bluuebunny/crossref_metadata_2025 huggingface dataset:
The work of older people and their informal caregivers in managing an acute health event in a hospital at home or hospital inpatient setting
Authors: Mäkelä Petra , Stott David , Godfrey Mary , Ellis Graham , Schiff Rebekah , Shepperd Sasha
Published: May 2020

Background

There is limited understanding of the contribution made by older people and their caregivers to acute healthcare in the home and how this compares to hospital inpatient healthcare.

Objectives

To explore the work of older people and caregivers at the time of an acute health event, the interface with professionals in a hospital and hospital at home (HAH) and how their experiences relate to the principles underpinning comprehensive geriatric assessment (CGA).

Design

A qualitative interview study within a UK multi-site participant randomised trial of geriatrician-led admission avoidance HAH, compared with hospital inpatient care.

Methods

We conducted semi-structured interviews with 34 older people (15 had received HAH and 19 hospital care) alone or alongside caregivers (29 caregivers; 12 HAH, 17 hospital care), in three sites that recruited participants to a randomised trial, during 2017–2018. We used normalisation process theory to guide our analysis and interpretation of the data.

Results

Patients and caregivers described efforts to understand changes in health, interpret assessments and mitigate a lack of involvement in decisions. Practical work included managing risks, mobilising resources to meet health-related needs, and integrating the acute episode into longer-term strategies. Personal, relational and environmental factors facilitated or challenged adaptive capacity and ability to manage.

Conclusions

Patients and caregivers contributed to acute healthcare in both locations, often in parallel to healthcare providers. Our findings highlight an opportunity for CGA-guided services at the interface of acute and chronic condition management to facilitate personal, social and service strategies extending beyond an acute episode of healthcare.
Sympathetic Activation in Hypertension: Importance of the Central Nervous System
Authors: Hirooka Yoshitaka
Published: May 2020

The sympathetic nervous system plays a critical role in the pathogenesis of hypertension. The central nervous system (CNS) organizes the sympathetic outflow and various inputs from the periphery. The brain renin–angiotensin system has been studied in various regions involved in controlling sympathetic outflow. Recent progress in cardiovascular research, particularly in vascular biology and neuroscience, as well as in traditional physiological approaches, has advanced the field of the neural control of hypertension in which the CNS plays a vital role. Cardiovascular research relating to hypertension has focused on the roles of nitric oxide, oxidative stress, inflammation, and immunity, and the network among various organs, including the heart, kidney, spleen, gut, and vasculature. The CNS mechanisms are similarly networked with these factors and are widely studied in neuroscience. In this review, I describe the development of the conceptual flow of this network in the field of hypertension on the basis of several important original research articles and discuss potential future breakthroughs leading to clinical precision medicine.
SMNN: batch effect correction for single-cell RNA-seq data via supervised mutual nearest neighbor detection
Authors: Yang Yuchen , Li Gang , Qian Huijun , Wilhelmsen Kirk C , Shen Yin , Li Yun
Published: May 2020

Batch effect correction has been recognized to be indispensable when integrating single-cell RNA sequencing (scRNA-seq) data from multiple batches. State-of-the-art methods ignore single-cell cluster label information, but such information can improve the effectiveness of batch effect correction, particularly under realistic scenarios where biological differences are not orthogonal to batch effects. To address this issue, we propose SMNN for batch effect correction of scRNA-seq data via supervised mutual nearest neighbor detection. Our extensive evaluations in simulated and real datasets show that SMNN provides improved merging within the corresponding cell types across batches, leading to reduced differentiation across batches over MNN, Seurat v3 and LIGER. Furthermore, SMNN retains more cell-type-specific features, partially manifested by differentially expressed genes identified between cell types after SMNN correction being biologically more relevant, with precision improving by up to 841.0%.
DenvInD: dengue virus inhibitors database for clinical and molecular research
Authors: Dwivedi Vivek Dhar , Arya Aditya , Yadav Pardeep , Kumar Rajesh , Kumar Vinod , Raghava Gajendra P S
Published: May 2020

Dengue virus (DENV) researchers often face challenges with the highly time-consuming process of collecting and curating information on known inhibitors during the standard drug discovery process. To this end, however, required collective information is not yet available on a single platform. Hence, we have developed the DenvInD database for experimentally validated DENV inhibitors against its known targets presently hosted at https://webs.iiitd.edu.in/raghava/denvind/. This database provides comprehensive information, i.e. PubChem IDs, SMILES, IC50, EC50, CC50, and wherever available Ki values of the 484 compounds in vitro validated as inhibitors against respective drug targets of DENV. Also, the DenvInD database has been linked to the user-friendly web-based interface and accessibility features, such as simple search, advanced search and data browsing. All the required data curation was conducted manually from the reported scientific literature and PubChem. The collected information was then organized into the DenvInD database using sequence query language under user interface by hypertext markup language. DenvInD is the first useful repository of its kind which would augment the DENV drug discovery research by providing essential information on known DENV inhibitors for molecular docking, computational screening, pharmacophore modeling and quantitative structure-activity relationship modeling.
New approaches for testing non-inferiority for three-arm trials with Poisson distributed outcomes
Authors: Ghosh Samiran , Paul Erina , Chowdhury Shrabanti , Tiwari Ram C.
Published: May 2020

With the availability of limited resources, innovation for improved statistical method for the design and analysis of randomized controlled trials (RCTs) is of paramount importance for newer and better treatment discovery for any therapeutic area. Although clinical efficacy is almost always the primary evaluating criteria to measure any beneficial effect of a treatment, there are several important other factors (e.g., side effects, cost burden, less debilitating, less intensive, etc.), which can permit some less efficacious treatment options favorable to a subgroup of patients. This leads to non-inferiority (NI) testing. The objective of NI trial is to show that an experimental treatment is not worse than an active reference treatment by more than a pre-specified margin. Traditional NI trials do not include a placebo arm for ethical reason; however, this necessitates stringent and often unverifiable assumptions. On the other hand, three-arm NI trials consisting of placebo, reference, and experimental treatment, can simultaneously test the superiority of the reference over placebo and NI of experimental treatment over the reference. In this article, we proposed both novel Frequentist and Bayesian procedures for testing NI in the three-arm trial with Poisson distributed count outcome. RCTs with count data as the primary outcome are quite common in various disease areas such as lesion count in cancer trials, relapses in multiple sclerosis, dermatology, neurology, cardiovascular research, adverse event count, etc. We first propose an improved Frequentist approach, which is then followed by it’s Bayesian version. Bayesian methods have natural advantage in any active-control trials, including NI trial when substantial historical information is available for placebo and established reference treatment. In addition, we discuss sample size calculation and draw an interesting connection between the two paradigms.
Synaptic autoimmunity: new insights into LGI1 antibody-mediated neuronal dysfunction
Authors: Zekeridou Anastasia , Pittock Sean J
Published: May 2020

This scientific commentary refers to ‘Distinctive binding properties of human monoclonal LGI1 autoantibodies determine pathogenic mechanisms’, by Ramberger et al. (doi:10.1093/brain/awaa104).
Molecular signature of slowly expanding lesions in progressive multiple sclerosis
Authors: Jäckle Katharina , Zeis Thomas , Schaeren-Wiemers Nicole , Junker Andreas , van der Meer Franziska , Kramann Nadine , Stadelmann Christine , Brück Wolfgang
Published: May 2020

Multiple sclerosis is an immune-mediated chronic inflammatory disease of the CNS that leads to demyelinated lesions in the grey and white matter. Inflammatory, active demyelinating white matter lesions predominate in the relapsing-remitting disease stages, whereas in the progressive stage the so-called slowly expanding lesion is characteristic. These lesions show an accumulation of macrophages/microglia at their borders, mediating the ongoing myelin breakdown and axonal degeneration. The exact pathogenetic mechanisms of lesion progression in chronic multiple sclerosis are still not clear. In the present study, we performed a detailed immunological and molecular profiling of slowly expanding lesions (n = 21) from 13 patients aged between 30 to 74 years (five females and eight males), focusing on macrophage/microglia differentiation. By applying the microglia-specific marker TMEM119, we demonstrate that cells accumulating at the lesion edge almost exclusively belonged to the microglia lineage. Macrophages/microglia can be subdivided into the M1 type, which are associated with inflammatory and degenerative processes, and M2 type, with protective properties, whereby also intermediate polarization phenotypes can be observed. By using a panel of markers characterizing M1- or M2-type macrophages/microglia, we observed a preferential accumulation of M1-type differentiated cells at the lesion edge, indicating a crucial role of these cells in lesion progression. Additionally, unbiased RNA microarray analyses of macrodissected lesion edges from slowly expanding and chronic inactive lesions as well as normal-appearing white matter were performed. In slowly expanding lesions, we identified a total of 165 genes that were upregulated and 35 genes that were downregulated. The upregulated genes included macrophage/microglia-associated genes involved in immune defence and inflammatory processes. Among the upregulated genes were ALOX15B, MME and TNFRSF25. We confirmed increased expression of ALOX15B by quantitative PCR, and of all three genes on the protein level by immunohistochemistry. In conclusion, the present study characterized in detail slowly expanding lesions in progressive multiple sclerosis and demonstrated a preferential accumulation of resident microglia with M1 differentiation at the lesion edge. Microarray analysis showed an increased expression of genes related to immune function, metabolic processes as well as transcription/translation. Thus, these genes may serve as future therapeutic targets to impede lesion progression.
Habituation of auditory startle reflex is a new sign of minimally conscious state
Authors: Hermann Bertrand , Salah Amina Ben , Perlbarg Vincent , Valente Mélanie , Pyatigorskaya Nadya , Habert Marie-Odile , Raimondo Federico , Stender Johan , Galanaud Damien , Kas Aurélie , Puybasset Louis , Perez Pauline , Sitt Jacobo D , Rohaut Benjamin , Naccache Lionel
Published: May 2020

Neurological examination of non-communicating patients relies on a few decisive items that enable the crucial distinction between vegetative state (VS)—also coined unresponsive wakefulness syndrome (UWS)—and minimally conscious state. Over the past 10 years, this distinction has proven its diagnostic value as well as its important prognostic value on consciousness recovery. However, clinicians are currently limited by three factors: (i) the current behavioural repertoire of minimally conscious state items is limited and restricted to a few cognitive domains in the goldstandard revised version of the Coma Recovery Scale; (ii) a proportion of ∼15–20% clinically VS/UWS patients are actually in a richer state than VS/UWS as evidenced by functional brain imaging; and (iii) the neurophysiological and cognitive interpretation of each minimally conscious state item is still unclear and debated. In the current study we demonstrate that habituation of the auditory startle reflex (hASR) tested at bedside constitutes a novel, simple and powerful behavioural sign that can accurately distinguish minimally conscious state from VS/UWS. In addition to enlarging the minimally conscious state items repertoire, and therefore decreasing the low sensitivity of current behavioural measures, we also provide an original and rigorous description of the neurophysiological basis of hASR through a combination of functional (high density EEG and 18F-fluorodeoxyglucose PET imaging) and structural (diffusion tensor imaging MRI) measures. We show that preservation of hASR is associated with the functional and structural integrity of a brain-scale fronto-parietal network, including prefrontal regions related to control of action and inhibition, and meso-parietal areas associated with minimally conscious and conscious states. Lastly, we show that hASR predicts 6-month improvement of consciousness. Taken together, our results show that hASR is a cortically-mediated behaviour, and suggest that it could be a new clinical item to clearly and accurately identify non-communicating patients who are in the minimally conscious state.
Prognostic Factors Among Children With Acute Encephalitis/Encephalopathy Associated With Viral and Other Pathogens
Authors: Hatachi Takeshi , Michihata Nobuaki , Inata Yu , Takeuchi Muneyuki , Matsui Hiroki , Fushimi Kiyohide , Yasunaga Hideo
Published: May 2020

Background

Acute encephalitis/encephalopathy (AE) associated with viral and other pathogens leads to neurological sequelae and mortality. Knowing the prognostic factors is therefore important for immediate interventions. We examined early-phase unfavorable prognostic factors among children with AE using a nationwide database.

Methods

We performed a retrospective cohort study using the Diagnosis Procedure Combination database, which includes approximately half of acute-care inpatients across Japan. We enrolled children aged ≤ 18 years who were hospitalized for AE and discharged from April 2010 to March 2018. The composite unfavorable outcome included the following at discharge: in-hospital death, tracheostomy, enteral tube feeding, and physical rehabilitation. Unfavorable prognostic factors were assessed using a multivariable Poisson regression model including patient characteristics, associated pathogens, and interventions within 2 days of admission adjusting for within-hospital clustering.

Results

This study included 9386 children with AE (median age, 3 years). A total of 241 (2.6%) in-hospital deaths occurred, and 2027 (21.6%) patients had the composite unfavorable outcome. Significant unfavorable prognostic factors were age 12–18 years, congenital anomalies, epilepsy, and Japan Coma Scale score of 100–300 at admission (ie, worse levels of consciousness). In contrast, herpes simplex virus infection and influenza virus infection were associated with favorable outcomes.

Conclusions

We identified early-phase (within 2 days of admission) unfavorable prognostic factors among children with AE. These findings will help identify patients who may benefit from early aggressive therapeutic interventions.
Valganciclovir Dosing for Cytomegalovirus Prophylaxis in Solid-organ Transplant Recipients on Continuous Veno-venous Hemodialysis
Authors: Jarrell Andrew S , Crow Jessica R , Strout Sara E , Kruer Rachel M , Toman Lindsey P , Dioverti-Prono Maria V , Lees Laura , Avery Robin K , Marzinke Mark A
Published: May 2020

Background

Optimal valganciclovir dosing for cytomegalovirus (CMV) prophylaxis in solid-organ transplant (SOT) patients on continuous veno-venous hemodialysis (CVVHD) is not known. Ganciclovir trough concentrations ≥0.60 μg/mL have been suggested for CMV prophylaxis. This study was conducted to determine if valganciclovir 450 mg enterally every 24 hours achieves ganciclovir trough concentrations ≥0.60 μg/mL in patients on CVVHD.

Methods

This single-center, prospective, open-label, pharmacokinetic study included adult SOT patients admitted to an intensive care unit from March 2018 to June 2019 on CVVHD. All patients were receiving valganciclovir 450 mg enterally every 24 hours for CMV prophylaxis prior to enrollment. Each patient had a peak and trough sample drawn at steady state.

Results

Ten SOT patients were included in the study (6 liver, 1 simultaneous liver-kidney, 2 bilateral lung, 1 heart). The mean ± SD age was 51.8 ± 14.0 years, and average body mass index was 27 ± 6.9 kg/m2. Ganciclovir trough concentrations ranged from 0.31 to 3.16 μg/mL, and 80% of participants have trough concentrations ≥0.60 μg/mL. No patients had documented neutropenia while on valganciclovir and CVVHD; 60% of patients had significant thrombocytopenia.

Conclusions

Valganciclovir 450 mg enterally every 24 hours achieved ganciclovir trough concentrations ≥0.60 μg/mL in most patients on CVVHD, similar to those reported with intravenous ganciclovir for prophylaxis in this population. Based on these data, valganciclovir may require dosing every 24 hours to achieve concentrations equivalent to ganciclovir. Neutropenia did not occur in the study period. Thrombocytopenia was common and likely multifactorial.
Clinical and Laboratory Predictors of In-hospital Mortality in Patients With Coronavirus Disease-2019: A Cohort Study in Wuhan, China
Authors: Wang Kun , Zuo Peiyuan , Liu Yuwei , Zhang Meng , Zhao Xiaofang , Xie Songpu , Zhang Hao , Chen Xinglin , Liu Chengyun
Published: May 2020

Background

This study aimed to develop mortality-prediction models for patients with coronavirus disease-2019 (COVID-19).

Methods

The training cohort included consecutive COVID-19 patients at the First People’s Hospital of Jiangxia District in Wuhan, China, from 7 January 2020 to 11 February 2020. We selected baseline data through the stepwise Akaike information criterion and ensemble XGBoost (extreme gradient boosting) model to build mortality-prediction models. We then validated these models by randomly collected COVID-19 patients in Union Hospital, Wuhan, from 1 January 2020 to 20 February 2020.

Results

A total of 296 COVID-19 patients were enrolled in the training cohort; 19 died during hospitalization and 277 discharged from the hospital. The clinical model developed using age, history of hypertension, and coronary heart disease showed area under the curve (AUC), 0.88 (95% confidence interval [CI], .80–.95); threshold, −2.6551; sensitivity, 92.31%; specificity, 77.44%; and negative predictive value (NPV), 99.34%. The laboratory model developed using age, high-sensitivity C-reactive protein, peripheral capillary oxygen saturation, neutrophil and lymphocyte count, d-dimer, aspartate aminotransferase, and glomerular filtration rate had a significantly stronger discriminatory power than the clinical model (P = .0157), with AUC, 0.98 (95% CI, .92–.99); threshold, −2.998; sensitivity, 100.00%; specificity, 92.82%; and NPV, 100.00%. In the subsequent validation cohort (N = 44), the AUC (95% CI) was 0.83 (.68–.93) and 0.88 (.75–.96) for the clinical model and laboratory model, respectively.

Conclusions

We developed 2 predictive models for the in-hospital mortality of patients with COVID-19 in Wuhan that were validated in patients from another center.
Functional modulation of atrio-ventricular conduction by enhanced late sodium current and calcium-dependent mechanisms in Scn5a1798insD/+ mice
Authors: Rivaud Mathilde R , Marchal Gerard A , Wolswinkel Rianne , Jansen John A , van der Made Ingeborg , Beekman Leander , Ruiz-Villalba Adrián , Baartscheer Antonius , Rajamani Sridharan , Belardinelli Luiz , van Veen Toon A B , Basso Cristina , Thiene Gaetano , Creemers Esther E , Bezzina Connie R , Remme Carol Ann
Published: May 2020

Aims

SCN5A mutations are associated with arrhythmia syndromes, including Brugada syndrome, long QT syndrome type 3 (LQT3), and cardiac conduction disease. Long QT syndrome type 3 patients display atrio-ventricular (AV) conduction slowing which may contribute to arrhythmogenesis. We here investigated the as yet unknown underlying mechanisms.

Methods and results

We assessed electrophysiological and molecular alterations underlying AV-conduction abnormalities in mice carrying the Scn5a1798insD/+ mutation. Langendorff-perfused Scn5a1798insD/+ hearts showed prolonged AV-conduction compared to wild type (WT) without changes in atrial and His-ventricular (HV) conduction. The late sodium current (INa,L) inhibitor ranolazine (RAN) normalized AV-conduction in Scn5a1798insD/+ mice, likely by preventing the mutation-induced increase in intracellular sodium ([Na+]i) and calcium ([Ca2+]i) concentrations. Indeed, further enhancement of [Na+]i and [Ca2+]i by the Na+/K+-ATPase inhibitor ouabain caused excessive increase in AV-conduction time in Scn5a1798insD/+ hearts. Scn5a1798insD/+ mice from the 129P2 strain displayed more severe AV-conduction abnormalities than FVB/N-Scn5a1798insD/+ mice, in line with their larger mutation-induced INa,L. Transverse aortic constriction (TAC) caused excessive prolongation of AV-conduction in FVB/N-Scn5a1798insD/+ mice (while HV-intervals remained unchanged), which was prevented by chronic RAN treatment. Scn5a1798insD/+-TAC hearts showed decreased mRNA levels of conduction genes in the AV-nodal region, but no structural changes in the AV-node or His bundle. In Scn5a1798insD/+-TAC mice deficient for the transcription factor Nfatc2 (effector of the calcium-calcineurin pathway), AV-conduction and conduction gene expression were restored to WT levels.

Conclusions

Our findings indicate a detrimental role for enhanced INa,L and consequent calcium dysregulation on AV-conduction in Scn5a1798insD/+ mice, providing evidence for a functional mechanism underlying AV-conduction disturbances secondary to gain-of-function SCN5A mutations.
Loss of the Polyketide Synthase StlB Results in Stalk Cell Overproduction in Polysphondylium violaceum
Authors: Narita Takaaki B , Kawabe Yoshinori , Kin Koryu , Gibbs Richard A , Kuspa Adam , Muzny Donna M , Richards Stephen , Strassmann Joan E , Sucgang Richard , Worley Kim C , Schaap Pauline
Published: May 2020

Major phenotypic innovations in social amoeba evolution occurred at the transition between the Polysphondylia and group 4 Dictyostelia, which comprise the model organism Dictyostelium discoideum, such as the formation of a new structure, the basal disk. Basal disk differentiation and robust stalk formation require the morphogen DIF-1, synthesized by the polyketide synthase StlB, the des-methyl-DIF-1 methyltransferase DmtA, and the chlorinase ChlA, which are conserved throughout Dictyostelia. To understand how the basal disk and other innovations evolved in group 4, we sequenced and annotated the Polysphondylium violaceum (Pvio) genome, performed cell type-specific transcriptomics to identify cell-type marker genes, and developed transformation and gene knock-out procedures for Pvio. We used the novel methods to delete the Pvio stlB gene. The Pvio stlB− mutants formed misshapen curly sorogens with thick and irregular stalks. As fruiting body formation continued, the upper stalks became more regular, but structures contained 40% less spores. The stlB− sorogens overexpressed a stalk gene and underexpressed a (pre)spore gene. Normal fruiting body formation and sporulation were restored in Pvio stlB− by including DIF-1 in the supporting agar. These data indicate that, although conserved, stlB and its product(s) acquired both a novel role in the group 4 Dictyostelia and a role opposite to that in its sister group.
Effects of electrical anisotropy on long-offset transient electromagnetic data
Authors: Liu Yajun , Yogeshwar Pritam , Hu Xiangyun , Peng Ronghua , Tezkan Bülent , Mörbe Wiebke , Li Jianhui
Published: May 2020

Electrical anisotropy of formations has been long recognized by field and laboratory evidence. However, most interpretations of long-offset transient electromagnetic (LOTEM) data are based on the assumption of an electrical isotropic earth. Neglecting electrical anisotropy of formations may cause severe misleading interpretations in regions with strong electrical anisotropy. During a large scale LOTEM survey in a former mining area in Eastern Germany, data was acquired over black shale formations. These black shales are expected to produce a pronounced bulk anisotropy. Here, we investigate the effects of electrical anisotropy on LOTEM responses through numerical simulation using a finite-volume time-domain (FVTD) algorithm. On the basis of isotropic models obtained from LOTEM field data, various anisotropic models are developed and analysed. Numerical results demonstrate that the presence of electrical anisotropy has a significant influence on LOTEM responses. Based on the numerical modelling results, an isolated deep conductive anomaly presented in the 2-D isotropic LOTEM electric field data inversion result is identified as a possible artifact introduced by using an isotropic inversion scheme. Trial-and-error forward modelling of the LOTEM electric field data using an anisotropic conductivity model can explain the data and results in a reasonable quantitative data fit. The derived anisotropic 2-D model is consistent with the prior geological information.
High-resolution lithosphere viscosity structure and the dynamics of the 2008 Wenchuan earthquake area: new constraints from magnetotelluric imaging
Authors: Zhu Tao , Zhan Yan , Unsworth Martyn , Zhao Guoze , Sun Xiangyu
Published: May 2020

Estimation of lithospheric viscosity remains challenging, especially for variations with spatial scales less than 100 km. Some recent studies have developed a method to determine viscosity structure from electrical conductivity models determined from magnetotelluric (MT) data. This method was initially applied to the extensional transition zone from the Great Basin to Colorado Plateau. Here, we use this approach to infer the effective lithospheric viscosity in a convergent setting by using an MT profile that crosses the eastern margin of the Tibetan Plateau. The profile extends from the Songpan-Ganzi block, crosses the 2008 Wenchuan earthquake epicentre region and ends in the Sichuan basin. The preferred viscosity structure is characterized by the middle-lower crustal viscosities in the range 2.42 × 1018 to 2.69 × 1021 Pa s below the Songpan-Ganzi block. In the Longmenshan fault zone and 2008 Wenchuan Ms8.0 earthquake area, the crustal viscosity is higher and in the range 4.32 × 1018 to 5.10 × 1021 Pa s with significant small-scale (<100 km) lateral variations. The MT-derived viscosities are consistent with previous regional-scale estimates but reveal the viscosity structure in more detail. The preferred geodynamic model can explain both the crustal deformation velocity and the small-scale lateral variations of surface topography. It implies that the crustal deformation is driven by mantle flow that results in a weak coupling of the upper and middle-lower crust beneath the eastern Tibetan Plateau. The inferred viscosity structure may help further understand the earthquake mechanisms in the Longmenshan fault zone.
Changing Norms: A Meta-Analytic Integration of Research on Social Norms Appeals
Authors: Rhodes Nancy , Shulman Hillary C , McClaran Nikki
Published: May 2020

Social norm appeals attempt to change behavior by modifying the prevailing view that a particular, usually harmful, behavior is less prevalent or less approved of in certain social contexts. These messages have been widely used, such as in safe-drinking campaigns targeted towards college students, but reviews of such efforts have been mixed. The present review used meta-analytic techniques to clarify the effects of social norm manipulations by synthesizing findings from 110 articles. We found consistent support for the effectiveness of social norm manipulations across various outcomes, although effect sizes overall tended to be small. There was also evidence that injunctive norms, though underutilized, may be more effective in changing behavior than previously considered. Moderator analyses demonstrated effects for methodological, sample, and message variables that offer insights into how norms function. The analysis also revealed significant heterogeneity, which underscores the need for more standardization in this area.
The effect of paternal exposure to immunosuppressive drugs on sexual function, reproductive hormones, fertility, pregnancy and offspring outcomes: a systematic review
Authors: Perez-Garcia L F , Dolhain R J E M , Vorstenbosch S , Bramer W , van Puijenbroek E , Hazes J M W , te Winkel B
Published: May 2020

BACKGROUND

Information regarding the possible influence of immunosuppressive drugs on male sexual function and reproductive outcomes is scarce. Men diagnosed with immune-mediated diseases and a wish to become a father represent an important neglected population since they lack vital information to make balanced decisions about their treatment.

OBJECTIVE AND RATIONALE

The aim of this research was to systematically review the literature for the influence of paternal immunosuppressive drug use on many aspects of male sexual health, such as sexual function, fertility, pregnancy outcomes and offspring health outcomes.

SEARCH METHODS

A systematic literature search was performed in the bibliographic databases: Embase (via Elsevier embase.com), MEDLINE ALL via Ovid, Cochrane Central Register of Trials (via Wiley) and Web of Science Core Collection. Additionally, Google Scholar and the Clinical trial registries of Europe and the USA were searched. The databases were searched from inception until 31 August 2019. The searches combined keywords regarding male sexual function and fertility, pregnancy outcomes and offspring health with a list of immunosuppressive drugs. Studies were included if they were published in English and if they included original data on male human exposure to immunosuppressive drugs. A meta-analysis was not possible to perform due to the heterogeneity of the data.

OUTCOMES

A total of 5867 references were identified, amongst which we identified 161 articles fulfilling the eligibility criteria. Amongst these articles, 50 included pregnancy and offspring outcomes and 130 included sexual health outcomes. Except for large Scandinavian cohorts, most of the identified articles included a small number of participants. While a clear negative effect on sperm quality was evident for sulfasalazine and cyclophosphamide, a dubious effect was identified for colchicine, methotrexate and sirolimus. In three articles, exposure to tumour necrosis factor-α inhibitors in patients diagnosed with ankylosing spondylitis resulted in improved sperm quality. The information regarding pregnancy and offspring outcomes was scant but no large negative effect associated with paternal immunosuppressive drug exposure was reported.

WIDER IMPLICATIONS

Evidence regarding the safety of immunosuppressive drugs in men with a wish to become a father is inconclusive. The lack of standardisation on how to evaluate and report male sexual function, fertility and reproduction as study outcomes in men exposed to immunosuppressive drugs is an important contributor to this result. Future research on this topic is needed and should be preferably done using standardised methods.
The Promises and the Challenges of Integrating Multi-Omics and Systems Biology in Comparative Stress Biology
Authors: Schwartz Tonia S
Published: May 2020

Comparative stress biology is inherently a systems biology approach with the goal of integrating the molecular, cellular, and physiological responses with fitness outcomes. In this way, the systems biology approach is expected to provide a holistic understanding of how different stressors result in different fitness outcomes, and how different individuals (or populations or species) respond to stressors differently. In this perceptive article, I focus on the use of multiple types of -omics data in stress biology. Targeting students and those researchers who are considering integrating -omics approaches in their comparative stress biology studies, I discuss the promise of the integration of these measures for furthering our holistic understanding of how organisms respond to different stressors. I also discuss the logistical and conceptual challenges encountered when working with -omics data and the current hurdles to fully utilize these data in studies of stress biology in non-model organisms.
Leading Terms of SL3 Web Invariants
Authors: Bazier-Matte Véronique , Douville Guillaume , Garver Alexander , Patrias Rebecca , Thomas Hugh , Yıldırım Emine
Published: May 2020

We use Khovanov and Kuperberg’s web growth rules to identify the leading term in the invariant associated to an $\textrm{SL}_3$ web diagram, with respect to a particular term order.
Methamphetamine Injection Among Young Men Who Have Sex With Men: Risk for Human Immunodeficiency Virus Transmission in a Los Angeles Cohort
Authors: Gorbach Pamina M , Javanbakht Marjan , Ragsdale Amy , Bolan Robert B , Flynn Risa , Mandler Raul , Shoptaw Steven
Published: May 2020

Background

Prevalence of methamphetamine (meth) injection and associated human immunodeficiency virus (HIV) risks among men who have sex with men (MSM) are unclear.

Methods

A total of 532 MSM completed 1880 mSTUDY study visits between August 2014 and June 2018 in Los Angeles, California. Assessments every 6 months included computer-assisted self-interviews and testing for sexually transmitted infections. Analyses by person and across visits adjusted for repeated measures.

Results

Of 532 participants, 51% (n = 276) reported meth use (past 6 months). Across 1880 visits, mutually exclusive substance use categories were as follows: 5% meth injection (5%), meth use without injection (33%), other substance use excluding meth (36%), and no substance use (26%). Comparisons across these categories respectively found that meth injectors reported higher prevalence of new sex partners (89%, 70%, 68%, and 51%, respectively), more were HIV positive (83%, 65%, 34%, and 50%), fewer were virally suppressed (53%, 48%, 61%, and 67%), and more had sexually transmitted infections (31%, 22%, 15%, and 15% (all P <.01).

Conclusions

Among the young MSM reporting meth injection in this Los Angeles cohort, elevated risks of acquiring or transmitting HIV suggest that they contribute significantly to sustaining the local HIV epidemic. Preventing transition to injection use has potential for HIV prevention.
UMLS users and uses: a current overview
Authors: Amos Liz , Anderson David , Brody Stacy , Ripple Anna , Humphreys Betsy L
Published: May 2020

The US National Library of Medicine regularly collects summary data on direct use of Unified Medical Language System (UMLS) resources. The summary data sources include UMLS user registration data, required annual reports submitted by registered users, and statistics on downloads and application programming interface calls. In 2019, the National Library of Medicine analyzed the summary data on 2018 UMLS use. The library also conducted a scoping review of the literature to provide additional intelligence about the research uses of UMLS as input to a planned 2020 review of UMLS production methods and priorities. 5043 direct users of UMLS data and tools downloaded 4402 copies of the UMLS resources and issued 66 130 951 UMLS application programming interface requests in 2018. The annual reports and the scoping review results agree that the primary UMLS uses are to process and interpret text and facilitate mapping or linking between terminologies. These uses align with the original stated purpose of the UMLS.
TREC-COVID: rationale and structure of an information retrieval shared task for COVID-19
Authors: Roberts Kirk , Alam Tasmeer , Bedrick Steven , Demner-Fushman Dina , Lo Kyle , Soboroff Ian , Voorhees Ellen , Wang Lucy Lu , Hersh William R
Published: May 2020

TREC-COVID is an information retrieval (IR) shared task initiated to support clinicians and clinical research during the COVID-19 pandemic. IR for pandemics breaks many normal assumptions, which can be seen by examining 9 important basic IR research questions related to pandemic situations. TREC-COVID differs from traditional IR shared task evaluations with special considerations for the expected users, IR modality considerations, topic development, participant requirements, assessment process, relevance criteria, evaluation metrics, iteration process, projected timeline, and the implications of data use as a post-task test collection. This article describes how all these were addressed for the particular requirements of developing IR systems under a pandemic situation. Finally, initial participation numbers are also provided, which demonstrate the tremendous interest the IR community has in this effort.
Real-world use of osimertinib for epidermal growth factor receptor T790M-positive non-small cell lung cancer in Japan
Authors: Ohe Yuichiro , Kato Terufumi , Sakai Fumikazu , Kusumoto Masahiko , Endo Masahiro , Saito Yoshinobu , Baba Tomohisa , Sata Masafumi , Yamaguchi Ou , Sakamoto Kei , Sugeno Masatoshi , Tamura Reiko , Tokimoto Toshimitsu , Shimizu Wataru , Gemma Akihiko
Published: May 2020

Objective

Adverse drug reactions (ADRs) during real-world osimertinib use were investigated in Japan.

Methods

Patients with epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer treated with second-line or later oral osimertinib per the Japanese package insert (80 mg once daily) were included. Data were collected between 28 March 2016 and 31 August 2018.

Results

The median observation period in the safety analysis population (n = 3578) was 343.0 days. ADRs (defined as adverse events whose causality to osimertinib could not be denied by the attending physicians or manufacturer) were reported in 58.1% (2079/3578) of patients. ADRs of interstitial lung disease events were reported in 6.8% (245/3578; Grade ≥ 3, 2.9% [104/3578]) of patients, of whom 29 (11.8%) died (0.8% of patients overall). ADRs of QT interval prolonged, liver disorder and haematotoxicity were reported in 1.3% (45/3578; Grade ≥ 3, 0.1% [5/3578]), 5.9% (212/3578; Grade ≥ 3, 1.0% [35/3578]) and 11.4% (409/3578; Grade ≥ 3, 2.9% [104/3578]) of patients, respectively. In the efficacy analysis population (n = 3563), 119 (3.3%) patients had complete responses, 2373 (66.6%) had partial responses and 598 (16.8%) had stable disease. The objective response rate was 69.9%; disease control rate was 86.7%; and median progression-free survival (PFS) was 12.3 months. At 6 and 12 months, PFS rates were 77.4% (95% confidence interval [CI], 75.9–78.9) and 53.2% (95% CI, 51.3–55.1) and overall survival rates were 88.3% (95% CI, 87.2–89.4) and 75.4% (95% CI, 73.8–77.0), respectively.

Conclusions

These data support the currently established benefit-risk assessment of osimertinib in this patient population.
3D-Printing to Address COVID-19 Testing Supply Shortages
Authors: Cox Jesse L , Koepsell Scott A
Published: May 2020

The recent SARS-CoV-2 outbreak has placed immense pressure on supply chains, including shortages in nasopharyngeal (NP) swabs. Here, we report our experience of using 3D-printing to rapidly develop and deploy custom-made NP swabs to address supply shortages at our healthcare institution.
Comparative accuracy of 1,3 beta-D glucan and galactomannan for diagnosis of invasive fungal infections in pediatric patients: a systematic review with meta-analysis
Authors: Singh Shreya , Singh Manvi , Verma Nipun , Sharma Minakshi , Pradhan Pranita , Chauhan Anil , Jaiswal Nishant , Chakrabarti Arunaloke , Singh Meenu
Published: May 2020

Invasive fungal infections (IFI) cause considerable morbidity and mortality in pediatric patients. Serum biomarkers such as 1,3-beta-D glucan (BDG) and galactomannan (GM) have been evaluated for the IFI diagnosis. However, most evidence regarding their utility is derived from studies in adult oncology patients. This systematic review aimed to compare the diagnostic accuracy of BDG and GM individually or in combination for diagnosing IFI in pediatric patients. PubMed, CINAHL, Embase, and Cochrane Library were searched until March 2019 for diagnostic studies evaluating both serum GM and BDG for diagnosing pediatric IFI. The pooled diagnostic odds ratio (DOR), specificity and sensitivity were computed. Receiver operating characteristics (ROC) curve and area under the curve (AUC) were used for summarizing overall assay performance. Six studies were included in the meta-analysis. The summary estimates of sensitivity, specificity, pooled DOR, AUC of the GM assay for proven or probable IFI were 0.74, 0.76, 13.25, and 0.845. The summary estimates of sensitivity, specificity, pooled DOR, AUC of the BDG assay were 0.70, 0.69, 4.3, and 0.722. The combined predictive ability of both tests was reported in two studies (sensitivity: 0.67, specificity: 0.877). Four studies were performed in hematology-oncology patients, while two were retrospective studies from pediatric intensive care units (ICUs). In the subgroup of hematology-oncology patients, DOR of BDG remained similar at 4.25 but increased to 40.28 for GM. We conclude that GM and BDG have a modest performance for identifying IFI in pediatric patients. GM has a better accuracy over BDG. Combining both improves the specificity at the cost of sensitivity.
A geometric method of analysis for the light curves of active galactic nuclei
Authors: Shoji Isao , Takata Tadafumi , Mizumoto Yoshihiko
Published: May 2020

We propose a geometric method of analysis for the light curves of active galactic nuclei (AGNs). The time series of flux ratio is modelled by possibly non-linear random oscillation without specifying the function form. Based on the model, we map the dynamic behaviour of flux ratio to a vector field on a manifold, and then analyse the vector field to retrieve information on the dynamic properties closely linked with the activity of AGNs. While the function form of the model is unspecified, the vector fields and those associated quantities can be estimated by applying a non-parametric filtering method. We illustrate the proposed analysis with an application to light curves of two AGNs supplied by the Kepler satellite. The application shows that the vector field, its derivative, and their combination will be used as the tools of picking up various signals that help understanding of the activity of AGNs. In addition, from a technical viewpoint, the non-parametric filtering method allows the estimation to be robust against outliers. The proposed analysis could be used as an alternative time series analysis of the optical variability other than the analysis by spectral densities or structure functions.
Properties of sub-Neptune atmospheres: TOI-270 system
Authors: Chouqar J , Benkhaldoun Z , Jabiri A , Lustig-Yaeger J , Soubkiou A , Szentgyorgyi A
Published: May 2020

We investigate the potential for the James Webb Space Telescope (JWST) to detect and characterize the atmospheres of the sub-Neptunian exoplanets in the TOI-270 system. Sub-Neptunes are considered more likely to be water worlds than gas dwarfs. We model their atmospheres using three atmospheric compositions – two examples of hydrogen-dominated atmospheres and a water-dominated atmosphere. We then simulate the infrared transmission spectra of these atmospheres for JWST instrument modes optimized for transit observation of exoplanet atmospheres: NIRISS, NIRSpec, and MIRI. We then predict the observability of each exoplanet’s atmosphere. TOI-270c and d are excellent targets for detecting atmospheres with JWST transmission spectroscopy, requiring only 1 transit observation with NIRISS, NIRSpec, and MIRI; higher signal-to-noise ratio can be obtained for a clear H-rich atmosphere. Fewer than three transits with NIRISS and NIRSpec may be enough to reveal molecular features. Water-dominated atmospheres require more transits. Water spectral features in water-dominated atmospheres may be detectable with NIRISS in two or three transits. We find that the detection of spectral features in a cloudy, H-rich atmosphere does not require integrations as long as those required for the water-dominated atmosphere, which is consistent with the differences in atmospheric mean molecular weight. TOI-270c and d could be prime targets for JWST transit observations of sub-Neptune atmospheres. These results provide useful predictions for observers who may propose to use JWST to detect and characterize the TOI-270 planet atmospheres.
Accretion-driven turbulence in filaments II: effects of self-gravity
Authors: Heigl S , Gritschneder M , Burkert A
Published: May 2020

We extend our previous work on simulations with the code ramses on accretion-driven turbulence by including self-gravity and study the effects of core formation and collapse. We show that radial accretion on to filaments drives turbulent motions which are not isotropic but radially dominated. In contrast to filaments without gravity, the velocity dispersion of self-gravitating filaments does not settle in an equilibrium. Despite showing similar amounts of driven turbulence, they continually dissipate their velocity dispersion until the onset of core formation. This difference is connected to the evolution of the radius as it determines the dissipation rate. In the non-gravitational case filament growth is not limited and its radius grows linearly with time. In contrast, there is a maximum extent in the self-gravitational case resulting in an increased dissipation rate. Furthermore, accretion-driven turbulence shows a radial profile which is anticorrelated with density. This leads to a constant turbulent pressure throughout the filament. As the additional turbulent pressure does not have a radial gradient it does not contribute to the stability of filaments and does not increase the critical line-mass. However, this radial turbulence does affect the radius of a filament, adding to the extent and setting its maximum value. Moreover, the radius evolution also affects the growth time-scale of cores which compared to the time-scale of collapse of an accreting filament limits core formation to high line-masses.
State-of-the-art AGN SEDs for photoionization models: BLR predictions confront the observations
Authors: Ferland G J , Done C , Jin C , Landt H , Ward M J
Published: May 2020

The great power offered by photoionization models of active galactic nuclei emission line regions has long been mitigated by the fact that very little is known about the spectral energy distribution (SED) between the Lyman limit, where intervening absorption becomes a problem, and  0.3 keV, where soft X-ray observations become possible. The emission lines themselves can, to some degree, be used to probe the SED, but only in the broadest terms. This paper employs a new generation of theoretical SEDs that are internally self-consistent, energy conserving, and tested against observations, to infer properties of the emission-line regions. The SEDs are given as a function of the Eddington ratio, allowing emission-line correlations to be investigated on a fundamental basis. We apply the simplest possible tests, based on the foundations of photoionization theory, to investigate the implications for the geometry of the emission-line region. The SEDs become more far-ultraviolet bright as the Eddington ratio increases, so the equivalent widths of recombination lines should also become larger, an effect that we quantify. The observed lack of correlation between Eddington ratio and equivalent width shows that the cloud covering factor must decrease as Eddington ratio increases. This would be consistent with recent models proposing that the broad-line region is a failed dusty wind off the accretion disc.