bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromatin context-dependent effects of epigenetic drugs on CRISPR-Cas9 editing
Authors: Schep Ruben , Trauernicht Max , Vergara Xabier , Friskes Anoek , Morris Ben , Gregoricchio Sebastian , Manzo Stefano G , Zwart Wilbert , Beijersbergen Roderick L , Medema René H , van Steensel Bas 
Published: July 2024

Abstract
The efficiency and outcome of CRISPR/Cas9 editing depends on the chromatin state at the cut site. It has been shown that changing the chromatin state can influence both the efficiency and repair outcome, and epigenetic drugs have been used to improve Cas9 editing. However, because the target proteins of these drugs are not homogeneously distributed across the genome, the efficacy of these drugs may be expected to vary from locus to locus. Here, we systematically analyzed this chromatin context-dependency for 160 epigenetic drugs. We used a human cell line with 19 stably integrated reporters to induce a double-stranded break in different chromatin environments. We then measured Cas9 editing efficiency and repair pathway usage by sequencing the mutational signatures. We identified 58 drugs that modulate Cas9 editing efficiency and/or repair outcome dependent on the local chromatin environment. For example, we find a subset of histone deacetylase inhibitors that improve Cas9 editing efficiency throughout all types of heterochromatin (e.g. PCI-24781), while others were only effective in euchromatin and H3K27me3-marked regions (e.g. apicidin). In summary, this study reveals that most epigenetic drugs alter CRISPR editing in a chromatin-dependent manner, and provides a resource to improve Cas9 editing more selectively at the desired location.
Geochemical Evidence of Water-Fluxed Crustal Melting in the Northern Colombian Andes
Authors: Errázuriz-Henao Carlos , Parolari Mattia , Gómez-Tuena Arturo , Gutiérrez-Aguilar Fabian , García-RodrÍguez Hermes 
Published: July 2024

Abstract
The compositions of crustal magmas are powerful tools for understanding the formation and differentiation of continents. However, the geochemical fingerprints that distinguish the two dominant mechanisms of crustal melting, namely dehydration and water-fluxed melting, are still controversial. To provide new insights into this problem, we discuss the petrogenesis of the Paipa Volcanic Complex (PVC), an isolated Quaternary volcanic field in the Colombian Eastern Cordillera. The PVC is characterized by peraluminous trondhjemite-like rhyolites with exceptionally high Na2O contents (~6 wt %), super-chondritic Nb/Ta (~27), elevated Sr/Y ratios (~120), spoon-shaped REE patterns, and enriched isotopic compositions that overlap with those of the local basement. They also exhibit high pre-eruptive H2O contents (~up to 9.5 wt %) and abundant Paleozoic zircon inheritances. We demonstrate that these characteristics are inconsistent with a process of intra-crustal differentiation from a mafic or intermediate mantle-derived precursor. Instead, we propose that the origin of the PVC is best explained by melting the local (meta)sedimentary basement under H2O-saturated conditions, at middle-crustal pressures (~1.3 GPa) and relatively low temperatures (~690–740°C), following the complete breakdown of plagioclase and biotite, and the formation of reactive peritectic amphibole. This scenario differs from the high-temperature dehydration melting conditions that have been widely proposed for the Andes and globally, which result in the production of water undersaturated magmas in equilibrium with anhydrous lithologies rich in plagioclase and/or garnet. Accordingly, we speculate that an external H2O flux was ultimately sourced from a buoyant, cold, and hydrated mantle wedge that was extensively metasomatized by fluids derived from the Nazca and Caribbean flat-slab fronts. These conditions depressed the asthenospheric mantle potential temperature, likely inhibiting mantle melting. In turn, they facilitated the infiltration and ascent of mantle-derived H2O through pre-existing crustal faults and shear zones. Our results indicate that water-fluxed melting could be a plausible mechanism for generating crustal magmas in orogenic regions where the availability of free H2O has been difficult to confirm.
Meeting expectations? Response of policy innovation labs to sustainable development goals
Authors: Hoss-Golan Esti , Gofen Anat , Wellstead Adam M 
Published: July 2024

Abstract
Introduced by the United Nations, Sustainable Development Goals (SDGs) aim at facilitating inclusive sustainable development. Responsiveness to SDGs is considered a key to addressing pressing development problems. The current literature focuses on the responsiveness of varied public organizations to SDGs, whereas SDGs’ responsiveness of policy innovation labs (PILs) is understudied. Aiming to address both persistent and emerging social and environmental problems, PILs are aligned with SDGs. On the other hand, PILs seek innovative ways to generate policy solutions in collaboration with citizens through experimental methods and thus are more committed to the local public rather than international organizations. This paper investigates to what extent and in what way PILs respond to SDGs during policy formulation processes, both implicitly and explicitly. Data draws on a database the authors developed, identifying 211 European PILs. Thematic coding of PILs’ websites reveals that 62.1% of the PILs implicitly promote at least one SDG. Additionally, sustainable cities and communities (SDG11) and good health and well-being (SDG3) are the two SDGs with the highest implicit-response rates, respectively. We apply grounded theory analysis from semi-structured interviews with senior PIL employees of 31 PILs to gauge their explicit views of SDGs. This inductive approach reveals three dimensions to SDGs: levels of responsiveness, different practices, and considerations that guide PILs on whether to comply with SDGs. A better understanding of PILs’ response to SDGs provides a more nuanced portrayal of PILs as organizations aiming to craft innovative policy solutions that align with international frameworks.
Partisan Poll Watchers and Americans’ Perceptions of Electoral Fairness
Authors: Cohen Mollie J , Sheagley Geoffrey 
Published: July 2024

Abstract
Poll watchers play an increasingly visible role in American elections, yet there is little research into how their presence shapes beliefs about electoral integrity. On the one hand, poll watchers—like other election observers—may lead voters to be more trusting in elections. On the other hand, poll watchers who expressly represent political parties may contribute to polarized views of electoral integrity. We address this gap with two conjoint experiments and one vignette experiment administered on large national samples. The conjoint experiments vary several features of election polling locations, including the presence of poll watchers, voter identification requirements, and other election regulations. We find that regulations around poll watchers shape views of election fairness, but that the nature of this influence depends on the type and partisanship of poll watchers who are present. The vignette experiment shows that perceptions of poll watchers decline when these individuals act in bad faith; effects are especially large for Republican respondents. These findings help identify the potential that poll watchers have to shape Americans’ beliefs about election fairness and integrity.
Missing Financial Data
Authors: Bryzgalova Svetlana , Lerner Sven , Lettau Martin , Pelger Markus 
Published: July 2024

Abstract
We document the widespread nature and structure of missing observations of firm fundamentals and show how to systematically handle them. Missing financial data affects more than 70% of firms that represent about half of the total market cap. Firm fundamentals have complex systematic missing patterns, invalidating traditional approaches to imputation. We propose a novel imputation method to obtain a fully observed panel of firm fundamentals that exploits both time-series and cross-sectional dependency of data to impute missing values and allows for general systematic patterns of missingness. We document important implications for risk premiums estimates, cross-sectional anomalies, and portfolio construction. (JEL C14, C38, C55, G12)
The lifelong orgasm gap: exploring age’s impact on orgasm rates
Authors: Gesselman Amanda N , Bennett-Brown Margaret , Dubé Simon , Kaufman Ellen M , Campbell Jessica T , Garcia Justin R 
Published: July 2024

AbstractBackgroundResearch demonstrates significant gender- and sexual orientation–based differences in orgasm rates from sexual intercourse; however, this “orgasm gap” has not been studied with respect to age.AimThe study sought to examine age-related disparities in orgasm rates from sexual intercourse by gender and sexual orientation.MethodsA survey sample of 24 752 adults from the United States, ranging in age from 18 to 100 years. Data were collected across 8 cross-sectional surveys between 2015 and 2023.OutcomesParticipants reported their average rate of orgasm during sexual intercourse, from 0% to 100%.ResultsOrgasm rate was associated with age but with minimal effect size. In all age groups, men reported higher rates of orgasm than did women. Men’s orgasm rates ranged from 70% to 85%, while women’s ranged from 46% to 58%. Men reported orgasm rates between 22% and 30% higher than women’s rates. Sexual orientation impacted orgasm rates by gender but not uniformly across age groups.Clinical TranslationThe persistence of the orgasm gap across ages necessitates a tailored approach in clinical practice and education, focusing on inclusive sexual health discussions, addressing the unique challenges of sexual minorities and aging, and emphasizing mutual satisfaction to promote sexual well-being for all.Strengths and LimitationsThis study is the first to examine the orgasm gap with respect to age, and does so in a large, diverse sample. Findings are limited by methodology, including single-item assessments of orgasm and a sample of single adults.ConclusionThis study revealed enduring disparities in orgasm rates from sexual intercourse, likely resulting from many factors, including sociocultural norms and inadequate sex education.
Novel biomarkers derived from the Maintenance of Wakefulness Test as predictors of sleepiness and response to treatment
Authors: Tracey Brian , Culp Mark , Fabregas Stephan , Mignot Emmanuel , Buhl Derek L , Volfson Dmitri 
Published: July 2024

Abstract
The Maintenance of Wakefulness Test (MWT) is a widely accepted objective test used to evaluate daytime somnolence and is commonly used in clinical studies evaluating novel therapeutics for excessive daytime sleepiness. In the latter, sleep onset latency (SOL) is typically the sole MWT endpoint. Here, we explored microsleeps, sleep probability measures derived from automated sleep scoring, and quantitative electroencephalography (qEEG) features as additional MWT biomarkers of daytime sleepiness, using data from a phase 1B trial of the selective orexin receptor 2 agonist danavorexton (TAK-925) in people with narcolepsy type 1 (NT1) or type 2 (NT2). Danavorexton treatment reduced the rate and duration of microsleeps during the MWT in NT1 (days 1 and 7; p ≤ .005) and microsleep rate in NT2 (days 1 and 7; p &lt; .0001). The use of an EEG-sleep-staging − derived measure to determine the probability of wakefulness for each minute revealed a novel metric to track changes in daytime sleepiness, which were consistent with the θ/α ratio, a known biomarker of drowsiness. The slopes of line-fits to both the log-transformed sleepiness score or log-transformed θ/α ratio correlated well to (inverse) MWT SOL for NT1 (R = 0.93 and R = 0.83, respectively) and NT2 (R = 0.97 and R = 0.84, respectively), suggesting that individuals with narcolepsy have increased sleepiness immediately after lights-off. These analyses demonstrate that novel EEG-based biomarkers can augment SOL as predictors of sleepiness and its response to treatment and provide a novel framework for the analysis of wake EEG in hypersomnia disorders.
Should I stay for local hormone therapy or should I go for radiofrequency to treat vulvovaginal atrophy? A patient preference trial
Authors: Dell'Utri Chiara MF , Manzoni Elisabetta , Bonfanti Irene , Marrocco Francesca , Barbara Giussy , Pifarotti Paola , Chiaffarino Francesca 
Published: July 2024

Abstract

Objective
To compare patient satisfaction rate in postmenopausal women who chose dynamic quadripolar radiofrequency or topical estrogens as their preferred treatment for genitourinary syndrome of menopause.

Methods
Patients were divided into two groups according to their preference: one was treated with estrogen therapy (ET) and the other with dynamic quadripolar radiofrequency treatment (RF). All patients included fulfilled a series of validated questionnaires, at baseline and at the 6-mo follow-up, in order to evaluate the discomfort degree associated with the presence of vulvovaginal atrophy and the impact of the reported symptoms on QoL and sexuality.

Results
After propensity score matching, the proportion of women considering themselves satisfied with their genital health conditions was extremely small at study entry (5.2% of the RF group and 6.9% of the ET group), while at a 6-mo follow-up, it increased to 46.7% and 46.6%, respectively. No statistically significant between-group differences were found regarding mean numerical rating scale scores for dryness and dyspareunia at follow-up (5.6 ± 2.6 vs 5.3 ± 2.3, P = 0.5; and 2.9 ± 2.5 vs 3.0 ± 2.7, P = 0.46). At 6-mo follow-up, we observed no statistically significant differences between the two groups regarding the other items evaluated. RF treatment was overall well tolerated.

Conclusion
The use of quadripolar radiofrequency devices seems effective, but it is not associated with better clinical outcomes compared with topical hormone treatment, which is a substantially cheaper and more convenient treatment for genitourinary syndrome of menopause. Therefore, we suggest limiting the use of dynamic quadripolar radiofrequency selectively when topical estrogens are not effective, not tolerated, or contraindicated.
Revenue Cycle Management: The Art and the Science
Authors: Chandawarkar Rajiv , Nadkarni Prakash , Barmash Elizabeth , Thomas Stephany , Capek Allison , Casey Kathleen , Carradero Freddy 
Published: July 2024

Summary:
Simply working hard is not enough to maintain a profitable clinical practice. Prompt and complete payment for services is just as critical. Revenue cycle management (RCM) tracks the payment process from patient scheduling through treatment, coding, billing, and reimbursement. Even though reimbursement rates for service codes are preset, and the service is documented, this apparently straightforward process is complicated by insurance payors, negotiated contracts, coding requirements, compliance regulators, and an ever-changing reimbursement environment. Not typically trained in RCM, physicians struggle with its demands of timeliness, accuracy, paperwork, and the constant scrutiny for underpayment or unfulfilled reimbursements. Consequently, they often relent to the pressures and simply accept the decreased reimbursements as “cost of doing business” or else relegate RCM to others on the team. In either case, they leave significant amounts of money on the table. Using published work in health care and other allied sectors, we present a systematic method to understand and improve RCM processes. It also creates a strong partnership between clinicians and their administrative counterparts. Optimizing RCM improves patient experience, reduces the time between submission of claims and payment, eliminates fraud at both the coding and patient levels, and increases cash flow, all of which create a financially stable clinical practice.
A Study on Symptoms of Pelvic Floor Dysfunction in Assigned Female at Birth Patients Diagnosed with Gender Dysphoria Undergoing Vaginectomy
Authors: Kjölhede Anders , Huss Fredrik , Kratz Gunnar 
Published: July 2024

Background:
A person diagnosed with gender dysphoria who was assigned female at birth (AFAB) may request a vaginectomy as part of gender-affirming treatment. The aim of this study was to investigate the impact of vaginectomy on symptoms of pelvic floor dysfunction (PFD).

Methods:
This is a cohort study on patient-reported symptoms of PFD in patients who were AFAB, diagnosed with gender dysphoria, and undergoing vaginectomy in a single surgical center. Patients responded to a questionnaire preoperatively and 1 year postoperatively. The questionnaire consisted of 33 questions, including a modified short-form version of the Pelvic Floor Distress Inventory (PFDI-20).

Results:
Twenty-three consecutive patients were included in the study and 20 patients (87%) completed the 1-year follow-up. The preoperative median PFDI-20 score was 24 (0–114) compared with 32 (0–168) at the 1-year follow-up (P = 0.07). Patients who had previously undergone neophallus construction with a metoidioplasty (n = 15) had no significant change between the preoperative and the 1-year postoperative PFDI-20 score [median 17.5 (0–114) and 27.5 (0–145) (P = 0.65), respectively]; whereas those with a groin flap phalloplasty (n = 5) had a significant increase in reported symptoms [median 37 (10–95) and 124 (45–168), respectively (P = 0.04)].

Conclusions:
Overall, vaginectomy could be performed without any major impact on symptoms of PFD. However, this seemed to be true mainly for patients with previous metoidioplasty, whereas patients with previous groin flap phalloplasty reported worsening of symptoms.
Web Site Accessibility Among Doctor of Physical Therapy Programs in the United States
Authors: Ness Brandon M. , Pathare Neeti , Wilhelm Mark P. , Wonsetler-Jones Elizabeth C. , Parent-Nichols Jennifer 
Published: July 2024

Introduction.
Given the impetus to improve accessibility for diverse learners seeking physical therapist education, it is critical that all entry points to access information have minimal barriers. This study identified Web site accessibility barriers among Doctor of Physical Therapy (DPT) programs in the United States.

Review of Literature.
Web site accessibility has been evaluated among many institutions of higher education, but none focused on DPT education. Individuals with disabilities may be adversely affected by Web site accessibility barriers.

Subjects.
This cross-sectional study included 262 DPT programs in the United States. Doctor of Physical Therapy program characteristics collected were geographic region, institutional control type (public/private), medical school affiliation, accreditation status, total institutional enrollment, and DPT class size.

Methods.
The Web Accessibility Evaluation (WAVE) Tool assessed data related to accessibility barriers among DPT program homepage Uniform Resource Locators. Three primary outcomes from the WAVE Tool included WAVE Total Errors, Error Density, and Total Alerts.

Results.
Web site homepage accessibility barriers varied among programs for WAVE Total Errors (range 0–150), Error Density (range 0–14.6%), and Total Alerts (range 1–331). Median Total Errors were greater among private (9.0) versus public (5.0) institution Web sites (P < .001). Median Total Errors were greater among those institutions not affiliated with a medical school (9.0) compared with those that had an affiliated medical school (7.0) (P = .04). No differences in accessibility barriers were identified according to geographic region or accreditation status (P > .05). Median Total Errors were significantly different between institutional enrollment quartiles (H[3] = 17.9, P < .001), with no differences noted between DPT class size quartiles for any outcome (P > .05). Generally, weak–fair inverse correlations were observed between student enrollment for the institution and Web site accessibility barrier outcomes.

Discussion and Conclusion.
Homepage accessibility barriers varied greatly among DPT programs in the United States. Factors, including being a private institution, no medical school affiliation, and lower institutional enrollment, were related to increased accessibility barriers.
David Henry Cushing. 14 March 1920—14 March 2008
Authors: Shepherd FRS John , Horwood Joe 
Published: July 2024

David Cushing was Britain's foremost twentieth-century marine fisheries ecologist, who did more than anyone else to develop the subject into a distinctive science over a career of more than 50 years. He was born and raised in Northumberland, and took both his first degree and a DPhil at Oxford, separated by war service in the Royal Artillery. He married Diana Antona-Traversi in 1943, and they had one daughter, Camilla. He worked for the whole of his career at the Fisheries Laboratory, Lowestoft, where he started in 1946 as a scientific officer, studying plankton off the northeast coast of England, and eventually becoming deputy director and head of the Fish Population Dynamics Divi­sion until his retirement in 1980. He published around 200 papers and reports, and wrote 11 books on marine ecology and fisheries, with four principal areas of interest: fisheries acoustics; planktonic biological production in the sea; the causes of the collapse of the North Sea herring; and the factors controlling recruitment of young fish, notably the influences of stock size and of climate. He famously proposed the match/mismatch hypothesis to explain how the great variability of fish recruitment arises from minor variations in climate from year to year.
He died on 14 March 2008, on his eighty-eighth birthday.
Activity-dependent lateral inhibition enables the synchronization of olfactory bulb projection neurons
Authors: Dalal Tal , Haddad Rafi 
Published: July 2024

AbstractInformation in the brain is represented by the activity of neuronal ensembles. These ensembles are adaptive and dynamic, formed and truncated based on the animal’s experience. One mechanism by which spatially distributed neurons form an ensemble is by synchronizing their spike times in response to a sensory event. In the olfactory bulb, odor stimulation evokes rhythmic gamma activity in spatially distributed mitral and tufted cells (MTCs). This rhythmic activity is thought to enhance the relay of odor information to the downstream olfactory targets. However, how specifically the odor-activated MTCs are synchronized is unknown. Here, we demonstrate that optogenetic activation of one set of MTCs can gamma-entrain the spiking activity of another set. This lateral synchronization was particularly effective when the recorded MTC fired at the gamma rhythm, facilitating the synchronization of only the substantially active MTCs. Furthermore, we show that lateral synchronization did not depend on the distance between the MTCs and is mediated by granule-cell layer neurons. In contrast, lateral inhibition between MTCs that reduced their firing rates was spatially restricted to adjacent MTCs and was not mediated by granule-cell layer neurons. This dissociation between these two interaction types suggests that they are mediated by different neural circuits. Our findings propose a simple yet robust mechanism by which spatially distributed neurons entrain each other spiking activity to form an ensemble.HighlightsMTC activation entrains the spike timing of other MTCs in an activity-dependent and distance-independent manner.MTC to MTC suppression is activity- and distance-dependentSpatially distributed Granule cell layer neurons control MTC’s spike timing, yet do not substantially affect their odor-evoked firing rate.