bluuebunny/crossref_metadata_2025_split huggingface dataset:
SCLERAL THICKNESS IN AUTOSOMAL DOMINANT BEST VITELLIFORM MACULAR DYSTROPHY
Authors: Ngo Wei Kiong , Fisher Yale L. , Silverman Ronald H. , Tsang Stephen H. , Spaide Richard F. 
Published: April 2023

Purpose:
The purpose of this study was to investigate the posterior and equatorial scleral thicknesses in patients with autosomal dominant Best disease, a condition that has chronic subretinal fluid.

Methods:
This was a retrospective study involving patients with Best disease and age-matched controls. Participants were evaluated with contact B-scan ultrasonography and enhanced depth imaging optical coherence tomography to evaluate scleral thickness in the posterior pole and equator. Univariate analysis and generalized estimating equations were used.

Results:
Of nine patients with genetically proven Best disease and 23 age-matched controls, there was no significant difference in the age or the gender proportion between groups. Subfoveal choroidal thickness and axial length were not significantly different between groups. Both posterior scleral (right eye; 1.38 mm vs. 0.89 mm, P < 0.001, and left eye; 1.39 mm vs. 0.83 mm, P < 0.001) and equatorial scleral (right eye; 0.61 mm vs. 0.42 mm, P = 0.003, and left eye; 0.55 mm vs. 0.41 mm, P = 0.017) thicknesses were much greater in cases as compared with controls. Multivariate analysis showed male sex and having Best disease were each significant predictor of posterior scleral thickness, and Best disease was the sole significant predictor for equatorial scleral thickness.

Conclusion:
BEST1 gene may have a developmental role leading to having a thicker sclera, influencing disease manifestation, and contributing to the accumulation of subretinal fluid in Best disease.
Epidemiology, Associated Factors, and Outcomes of Intensive Care Unit–Acquired Infections Caused by Multidrug-Resistant Organism in Critically Ill Patients
Authors: Sáez de la Fuente Ignacio , Sáez de la Fuente Javier , Chacón Alves Silvia , Molina Collado Zaira , Lesmes González de Aledo Amanda , Martín Badía Isaías , González Fernández María , Temprano Vázquez Susana , Sánchez Izquierdo Riera José Ángel 
Published: May 2023

Abstract

Background
Nosocomial infections are a major health problem in the intensive care unit (ICU). Limited data exist on the epidemiology of ICU-acquired multidrug-resistant (MDR) microorganism infection. The study aimed to define the clinical characteristics, risk factors, and outcomes associated with the occurrence of an ICU-acquired MDR infection.

Methods
This is a retrospective, observational, single-center, case-control study, including all patients admitted to the unit between January 2015 and December 2019.

Results
During the study period, 3507 patients were admitted in the ICU. The overall incidence of ICU nosocomial infection was 9.6%, whereas the incidence of MDR infection was 0.9%, remaining stable throughout the study period. Based on multivariate analysis, only the presence of neutropenia on admission, days of mechanical ventilation, days with a urinary catheter, and ICU length of stay were identified as clinical factors independently associated with MDR infections. The occurrence of these infections was associated with increased length of stay and need for invasive devices, although there were no differences in associated mortality between groups. There was a 46% rate of pathogen-directed antibiotic treatment in cases of MDR infection, although when empirical treatment is used, MDR patients were less likely to receive initial appropriate antimicrobial therapy (25% vs 7%; P < 0.001).

Conclusions
Multidrug-resistant infections presented a nonnegligible incidence and are associated with the existence of immunosuppression before admission, as well as the need for mechanical ventilation, urinary catheter, and prolonged ICU stay. They represent an increase in patient morbidity, although they are not related to an increase in mortality.
Youth Sport Specialization and Risk of Injury: A General Review
Authors: Strosser Stephen 
Published: April 2023

Objective:
The purpose of this literature review was to analyze, understand, and disclose prior empirical findings about the injury risks associated with youth sport specialization.

Data Sources:
Articles were included in this review if they examined the association between youth sport specialization status and injury. Nine articles from 5 journals met these criteria. All articles summarized the findings of cross-sectional (N = 5) or cohort studies (N = 4).

Main Results:
Each article included in this review indicated that specialized youth athletes are more susceptible to injury. Only 5 studies assessed the injury risks linked to specialization independent of sport training volume. These studies produced contradictory results.

Conclusions:
Although specialized youth athletes are more prone to injury, future research is needed to determine the independent and inherent injury risk associated with specialization. Nevertheless, youth athletes should refrain from specialization until at least adolescence.
Bringing Gender-Affirming Care to Primary Care
Authors: Mueller Rebecca C. , DeSimone M. Elayne 
Published: April 2023

Background:
An increasing number of individuals who identify as transgender and gender diverse require informed and compassionate health care, yet there is a dearth of research about which educational strategies are best used to provide nurses and nurse practitioners the foundation upon which to provide appropriate health care.

Purpose:
This study evaluated a multimodal approach that included guided readings, a transgender patient panel, standardized patient simulation, and group discussion.

Methods:
The Sexual Orientation Counselor Competency Scale was administered pre- and postintervention.

Results:
Results demonstrated increases in knowledge, skills, and attitudes among the 16 participants. A high level of satisfaction was expressed for the overall program, but especially for the patient panel and standardized patient encounter.

Conclusions:
Nurse educators are encouraged to include information about health care of the transgender patient into curricula.
Adverse Patient Safety Events During the COVID-19 Epidemic
Authors: Yackel Edward E. , Knowles Regina , Jones Carol M. , Turner James , Pendley Louis Robin , Mazzia Lisa M. , Mills Peter D. 
Published: May 2023

The coronavirus disease 2019 (COVID-19) epidemic has exposed vulnerabilities within the U.S. healthcare system and globally. This study reviewed COVID-related high-harm patient safety events in the Veterans Health Administration to further our knowledge of the effects of the COVID-19 pandemic on patient safety.

Methods
A retrospective descriptive analysis of patient safety events related to COVID-19 was performed on data that were submitted in the Joint Patient Safety Event Reporting System and Root Cause Analysis databases to the VHA National Center for Patient Safety from March 2020 to February 2021. Events were coded for type of event, location, and cause of event.

Results
Delays in care and staff/patients exposed to COVID-19 were the most common types of patient safety events, followed by COVID-19–positive patients eloping, laboratory processing errors, and one wrong procedure. The most frequently cited locations where events took place were emergency departments, medical units, community living centers, and intensive care units. Confusion over procedures, care not provided because of COVID-19, and failure to identify COVID-positive patient before they exposed others to COVID were the most common causes for patient safety events.

Discussion
Our results are similar to other studies of patient safety during the first year of the COVID-19 pandemic. Based on these results, we recommend the following: (1) focus on patient safety culture, leadership, and governance; (2) proactively develop competency checklists, cognitive aids, and other tools for healthcare staff who are working in new or unfamiliar clinical settings; (3) augment or enhance communication efforts with patient safety huddles or briefings at all levels within a healthcare organization to proactively uncover risk and mitigate fear by explaining changes in policies and procedures; and (4) maximize the use of quality and patient safety experts who are knowledgeable in system and human factor theories as well as change management to assist in redesigning clinical workflows and processes.
Serum Angiotensin-Converting Enzyme Methylation Level and Its Significance in Patients With Comorbid Major Depressive Disorder and Hypertension
Authors: Abula Gulibakeranmu , Li Jinxian , Ma Rui , Zhang Tin , Aji Adila , Zhang Yi 
Published: April 2023

Objective
Major depressive disorder (MDD) often coexists with hypertension (HYT). DNA methylation has elicited vital functionality in their development. Angiotensin-converting enzyme (ACE) is a vital enzyme in blood pressure. This study investigated the effect of ACE methylation on depression and HYT severity in patients with comorbid MDD and HYT (MDD + HYT).

Methods
A total of 119 patients (41 men, 78 women, average age: 56.8 ± 9.1 years) with MDD + HYT were enrolled, with 89 healthy subjects (29 men, 60 women, average age: 57.4 ± 9.7 years) were enrolled. The Hamilton Depression Rating Scale-17 and self-rating depression scale scoring scales were used to assess the depression degree of patients, serum ACE methylation level in MDD + HYT patients was measured by means of bisulfite sequencing polymerase chain reaction, with subsequent analysis of the diagnostic efficacy of ACE methylation for MDD + HYT. The independent risk factors for sMDD + HYT were explored.

Results
Serum ACE methylation levels were significantly increased in MDD + HYT patients. The area under the curve of serum ACE methylation level for accurate diagnosis of MDD + HYT was 0.8471, and the cut-off value was 26.9 (sensitivity 83.19%, specificity 73.03%). ACE methylation was an independent risk factor for sMDD + HYT (P = 0.014; odds ratio, 1.071; 95% confidence interval = 1.014–1.131).

Conclusion
The elevated serum ACE methylation level (P < 0.001) in patients with MDD + HYT elicited definite diagnostic values for MDD + HYT, and ACE methylation level was independently correlated with sMDD + HYT (P < 0.05).
Timing mechanisms to control heart rhythm and initiate arrhythmias: roles for intracellular organelles, signalling pathways and subsarcolemmal Ca2+
Authors: Terrar Derek A. 
Published: May 2023

Rhythms of electrical activity in all regions of the heart can be influenced by a variety of intracellular membrane bound organelles. This is true both for normal pacemaker activity and for abnormal rhythms including those caused by early and delayed afterdepolarizations under pathological conditions. The influence of the sarcoplasmic reticulum (SR) on cardiac electrical activity is widely recognized, but other intracellular organelles including lysosomes and mitochondria also contribute. Intracellular organelles can provide a timing mechanism (such as an SR clock driven by cyclic uptake and release of Ca2+, with an important influence of intraluminal Ca2+), and/or can act as a Ca2+store involved in signalling mechanisms. Ca2+plays many diverse roles including carrying electric current, driving electrogenic sodium–calcium exchange (NCX) particularly when Ca2+is extruded across the surface membrane causing depolarization, and activation of enzymes which target organelles and surface membrane proteins. Heart function is also influenced by Ca2+mobilizing agents (cADP-ribose, nicotinic acid adenine dinucleotide phosphate and inositol trisphosphate) acting on intracellular organelles. Lysosomal Ca2+release exerts its effects via calcium/calmodulin-dependent protein kinase II to promote SR Ca2+uptake, and contributes to arrhythmias resulting from excessive beta-adrenoceptor stimulation. A separate arrhythmogenic mechanism involves lysosomes, mitochondria and SR. Interacting intracellular organelles, therefore, have profound effects on heart rhythms and NCX plays a central role.This article is part of the theme issue ‘The heartbeat: its molecular basis and physiological mechanisms’.
Compendium of clinical variant classification for 2,247 uniqueABCA4variants to improve genetic medicine access for Stargardt Disease
Authors: Cornelis Stéphanie S. , Bauwens Miriam , Haer-Wigman Lonneke , De Bruyne Marieke , Pantrangi Madhulatha , De Baere Elfride , Hufnagel Robert B. , Dhaenens Claire-Marie , Cremers Frans P.M. 
Published: April 2023

AbstractBiallelic variants inABCA4cause Stargardt disease (STGD1), the most frequent heritable macular disease. Determination of the pathogenicity of variants inABCA4proves to be difficult due to 1) the high number of benign and pathogenic variants in the gene; 2) the presence of complex alleles; 3) the extensive variable expressivity of this disease and 4) reduced penetrance of hypomorphic variants. Therefore, the classification of many variants inABCA4is currently of uncertain significance. Here we complemented theABCA4Leiden Open Variation Database (LOVD) with data from ∼11,000 probands withABCA4-associated inherited retinal diseases from literature up to the end of 2020. We carefully adapted the ACMG/AMP classifications toABCA4and assigned these classifications to all 2,247 unique variants from theABCA4LOVD to increase the knowledge of pathogenicity. In total, 1,247 variants were categorized with a Likely Pathogenic or Pathogenic classification, whereas 194 variants were categorized with a Likely Benign or Benign classification. This uniform and improved structured reclassification, incorporating the largest dataset ofABCA4-associated retinopathy cases so far, will improve both the diagnosis as well as genetic counselling for individuals withABCA4-associated retinopathy.
Long-read genome assembly of the insect model organismTribolium castaneumreveals spread of satellite DNA in gene-rich regions by recurrent burst events
Authors: Marin Volarić , Evelin Despot-Slade , Damira Veseljak , Brankica Mravinac , Nevenka Meštrović 
Published: April 2023

AbstractEukaryotic genomes are replete with satellite DNAs (satDNAs), large stretches of tandemly repeated sequences which are mostly underrepresented in genome assemblies. Here we combined Nanopore long-read sequencing with a reference-guided assembly approach, to generate an improved, high-quality genome assembly TcasONT of the model beetleTribolium castaneum. Enriched by 45 Mb in the repetitive part, the new assembly comprises almost the entire genome sequence. We used the enhanced assembly to conduct global and in-depth analyses of abundant euchromatic satDNAs, Cast1-Cast9. Contrary to the commonly adopted view, our finding showed the extensive spread of satDNAs in gene-rich regions, including long arrays. The results of the principal component analysis of monomers and sequence similarity relationships between satDNA arrays, revealed an occurrence of recent satDNAs array exchange between different chromosomes. We proposed a scenario of their genome dynamics characterized by repeated bursts of satDNAs spreading through euchromatin, followed by a process of elongation and homogenization of arrays. We also found that suppressed recombination on the X chromosome has no significant effect on the spread of satDNAs, but rather tolerates the amplification of these satDNAs into longer arrays. Analyses of arrays’ neighboring regions showed a tendency of one Cast satDNA to be associated with transposon-like elements. Using 2D electrophoresis followed by Southern blotting, we proved Cast satDNAs presence in the fraction of extrachromosomal circular DNA (eccDNA). We point to two mechanisms that enable the said satDNA spread to occur: transposition by transposable elements and insertion mediated by eccDNA. The presence of such a large proportion of satDNA in gene-rich regions inevitably gives rise to speculation about their possible influence on gene expression.
Genomewide association study of epiretinal membrane: discovery of significant risk loci in each of three American populations
Authors: Gelernter Joel , Levey Daniel , Galimberti Marco , Harrington Kelly , Zhou Hang , Adhikari Keyrun , Gaziano J. Michael , Eliott Dean , Stein Murray B. 
Published: April 2023

AbstractIMPORTANCEEpiretinal membrane (ERM) is a common retinal condition characterized by the presence of fibrocellular tissue on the retinal surface, often with consequent loss of vision and visual distortion.OBJECTIVEGenomewide association studies (GWAS) can reveal the biology underlying complex genetic traits like ERM; there have been no previous large-scale GWAS of this trait.DESIGNWe used electronic health record diagnosis to identify Million Veteran Program (MVP) participants with ERM in three populations for genomewide association analysis and further statistical investigation of the results.SETTINGVeterans who volunteered for the nationwide Department of Veterans Affairs MVP study, eligible because they have used Veterans Health Administration facilitiesPARTICIPANTS31,374 European-American (EUR) cases and 414,052 EUR controls, 4,739 African-American (AFR) cases and 107,773 AFR controls, and 2,119 Latino (Admixed American, AMR) cases and 36,163 AMR controls – a total of 38,232 cases and 557,988 controls.METHODSWe completed GWAS in each population separately, then results were meta-analyzed. We also evaluated genetic correlation with other traits in external samples, and completed pathway enrichment analyses.MAIN OUTCOME MEASURESGenomewide-significant association with ERM.RESULTSGenomewide significant associations were observed in all three populations studied: 31 risk loci in EUR subjects, 3 in AFR, and 2 in AMR, with 48 identified in trans-ancestry meta-analysis. The most strongly associated locus in both EUR (rs9823832, p=9.06×10−37) and the meta-analysis (rs28630834, p=2.90×10−37) wasDHX36(DEAH-Box Helicase 36). We investigated expression quantitative trait locus associations for eye related function and found several GWS variants associate to alterations in gene expression in the macula, includingDHX36*rs9438. ERM showed significant genetic correlation to depression and to disorders of the vitreous. Pathway enrichment analyses implicated collagen and collagen-adjacent mechanisms, among others.CONCLUSIONS AND RELEVANCEThis well-powered ERM GWAS has identified novel genetic associations, some very strong, that point to biological mechanisms for ERM and merit further investigation.
A Linear Mixed Model with Measurement Error Correction (LMM-MEC): A Method for Summary-data-based Multivariable Mendelian Randomization
Authors: Ding Ming , Zou Fei 
Published: April 2023

ABSTRACTSummary-data-based multivariable Mendelian randomization (MVMR) methods, such as MVMR-Egger, MVMR-IVW, MVMR median-based, and MVMR-PRESSO, assess the causal effects of multiple risk factors on disease. However, accounting for variances in summary statistics related to risk factors remains a challenge. We propose a linear mixed model with measurement error correction (LMM-MEC) that accounts for the variance of summary statistics for both disease outcomes and risk factors. In step I, a linear mixed model is applied to account for the variance in disease summary statistics. Specifically, if heterogeneity is present in disease summary statistics, we treat it as a random effect and adopt an iteratively re-weighted least squares algorithm to estimate causal effects. In step II, we treat the variance in the summary statistics of risk factors as multiple measurement errors and apply a regression calibration method for simultaneous multiple measurement error correction. In a simulation study, when using independent genetic variants as instrumental variables (IV), our method showed comparable performance to existing MVMR methods under conditions of no pleiotropy or balanced pleiotropy with the outcome, and it exhibited higher coverage rates and power under directional pleiotropy. Similar findings were observed when using genetic variants with low to moderate linkage disequilibrium (LD) (0 <ρ2≤ 0.3) as IVs, although coverage rates reduced for all methods compared to using independent genetic variants as IVs. In the application study, we examined causal associations between correlated cholesterol biomarkers and longevity. By including 739 genetic variants selected based on P values <5×10-5from GWAS and allowing for low LD (ρ2≤ 0.1), our method identified that large LDL-c were causally associated with lower likelihood of achieving longevity.
Clinical value of cortical bursting in preterm infants with intraventricular haemorrhage
Authors: Koskela Tuomas , Meek Judith , Huertas-Ceballos Angela , Kendall Giles S , Whitehead Kimberley 
Published: April 2023

AbstractObjectiveIn healthy preterm infants, cortical burst rate and temporal dynamics predict important measures such as brain growth. We hypothesised that in preterm infants with germinal matrix-intraventricular haemorrhage (GM-IVH), cortical bursting could provide prognostic information. We determined how cortical bursting was influenced by the injury, and whether this was related to developmental outcome.MethodsWe identified 47 EEGs from 33 infants with GM-IVH ≥grade II (median gestational age: 25 weeks), acquired between 24-40 weeks corrected gestational age as part of routine clinical care. In a subset of 33 EEGs from 25 infants with asymmetric injury, we used the least-affected hemisphere as an internal control. We tested whether cortical burst rate predicted death or severe motor impairment (median 2 years follow-up; range 1-2 years corrected).ResultsGM-IVH depressed central cortical burst rate. Bursts over the worst-affected hemisphere were less likely to immediately follow (within 1 second) bursts over the least-affected hemisphere than vice versa. Lower burst rate was modestly associated with death or severe motor impairment (specificity 93%, sensitivity 37%).ConclusionsEEG can quantitatively index the functional injury after GM-IVH.SignificanceHigher cortical burst rate is reassuring for a positive motor outcome over the first 2 years.HighlightsGM-IVH depresses cortical burst rateGM-IVH unbalances inter-hemispheric burst dynamicsHigher burst rate following GM-IVH is associated with positive motor outcome at median 2 years