bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelet-Rich Plasma in Melasma—A Systematic Review
Authors: Sarkar Rashmi , Gupta Meghna 
Published: November 2021

BACKGROUND
Melasma is a common relapsing hyperpigmentation disorder, which is often difficult to treat. Platelet-rich plasma (PRP) is a novel modality often used to treat acne scars, androgenic alopecia, chronic wounds, and skin rejuvenation. Recently, it has had a promising role in the treatment of melasma.

OBJECTIVE
To review the published evidence on the efficacy and safety of PRP in the treatment of melasma.

MATERIALS AND METHODS
A systematic review was performed. A meta-analysis could not be performed because of methodological differences across studies and data heterogeneity.

RESULTS
Seven studies were fulfilled and analyzed. Most studies used intradermal injections of PRP and have shown significant improvement in melasma. Microneedling mediated delivery of PRP has been tried in melasma with good results. A single study showed no additional benefit of PRP in patients treated with topical tranexamic acid. Another study showed no benefit of intense pulsed light in patients treated with intradermal PRP.

CONCLUSION
Platelet-rich plasma inhibits the melanin synthesis through its various components acting through several mechanisms. It demonstrates a moderate grade of recommendation according to the Oxford Center for Evidence-Based Medicine 2011 standards.
Metacarpal bone diameter increases constantly in adult females, but escalated resorption of the inner surface at menopause explains the observed decreased bone mineral density at digital X-ray radiogrammetry
Authors: Samuelsson Carl , Wilczek Michael , Kälvesten Johan , Qureshi Abdul Rashid , Brismar Torkel B. 
Published: November 2021

Abstract

Objective:
To assess how bone morphology and mineralization changes with age, in women by digital X-ray radiogrammetry (DXR). DXR has potential as a screening tool for osteoporosis, as it can evaluate bone mineralization similarly to dual-energy X-ray absorptiometry.

Methods:
The nondominant hand was analyzed with DXR in 13,285 women ages 40-74 years undergoing mammography. 1,556 women attended two consecutive examinations with 18 to 24 months interval. Changes in bone parameters were calculated and compared in 5-year age groups. Regression analysis and ANOVA tests were performed.

Results:
Univariate linear regression showed no significant difference in age or bone size between the groups with single or consecutive measurements. In the group with consecutive measurements, the average inner diameter (DXR-ID) of the metacarpals significantly increased with age from 0.38 cm in the 40-45 years age span to 0.47 cm in the 65+ age group (P < 0.001), whereas DXR bone mineral density (DXR-BMD) decreased from 0.59 g/cm2 to 0.50 g/cm2 in the same age groups (P < 0.001). Intraindividual measurements showed a fourfold increase in yearly DXR-ID increase and concurrent DXR-BMD loss between 50 and 59 years of age (P < 0.001). The outer diameter only increased significantly between the youngest and oldest age group (P < 0.001).

Conclusions:
The faster decrease in DXR-BMD observed during and after menopause is caused by resorption of the inner cortical surface, not matched by outer diameter increase. We speculate that most bones in the human body grow in the same pattern as observed in the metacarpals, partly explaining decreasing BMD at DXR and dual-energy X-ray absorptiometry.

Video Summary:

http://links.lww.com/MENO/A832.
Association between eating alone and cardiovascular diseases in elderly women: a cross-sectional study of KNHANES 2016 data
Authors: Choi Han-Gyo , Kim Hye-Jin , Kang Seok-Jung 
Published: November 2021

Abstract

Objective:
To investigate differences in health behaviors, nutritional status, and the likelihood of having cardiovascular diseases and its risk factors according to the presence of an eating companion in older women.

Methods:
Using 2016 Korean National Health and Nutrition Examination Survey VII-1 data, 590 menopausal women aged ≥65 years were analyzed in this cross-sectional study. Participants who ate more than two meals a day alone were assigned to an eating-alone (EA) group and those who ate more than two meals a day with others were assigned to an eating-with-others (EO) group. Complex-samples general linear analysis, t tests, and logistic regression were used for the analysis of the data.

Results:
Awareness of nutrition labels (P = 0.012), using of nutrition labels (P = 0.014), and impact of nutrition labels (P = 0.016) were lower in the EA group than in the EO group. The intake of energy, carbohydrates, dietary fiber, sodium, and potassium was lower in the EA group than in the EO group (P < 0.05). The likelihood of having angina was 2.58 times higher in the EA group than in the EO group (95% CI, 1.20-5.55).

Conclusions:
Older women who ate alone had poorer nutritional knowledge and intake. In addition, eating alone in older women was strongly associated with the prevalence of angina. Thus, it is necessary to consider nutrition education and cardiovascular disease screening for older women who mainly eat alone.
Targeting Versus Tailoring Educational Videos for Encouraging Deceased Organ Donor Registration in Black-Owned Barbershops
Authors: Wall Stephen P. , Castillo Patricio , Shuchat-Shaw Francine , Norman Elizabeth , Brown David , Martinez-López Natalia , López-Ríos Mairyn , Seixas Azizi A. , Plass Jan L. , Ravenell Joseph E. 
Published: November 2021

AbstractIn the U.S., Black men have highest risk for requiring kidney transplants but are among those least likely to register for organ donation. Prior outreach used videos culturally targeted for Black communities, yet registration rates remain insufficient to meet demand. Therefore, we assessed whether generic versus videos culturally targeted or personally tailored based on prior organ donation beliefs differentially increase organ donor registration. In a randomized controlled trial, 1,353 participants in Black-owned barbershops viewed generic, targeted, or tailored videos about organ donation. Logistic regression models assessed relative impact of videos on: 1) immediate organ donor registration, 2) taking brochures, and 3) change in organ donation willingness stage of change from baseline. Randomization yielded approximately equal groups related to demographics and baseline willingness and beliefs. Neither targeted nor tailored videos differentially affected registration compared with the generic video, but participants in targeted and tailored groups were more likely to take brochures. Targeted (OR=1.74) and tailored (OR=1.57) videos were associated with incremental increases in organ donation willingness stage of change compared to the generic video. Distributing culturally targeted and individually tailored videos increased organ donor willingness stage of change among Black men in black-owned barbershops but was insufficient for encouraging registration.
Interpretable Visualization of Scientific Hypotheses in Literature-based Discovery
Authors: Tyagin Ilya , Safro Ilya 
Published: November 2021

ABSTRACTIn this paper we present an approach for interpretable visualization of scientific hypotheses that is based on the idea of semantic concept interconnectivity, network-based and topic modeling methods. Our visualization approach has numerous adjustable parameters which provides the domain experts with additional flexibility in their decision making process. We also make use of the Unified Medical Language System metadata by integrating it directly into the resulting topics, and adding the variability into hypotheses resolution. To demonstrate the proposed approach in action, we deployed end-to-end hypothesis generation pipeline AGATHA, which was evaluated by BioCreative VII experts with COVID-19-related queries.
Consequences of endogenous and virally-induced hyperphosphorylated tau on behavior and cognition in a rat model of Alzheimer’s disease
Authors: Kelberman Michael A. , Anderson Claire R. , Chlan Eli , Rorabaugh Jacki M. , McCann Katharine E. , Weinshenker David 
Published: November 2021

AbstractBackgroundThe locus coeruleus (LC) is one of the earliest brain regions to accumulate hyperphosphorylated tau, but a lack of animal models that recapitulate this pathology has hampered our ability to understand its contributions to the pathophysiology of Alzheimer’s disease (AD).ObjectiveWe previously reported that TgF344-AD rats, which overexpress mutant human amyloid precursor protein and presenilin-1, accumulate early endogenous hyperphosphorylated tau in the LC. Here, we used TgF344-AD rats and a wild-type (WT) human tau virus to interrogate the effects of endogenous hyperphosphorylated rat tau and human tau in the LC on AD-related neuropathology and behavior.MethodsTwo-month old TgF344-AD and WT rats received bilateral LC infusions of WT human tau or mCherry control virus driven by the noradrenergic-specific PRSx8 promoter. Rats were subsequently assessed at 6 and 12 months for arousal (sleep latency), anxiety-like behavior (open field, elevated plus maze, novelty-suppressed feeding), passive coping (forced swim task), and learning and memory (Morris water maze and fear conditioning). Hippocampal microglia, astrocyte, and AD pathology were evaluated using immunohistochemistry.ResultsIn general, the effects of age were more pronounced than genotype or treatment; older rats displayed greater hippocampal pathology, took longer to fall asleep, had reduced locomotor activity, floated more, and had impaired cognition compared to younger animals. TgF344-AD rats showed increased anxiety-like behavior and impaired learning and memory. The tau virus had negligible influence on most measures.ConclusionEffects of hyperphosphorylated tau on AD-like neuropathology and behavioral symptoms were subtle. Further investigation of different forms of tau is warranted.
Intratumoral delivery of engineered recombinant modified vaccinia virus Ankara expressing Flt3L and OX40L generates potent antitumor immunity through activating the cGAS/STING pathway and depleting tumor-infiltrating regulatory T cells
Authors: Yang Ning , Wang Yi , Liu Shuaitong , Luna Joseph M. , Mazo Gregory , Tan Adrian Y. , Zhang Tuo , Wang Jiahu , Yan Wei , Choi John , Rossi Anthony , Xiang Jenny Zhaoying , Rice Charles M. , Merghoub Taha , Wolchok Jedd D. , Deng Liang 
Published: November 2021

SummaryIntratumoral (IT) delivery of immune-activating viruses can serve as an important strategy to turn “cold” tumors into “hot” tumors, resulting in overcoming resistance to immune checkpoint blockade (ICB). Modified vaccinia virus Ankara (MVA) is a highly attenuated, non-replicative vaccinia virus that has a long history of human use. Here we report that IT recombinant MVA (rMVA), lacking E5R encoding an inhibitor of the DNA sensor cyclic GMP-AMP synthase (cGAS), expressing a dendritic cell growth factor, Fms-like tyrosine kinase 3 ligand (Flt3L), and a T cell co-stimulator, OX40L, generates strong antitumor immunity, which is dependent on CD8+ T cells, the cGAS/STING-mediated cytosolic DNA-sensing pathway, and STAT1/STAT2-mediated type I IFN signaling. Remarkably, IT rMVA depletes OX40hi regulatory T cells via OX40L/OX40 interaction and IFNAR signaling. Taken together, our study provides a proof-of-concept for improving MVA-based cancer immunotherapy, through modulation of both innate and adaptive immunity.One Sentence SummaryIntratumoral delivery of recombinant MVA for cancer immunotherapy
Highly-Sensitive Lineage Discrimination of SARS-CoV-2 Variants through Allele-Specific Probe Polymerase Chain Reaction
Authors: Ratcliff Jeremy , Al-Beidh Farah , Bibi Sagida , Bonsall David , Costa Clemens Sue Ann , Estcourt Lise , Evans Amy , Fish Matthew , Folegatti Pedro M. , Gordon Anthony C. , Jay Cecilia , Jennings Aislinn , Laing Emma , Lambe Teresa , MacIntyre-Cockett George , Menon David , Mouncey Paul R. , Nguyen Dung , Pollard Andrew J. , Ramasamy Maheshi N. , Roberts David J. , Rowan Kathryn M. , Rynne Jennifer , Shankar-Hari Manu , Williams Sarah , Harvala Heli , Golubchik Tanya , Simmonds Peter ,   the AMPHEUS Project, REMAP-CAP Immunoglobulin Domain UK Investigators, and Oxford COVID-19 Vaccine Trial Group
Published: November 2021

AbstractIntroductionTools to detect SARS-Coronavirus-2 variants of concern and track the ongoing evolution of the virus are necessary to support public health efforts and the design and evaluation of novel COVID-19 therapeutics and vaccines. Although next-generation sequencing (NGS) has been adopted as the gold standard method for discriminating SARS-CoV-2 lineages, alternative methods may be required when processing samples with low viral loads or low RNA quality.MethodsAn allele-specific probe polymerase chain reaction (ASP-PCR) targeting lineage-specific single nucleotide polymorphisms (SNPs) was developed and used to screen 1,082 samples from two clinical trials in the United Kingdom and Brazil. Probit regression models were developed to compare ASP-PCR performance against 1,771 NGS results for the same cohorts.ResultsIndividual SNPs were shown to readily identify specific variants of concern. ASP-PCR was shown to discriminate SARS-CoV-2 lineages with a higher likelihood than NGS over a wide range of viral loads. Comparative advantage for ASP-PCR over NGS was most pronounced in samples with Ct values between 26-30 and in samples that showed evidence of degradation. Results for samples screened by ASP-PCR and NGS showed 99% concordant results.DiscussionASP-PCR is well-suited to augment but not replace NGS. The method can differentiate SARS-COV-2 lineages with high accuracy and would be best deployed to screen samples with lower viral loads or that may suffer from degradation. Future work should investigate further destabilization from primer:target base mismatch through altered oligonucleotide chemistry or chemical additives.
PrP concentration in the central nervous system: regional variability, genotypic effects, and pharmacodynamic impact
Authors: Mortberg Meredith A , Zhao Hien T , Reidenbach Andrew G , Gentile Juliana E , Kuhn Eric , O’Moore Jill , Dooley Patrick M , Connors Theresa R , Mazur Curt , Allen Shona W , Trombetta Bianca A , McManus Alison , Moore Matthew R , Liu Jiewu , Cabin Deborah E , Kordasiewicz Holly B , Mathews Joel , Arnold Steven E , Vallabh Sonia M , Minikel Eric Vallabh 
Published: November 2021

AbstractPrion protein (PrP) concentration controls the kinetics of prion replication and is a genetically and pharmacologically validated therapeutic target for prion disease. In order to evaluate PrP concentration as a pharmacodynamic biomarker and assess its contribution to known prion disease risk factors, we developed and validated a plate-based immunoassay reactive for PrP across six species of interest and applicable to brain and cerebrospinal fluid (CSF). PrP concentration varies dramatically between different brain regions in mice, cynomolgus macaques, and humans. PrP expression does not appear to contribute to the known risk factors of age, sex, or common PRNP genetic variants. CSF PrP is lowered in the presence of rare pathogenic PRNP variants, with heterozygous carriers of P102L displaying 55% and of D178N just 31% the CSF PrP concentration of mutation-negative controls. In rodents, pharmacologic reduction of brain Prnp RNA is reflected in brain parenchyma PrP, and in turn in CSF PrP, validating CSF as a sampling compartment for the effect of PrP-lowering therapy. Our findings support the use of CSF PrP as a pharmacodynamic biomarker for PrP-lowering drugs, and suggest that relative reduction from individual baseline CSF PrP concentration may be an appropriate marker for target engagement.
Effects of a single 10mg dose of empagliflozin on postprandial insulin kinetics in patients with postbariatric hypoglycaemia
Authors: Schiavon Michele , Herzig David , Matthias Hepprich , Donath Marc Y. , Man Chiarra Dall , Bally Lia 
Published: November 2021

ABSTRACTIntroductionPostbariatric hypoglycaemia (PBH) is an increasingly recognized late metabolic complication of Roux-en-Y gastric bypass (GB) surgery. PBH typically manifests with a fact occurring post-meal hyperglycaemic peak, followed by a disproportionately exaggerated insulin response leading to low glucose levels. On this basis, we evaluated the effect of a single dose of empagliflozin 10mg vs. placebo on parameters of insulin kinetics.Materials and methodsInsulin secretion, hepatic insulin extraction and total insulin clearance were evaluated after a single of empagliflozin 10mg vs. placebo followed by a standardized liquid mixed meal were evaluated in 11 subjects with confirmed PBH after GB over 3h. Parameters of interest were calculated using established mathematical models. Indices were compared between the groups using the Wilcoxon signed-rank test.ResultsTotal beta-cell responsiveness tends to be lower with empagliflozin vs. placebo (24.83±11.00 vs. 27.15±9.68 [10−9 min-1], p=0.150). Total first-pass hepatic insulin extraction increased after empagliflozin compared to placebo (49.6±14.2 vs. 39.7±12.1 %, p=0.006), while no significant effect of empaglizflozin on basal first-pass hepatic insulin extraction was observed (79.7±7.1 vs. 81.1±6.6 %, p=0.521). Total insulin clearance resulted to be significantly lower after empagliflozin compared to placebo (3.91±1.58 vs. 3.00±1.27 l/min, p=0.002).ConclusionThe present analysis suggests that the hypoglycaemia-attenuating effect of SGLT2-inhibition in patients with PBH is mainly mediated by an increment in insulin clearance, with also a tendency to a reduction in insulin secretion.
Using Machine Learning to Elucidate the Spatial and Genetic Complexity of the Ascending Aorta
Authors: Nekoui Mahan , Pirruccello James P. , Di Achille Paolo , Choi Seung Hoan , Friedman Samuel N. , Nauffal Victor , Ng Kenney , Batra Puneet , Ho Jennifer E. , Philippakis Anthony A. , Lubitz Steven A. , Lindsay Mark E. , Ellinor Patrick T. 
Published: November 2021

BackgroundThe left ventricular outflow tract (LVOT) and ascending aorta are spatially complex, with distinct pathologies and embryologic origins. Prior work examined genetics of thoracic aortic diameter in a single plane. We sought to elucidate the genetic basis for the diameter of the LVOT, the aortic root, and the ascending aorta.MethodsWe used deep learning to analyze 2.3 million cardiac magnetic resonance images from 43,317 UK Biobank participants. We computed the diameters of the LVOT, the aortic root, and at six locations in the ascending aorta. For each diameter, we conducted a genome-wide association study and generated a polygenic score. Finally, we investigated associations between these polygenic scores and disease incidence.Results79 loci were significantly associated with at least one diameter. Of these, 35 were novel, and a majority were associated with one or two diameters. A polygenic score of aortic diameter approximately 13mm from the sinotubular junction most strongly predicted thoracic aortic aneurysm in UK Biobank participants (n=427,016; HR=1.42 per standard deviation; CI=1.34-1.50, P=6.67×10−21). A polygenic score predicting a smaller aortic root was predictive of aortic stenosis (n=426,502; HR=1.08 per standard deviation; CI=1.03-1.12, P=5×10−6).ConclusionsWe detected distinct common genetic loci underpinning the diameters of the LVOT, the aortic root, and at several segments in the ascending aorta. We spatially defined a region of aorta whose genetics may be most relevant to predicting thoracic aortic aneurysm. We further described a genetic signature that may predispose to aortic stenosis. Understanding the genetic contributions to the diameter of the proximal aorta may enable identification of individuals at risk for life-threatening aortic disease and facilitate prioritization of therapeutic targets.
A Framework for Falsifiable Explanations of Machine Learning Models with an Application in Computational Pathology
Authors: Schuhmacher David , Schörner Stephanie , Küpper Claus , Großerueschkamp Frederik , Sternemann Carlo , Lugnier Celine , Kraeft Anna-Lena , Jütte Hendrik , Tannapfel Andrea , Reinacher-Schick Anke , Gerwert Klaus , Mosig Axel 
Published: November 2021

AbstractIn recent years, deep learning has been the key driver of breakthrough developments in computational pathology and other image based approaches that support medical diagnosis and treatment. The underlying neural networks as inherent black boxes lack transparency, and are often accompanied by approaches to explain their output. However, formally defining explainability has been a notorious unsolved riddle. Here, we introduce a hypothesis-based framework for falsifiable explanations of machine learning models. A falsifiable explanation is a hypothesis that connects an intermediate space induced by the model with the sample from which the data originate. We instantiate this framework in a computational pathology setting using label-free infrared microscopy. The intermediate space is an activation map, which is trained with an inductive bias to localize tumor. An explanation is constituted by hypothesizing that activation corresponds to tumor and associated structures, which we validate by histological staining as an independent secondary experiment.
Distilling a High Precision Drug Adverse Effect Benchmark Using Wikipedia’s Wisdom of the Crowd
Authors: Bilu Yonatan , Yanover Chen 
Published: November 2021

ABSTRACTBackgroundLarge datasets of relational medical data, such as the adverse effects of drugs or vaccines, typically attain their large size, by relying on automatic, or semi-automatic, methods for generation. This often comes with a compromise on the precision of the generated data, which can be at least partially alleviated by having experts curate the data.AimSince having experts review a large dataset can be costly and time consuming, here we suggest using Wikipedia for this task – that is, augment the automatic generation step by an automatic curation step based on the expert knowledge accumulated in Wikipedia.MethodsTo curate a dataset of adverse drug effects (ADEs), we suggest retrieving the Wikipedia page associated with the drug, and checking whether the ADE appears in the sections describing adverse effects. Drug indications, typically described in the opening paragraph of the page, are similarly filtered out.ResultsWe use the method to curate two large adverse drug effect datasets and show that the obtained datasets have a much higher precision relative to their originating ones.ConclusionsAlgorithms which aim to infer drug-ADE relations, should at the very least be able to identify the “clear cut” cases. The high-precision benchmark constructed herein may therefore be a valuable resource for the evaluation of such algorithms.
Equipment-free detection of SARS-CoV-2 and Variants of Concern using Cas13
Authors: Arizti-Sanz Jon , Bradley A’Doriann , Zhang Yibin B. , Boehm Chloe K. , Freije Catherine A. , Grunberg Michelle E. , Kosoko-Thoroddsen Tinna-Solveig F. , Welch Nicole L. , Pillai Priya P. , Mantena Sreekar , Kim Gaeun , Uwanibe Jessica N. , John Oluwagboadurami G. , Eromon Philomena E. , Kocher Gregory , Gross Robin , Lee Justin S. , Hensley Lisa E. , Happi Christian T. , Johnson Jeremy , Sabeti Pardis C. , Myhrvold Cameron 
Published: November 2021

AbstractThe COVID-19 pandemic, and the recent rise and widespread transmission of SARS-CoV-2 Variants of Concern (VOCs), have demonstrated the need for ubiquitous nucleic acid testing outside of centralized clinical laboratories. Here, we develop SHINEv2, a Cas13-based nucleic acid diagnostic that combines quick and ambient temperature sample processing and lyophilized reagents to greatly simplify the test procedure and assay distribution. We benchmarked a SHINEv2 assay for SARS-CoV-2 detection against state-of-the-art antigen-capture tests using 96 patient samples, demonstrating 50-fold greater sensitivity and 100% specificity. We designed SHINEv2 assays for discriminating the Alpha, Beta, Gamma and Delta VOCs, which can be read out visually using lateral flow technology. We further demonstrate that our assays can be performed without any equipment in less than 90 minutes. SHINEv2 represents an important advance towards rapid nucleic acid tests that can be performed in any location.