bluuebunny/crossref_metadata_2025_split huggingface dataset:
Iridocorneal Angle Assessment After Laser Iridotomy With Swept-source Optical Coherence Tomography
Authors: Meduri Enrico , Gillmann Kevin , Bravetti Giorgio E. , Niegowski Letitia J. , Mermoud André , Weinreb Robert N. , Mansouri Kaweh 
Published: September 2020

Aim:
To investigate the reliability of anterior chamber angle (ACA) measurements in narrow angles and assess the effect of laser peripheral iridotomy (LPI) on these measurements using novel swept-source optical coherence tomography (SS-OCT) technology.

Materials and Methods:
In this prospective observational study, patients with gonioscopically narrow angles were enrolled and scheduled for prophylactic LPI. Twelve ACA sections were obtained in each eye using SS-OCT (ANTERION, Heidelberg Engineering, Germany) before and after Nd:YAG LPI. A built-in algorithm calculated ACA measurements after manual identification of the scleral spur and ACA recess. Eight ACA parameters were evaluated: ACA (ACA 500, ACA 750); scleral spur angle (SSA 500, SSA 750); angle opening distance (AOD 500, AOD 750); and trabecular iris space area (TISA 500, TISA 750). The effect of LPI was assessed for each parameter, both nasally and temporally.

Results:
Ten patients (18 eyes) were enrolled (mean age, 61.8±13.6 y; 60.0% female individuals). On average, the ACA was wider nasally than temporally (P=0.004). LPI significantly widened the ACA (range, 26.7-29.4%; P<0.05). ACA 500 increased by 29.4% (P<0.001), ACA 750 by 29.2% (P=0.002), SSA 500 by 27.3% (P=0.003), SSA 750 by 28.1% (P=0.001), AOD 500 by 28.6% (P=0.009), AOD 750 by 28.6% (P=0.003), TISA 500 by 27.3% (P=0.004), and TISA 750 by 26.7% (P=0.200).

Conclusions:
SS-OCT ANTERION imaging can be used to reliably measure ACA before and after LPI. ACA, AOD, SSA, and TISA are all valid ACA measurement methods.
Lower Eyelid Horizontal Tightening in Prostaglandin Associated Periorbitopathy
Authors: Procianoy Fernando , P.L. Lang Martha , J.L. Bocaccio Francisco 
Published: September 2020

Purpose:
To determine the effect of chronic topical use of prostaglandin analogs for glaucoma on lower eyelid tension.

Methods:
A prospective case–control study was performed. Lower eyelid tension was measured in a group of glaucoma patients (73 eyelids) using prostaglandin analogs and a paired control group (87 eyelids). Seven glaucoma patients with unilateral use of prostaglandin analogs had the lower eyelid tension of the exposed side compared with the contralateral eyelid. Eyelid tension was digitally measured in photographs in neutral position and after manual downward traction in the center of the eyelid (modified distraction test). Duration of drug exposition, age, use of other topical medication and other prostaglandin-associated periorbitopathy signs as long eyelashes, eyelid hyperemia, eyelid pigmentation, and deepening of upper eyelid sulcus were recorded for analysis.

Results:
Mean lower eyelid tension in prostaglandin group was significantly higher than in control group: distraction 5.26 mm (SD 1.52) versus 6.80 mm (SD 1.29) (p < 0.001). On the unilateral prostaglandin use intragroup comparison, mean lower eyelid distraction in prostaglandin side was 4.24 mm (SD 1.80) and in control side was 6.79 mm (SD 1.63) (p < 0.012). Beta blocker and carbonic anhydrase inhibitor concomitant use was associated with lower eyelid tension measures in prostaglandin users. Presence of long eyelashes was associated with higher eyelid tension. All other measured variables did not demonstrate interaction with eyelid tension.

Conclusions:
Chronic topical use of prostaglandin analogs for glaucoma is associated with lower eyelid tightening.
Does gender matter: sex-specific aspects of symptoms, outcome, and therapy of obstructive sleep apnea
Authors: Schiza Sophia E. , Bouloukaki Izolde 
Published: September 2020

Purpose of review
Obstructive sleep apnea (OSA) has historically been considered as a male disease. As a result, female individuals with OSA were often under-diagnosed and under-treated compared with male individuals. However, recent data suggest that several OSA-associated adverse cardiovascular outcomes are more pronounced in women.

Recent findings
This review provides a summary of the most relevant recent evidence with regard to sex-specific OSA characteristics, including atypical symptoms, greater quality of life impairment and several more pronounced adverse outcomes in female individuals compared with male individuals. It also provides updated evidence on the influence of female gender on under-treatment of OSA with limited evidence supporting gender differences in the effects of OSA treatment.

Summary
There is evidence suggesting gender-based differences in the frequency, severity, clinical presentation, and outcomes of OSA. The recognition of these gender differences could improve screening with development of female-specific screening instruments, early diagnosis, and individualized therapeutic plans towards better disease management and its outcomes.
Novosphingobium ovatum sp. nov., isolated from a freshwater mesocosm
Authors: Chen Wen-Ming , Cai Cheng-Ye , Sheu Der-Shyan , Tsai Jyh-Ming , Sheu Shih-Yi 
Published: September 2020

A bacterial strain, designated FSY-8T, was isolated from a freshwater mesocosm in Taiwan and characterized using the polyphasic taxonomy approach. Cells of strain FSY-8T were aerobic, Gram-stain-negative, rod-shaped, non-motile and formed yellow coloured colonies on Reasoner's 2A agar. Growth occurred at 20–40 °C (optimum, 30–37 °C) and pH 5–7 (optimum, pH 6) and in the presence of 0–0.5 % NaCl (optimum, 0 %, w/v). The major fatty acids (>10 %) of strain FSY-8T were summed feature 8 (C18 : 1
ω7c and/or C18 : 1
ω6c) and summed feature 3 (C16 : 1
ω7c and/or C16 : 1
ω6c). The polar lipid profile consisted of a mixture of phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, phosphatidylmonomethylethanolamine, phosphatidyldimethylethanolamine, sphingoglycolipid, diphosphatidylglycerol, an uncharacterized aminophospholipid, an uncharacterized glycolipid and an uncharacterized lipid. The major polyamine was spermidine. The major isoprenoid quinone was Q-10. The DNA G+C content was 64.8 mol %. Phylogenetic analyses based on 16S rRNA gene sequences and coding sequences of 92 protein clusters indicated that strain FSY-8T formed a phylogenetic lineage in the genus

Novosphingobium

. Strain FSY-8T showed 71.6–77.2 % average nucleotide identity and 19.9–22.8 % digital DNA–DNA hybridization identity with the strains of other

Novosphingobium

species. On the basis of phenotypic and genotypic properties and phylogenetic inference, strain FSY-8T should be classified in a novel species of the genus

Novosphingobium

, for which the name Novosphingobium ovatum sp. nov. is proposed. The type strain is FSY-8T (=BCRC 81051T=LMG 30053T=KCTC 52812T).
TERT promoter mutation analysis for blood-based diagnosis and monitoring of gliomas
Authors: Muralidharan Koushik , Yekula Anudeep , Small Julia L. , Rosh Zachary S. , Kang Keiko M. , Wang Lan , Lau Spencer , Zhang Hui , Lee Hakho , Bettegowda Chetan , Chicoine Michael R. , Kalkanis Steven N. , Shankar Ganesh M. , Nahed Brian V. , Curry William T. , Jones Pamela S. , Cahill Daniel P. , Balaj Leonora , Carter Bob S. 
Published: September 2020

AbstractLiquid biopsy offers a minimally invasive tool to diagnose and monitor the heterogeneous molecular landscape of tumors over time and therapy. Gliomas have been challenging to sample with blood-based liquid biopsy due to low levels of circulating tumor-derived nucleic acid, and prior efforts have shown specific point mutations in less than 5% of glioma patients. Detection of TERT promoter mutations (C228T, C250T) in cfDNA has been successful for some systemic cancers but has yet to be demonstrated in gliomas, despite the high prevalence of these mutations in glioma tissue (>60% of all tumors). Here, we developed a novel digital droplet PCR (ddPCR) assay, that incorporates features to improve sensitivity and allows for the simultaneous detection and longitudinal monitoring of two TERT promoter mutations (C228T and C250T) in cfDNA from the plasma of glioma patients. In baseline performance in tumor tissue, (n= 157 samples), the assay had perfect concordance with an independently performed clinical pathology laboratory assessment of TERT promoter mutations in the same tumor samples (95% CI 94%-100%). Extending to matched plasma samples, we detected TERT mutations in both discovery and blinded multi-institution validation cohorts with an overall sensitivity of 62.5% (95% CI 52%-73%) and a specificity of 90% (95% CI 80%-96%) compared to the gold standard tumor tissue-based detection of TERT mutations. Upon longitudinal monitoring in 5 patients, we report that peripheral TERT mutant allele frequency reflects the clinical course of the disease with levels decreasing after surgical intervention and therapy and increasing with tumor progression. Our results demonstrate the feasibility of detecting circulating cfDNA TERT promoter mutations in glioma patients with clinically relevant sensitivity and specificity using a novel, enhanced ddPCR approach. The functionality of this assay also suggests a new clinical role for plasma-based cfDNA analysis to complement tissue-based histopathologic and molecular characterization for diagnosis and spatiotemporal monitoring of brain tumors.
Multiplexed, Microscale, Microarray-based Serological Assay for Antibodies Against All Human-Relevant Coronaviruses
Authors: Dawson Erica D. , Kuck Laura R. , Blair Rebecca H. , Taylor Amber W. , Toth Evan , Knight Vijaya , Rowlen Kathy L. 
Published: September 2020

ABSTRACTRapid, sensitive, and precise multiplexed assays for serological analysis during candidate COVID-19 vaccine development would streamline clinical trials. The VaxArray Coronavirus (CoV) SeroAssay quantifies IgG antibody binding to 9 pandemic, potentially pandemic, and endemic human CoV spike antigens in 2 hours with automated results analysis. IgG antibodies in serum bind to the CoV spike protein capture antigens printed in a microarray format and are labeled with a fluorescent anti-species IgG secondary label. The assay demonstrated excellent lower limits of quantification ranging from 0.3 – 2.0 ng/mL and linear dynamic ranges of 76 to 911-fold. Average precision of 11% CV and accuracy (% recovery) of 92.5% over all capture antigens were achieved over 216 replicates representing 3 days and 3 microarray lots. Clinical performance on 263 human serum samples (132 SARS-CoV-2 negatives and 131 positives based on donor-matched RT-PCR and/or date of collection) produced 98.5% PPA (sensitivity) and 100% NPA (specificity).
Effectiveness of smartphone-based Community Case Management on urgent referral, re-consultation and hospitalization of children under-5 in Malawi: Results of a cluster-randomized, stepped-wedge trial
Authors: Chirambo Griphin Baxter , Thompson Matthew , Hardy Victoria , Ide Nicole , Hwang Phillip H. , Dharmayat Kanika I. , Mastellos Nikolaos , Heavin Ciara , O’Connor Yvonne , Muula Adamson S. , Andersson Bo , O’Donoghue John , Carlsson Sven , Tran Tammy , Chen-ling Hsieh Jenny , Lee Hsin-yi , Fitzpatrick Annette , Wu Joseph Tsung Shu 
Published: September 2020

AbstractBackgroundIntegrated community case management (CCM) has led to reductions in child mortality in Malawi from illnesses such as malaria, pneumonia and diarrhoea. However, adherence to CCM guidelines is often poor, potentially leading to inappropriate clinical decisions and outcomes. We determined the impact of an electronic version of CCM (eCCM) application on referral, re-consultation and hospitalization rates of children presenting to village clinics in Malawi.MethodsA stepped-wedge cluster-randomized trial compared paper-based CCM (control) with and without use of an eCCM app on smartphones from November 2016 to April 2017.A total of 102 village clinics from two districts in Northern Malawi were assigned to one of six clusters which were randomized to the sequencing of crossover from the control to the intervention phases, as well as the duration of exposure in each phase. Children ≥2 months to <5 years presenting with acute illness were enrolled consecutively by Health Surveillance Assistants (HSAs). The primary outcome of urgent referrals to higher-level facilities was evaluated using multi-level mixed effects models. A logistic regression model with random effect of cluster and fixed effect for each step was fitted. Adjustment for potential confounders included baseline factors, such as patient’s age, sex, and geographical location of village clinics. Calendar time was adjusted for in the analysis.ResultsA total of 6965 children were recruited, 3421 in the control and 3544 in the intervention phase. After adjusting for calendar time, children in the intervention phase were more likely to be urgently referred to a higher-level health facility compared with children in the control phase (OR 2.02, 95% CI 1.27-3.23; p<0.01). Overall, children in the intervention arm had lower odds of attending a repeat HSA consultation (OR 0.45, 95% CI 0.34-0.59; p<0.01) or hospital admission (OR 0.75, 95% CI 0.62-0.90; p<0.01), but after adjusting for time these differences were not significant (p>0.05).ConclusionsAddition of eCCM decision support led to a greater proportion of children being referred to higher-level facilities, with no apparent increase in hospital admissions or repeat consultations in village clinics. Our findings provide support for the implementation of eCCM tools in Malawi and other Low and Middle Income Countries (LMIC), with a need for ongoing assessment of effectiveness and integration with national digital health strategies.Trial registrationhttp://ClinicalTrials.gov; NCT02763345. Registered 3 May 2016
A Mental Health Paradox: Mental health was both a motivator and barrier to physical activity during the COVID-19 pandemic
Authors: Marashi Maryam , Nicholson Emma , Ogrodnik Michelle , Fenesi Barbara , Heisz Jennifer 
Published: September 2020

AbstractThe COVID-19 pandemic has impacted the mental health, physical activity, and sedentary behavior of citizens worldwide. Using an online survey with 1669 respondents, we sought to understand why and how by querying about perceived barriers and motivators to physical activity that changed because of the pandemic, and how those changes impacted mental health. Consistent with prior reports, our respondents were less physically active (aerobic activity, −11%,p<0.05; strength-based activity, −30%,p<0.01) and more sedentary (+11%,p<0.01) during the pandemic as compared to 6-months before. The pandemic also increased psychological stress (+22%,p<0.01) and brought on moderate symptoms of anxiety and depression. Respondents’ whose mental health deteriorated the most were also the ones who were least active (depressionr= −.21,p<0.01; anxietyr= −.12,p<0.01). The majority of respondents were unmotivated to exercise because they were too anxious (+8%,p<0.01), lacked social support (+6%,p=<0.01), or had limited access to equipment (+23%,p<0.01) or space (+41%,p<0.01). The respondents who were able to stay active reported feeling less motivated by physical health outcomes such as weight loss (−7%,p<0.01) or strength (−14%,p<0.01) and instead more motivated by mental health outcomes such as anxiety relief (+14%,p<0.01). Coupled with previous work demonstrating a direct relationship between mental health and physical activity, these results highlight the potential protective effect of physical activity on mental health and point to the need for psychological support to overcome perceived barriers so that people can continue to be physically active during stressful times like the pandemic.
Sex-dependent pathways in hepatocarcinogenesis triggered by deregulated cholesterol synthesis
Authors: Blagotinšek Cokan Kaja , Urlep Žiga , Lorbek Gregor , Matz-Soja Madlen , Skubic Cene , Perše Martina , Jeruc Jera , Juvan Peter , Režen Tadeja , Rozman Damjana 
Published: September 2020

ABSTRACTWe uncover novel pathways of sex-dependent hepatocarcinogenesis due to chronic repression of cholesterol synthesis at the lanosterol 14α-demethylase (CYP51) step. The response to metabolic insult determined by global liver transcriptome, qPCR and sterol metabolite analysis, together with blood parameters, revealed molecular signatures that differ between females and males. The data deduced from the mouse model are highly relevant for humans. The dampened hepatic metabolism presents a hallmark of carcinogenesis, particularly in ageing females, with increased plasma cholesterol and HDL, and a substantial negative enrichment of transcription factors from lipid metabolism, such as NR1B1, LXRα, LRH1, and FXR. Importantly, the carcinogenic signalling pathways (ECM-receptor interaction and PI3K/Akt) are positively enriched, albeit with sex-dependent gene targets. The activated TGF-β, mTOR, Wnt, and estrogen signalling worsen the phenotype, with NFATC1/2 being central to the female phenotype. This collectively leads to activated cell death and diminished basal metabolism. In conclusion, our data underline sex as an important biological variable of hepatocarcinogenesis. We uncover novel cholesterol-dependent transcription factors and signalling pathways as cancer markers in the ageing females.SignificanceChronic repression of the late part of cholesterol synthesis provokes hepatocarcinogenesis with sex-dependent modulation of signalling pathways and transcription factors. Aging females show specific metabolic signatures and a more aggrevated phenotype of metabolism-related HCC.
Soluble RANKL exaggerates hindlimb suspension-induced osteopenia but not muscle protein balance
Authors: Speacht Toni L. , Lang Charles H. , Donahue Henry J. 
Published: September 2020

ABSTRACTWe examined the hypothesis that exaggerating unloading-induced bone loss using a combination of hindlimb suspension (HLS) and exogenous injections of receptor activator of nuclear factor kappa-B ligand (RANKL) also exaggerates muscle loss. Forty, male C57Bl/6J mice (16 weeks) were subjected to HLS or normal ambulation (ground control, GC) for 14 days. Mice received 3 intraperitoneal injections of either human recombinant soluble RANKL or PBS as control (n=10/group) at 24 hour intervals starting on Day 1 of HLS. GC + RANKL and HLS mice exhibited similar decreases in trabecular bone volume and density in both proximal tibias and distal femurs. However, RANKL affected trabecular number, separation, and connectivity density, while HLS decreased trabecular thickness. The combination of RANKL and HLS exacerbated these changes. Similarly, GC + RANKL and HLS mice saw comparable decreases in cortical bone volume, thickness, and strength in femur midshafts, and combination treatment exacerbated these changes. Plasma concentrations of P1NP were increased in both groups receiving RANKL, while CTX concentrations were unchanged. HLS decreased gastrocnemius weight and was associated with a reduction in global protein synthesis, and no change in proteasome activity. This change was correlated with a decrease in S6K1 and S6 phosphorylation, but no change in 4E-BP1 phosphorylation. Injection of RANKL did not alter muscle protein metabolism in GC or HLS mice. Our results suggest that injection of soluble RANKL exacerbates unloading-induced bone loss, but not unloading-induced muscle loss. This implies a temporal disconnect between muscle and bone loss in response to unloading.
Epithelial and neutrophil interactions and coordinated response toShigellain a human intestinal enteroid-neutrophil co-culture model
Authors: Lemme-Dumit Jose M. , Doucet Michele , Zachos Nicholas C. , Pasetti Marcela F. 
Published: September 2020

AbstractPolymorphonuclear neutrophils (PMN) are recruited to the gastrointestinal mucosa in response to inflammation, injury, and infection. Herein, we report the development and the characterization of anex vivotissue co-culture model consisting of human primary intestinal enteroid monolayers and PMN, and a mechanistic interrogation of PMN-epithelial cell interaction and response toShigella, a primary cause of childhood dysentery. Cellular adaptation and tissue integration, barrier function, PMN phenotypic and functional attributes, and innate immune responses were examined. PMN within the enteroid monolayers acquired a distinct activated/migratory phenotype that was influenced by direct epithelial cell contact as well as by molecular signals. Seeded on the basal side of the intestinal monolayer, PMN intercalated within the epithelial cells and moved paracellularly toward the apical side. Co-cultured PMN also increased basal secretion of IL-8.Shigellaadded to the apical surface of the monolayers evoked additional PMN phenotypic adaptations, including increased expression of cell surface markers associated with chemotaxis and cell degranulation (CD47, CD66b, and CD88). ApicalShigellainfection triggered rapid transmigration of PMN to the luminal side, NET formation as well as bacterial phagocytosis and killing.Shigellainfection modulated cytokine production in the co-culture; apical MCP-1, TNF-α, and basolateral IL-8 production were downregulated, while basolateral IL-6 secretion was increased. We demonstrated, for the first time, PMN phenotypic adaptation, mobilization, and coordinated epithelial cell-PMN innate response uponShigellainfection in the human intestinal environment. The enteroid monolayer-PMN co-culture represents a technical innovation for mechanistic interrogation of gastrointestinal physiology, host-microbe interaction, innate immunity, and evaluation of preventive/therapeutic tools.ImportanceStudies of mucosal immunity and microbial host cell interaction have traditionally relied on animal models andin vitrotissue culture using immortalized cancer cell lines, which render non-physiological and often unreliable results. Herein we report the development and characterization of anex vivoenteroid-PMN co-culture consisting of normal human intestinal epithelium and a mechanistic interrogation of PMN and epithelial cell interaction and function in the context ofShigellainfection. We demonstrated tissue-driven phenotypic and functional adaptation of PMN and a coordinated epithelial cell and PMN response toShigella, a primary cause of dysentery in young children in the developing world.
A multi-scale pipeline linking drug transcriptomics with pharmacokinetics predictsin vivointeractions of tuberculosis drugs
Authors: Cicchese Joseph , Sambarey Awanti , Kirschner Denise , Linderman Jennifer , Chandrasekaran Sriram 
Published: September 2020

AbstractTuberculosis (TB) is the deadliest infectious disease worldwide. The design of new treatments for TB is hindered by the large number of candidate drugs, drug combinations, dosing choices, and complex pharmaco-kinetics/dynamics (PK/PD). Here we study the interplay of these factors in designing combination therapies by linking a machine-learning model, INDIGO-MTB, which predictsin vitrodrug interactions using drug transcriptomics, with a multi-scale model of drug PK/PD and pathogen-immune interactions calledGranSim. We calculate anin vivodrug interaction score (iDIS) from dynamics of drug diffusion, spatial distribution, and activity within lesions against various pathogen sub-populations. The iDIS of drug regimens evaluated against non-replicating bacteria significantly correlates with efficacy metrics from clinical trials. Our approach identifies mechanisms that can amplify synergistic or mitigate antagonistic drug interactionsin vivoby modulating the relative distribution of drugs. Our mechanistic framework enables efficient evaluation ofin vivodrug interactions and optimization of combination therapies.