bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inefficient Sox9 upregulation and absence of Rspo1 repression lead to sex reversal in the B6.XYTIR mouse gonad
Authors: Cao Jiangqin , El Mansouri Fatima , Reynoso Sofia , Liu Zongping , Zhu Jiaqiao , Taketo Teruko 
Published: February 2024

Abstract
Sry on the Y-chromosome upregulates Sox9, which in turn upregulates a set of genes such as Fgf9 to initiate testicular differentiation in the XY gonad. In the absence of Sry expression, genes such as Rspo1, Foxl2, and Runx1 support ovarian differentiation in the XX gonad. These two pathways antagonize each other to ensure the development of only one gonadal sex in normal development. In the B6.YTIR mouse, carrying the YTIR-chromosome on the B6 genetic background, Sry is expressed in a comparable manner with that in the B6.XY mouse, yet, only ovaries or ovotestes develop. We asked how testicular and ovarian differentiation pathways interact to determine the gonadal sex in the B6.YTIR mouse. Our results showed that (1) transcript levels of Sox9 were much lower than in B6.XY gonads while those of Rspo1 and Runx1 were as high as B6.XX gonads at 11.5 and 12.5 days postcoitum. (2) FOXL2-positive cells appeared in mosaic with SOX9-positive cells at 12.5 days postcoitum. (3) SOX9-positive cells formed testis cords in the central area while those disappeared to leave only FOXL2-positive cells in the poles or the entire area at 13.5 days postcoitum. (4) No difference was found at transcript levels of all genes between the left and right gonads up to 12.5 days postcoitum, although ovotestes developed much more frequently on the left than the right at 13.5 days postcoitum. These results suggest that inefficient Sox9 upregulation and the absence of Rspo1 repression prevent testicular differentiation in the B6.YTIR gonad.
Long-range connections damage in white matter hyperintensities affects information processing speed
Authors: Lu Tong , Wang Zan , Zhu Yixin , Wang Mengxue , Lu Chun-Qiang , Ju Shenghong 
Published: February 2024

Abstract
White matter hyperintensities, one of the major markers of cerebral small vessel disease, disrupt the integrity of neuronal networks and ultimately contribute to cognitive dysfunction. However, a deeper understanding of how white matter hyperintensities related to the connectivity patterns of brain hubs at the neural network level could provide valuable insights into the relationship between white matter hyperintensities and cognitive dysfunction. A total of 36 patients with moderate to severe white matter hyperintensities (Fazekas score ≥ 3) and 34 healthy controls underwent comprehensive neuropsychological assessments and resting-state functional MRI scans. The voxel-based graph-theory approach-functional connectivity strength was employed to systematically investigate the topological organization of the whole-brain networks. The white matter hyperintensities patients performed significantly worse than the healthy controls in episodic memory, executive function and information processing speed. Additionally, we found that white matter hyperintensities selectively affected highly connected hub regions, predominantly involving the medial and lateral prefrontal, precuneus, inferior parietal lobule, insula and thalamus. Intriguingly, this impairment was connectivity distance-dependent, with the most prominent disruptions observed in long-range connections (e.g. 100–150 mm). Finally, these disruptions of hub connectivity (e.g. the long-range functional connectivity strength in the left dorsolateral prefrontal cortex) positively correlated with the cognitive performance in white matter hyperintensities patients. Our findings emphasize that the disrupted hub connectivity patterns in white matter hyperintensities are dependent on connection distance, especially longer-distance connections, which in turn predispose white matter hyperintensities patients to worse cognitive function.
From tugs to treatments: a systematic review on pharmacological interventions for trichotillomania
Authors: Ghani Hira , Podwojniak Alicia , Tan Isabella J , Fliorent Rebecca , Jafferany Mohammad 
Published: February 2024

Abstract

Background
Trichotillomania (TTM) is a psychiatric disorder with dermatological consequences, characterized by recurrent hair pulling. It affects 1–3% of the population, and often coexists with other psychiatric disorders, leading to emotional distress. Effective management of TTM can be challenging because of underdiagnosis, symptom heterogeneity and stigma. Pharmacological interventions, including selective serotonin reuptake inhibitors and N-acetyl cysteine (NAC) are commonly used.

Objectives
To assess the existing literature on pharmacotherapy for TTM and identify potential avenues for future research and treatment advancements.

Methods
A systematic review of the literature was performed using PubMed and Scopus databases within the past 10 years (PROSPERO: CRD42023454009). Included studies assessed pharmacotherapy for TTM and provided insights into current evidence and potential directions for future research and treatment advancements.

Results
In total, 23 articles were identified that met inclusion criteria. The most successful interventions were NAC, aripiprazole and monoamine oxidase inhibitors. NAC was identified as the most impressive adjunctive therapy to selective serotonin reuptake inhibitors and behavioural therapies in treatment through its mechanism of decreased glutamate-induced excitatory neuronal damage, with adjunctive antioxidant properties. Most of the other therapeutics that were identified require further research and controlled trials to validate their findings.

Conclusions
Even if successful therapeutic outcomes are achieved, it is important to consider the patient’s comorbidities and to combine pharmacological interventions with behavioural therapy interventions to comprehensively manage TTM.
Functional parcellation of the neonatal cortical surface
Authors: Myers Michael J , Labonte Alyssa K , Gordon Evan M , Laumann Timothy O , Tu Jiaxin C , Wheelock Muriah D , Nielsen Ashley N , Schwarzlose Rebecca F , Camacho M Catalina , Alexopoulos Dimitrios , Warner Barbara B , Raghuraman Nandini , Luby Joan L , Barch Deanna M , Fair Damien A , Petersen Steven E , Rogers Cynthia E , Smyser Christopher D , Sylvester Chad M 
Published: February 2024

Abstract
The cerebral cortex is organized into distinct but interconnected cortical areas, which can be defined by abrupt differences in patterns of resting state functional connectivity (FC) across the cortical surface. Such parcellations of the cortex have been derived in adults and older infants, but there is no widely used surface parcellation available for the neonatal brain. Here, we first demonstrate that existing parcellations, including surface-based parcels derived from older samples as well as volume-based neonatal parcels, are a poor fit for neonatal surface data. We next derive a set of 283 cortical surface parcels from a sample of n = 261 neonates. These parcels have highly homogenous FC patterns and are validated using three external neonatal datasets. The Infomap algorithm is used to assign functional network identities to each parcel, and derived networks are consistent with prior work in neonates. The proposed parcellation may represent neonatal cortical areas and provides a powerful tool for neonatal neuroimaging studies.
Alterations in magnetic properties of crystals of trinuclear copper complexes: isolated entities versus one-dimensional chains
Authors: Hosoya Yosuke , Yoshikawa Hiroki , Tsukamoto Arata , Sugawa Kosuke , Otsuki Joe 
Published: February 2024

Abstract
We obtained two types of crystals of a complex under different crystallization conditions, each exhibiting distinct molecular arrangements and magnetic interactions: one type consists of isolated complexes, while the other forms one-dimensional chains without extra bridging ligands. This approach provides a new avenue for tuning the magnetic properties of metal-complex-based materials.
Durability of Protection Against COVID-19 Through the Delta Surge for the NVX-CoV2373 Vaccine
Authors: Follmann Dean , Mateja Allyson , Fay Michael P , Magaret Craig A , Huang Yunda , Fong Youyi , Angier Heather , Nason Martha , Gay Cynthia L , Kotloff Karen , Woo Wayne , Cho Iksung , Dunkle Lisa M 
Published: February 2024

Abstract

Background
Protein-based vaccines for coronavirus disease 2019 (COVID-19) provide a traditional vaccine platform with long-lasting protection for non–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogens and may complement messenger RNA vaccines as a booster dose. While NVX-CoV2373 showed substantial early efficacy, the durability of protection has not been delineated.

Methods
The PREVENT-19 vaccine trial used a blinded crossover design; the original placebo arm received NVX-CoV2373 after efficacy was established. Using novel statistical methods that integrate surveillance data of circulating strains with post-crossover cases, we estimated placebo-controlled vaccine efficacy and durability of NVX-CoV2373 against both pre-Delta and Delta strains of SARS-CoV-2.

Results
Vaccine efficacy against pre-Delta strains of COVID-19 was 89% (95% CI, 75–95%) and 87% (72–94%) at 0 and 90 days after 2 doses of NVX-CoV2373, respectively, with no evidence of waning (P = .93). Vaccine efficacy against the Delta strain was 88% (71–95%), 82% (56–92%), and 77% (44–90%) at 40, 120, and 180 days, respectively, with evidence of waning (P &lt; .01). In sensitivity analyses, the estimated Delta vaccine efficacy at 120 days ranged from 66% (15–86%) to 89% (74–95%) per various assumptions of the surveillance data.

Conclusions
NVX-CoV2373 has high initial efficacy against pre-Delta and Delta strains of COVID-19 with little evidence of waning for pre-Delta strains through 90 days and moderate waning against Delta strains over 180 days.
Reduced Vancomycin Susceptibility in Clostridioides difficile Is Associated With Lower Rates of Initial Cure and Sustained Clinical Response
Authors: Eubank Taryn A , Dureja Chetna , Garey Kevin W , Hurdle Julian G , Gonzales-Luna Anne J 
Published: February 2024

Abstract

Background
Epidemiologic studies have shown decreasing vancomycin susceptibility among clinical Clostridioides difficile isolates, but the impact on patient outcomes is unknown. We hypothesized that reduced vancomycin susceptibility would be associated with decreased rates of sustained clinical response (SCR).

Methods
This multicenter cohort study included adults with C. difficile infection (CDI) treated with oral vancomycin between 2016 and 2021. Clostridioides difficile isolates underwent agar dilution vancomycin susceptibility testing, ribotyping, and Sanger sequencing of the vancomycin resistance vanR gene. Reduced susceptibility was defined as vancomycin minimum inhibitory concentration (MIC) &gt;2 μg/mL. The primary outcome was 30-day SCR; secondary outcomes were 14-day initial cure, 30-day recurrence, and 30-day mortality. Exploratory analysis assessed the association between the VanR Thr115Ala polymorphism, susceptibility, and outcomes.

Results
A high proportion (34% [102/300]) of C. difficile isolates exhibited reduced vancomycin susceptibility (range, 0.5–16 μg/mL; MIC50/90 = 2/4 μg/mL). Ribotype 027 accounted for the highest proportion (77.4% [41/53]) of isolates with reduced vancomycin susceptibility. Overall, 83% (249) of patients achieved 30-day SCR. Reduced vancomycin susceptibility was associated with lower rates of 30-day SCR (76% [78/102]) than vancomycin-susceptible strains (86% [171/198]; P = .031). A significantly lower rate of 14-day initial cure was also observed among individuals infected with strains with reduced vancomycin susceptibility (89% vs 96%; P = .04). Reduced susceptibility remained an independent predictor of 30-day SCR in multivariable modeling (odds ratio, 0.52 [95% confidence interval, .28–.97]; P = .04).

Conclusions
Reduced vancomycin susceptibility in C. difficile was associated with decreased odds of 30-day SCR and lower 14-day initial cure rates in the studied patient cohort.
Effect of lipid-lowering therapies on C-reactive protein levels: a comprehensive meta-analysis of randomized controlled trials
Authors: Xie Sining , Galimberti Federica , Olmastroni Elena , Luscher Thomas F , Carugo Stefano , Catapano Alberico L , Casula Manuela ,   META-LIPID Group, Catapano Alberico L , Casula Manuela , Galimberti Federica , Olmastroni Elena , Xie Sining , Wanner Christoph , Yusuf Salim , Maggioni Aldo , Kirby Adrienne , Ogawa Hiroshi , Hoogeveen Ellen K , Seljeflot Ingebjørg , Welty Francine K , Benderly Michal , Manson JoAnn E , Wolski Kathy , Cannon Christopher P , Raal Frederick J , Kallend David , Foody JoAnne , Louie Michael 
Published: February 2024

Abstract
Chronic low-degree inflammation is a hallmark of atherosclerotic cardiovascular (CV) disease. To assess the effect of lipid-lowering therapies on C-reactive protein (CRP), a biomarker of inflammation, we conducted a meta-analysis according to the PRISMA guidelines. Databases were searched from inception to July 2023. Inclusion criteria were: (i) randomized controlled trials (RCTs) in human, Phase II, III, or IV; (ii) English language; (iii) comparing the effect of lipid-lowering drugs vs. placebo; (iv) reporting the effects on CRP levels; (v) with intervention duration of more than 3 weeks; (vi) and sample size (for both intervention and control group) over than 100 subjects. The between-group (treatment-placebo) CRP absolute mean differences and 95% confidence intervals were calculated for each drug class separately. A total of 171 668 subjects from 53 RCTs were included. CRP levels (mg/L) were significantly decreased by statins [−0.65 (−0.87 to −0.43), bempedoic acid; −0.43 (−0.67 to −0.20), ezetimibe; −0.28 (−0.48 to −0.08)], and omega-3 fatty acids [omega3FAs, −0.27 (−0.52 to −0.01)]. CRP was reduced by −0.40 (−1.17 to 0.38) with fibrates, although not statistically significant. A slight increase of CRP concentration was observed for proprotein convertase subtilisin/kexin type 9 inhibitors [0.11 (0.07–0.14)] and cholesteryl-ester transfer protein inhibitors [0.10 (0.00–0.21)], the latter being not statistically significant. Meta-regression analysis did not show a significant correlation between changes in CRP and LDL cholesterol (LDL-C) or triglycerides. Statins, bempedoic acid, ezetimibe, and omega3FAs significantly reduce serum CRP concentration, independently of LDL-C reductions. The impact of this anti-inflammatory effect in terms of CV prevention needs further investigation.
Questionnaire for diagnosis and response to therapy in rumination syndrome
Authors: Pomenti Sydney F , Tsang Amanda J , Khan Abraham R , Katz Philip O , Katzka David A 
Published: February 2024

Summary
Rumination is a behavioral disorder characterized by regurgitation of food without retching. It is diagnosed clinically by the Rome Criteria and treated primarily by diaphragmatic breathing. Despite diagnosis and follow-up being based on symptomatic responses to therapies, there are no published or validated questionnaires. To address this care-gap, a rumination questionnaire was developed and reviewed by two expert esophagologists and five patients diagnosed with rumination. Ultimately, an eight-point questionnaire with scoring ranging from −1 to 10 was finalized. This newly developed questionnaire was implemented on five additional patients diagnosed clinically with rumination syndrome with improvement after interventions noted.
The outcomes of patients with septic shock treated with propafenone compared to amiodarone for supraventricular arrhythmias are related to end-systolic left atrial volume
Authors: Waldauf P , Porizka M , Horejsek J , Otahal M , Svobodova E , Jurisinova I , Maly M , Brozek T , Rulisek J , Trachta P , Tencer T , Krajcova A , Duska F , Balik M 
Published: February 2024

Abstract

Background
A recently published trial has shown no differences in outcomes between patients with new-onset supraventricular arrhythmia (SVA) in septic shock treated with either propafenone or amiodarone. However, these outcome data have not been evaluated in relation to the presence or absence of a dilated left atrium (LA).

Methods
Patients with SVA and a left ventricular ejection fraction ≥35% were randomized to receive intravenous propafenone (70mg bolus followed by 400-840mg/24h) or amiodarone (300mg bolus followed by 600-1800mg/24h). They were divided into groups based on whether their end-systolic left atrial volume (LAVI) was ≥40 ml/m². The subgroup outcomes assessed were survival at ICU discharge, 1-month, 3-months, 6-months, and 12-months.

Results
Propafenone cardioverted earlier (p=0.009) and with fewer recurrences (p=0.001) in the patients without LA enlargement (n=133). Patients with LAVI˂40ml/m2 demonstrated a mortality benefit of propafenone over the follow up of 1-year (Cox regression, HR 0.6 (95% CI 0.4; 0.9), p=0.014). Patients with dilated LA (n=37) achieved rhythm control earlier in amiodarone (p=0.05) with similar rates of recurrences (p=0.5) compared to propafenone. The outcomes for patients with LAVI≥40 ml/m2 were less favourable with propafenone compared to amiodarone at 1-month (HR 3.6 (95% CI 1.03; 12.5), p=0.045) however, it did not reach statistical significance at 1 year (HR 1.9 (95% CI 0.8; 4.4), p=0.138).

Conclusion
Patients with non-dilated LA who achieved rhythm control with propafenone in the setting of septic shock had better short-term and long-term outcomes than those treated with amiodarone, which seemed to be more effective in patients with LAVI≥40 ml/m².

Trial registration
ClinicalTrials.gov Identifier: NCT03029169, registered on 24th of January 2017
Initial experience, safety, and feasibility using remote access or onsite technical support for complex ablation procedures: results of the REMOTE study
Authors: Heeger Christian-H , Vogler Julia , Eitel Charlotte , Feher Marcel , Popescu Sorin Ștefan , Kirstein Bettina , Hatahet Sascha , Subin Benham , Kuck Karl-Heinz , Tilz Roland R 
Published: February 2024

Abstract

Aims
Electroanatomical mapping (EAM) systems are essential for the treatment of cardiac arrhythmias. The EAM system is usually operated by qualified staff or field technical engineers from the control room. Novel remote support technology allows for remote access of EAM via online services. Remote access increases the flexibility of the electrophysiological lab, reduces travel time, and overcomes hospital access limitations especially during the COVID-19 pandemic. Here, we report on the feasibility and safety of EAM remote access for cardiac ablation procedures.

Methods and results
Mapping and ablation were achieved by combining the EnsiteX™ EAM system and the integrated Ensite™ Connect Remote Support software, together with an integrated audiovisual solution system for remote support (Medinbox). Communication between the operator and the remote support was achieved using an incorporated internet-based common communication platform (Zoom™), headphones, and high-resolution cameras. We investigated 50 remote access–assisted consecutive electrophysiological procedures from September 2022 to February 2023 (remote group). The data were compared with matched patients (n = 50) with onsite support from the control room (control group). The median procedure time was 100 min (76, 120; remote) vs. 86 min (60, 110; control), P = 0.090. The procedural success (both groups 100%, P = 0.999) and complication rate (remote: 2%, control: 0%, P = 0.553) were comparable between the groups. Travel burden could be reduced by 11 280 km.

Conclusion
Remote access for EAM was feasible and safe in this single-centre study. Procedural data were comparable to procedures with onsite support. In the future, this new solution might have a great impact on facilitating electrophysiological procedures.
Decoding 2.3 million ECGs: interpretable deep learning for advancing cardiovascular diagnosis and mortality risk stratification
Authors: Lu Lei , Zhu Tingting , Ribeiro Antonio H , Clifton Lei , Zhao Erying , Zhou Jiandong , Ribeiro Antonio Luiz P , Zhang Yuan-Ting , Clifton David A 
Published: February 2024

Abstract

Aims
Electrocardiogram (ECG) is widely considered the primary test for evaluating cardiovascular diseases. However, the use of artificial intelligence (AI) to advance these medical practices and learn new clinical insights from ECGs remains largely unexplored. We hypothesize that AI models with a specific design can provide fine-grained interpretation of ECGs to advance cardiovascular diagnosis, stratify mortality risks, and identify new clinically useful information.

Methods and results
Utilizing a data set of 2 322 513 ECGs collected from 1 558 772 patients with 7 years follow-up, we developed a deep-learning model with state-of-the-art granularity for the interpretable diagnosis of cardiac abnormalities, gender identification, and hypertension screening solely from ECGs, which are then used to stratify the risk of mortality. The model achieved the area under the receiver operating characteristic curve (AUC) scores of 0.998 (95% confidence interval (CI), 0.995–0.999), 0.964 (95% CI, 0.963–0.965), and 0.839 (95% CI, 0.837–0.841) for the three diagnostic tasks separately. Using ECG-predicted results, we find high risks of mortality for subjects with sinus tachycardia (adjusted hazard ratio (HR) of 2.24, 1.96–2.57), and atrial fibrillation (adjusted HR of 2.22, 1.99–2.48). We further use salient morphologies produced by the deep-learning model to identify key ECG leads that achieved similar performance for the three diagnoses, and we find that the V1 ECG lead is important for hypertension screening and mortality risk stratification of hypertensive cohorts, with an AUC of 0.816 (0.814–0.818) and a univariate HR of 1.70 (1.61–1.79) for the two tasks separately.

Conclusion
Using ECGs alone, our developed model showed cardiologist-level accuracy in interpretable cardiac diagnosis and the advancement in mortality risk stratification. In addition, it demonstrated the potential to facilitate clinical knowledge discovery for gender and hypertension detection which are not readily available.