bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of Telemedicine Parity Requirements on Telehealth Utilization in the United States During the COVID-19 Pandemic
Authors: Lee Hyunjung , Singh Gopal K. 
Published: March 2023

Background:
Research has shown a dramatic increase in telehealth utilization during the COVID-19 pandemic and marked socioeconomic disparities in telehealth utilization. However, previous studies have shown discrepant findings on the association between the state's telehealth payment parity laws and telehealth utilization, and dearth of differential impact studies by subgroups.

Methods:
Using a nationally representative Household Pulse Survey from April 2021 to August 2022 and the logistic regression modeling, we estimated the impact of parity payment laws on overall, video, and phone telehealth utilization and related disparities by race and ethncity during the pandemic.

Results:
We found that adults in parity states had 23% higher odds of telehealth utilization (odds ratio [OR] = 1.23; 95% confidence interval [CI], 1.14-1.33) and 124% higher odds of video telehealth utilization (OR = 2.24; 95% CI, 1.95-2.57) than their counterparts in nonparity states. In parity states, non-Hispanic White adults had 24% higher odds of telehealth utilization (OR = 1.24; 95% CI: 1.14, 1.35) and non-Hispanic Black adults had 31% higher odds of telehealth utilization (OR = 1.31; 95% CI: 1.03, 1.65), compared with those in nonparity states. For Hispanics, non-Hispanic Asians, and non-Hispanic other races, there was not a statistically significant effect of parity act on overall telehealth utilization.

Conclusions:
Given inequalities in telehealth utilization, increased state policy efforts are needed to reduce access disparities during the ongoing pandemic and beyond.
Effectiveness of Pelvic Floor Muscle Training for Patients Following Low Anterior Resection
Authors: Kim Young Man , Oh Eui Geum 
Published: March 2023

PURPOSE:
The purpose of this systematic review was to identify the effects of pelvic floor muscle training (PFMT) on bowel function and health-related quality of life among patients who have undergone low anterior resection.

METHODS:
A systematic review and meta-analysis of pooled findings was conducted according to PRISMA guidelines.

SEARCH STRATEGY:
A literature search was completed using PubMed, EMBASE, Cochrane, and CINAHL electronic databases; we searched studies published in English and Korean languages. Two reviewers independently selected relevant studies, evaluated their methodological quality, and extracted data. Meta-analysis was conducted of pooled findings.

FINDINGS:
Thirty-six of 453 articles retrieved were read in full and 12 articles were included in the systematic review. In addition, pooled findings from 5 studies were selected for meta-analysis. Analysis revealed that PFMT reduced bowel dysfunction (mean difference [MD] −2.39, 95% confidence interval [CI] −3.79 to −0.99) and improved several domains of health-related quality of life: lifestyle (MD 0.49, 95% CI 0.15 to 0.82), coping (MD 0.36, 95% CI 0.04 to 0.67), depression (MD 0.46, 95% CI 0.23 to 0.70), and embarrassment (MD 0.24, 95% CI 0.01 to 0.46).

IMPLICATIONS:
Findings suggested PFMT is effective for improving bowel function and enhancing multiple domains of health-related quality of life after low anterior resection. Further well-designed studies are required to confirm our conclusions and provide stronger evidence for the effects of this intervention.
Cross-ancestry genome-wide association study and systems-level integrative analyses implicate new risk genes and therapeutic targets for depression
Authors: Li Yifan , Dang Xinglun , Chen Rui , Wang Junyang , Li Shiwu , Mitchell Brittany L. , Yao Yong-Gang , Li Ming , Li Tao , Zhang Zhijun , Luo Xiong-Jian 
Published: March 2023

AbstractDeciphering the genetic architecture of depression is pivotal for characterizing the associated pathophysiological processes and development of new therapeutics. Here we conducted a cross-ancestry genome-wide meta-analysis on depression (416,437 cases and 1,308,758 controls) and identified 287 risk loci, of which 140 are new. Variant-level fine-mapping prioritized potential causal variants and functional genomic analysis identified variants that regulate the binding of transcription factors. We validated that 80% of the identified functional variants are regulatory variants and expression quantitative trait loci (eQTL) analysis uncovered the potential target genes regulated by the prioritized risk variants. Gene-level analysis, including transcriptome-wide association study (TWAS), proteome-wide association study (PWAS), colocalization and Mendelian randomization-based analyses, prioritized potential causal genes and drug targets. Combining evidence from different analyses revealed likely causal genes, includingTMEM106B, CTNND1, EPHB2, AREL1, CSE1L, RAB27B, SATU1, TMEM258, DCC, etc. Pathway analysis showed significant enrichment of depression risk genes in synapse-related pathways. Finally, we showed thatTmem106bknockdown resulted in depression-like behaviors in mice, supporting involvement ofTmem106bin depression. Our study identified new risk loci, likely causal variants and genes for depression, providing important insights into the genetic architecture of depression and potential therapeutic targets.
The Effectiveness of Advance Care Planning Training for Care Home Staff: a Systematic Review
Authors: Barber-Fleming Victoria Ann , Mann Mala , Mead Gillian , Gleeson Aoife 
Published: March 2023

AbstractIn line with population ageing, the number of global deaths is predicted to increase. There have been projections that, within the next 20 years, in England and Wales, care homes may become the most common place of death. In order to respect the autonomy of their residents, it is therefore, vital that care home staff are able to have Advance Care Planning conversations. However, care home staff may lack the knowledge or confidence to have such discussions. Further, a systematic review found a paucity of evidence about whether Advance Care Planning training interventions for care home staff are effective. New, higher quality studies are now available, justifying this review update. We sought to address two questions: 1) ‘What Advance Care Planning education interventions exist for care home staff?’ and 2) ‘how effective are these interventions?’ All measurable outcomes of effectiveness (e.g. health system/resource-related, patient/relative-related, staff-related) including both qualitative and quantitative measures of effectiveness were considered.DesignThe review adheres to the Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) and is registered on PROSPERO (ID: CRD42022337865). Original research evaluating Advance Care Planning education for care home staff and reporting any measurable outcome of effectiveness was included. We searched Ovid Medline All, Ovid Embase, Cochrane Central Register of Controlled Trials, EBSCO CINAHL, EBSCO ERIC, and Ovid PsycINFO from March 2018 (3 months prior to original review search cut-off) to June 2022, with supplemental journal and website searches. The results were synthesised by narrative synthesis.FindingsThe current review update almost doubled the number of included studies in a relatively short period. This review includes 10 studies (n = 310 care homes), from the UK, Belgium, Norway and Canada. UK studies were mainly related to the Gold Standard Framework for Care Homes. Two studies adopted multi-component education interventions. Outcome measures included resident/family, staff and health service-related concepts. Even after identifying a further 5 papers, there remains insufficient evidence to determine the effectiveness of Advance Care Planning education interventions for care home staff.ConclusionsAdvance Care Planning education interventions are heterogeneous and often complex in their design, flexibility, target populations, and outcomes. There remains insufficient data to determine the effectiveness of Advance Care Planning education interventions for care home staff, with a particularly urgent need to agree on outcome measures of the effectiveness. Future research could consider updating the existing Delphi consensus on outcome measures for evaluating Advance Care Planning, in light of this systematically collected evidence, with a view to agreeing outcomes that are specific to Advance Care Planning education interventions for care home staff.
Photoluminescence brightening of single-walled carbon nanotubes through conjugation with graphene quantum dots
Authors: Sajjadi Sayyed Hashem , Wu Shang-Jung , Reggente Melania , Sharif Niloufar , Boghossian Ardemis A. 
Published: March 2023

AbstractSpanning the tissue transparency window, the near-infrared (NIR) photoluminescence (PL) of single-walled carbon nanotubes (SWCNTs) can optically penetrate biological tissue for deep-tissue imaging and optical sensing. SWCNTs are often functionalized with single-stranded DNA (ssDNA) to yield biocompatible, responsive, and selective sensors. However, the low brightness of these ssDNA-wrapped SWCNTs sensors restricts the depth at which such sensors can be implanted in the tissue. This work demonstrates the PL enhancement of ssDNA-wrapped SWCNTs by incorporating biocompatible graphene quantum dots (GQDs). Two kinds of GQDs, pristine (PGQDs) and nitrogen-doped (NGQDs), were fabricated and characterized. Thermodynamically, both GQDs were shown to significantly increase the fluorescence efficiency of ssDNA-SWCNTs with the same degree of PL enhancement after 3 h. Furthermore, a correlation between the diameter of the SWCNTs and the PL enhancement factor was found; the larger the SWCNT diameter, the higher the PL increase upon adding GQDs. For instance, a 30-fold enhancement was achieved for (8,6) chirality while it was only 2-fold for the (6,5) chirality. Our experiments showed that adding GQDs increases the surface coverage of SWCNTs suspended by ssDNA, limiting water molecules’ access to the nanotube surface, thus increasing the fluorescence efficiency. Kinetically, NGQDs brightened SWCNTs much faster than PGQDs. The PL intensity reached a plateau in 2 min following the addition of NGQDs, while it was still increasing even after 1 h upon the addition of PGQDs. We show that NGQDs can act as reducing agents to decrease the amount of dissolved oxygen, which quenches the SWCNTs PL. This advancement provides a promising tool for engineering the brightness of NIR sensors for biomedical applications such as single-molecule imaging of individual SWCNTs using NIR confocal microscopy and deep tissue sensing.
Comparative Proteomic Analysis of Paired Human Milk Fat Globules and Membranes and Mouse Milk Fat Globules Identifies Core Cellular Systems Contributing to Mammary Lipid Trafficking and Secretion
Authors: Carli Jayne F. Martin , Monks Jenifer , McManaman James L. 
Published: March 2023

AbstractHuman milk delivers critical nutritional and immunological support to the infant. The milk fat globule and its membrane contain many bioactive components, yet the mechanism of milk fat secretion and how milk fat globule (MFG) components are regulated are poorly defined. In this study, we perform quantitative proteomic profiling of milk fat globules from human and mouse milk, as well as from isolated membranes physically disrupted from human milk fat globules.Using paired analyses of the human samples we report membrane enrichment of the proteins involved in docking/tethering the lipid droplet to the membrane as well as minor components involved in the signaling pathway for secretion. Comparing abundance between human and mouse milk fat globules we find that 8 of 12 major milk fat globule proteins are shared between the two species. Comparative pathway enrichment analyses between human and mouse samples reveal similarities in shared membrane trafficking and signaling pathways involved in milk fat secretion. Our results advance knowledge of the composition and relative quantities of proteins in human and mouse milk fat globules in greater detail, provide a quantitative profile of specifically enriched human milk fat globule membrane proteins, and identify core cellular systems involved in milk lipid secretion.
Far From Home: Evolution of haploid and diploid populations reveals common, strong, and variable pleiotropic effects in non-home environments
Authors: Chen Vivian K. , Johnson Milo S. , Hérissant Lucas , Humphrey Parris T. , Yuan David C. , Li Yuping , Agarwala Atish , Hoelscher Samuel B. , Petrov Dmitri A. , Desai Michael M. , Sherlock Gavin 
Published: March 2023

AbstractAdaptation is driven by the selection for beneficial mutations that provide a fitness advantage in the specific environment in which a population is evolving. However, environments are rarely constant or predictable. When an organism well adapted to one environment finds itself in another, pleiotropic effects of mutations that made it well adapted to its former environment will affect its success. To better understand such pleiotropic effects, we evolved both haploid and diploid barcoded budding yeast populations in multiple environments, isolated adaptive clones, and then determined the fitness effects of adaptive mutations in “non-home” environments in which they were not selected. We find that pleiotropy is common, with most adaptive evolved lineages showing fitness effects in non-home environments. Consistent with other studies, we find that these pleiotropic effects are unpredictable: they are beneficial in some environments and deleterious in others. However, we do find that lineages with adaptive mutations in the same genes tend to show similar pleiotropic effects. We also find that ploidy influences the observed adaptive mutational spectra in a condition-specific fashion. In some conditions, haploids and diploids are selected with adaptive mutations in identical genes, while in others they accumulate mutations in almost completely disjoint sets of genes.
Fat2 polarizes Lar and Sema5c to coordinate the motility of collectively migrating epithelial cells
Authors: Williams Audrey Miller , Horne-Badovinac Sally 
Published: March 2023

AbstractMigrating epithelial cells globally align their migration machinery to achieve tissue-level movement. Biochemical signaling across leading-trailing cell-cell interfaces can promote this alignment by partitioning migratory behaviors like protrusion and retraction to opposite sides of the interface. However, how the necessary signaling proteins become organized at this site is poorly understood. The follicular epithelial cells ofDrosophila melanogasterhave two signaling modules at their leading-trailing interfaces—one composed of the atypical cadherin Fat2 and the receptor tyrosine phosphatase Lar, and one composed of Semaphorin 5c and its receptor Plexin A. Here we show that these modules form one interface signaling system with Fat2 at its core. Trailing edge-enriched Fat2 concentrates both Lar and Sema5c at cells’ leading edges, likely by slowing their turnover at this site. Once localized, Lar and Sema5c act in parallel to promote collective migration. Our data suggest a model in which Fat2 couples and polarizes the distributions of multiple effectors that work together to align the migration machinery of neighboring cells.
The effect of lifelong physical (in)activity on knee extensor force control
Authors: Pethick Jamie 
Published: March 2023

AbstractIt is well-documented that older adults exhibit a greater magnitude and decreased complexity of muscle force fluctuations in comparison to young adults. To date, however, research on this age-related loss of force control has focused on heterogeneous groups of inactive/moderately active older adults, despite accumulating evidence that high levels of lifelong physical activity (such as that exhibited by Masters athletes) has a protective effect on neuromuscular function and morphology. The present study compared healthy young adults (aged < 35; n = 14), healthy but inactive older adults (aged > 55; n = 13) and Masters athletes (aged > 55; n = 14) in order to discern the effects of lifelong physical (in)activity on muscle force control. Force control was assessed during isometric knee extension contractions at 10, 20 and 40% maximal voluntary contraction (MVC) and was quantified according to the magnitude (coefficient of variation [CV]) and complexity (approximate entropy [ApEn]; detrended fluctuation analysis [DFA] α) of force fluctuations. Inactive older adults exhibited significantly greater CV, indicative of poorer force steadiness, than young adults and Masters athletes during contractions at 10, 20 and 40% MVC (allP< 0.001). There were no significant differences in CV between the young adults and Masters athletes. These results indicate that lifelong physical activity has a protective effect against the age-related loss of muscle force control and suggest that, up to this point, our understanding of the age-related loss of muscle force control has been confounded by the effects of physical inactivity.Key pointsAgeing is associated with a decrease in muscle force control (i.e., poorer steadiness and adaptability), though to date this has largely been studied in inactive older adultsLifelong physical activity, such as that exhibited by Masters athletes, has a protective role against many age-related decrements in neuromuscular physiology and functionThis study compared force control, during contractions at intensities typical of the requirements of activities of daily living, in healthy young adults, healthy but inactive older adults and age-matched Masters athletesMasters athletes exhibited significantly better force steadiness than their inactive counterparts and no difference in steadiness compared to young adultsLifelong physical activity appears to modulate the age-related loss of force control, indicating that our current understanding of this loss of force control may be contaminated by the negative effects of inactivity
Unexpected plasma gonadal steroid and reproductive hormone levels across the mouse estrous cycle
Authors: Wall Ellen G. , Desai Reena , Aung Zin Khant , Yeo Shel Hwa , Grattan David R. , Handelsman David J. , Herbison Allan E. 
Published: March 2023

AbstractDespite the importance of the mouse in biomedical research, the levels of circulating gonadal steroids across the estrous cycle are not established with any temporal precision. Using liquid chromatography-mass spectrometry, now considered the gold standard for steroid hormone analysis, we aimed to generate a detailed profile of gonadal steroid levels across the estrous cycle of C57BL/6J mice. For reference, luteinizing hormone (LH) and prolactin concentrations were measured in the same samples by sandwich ELISA. Terminal blood samples were collected at 8-hour intervals (10 am, 6 pm, 2 am) throughout the four stages of the estrous cycle. As expected, the LH surge was detected at 6 pm on proestrus with a mean (±SEM) concentration of 11±3 ng/mL and occurred coincident with the peak in progesterone levels (22±4 ng/mL). Surprisingly, estradiol concentrations peaked at 10 am on diestrus (51±8 pg/mL), with levels on proestrus 6 pm reaching only two-thirds of this value (31±5 pg/mL). We also observed a proestrous peak in prolactin concentrations (132.5±17 ng/mL) that occurred earlier than expected at 2 am. Estrone and androstenedione levels were often close to the LOD and showed no consistent changes across the estrous cycle. Testosterone levels were rarely above the LOD (0.01 ng/mL). These observations provide the first detailed assessment of fluctuating gonadal steroid and reproductive hormone levels across the mouse estrous cycle and indicate that species differences exist between mice and other spontaneously ovulating species.
Meta-Research: understudied genes are lost in a leaky pipeline between genome-wide assays and reporting of results
Authors: Richardson Reese AK , Navarro Heliodoro Tejedor , Nunes Amaral Luis A , Stoeger Thomas 
Published: March 2023

AbstractPresent-day publications on human genes primarily feature genes that already appeared in many publications prior to completion of the Human Genome Project in 2003. These patterns persist despite the subsequent adoption of high-throughput technologies, which routinely identify novel genes associated with biological processes and disease. Although several hypotheses for bias in the selection of genes as research targets have been proposed, their explanatory powers have not yet been compared. Our analysis suggests that understudied genes are systematically abandoned in favor of better-studied genes between the completion of -omics experiments and the reporting of results. Understudied genes remain abandoned by studies that cite these -omics experiments. Conversely, we find that publications on understudied genes may even accrue a greater number of citations. Among 45 biological and experimental factors previously proposed to affect which genes are being studied, we find that 33 are significantly associated with the choice of hit genes presented in titles and abstracts of - omics studies. To promote the investigation of understudied genes we condense our insights into a tool,find my understudied genes(FMUG), that allows scientists to engage with potential bias during the selection of hits. We demonstrate the utility of FMUG through the identification of genes that remain understudied in vertebrate aging. FMUG is developed in Flutter and is available for download at fmug.amaral.northwestern.edu as a MacOS/Windows app.
Genome instability footprint under rapamycin and hydroxyurea treatments
Authors: Li Jing , Stenberg Simon , Yue Jia-Xing , Mikhalev Ekaterina , Thompson Dawn , Warringer Jonas , Liti Gianni 
Published: March 2023

SummaryThe mutational processes dictating the accumulation of mutations in genomes are shaped by genetic background, environment and their interactions. Accurate quantification of mutation rates and spectra under drugs has important implications in disease treatment. Here, we used whole-genome sequencing and time-resolved growth phenotyping of yeast mutation accumulation lines to give a detailed view of the mutagenic effects of rapamycin and hydroxyurea on the genome and cell growth. Mutation rates depended on the genetic backgrounds, but were only marginally affected by rapamycin. As a remarkable exception, rapamycin treatment was associated with frequent chromosome XII amplifications, which compensated for rapamycin induced rDNA repeat contraction on this chromosome and served to maintain rDNA content homeostasis and fitness. In hydroxyurea, a wide range of mutation rates were elevated regardless of the genetic backgrounds, with a particularly high occurrence of aneuploidy that associated with dramatic fitness loss. Hydroxyurea also induced a high T-to-G transversion rate that reversed the common G/C-to-A/T bias in yeast and gave rise to a broad range of structural variants, including mtDNA deletions. The hydroxyurea mutation footprint was consistent with the activation of error-prone DNA polymerase activities and non-homologues end joining repair pathways. Taken together, our study provides an in-depth view of mutation rates and signatures in rapamycin and hydroxyurea and their impact on cell fitness, which brings insights for assessing their chronic effects on genome integrity.