bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved base editing and functional screening inLeishmaniavia co-expression of the AsCas12a ultra variant, a T7 RNA Polymerase, and a cytosine base editor
Authors: May Nicole Herrmann , Cao Ngoc Anh , Schmid Annika , Link Fabian , Arias-del-Angel Jorge , Meiser Elisabeth , Beneke Tom 
Published: February 2024

ABSTRACTThe ability to analyse the function of all genes in a genome is highly desirable, yet challenging inLeishmaniadue to a repetitive genome, limited DNA repair mechanisms and lack of RNA interference in most species. While our introduction of a cytosine base editor (CBE) demonstrated potential to overcome these limitations (Engstler and Beneke (2023)), challenges remained, including low transfection efficiency, variable editing rates across species, parasite growth effects, and competition between deleterious and non-deleterious mutations. Here, we present an optimized approach addressing these issues.We identified a T7 RNAP promoter variant ensuring high editing rates acrossLeishmaniaspecies without compromising growth. A revised CBE single-guide RNAs (sgRNAs) scoring system was developed to prioritize STOP codon generation. Additionally, a triple-expression construct was created for stable integration of CBE sgRNA expression cassettes into aLeishmaniasafe harbor locus using AsCas12a ultra-mediated DNA double-strand breaks, increasing transfection efficiency by ∼400-fold to one transfectant per 70 transfected cells. Using this improved system for a small-scale proof-of-principle pooled screen, we successfully confirmed the essential and fitness-associated functions of CK1.2, CRK2, CRK3, AUK1/AIRK, TOR1, IFT88, IFT139, IFT140 and RAB5A inL. mexicana, demonstrating a significant improvement over our previous method. Lastly, we show the utility of co-expressing AsCas12a ultra, T7 RNAP and CBE for hybrid CRISPR gene replacement and base editing within the same cell line.Overall, these improvements will broaden the range of possible gene editing applications inLeishmaniaspecies and will enable a variety of loss-of-function screens in the near future.
Cannabis Use and Cannabis Use Disorder among U.S. Adults with Psychiatric Disorders: 2001-2002 and 2012-2013
Authors: Hasin Deborah S. , Mannes Zachary L. , Livne Ofir , Fink David S. , Martins Silvia S. , Stohl Malki , Olfson Mark , Cerdá Magdalena , Keyes Katherine M. , Keyhani Salomeh , Wisell Caroline G. , Bujno Julia M. , Saxon Andrew 
Published: February 2024

AbstractObjectiveRates of cannabis use disorder (CUD) have increased disproportionately among Veterans Health Administration (VHA) patients with psychiatric disorders, but determining whether such an increase occurred more generally among U.S. adults requires nationally representative data.MethodsData came from 2001-2002 (n=43,093) and 2012-2013 (n=36,309) national surveys. Outcomes were any past-year non-medical cannabis use, frequent non-medical use (≥3 times weekly), and DSM-IV CUD. Psychiatric disorders included mood, anxiety disorders, antisocial personality disorder, and bipolar I. Logistic regressions were used to generate predicted marginal prevalences of the outcomes for each survey, risk differences calculated, and additive interaction tests determined whether between-survey differences in risk of cannabis outcomes differed between those with and without psychiatric conditions.ResultsCannabis outcome prevalences increased more among those with than without any psychiatric disorder. The difference in prevalence differences included any past-year non-medical cannabis use, 2.45% (95%CI=1.29, 3.62); frequent non-medical cannabis use, 1.58% (95%CI=0.83, 2.33); CUD, 1.40% (95%CI=0.58, 2.21). For each specific disorder, prevalences increased more among those with the disorder, except CUD among those with antisocial personality disorder.ConclusionsIn the U.S. general population, rates of cannabis use and CUD increased at a greater rate among adults with psychiatric disorders, similar to findings from VHA patients. These results suggest that although VHA patients are not representative of all U.S. adults, findings from this important patient group can be informative. As U.S. cannabis use continues to expand, greater clinical and policy attention to CUD is needed for adults with psychiatric disorders.
Epigenetic timing effects on child developmental outcomes: A longitudinal meta-regression of findings from the Pregnancy And Childhood Epigenetics Consortium
Authors: Neumann Alexander , Sammallahti Sara , Cosin-Tomas Marta , Reese Sarah E , Suderman Matthew , Alemany Silvia , Almqvist Catarina , Andrusaityte Sandra , Arshad Syed H , Bakermans-Kranenburg Marian J , Beilin Lawrence , Breton Carrie , Bustamante Mariona , Czamara Darina , Dabelea Dana , Eng Celeste , Eskenazi Brenda , Fuemmeler Bernard F , Gilliland Frank D , Grazuleviciene Regina , Håberg Siri E , Herberth Gunda , Holland Nina , Hough Amy , Hu Donglei , Huen Karen , Hüls Anke , Jin Jianping , Julvez Jordi , Koletzko Berthold V , Koppelman Gerard H , Kull Inger , Lu Xueling , Maitre Léa , Mason Dan , Melén Erik , Merid Simon K , Molloy Peter L , Mori Trevor A , Mulder Rosa H , Page Christian M , Richmond Rebecca C , Röder Stefan , Ross Jason P , Schellhas Laura , Sebert Sylvain , Sheppard Dean , Snieder Harold , Starling Anne P , Stein Dan J , Tindula Gwen , van IJzendoorn Marinus H , Vonk Judith , Walton Esther , Witonsky Jonathan , Xu Cheng-Jian , Yang Ivana V , Yousefi Paul D , Zar Heather J , Zenclussen Ana C , Zhang Hongmei , Tiemeier Henning , London Stephanie J , Felix Janine F , Cecil Charlotte 
Published: February 2024

AbstractDNA methylation (DNAm) is a developmentally dynamic epigenetic process, yet we still know little about how epigenetic effects on health outcomes vary over time; whether DNAm alterations during certain periods of development are more informative than others; and whether epigenetic timing effects differ by outcome. To address these questions, we applied longitudinal meta-regression to published meta-analyses from the PACE consortium that examine DNAm at multiple time points (prospectively at birth and cross-sectionally in childhood) in relation to the same child outcome (ADHD, general psychopathology, sleep, BMI, asthma). Our findings reveal three new insights: (i) across outcomes, effects sizes are larger when DNAm is measured in childhood compared to at birth; (ii) higher effect sizes do not necessarily translate into more significant findings, as associations also become noisier in childhood for most outcomes (i.e. showing larger standard errors); and (iii) DNAm signals are highly time-specific while showing pleiotropy across health outcomes.
Prediction of
Pcc
states in a quark model
Authors: Yan Ye , Huang Hongxia , Zhu Xinmei , Ping Jialun 
Published: February 2024

Inspired by the observation of hidden-charm pentaquark Pc and Pcs states by the LHCb Collaboration, we explore the qqcc¯c (q=u or d) pentaquark systems in the quark delocalization color screening model. The interaction between baryons and mesons and the influence of channel coupling are studied in this work. Three compact qqcc¯c pentaquark states are obtained, whose masses are 5259 MeV with I(JP)=0(1/2−), 5396 MeV with I(JP)=1(1/2−), and 5465 MeV with I(JP)=1(3/2−). Two molecular states are obtained, which are I(JP)=0(1/2−)ΛcJ/ψ with 5367 MeV and I(JP)=0(5/2−)  Ξcc*D¯* with 5690 MeV. These predicted states may provide important information for future experimental search.

Published by the American Physical Society
2024
Toward teacher residency program implementation: navigating the complexities
Authors: Mazzye Doreen L. , Gujarati Joan 
Published: February 2024

PurposeResearch in this field is becoming increasingly clear that a teacher residency program (TRP) has a strong potential for developing effective teachers in a teacher preparation context. There are specific features of a TRP that yield results in the development of teachers. However, there are often barriers to full implementation of a TRP that schools and university partnerships must consider and resolve. The purpose of this article is to disseminate the lessons we have learned and processes we have developed in navigating the barriers and complexities of shifting toward a TRP.Design/methodology/approachThe university faculty members with a dual role as Professional Development School (PDS) liaisons examine, reflect on, and present their multiyear process of moving from an undergraduate traditional teacher preparation model to a teacher residency model.FindingsIn response to the barriers of funding, defining roles and responsibilities, and changes in leadership, we developed an undergraduate residency blueprint to navigate these challenges productively. One of the goals of this document is to provide clarity for all stakeholders as well as be a transparent solution for leadership transitions. The blueprint serves as a guide for the details of residency program design.Originality/valueIn movement toward a TRP, there are often barriers to full implementation that schools and university partnerships must consider and resolve. This article provides a model for partnerships seeking to navigate teacher residency work.
dentist: Quantifying uncertainty by sampling points around maximum likelihood estimates
Authors: Boyko James D. , O'Meara Brian C. 
Published: February 2024

AbstractIt is standard statistical practice to provide measures of uncertainty around parameter estimates. Unfortunately, this very basic and necessary enterprise is often absent in macroevolutionary studies using maximum likelihood estimates (MLEs).dentist is an R package that allows an approximation of confidence intervals (CI) around parameter estimates without an analytic solution to likelihood equations. This package works by ‘denting’ the likelihood surface by sampling points a specified distance around the MLE following what is essentially a Metropolis‐Hastings walk.We describe the importance of estimating uncertainty around parameter estimates, as well as demonstrate the ability of dentist to accurately approximate CI.We introduce several plotting tools to visualize the results of a dentist analysis. dentist is freely available fromhttps://github.com/bomeara/dentist, written in the R language, and can be used for any given likelihood function.
Adult genital psoriasis: An updated review for clinicians
Authors: Wu Michelle , Fischer Gayle 
Published: February 2024

AbstractGenital psoriasis is a chronic inflammatory skin condition that has been reported in up to 63% of patients with psoriasis on other parts of their skin. It has a profound impact on quality of life and sexual function which is often overlooked by current severity scores. Despite its prevalence and disease burden, genital psoriasis remains largely under‐reported and under‐treated. Historically, this was due to the impracticality and limited efficacy data of standard psoriasis treatments when applied to genital skin. However, there have been recent advancements with several new agents currently being developed and evaluated for genital psoriasis. This clinical review aims to provide an overview of the current evidence regarding the clinical features of genital psoriasis, available management options and tools for assessing patients' quality of life. Key takeaways from this review emphasise the recognition of genital psoriasis as a chronic and debilitating condition, unique in its impact on patients' quality of life, necessitating sensitive and attentive approaches to address their needs.
Alterations in gut microbiome associated with severity of atopic dermatitis in infants
Authors: Liu Xiaoyi , Cai Meiqin , Chen Meiru , Chen Ji , Zhu Tingyu , Wu Shiyin , Jia Jie 
Published: February 2024

AbstractBackgroundAtopic dermatitis (AD) often arises in infancy, and gut microbial dysbiosis is associated with the development of AD. However, less is known about specific changes in early‐life gut microbiome associated with AD and AD severity. This study aims to reveal the gut microbial composition and function profiles associated with the severity of AD in infants.MethodsSixty‐two infants (mean [SD] age, 4.7[1.9] months) with different severities of AD were enrolled and divided into three groups (mild, moderate and severe) according to the Scoring Atopic Dermatitis (SCORAD) index. The profiles of gut microbial composition and function were analysed by sequencing 16S ribosomal RNA amplicons. Quality of life on children and the family was evaluated using published questionnaires.ResultsDecreased levels of Clostridium sensu stricto, Collinsella and increased level of Parabacteroides presented in the severe AD group compared with the mild AD group after adjusting potential confounders (p < 0.05). There were strong positive correlations between the Scoring Atopic Dermatitis (SCORAD) index and the relative abundance (RA) of Bacteroides and functional pathways for metabolism of sphingolipids and glycosphingolipids (p < 0.05). The SCORAD index was negatively correlated with the RA of Clostridium sensu stricto (p < 0.05), and was also positively correlated with the index of quality of life on children and the family (p < 0.05).ConclusionDiscrepancies in gut microbial composition and functional pathways were observed in infants with mild‐to‐severe AD. Alterations in butyrate‐producing bacteria (Clostridium sensu stricto), sphingolipid‐producing bacteria (Parabacteroides, Bacteroides), and related functional pathways were associated with the severity of AD infants.
El disco es cultura: Sonic artifacts and Latinx Chicago
Authors: Chávez Alex E. 
Published: February 2024

AbstractIn music production, a sonic artifact refers to sonic material that is accidental or unwanted, typically the result of the manipulation of sound. This understanding connotes both physical and figurative meanings: artifact as material alteration and as subjectively defined auditory disturbance. Both meanings attune the act of listening to noise—the perception of which relies on normative conceptions of rationality. This article takes up the sonic artifact as an aesthetic figure to listen to Latinx Chicago with attention to vinyl records (or discos) as literal material artifacts and asks: how do discos broadcast—in embodied and symbolic ways—the racialized politics of urban territory, and in turn amplify forms of spatial entitlement? Chicago's racial geography relies on the social reproduction of valuable forms of inequality that render Latinx communities displaceable, or unheard. What place‐making strategies emerge given such profound and intersecting dispossessions, and how are they amplified within the aural public sphere? El disco es cultura provides one answer. As curatorial practice, it embodies a phonoaesthetic assemblage of transcultural and transhemispheric sounds and connections that avails sonic artifacts as layered auditory experiences forged within the politics of displacement, pointing us toward the materiality of Latinx place‐making aesthetics and auditory fields of social recognition.
Staffs' experiences and strategies to maintain care for individuals with intellectual disabilities living in supported living facilities during the Covid‐19 pandemic
Authors: Ersfjord Ellen M. I. , Plasil Tanja , Johnsen Hege M. 
Published: February 2024

AbstractBackgroundWe explored the experiences of staff working in Norwegian community‐based living facilities, caring for people with intellectual disabilities during the Covid‐19 pandemic, and what self‐regulatory strategies staff used to maintain health and care service delivery and contribute to organisational resilience.MethodsA qualitative design was utilized. Data were collected from September 2021 to April 2022 with individual and focus group interviews. In this study, 25 staff members participated. Thematic analysis was conducted.FindingsFive main themes were identified regarding the experiences of staff during the pandemic: Lockdown of facilities, social isolation of residents, lack of health follow‐up, high sick leave rates and communication challenges. Only some of the strategies to mitigate pandemic‐related challenges were based on current Norwegian infection control guidelines. Some strategies were successful while others were not and some were negligent and challenged the delivery of health and care services for the residents.ConclusionsOur study shows that people with intellectual disabilities living in the community‐based living facilities were subjected to human rights violations and violations of the Norwegian infection control law. This was caused by a lack of several important organisational qualities in the facilities.
ASXL3‐related disorder: Molecular phenotyping and comprehensive review providing insights into disease mechanism
Authors: Woods Emily , Holmes Nicola , Albaba Shadi , Evans Iwan R. , Balasubramanian Meena 
Published: February 2024

AbstractASXL3‐related disorder, sometimes referred to as Bainbridge‐Ropers syndrome, was first identified as a distinct neurodevelopmental disorder by Bainbridge et al. in 2013. Since then, there have been a number of case series and single case reports published worldwide. A comprehensive review of the literature was carried out. Abstracts were screened, relevant literature was analysed, and descriptions of common phenotypic features were quantified. ASXL3 variants were collated and categorised. Common phenotypic features comprised global developmental delay or intellectual disability (97%), feeding problems (76%), hypotonia (88%) and characteristic facial features (93%). The majority of genetic variants were de novo truncating variants in exon 11 or 12 of the ASXL3 gene. Several gaps in our knowledge of this disorder were identified, namely, underlying pathophysiology and disease mechanism, disease contribution of missense variants, relevance of variant location, prevalence and penetrance data. Clinical information is currently limited by patient numbers and lack of longitudinal data, which this review aims to address.
Management of acute and chronic pelvic sepsis after total mesorectal excision for rectal cancer—a 10‐year experience of a national referral centre
Authors: Sharabiany Sarah , Joosten Johanna J. , Musters Gijsbert D. , Talboom Kevin , Tanis Pieter J. , Bemelman Wilhelmus A. , Hompes Roel 
Published: February 2024

AbstractAimUncontrolled pelvic sepsis following rectal cancer surgery may lead to dramatic consequences with significant impact on patients' quality of life. The aim of this retrospective observational study is to evaluate management of pelvic sepsis after total mesorectal excision for rectal cancer at a national referral centre.MethodReferred patients with acute or chronic pelvic sepsis after sphincter preserving rectal cancer resection, with the year of referral between 2010 and 2014 (A) or between 2015 and 2020 (B), were included. The main outcome was control of pelvic sepsis at the end of follow‐up, with healed anastomosis with restored faecal stream (RFS) as co‐primary outcome.ResultsIn total 136 patients were included: 49 in group A and 87 in group B. After a median follow‐up of 82 months (interquartile range 35–100) in group A and 42 months (interquartile range 22–60) in group B, control of pelvic sepsis was achieved in all patients who received endoscopic vacuum assisted surgical closure (7/7 and 2/2), in 91% (19/21) and 89% (31/35) of patients who received redo anastomosis (P = 1.000) and in 100% (18/18) and 95% (41/43) of patients who received intersphincteric resection (P = 1.000), respectively. Restorative procedures resulted in a healed anastomosis with RFS in 61% (17/28) of patients in group A and 68% (25/37) of patients in group B (P = 0.567).ConclusionHigh rates of success can be achieved with surgical salvage of pelvic sepsis in a dedicated tertiary referral centre, without significant differences over time. In well selected and motivated patients a healed anastomosis with RFS can be achieved in the majority.
Changing Trees, Enduring Forests: Institutional Bricolage, Gradual Change and Community Forestry among Yucatec Mayans in Mexico
Authors: Mendoza Fuente Noé Manuel , Marin Andrei 
Published: February 2024

ABSTRACTThis article seeks to understand why community forestry enterprises in the Mayan rainforest of Mexico are losing ground, while middlemen and manufacturers are regaining control over forestry resources. It focuses on the case of the Ejido San Felipe Oriente where an NGO codesigned a commercialization platform with the objective of bringing together local cooperatives to negotiate in the market from a position of strength. The project was hampered by an internal rupture in the ejido; in investigating this rupture, the authors use the concept of institutional bricolage to understand local power struggles, and the theory of gradual change to search for historical causal mechanisms. They find that the proximate causes of the rupture were family rivalries, suspicions of embezzlement, unfair exclusions, and the disruption of customary practices regarding the distribution of monetary benefits. However, historical continuities lay beneath the power struggle: ejidos in the Yucatan Peninsula have used their function as intermediaries to subordinate local interests rather than promote endogenous development. The authors advocate for an institutional design process that takes account of the unconscious and taken‐for‐granted meanings that influence institutional adaptation; they encourage development practitioners promoting community forestry enterprises in the Mayan rainforest of Mexico to address historical continuities in local institutions as a focal target of development interventions.
The number of nephroprotection targets attained is associated with cardiorenal outcomes and mortality in patients with diabetic kidney disease. The CKD‐REIN cohort study
Authors: Bonnet Fabrice , Balkau Beverley , Lambert Oriane , Diawara Yakhara , Combe Christian , Frimat Luc , Laville Maurice , Liabeuf Sophie , Massy Ziad A. , Metzger Marie , Stengel Bénédicte , Alencar de Pinho Natalia , Fouque Denis 
Published: February 2024

AbstractAimThe risk of cardiorenal events remains high among patients with diabetes and chronic kidney disease (CKD), despite the prescription of recommended treatments. We aimed to determine whether the attainment of a combination of nephroprotection targets at baseline (glycated haemoglobin <7.0%, urinary albumin‐creatinine ratio <300 mg/g, blood pressure <130/80 mmHg, renin‐angiotensin system inhibition) was associated with better cardiorenal outcomes and lower mortality.Materials and MethodsFrom the prospective French CKD‐REIN cohort, we studied 1260 patients with diabetes and CKD stages 3‐4 (estimated glomerular filtration rate: 15‐60 ml/min/1.73 m2); 69% were men, and at inclusion, mean ± SD age: 70 ± 10 years; estimated glomerular filtration rate: 33 ± 11 ml/min/1.73 m2. The median follow‐up was 4.9 years.ResultsIn adjusted Cox regression models, the attainment of two nephroprotection targets was consistently associated with a lower risk of cardiorenal events [hazard ratio 0.70 (95% confidence interval 0.57‐0.85)], incident kidney failure with replacement therapy [0.58 (0.43‐0.77)], four major adverse cardiovascular events (cardiovascular death, myocardial infarction, stroke, hospitalization for heart failure) [0.75 (0.57‐0.99)] and all‐cause mortality [0.59 (0.42‐0.82)] when compared with the attainment of zero or one target. For patients with a urinary albumin‐creatinine ratio ≥300 mg/g, those who attained at least two targets had lower hazard ratios for cardiorenal events [0.61 (0.39‐0.96)], four major adverse cardiovascular events [0.53 (0.28‐0.98)] and all‐cause mortality [0.35 (0.17‐0.70)] compared with those who failed to attain any targets.ConclusionsThese findings suggest that the attainment of a combination of nephroprotection targets is associated with better cardiorenal outcomes and a lower mortality rate in people with diabetic kidney disease.