone level of > 300.5 ng/dL and FSH level of ≤ 17.25 mIU/mL have higher success rate for sperm retrieval.
Effects of Hypericum perforatum (St John's wort) on the pharmacokinetics and pharmacodynamics of rivaroxaban in humans
Authors: Scholz Irene , Liakoni Evangelia , Hammann Felix , Grafinger Katharina Elisabeth , Duthaler Urs , Nagler Michael , Krähenbühl Stephan , Haschke Manuel 
Published: September 2020

AimsTo investigate the influence of a cytochrome P450 CYP3A4 and efflux transporter P‐glycoprotein (P‐gp) inducing Hypericum perforatum extract on the pharmacokinetics and pharmacodynamics of rivaroxaban.MethodsOpen‐label, nonrandomized, sequential treatment interaction study. Following CYP3A4 and P‐gp phenotyping using low‐dose midazolam and fexofenadine, 12 healthy volunteers received a single oral dose of 20 mg rivaroxaban and rivaroxaban plasma concentrations and inhibition of the activated coagulation factor X (factor Xa) activity were measured prior to and up to 48 h postdosing. The procedures were repeated after 2 weeks’ treatment with the H. perforatum extract.ResultsThe geometric mean ratios for the area under the concentration–time curve and Cmax of rivaroxaban after/before induction with the H. perforatum extract were 0.76 (90% confidence interval [CI] 0.70, 0.82) and 0.86 (90% CI 0.76, 0.97), respectively. Inhibition of factor Xa activity was reduced with a geometric mean area under the effect–time curve ratio after/before induction of 0.80 (90% CI 0.71, 0.89). No clinically significant differences were found regarding Tmax (median 1.5 vs 1 h, P = .26) and terminal elimination half‐life (mean 10.6 vs 10.8 h, P = .93) of rivaroxaban. The H. perforatum extract significantly induced CYP3A4 and P‐gp activity, as evidenced by phenotyping.ConclusionThe CYP3A4/P‐gp inducing H. perforatum extract caused a decrease of rivaroxaban exposure with a proportional decrease of the pharmacodynamic effect. Although the data do not justify a contraindication for the combination or a systematic adjustment of rivaroxaban dosage, avoidance of the combination or laboratory monitoring should be considered in patients taking hyperforin‐containing H. perforatum extracts with rivaroxaban.
Structural basis of AMPA receptor inhibition by trans‐4‐butylcyclohexane carboxylic acid
Authors: Yelshanskaya Maria V. , Singh Appu K. , Narangoda Chamali , Williams Robin S.B. , Kurnikova Maria G. , Sobolevsky Alexander I. 
Published: September 2020

Background and PurposeAMPA receptors, which shape excitatory postsynaptic currents and are directly involved in overactivation of synaptic function during seizures, represent a well‐accepted target for anti‐epileptic drugs. Trans‐4‐butylcyclohexane carboxylic acid (4‐BCCA) has emerged as a new promising anti‐epileptic drug in several in vitro and in vivo seizure models, but the mechanism of its action remained unknown. The purpose of this study is to characterize structure and dynamics of 4‐BCCA interaction with AMPA receptors.Experimental ApproachWe studied the molecular mechanism of AMPA receptor inhibition by 4‐BCCA using a combination of X‐ray crystallography, mutagenesis, electrophysiological assays, and molecular dynamics simulations.Key ResultsWe identified 4‐BCCA binding sites in the transmembrane domain (TMD) of AMPA receptor, at the lateral portals formed by transmembrane segments M1–M4. At this binding site, 4‐BCCA is very dynamic, assumes multiple poses, and can enter the ion channel pore.Conclusion and Implications4‐BCCA represents a low‐affinity inhibitor of AMPA receptors that acts at the TMD sites distinct from non‐competitive inhibitors, such as the anti‐epileptic drug perampanel and the ion channel blockers. Further studies might examine the possibsility of synergistic use of these inhibitors in treatment of epilepsy and a wide range of neurological disorders and gliomas.LINKED ARTICLESThis article is part of a themed issue on Structure Guided Pharmacology of Membrane Proteins (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.14/issuetoc
Structural determinants of TRPV4 inhibition and identification of new antagonists with antiviral activity
Authors: Doñate‐Macian Pablo , Duarte Yorley , Rubio‐Moscardo Fanny , Pérez‐Vilaró Gemma , Canan Jonathan , Díez Juana , González‐Nilo Fernando , Valverde Miguel A. 
Published: September 2020

Background and PurposeThe transient receptor potential vanilloid 4 (TRPV4) cation channel participates in multiple physiological processes and is also at the core of different diseases, making this channel an interesting pharmacological target with therapeutic potential. However, little is known about the structural elements governing its inhibition.Experimental ApproachWe have now combined in silico drug discovery and molecular dynamics simulation based on Xenopus tropicalis xTRPV4 structure with functional studies measuring cell Ca2+ influx mediated by human TRPV4 channel to characterize the binding site of known TRPV4 inhibitors and to identify novel small molecule channel modulators.Key ResultsWe have found that the inhibitor HC067047 binds to a pocket conformed by residues from S2–S3 linker (xTRPV4‐D542), S4 (xTRPV4‐M583 and Y587 and S5 (xTRPV4‐D609 and F613). This pocket was also used for structure‐based virtual screening in the search of novel channel modulators. Forty potential hits were selected based on the lower docking scores (from ~250,000 compounds) and their effect upon TRPV4 functionally tested. Three were further analysed for stability using molecular dynamics simulation and functionally tested on TRPV4 channels carrying mutations in the binding pocket. Compound NSC151066, shown to require residue xTRPV4‐M583 for its inhibitory effect, presented an IC50 of 145 nM and demonstrated to be an effective antiviral against Zika virus with a potency similar to HC067047.Conclusion and ImplicationsTogether, we propose structural insights into the inhibition of TRPV4 and how this information can be used for the design of novel channel modulators.LINKED ARTICLESThis article is part of a themed issue on Structure Guided Pharmacology of Membrane Proteins (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.14/issuetoc
Methnaridine is an orally bioavailable, fast‐killing and long‐acting antimalarial agent that cures Plasmodium infections in mice
Authors: Wang Weisi , Yao Junmin , Chen Zhuo , Sun Yiming , Shi Yuqing , Wei Yufen , Zhou Hejun , Yu Yingfang , Li Shizhu , Duan Liping 
Published: September 2020

Background and PurposeMalaria is one of the deadliest diseases in the world. Novel chemotherapeutic agents are urgently required to combat the widespread Plasmodium resistance to frontline drugs. Here, we report the discovery of a novel benzonaphthyridine antimalarial, methnaridine, which was identified using a structural optimization strategy.Experimental ApproachAn integrated pharmacological approach was used to evaluate the antimalarial profile of methnaridine. The pharmacokinetic properties of methnaridine were investigated along with the associated safety profile. Host immune response patterns were also analysed.Key ResultsMethnaridine exhibited potent antimalarial activity against P. falciparum (3D7: IC50 = 0.0066 μM; Dd2: IC50 = 0.0056 μM). In P. berghei‐infected mice, oral administration effectively suppressed parasitemia (ED50 = 0.52 mg·kg−1·day−1) and cured the established infection (CD50 = 10.13 mg·kg−1·day−1). These results are equivalent to or better than those of other antimalarial agents in clinical use. Notably, a four‐dose oral regimen at a dosage of 25 mg·kg−1 achieved a complete cure of P. berghei infection in mice. Methnaridine exhibited a rapid parasiticidal profile (PCT99 = 36.0 h) and showed no cross‐resistance to chloroquine. Pharmacokinetic studies revealed that methnaridine is readily absorbed, long‐lasting and slowly cleared. The safety profile of methnaridine is also satisfactory (maximum tolerated dose = 1,125 mg·kg−1). In addition, following methnaridine treatment, infection‐induced Th1 immune response was almost fully alleviated in mice.Conclusion and ImplicationsMethnaridine is an orally bioavailable, fast‐acting and long‐lasting agent with excellent antimalarial properties. Our study highlights the potential of methnaridine for clinical development as a promising antimalarial candidate.