bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hi-GeoMVP: a hierarchical geometry-enhanced deep learning model for drug response prediction
Authors: Chen Yurui , Zhang Louxin 
Published: April 2024

Abstract

Motivation
Personalized cancer treatments require accurate drug response predictions. Existing deep learning methods show promise but higher accuracy is needed to serve the purpose of precision medicine. The prediction accuracy can be improved with not only topology but geometrical information of drugs.

Results
A novel deep learning methodology for drug response prediction is presented, named Hi-GeoMVP. It synthesizes hierarchical drug representation with multi-omics data, leveraging graph neural networks and variational autoencoders for detailed drug and cell line representations. Multi-task learning is employed to make better prediction, while both 2D and 3D molecular representations capture comprehensive drug information. Testing on the GDSC dataset confirms Hi-GeoMVP’s enhanced performance, surpassing prior state-of-the-art methods by improving the Pearson correlation coefficient from 0.934 to 0.941 and decreasing the root mean square error from 0.969 to 0.931. In the case of blind test, Hi-GeoMVP demonstrated robustness, outperforming the best previous models with a superior Pearson correlation coefficient in the drug-blind test. These results underscore Hi-GeoMVP’s capabilities in drug response prediction, implying its potential for precision medicine.

Availability and implementation
The source code is available at https://github.com/matcyr/Hi-GeoMVP
Genital evolution in the dark: characterization of male and female genitalia in cave mollies and their surface ancestors (Poecilia mexicana, Poeciliidae)
Authors: Johnson Erik S , Johnson Soren D , McNemee Rachel , Greenway Ryan , Arias Rodriguez Lenin , Tobler Michael 
Published: April 2024

Abstract
Animal genitalia evolve rapidly because of coevolution between male and female traits. However, how the ecological context in which mating occurs might modulate the evolution of genital traits remains poorly understood. We investigated how a change in the sensory environment (the absence of light upon cave colonization) impacted the expression of genital traits in a live-bearing fish, Poecilia mexicana (Poeciliidae), with populations in adjacent cave and surface habitats. Quantifying characteristics of the female urogenital aperture and the male gonopodium (a modified anal fin used for copulation), we found significant differences in genital traits of both sexes. Females from cave populations exhibited larger and more rounded genitalia. Males from cave populations exhibited a significantly enlarged palp, a fleshy gonopodial appendage that has been hypothesized to have sensory functions. Our results suggest that genital traits can diverge rapidly among closely related populations exposed to different environmental conditions. The absence of light could impact genital evolution directly, if some genital structures have sensory functions that compensate for the lack of visual information during copulation, or indirectly, if the absence of light impacts dynamics of sexual conflict or cryptic female choice that arise through the interaction between the sexes.
Autism-associated brain differences can be observed in utero using MRI
Authors: Ortug Alpen , Guo Yurui , Feldman Henry A , Ou Yangming , Warren Jose Luis Alatorre , Dieuveuil Harrison , Baumer Nicole T , Faja Susan K , Takahashi Emi 
Published: April 2024

AbstractDevelopmental changes that occur before birth are thought to be associated with the development of autism spectrum disorders. Identifying anatomical predictors of early brain development may contribute to our understanding of the neurobiology of autism spectrum disorders and allow for earlier and more effective identification and treatment of autism spectrum disorders. In this study, we used retrospective clinical brain magnetic resonance imaging data from fetuses who were diagnosed with autism spectrum disorders later in life (prospective autism spectrum disorders) in order to identify the earliest magnetic resonance imaging-based regional volumetric biomarkers. Our results showed that magnetic resonance imaging-based autism spectrum disorder biomarkers can be found as early as in the fetal period and suggested that the increased volume of the insular cortex may be the most promising magnetic resonance imaging-based fetal biomarker for the future emergence of autism spectrum disorders, along with some additional, potentially useful changes in regional volumes and hemispheric asymmetries.
Modulatory effects of low-intensity retinal ultrasound stimulation on rapid and non-rapid eye movement sleep
Authors: Wang Teng , Wang Mengran , Wang Jiawei , Li Zhen , Yuan Yi 
Published: April 2024

AbstractPrior investigations have established that the manipulation of neural activity has the potential to influence both rapid eye movement and non-rapid eye movement sleep. Low-intensity retinal ultrasound stimulation has shown effectiveness in the modulation of neural activity. Nevertheless, the specific effects of retinal ultrasound stimulation on rapid eye movement and non-rapid eye movement sleep, as well as its potential to enhance overall sleep quality, remain to be elucidated. Here, we found that: In healthy mice, retinal ultrasound stimulation: (i) reduced total sleep time and non-rapid eye movement sleep ratio; (ii) changed relative power and sample entropy of the delta (0.5–4 Hz) in non-rapid eye movement sleep; and (iii) enhanced relative power of the theta (4–8 Hz) and reduced theta-gamma coupling strength in rapid eye movement sleep. In Alzheimer’s disease mice with sleep disturbances, retinal ultrasound stimulation: (i) reduced the total sleep time; (ii) altered the relative power of the gamma band during rapid eye movement sleep; and (iii) enhanced the coupling strength of delta-gamma in non-rapid eye movement sleep and weakened the coupling strength of theta-fast gamma. The results indicate that retinal ultrasound stimulation can modulate rapid eye movement and non-rapid eye movement-related neural activity; however, it is not beneficial to the sleep quality of healthy and Alzheimer’s disease mice.
Effectiveness and Safety of Ustekinumab for Ulcerative Colitis: A Brazilian Multicentric Observational Study
Authors: Parra Rogério Serafim , Chebli Júlio Maria Fonseca , de Azevedo Matheus Freitas Cardoso , Chebli Liliana Andrade , Zabot Gilmara Pandolfo , Cassol Ornella Sari , de Sá Brito Fróes Renata , Santana Genoile Oliveira , Lubini Márcio , Magro Daniela Oliveira , Imbrizi Marcello , Moraes Antonio Carlos da Silva , Teixeira Fabio Vieira , Alves Junior Antonio José Tiburcio , Gasparetti Junior Newton Luiz Tricarico , da Costa Ferreira Sandro , Queiroz Natália Sousa Freitas , Kotze Paulo Gustavo , Féres Omar 
Published: April 2024

Abstract

Background
Real-world data on the effectiveness and safety of ustekinumab (UST) in ulcerative colitis (UC) are lacking in Latin America. In this study, we aimed to describe the effectiveness and safety of UST in a real-world multicenter cohort of Brazilian patients with UC.

Methods
We conducted a multicenter retrospective observational cohort study, including patients with moderate-to-severe UC (total Mayo score 6–12, with an endoscopic subscore of 2 or 3) who received UST. The co-primary endpoints were clinical remission, defined as a total Mayo score ≤2 at 1 year, with a combined rectal bleeding and stool frequency subscore of ≤1, and endoscopic remission (endoscopic Mayo subscore of 0) within 1 year from baseline. Secondary endpoints included clinical response between weeks 12 and 16, endoscopic response within 1 year of starting UST, steroid-free clinical remission at week 52, and biochemical remission at week 52. We also evaluated UST treatment persistence and safety.

Results
A total of 50 patients were included (female, n = 36, 72.0%), with a median disease duration of 9.2 years (1–27). Most patients had extensive colitis (n = 38, 76.0%), and 43 (86.0%) were steroid dependent at baseline. Forty patients (80.0%) were previously exposed to biologics (anti-TNF drugs, n = 31; vedolizumab [VDZ], n = 27). The co-primary endpoints of clinical remission at 1 year and endoscopic remission within 1 year were achieved by 50.0% and 36.0% of patients, respectively. Clinical response at weeks 12–16 was 56.0%, and endoscopic response, steroid-free clinical remission, and biochemical remission at week 52 were 68.0%, 46.5%, and 50.0%, respectively. The UST treatment persistence rate at 24 months was 73.7%. During the follow-up, 10 patients (20.0%) were hospitalized, mostly due to disease progression, and 3 patients required colectomy. Nine patients (18.0%) discontinued the drug mainly due to a lack of effectiveness. Twenty-seven adverse events (AEs) were reported, 16 of which were considered as serious AEs.

Conclusions
In this real-world cohort of difficult-to-treat UC patients, UST was associated with improvements in clinical, biochemical, and endoscopic outcomes. The safety profile was favorable, consistent with the known profile of UST.
Impact of the method of calculating 30-day readmission rate after hospitalization for heart failure. Data from the VancOuver CoastAL Acute Heart Failure (VOCAL-AHF) registry
Authors: Salimian Samaneh , Virani Sean A , Roston Thomas M , Yao Ren Jie Robert , Turgeon Ricky D , Ezekowitz Justin , Hawkins Nathaniel M 
Published: April 2024

Abstract

Background
Thirty-day readmission rate after heart failure (HF) hospitalization is widely used to evaluate healthcare quality. Methodology may substantially influence estimated rates. We assessed the impact of different definitions on HF and all-cause readmission rates.

Methods
Readmission rates were examined in 1835 patients discharged following HF hospitalization using 64 unique definitions derived from five methodological factors: (1) International Classification of Diseases-10 codes (broad vs. narrow), (2) index admission selection (single admission only first-in-year vs. random sample; or multiple admissions in year with vs. without 30-day blanking period), (3) variable denominator (number alive at discharge vs. number alive at 30 days), (4) follow-up period start (discharge date vs. day following discharge), and (5) annual reference period (calendar vs. fiscal). The impact of different factors was assessed using linear regression.

Results
The calculated 30-day readmission rate for HF varied more than two-fold depending solely on the methodological approach (6.5–15.0%). All-cause admission rates exhibited similar variation (18.8–29.9%). The highest rates included all consecutive index admissions (HF 11.1–15.0%, all-cause 24.0–29.9%), and the lowest only one index admission per patient per year (HF 6.5–11.3%, all-cause 18.8–22.7%). When including multiple index admissions and compared with blanking the 30-day post-discharge, not blanking was associated with 2.3% higher readmission rates. Selecting a single admission per year with a first-in-year approach lowered readmission rates by 1.5%, while random-sampling admissions lowered estimates further by 5.2% (P &lt; 0.001).

Conclusion
Calculated 30-day readmission rates varied more than two-fold by altering methods. Transparent and consistent methods are needed to ensure reproducible and comparable reporting.
Outcome after extracorporeal membrane oxygenation therapy in Norwood patients before the bidirectional Glenn operation
Authors: Seeber Fabian , Krenner Niklas , Sames-Dolzer Eva , Tulzer Andreas , Srivastava Ishita , Kreuzer Michaela , Mair Roland , Gierlinger Gregor , Nawrozi Mohammad-Paimann , Mair Rudolf 
Published: April 2024

Abstract

OBJECTIVES
Patients after the Norwood procedure are prone to postoperative instability. Extracorporeal membrane oxygenation (ECMO) can help to overcome short-term organ failure. This retrospective single-centre study examines ECMO weaning, hospital discharge and long-term survival after ECMO therapy between Norwood and bidirectional Glenn palliation as well as risk factors for mortality.

METHODS
In our institution, over 450 Norwood procedures have been performed. Since the introduction of ECMO therapy, 306 Norwood operations took place between 2007 and 2022, involving ECMO in 59 cases before bidirectional Glenn. In 48.3% of cases, ECMO was initiated intraoperatively post-Norwood. Patient outcomes were tracked and mortality risk factors were analysed using uni- and multivariable testing.

RESULTS
ECMO therapy after Norwood (median duration: 5 days; range 0–17 days) saw 31.0% installed under CPR. Weaning was achieved in 46 children (78.0%), with 55.9% discharged home after a median of 45 (36–66) days. Late death occurred in 3 patients after 27, 234 and 1541 days. Currently, 30 children are in a median 4.8 year (3.4–7.7) follow-up. At the time of inquiry, 1 patient awaits bidirectional Glenn, 6 are at stage II palliation, Fontan was completed in 22 and 1 was lost to follow-up post-Norwood. Risk factor analysis revealed dialysis (P &lt; 0.001), cerebral lesions (P = 0.026), longer ECMO duration (P = 0.002), cardiac indication and lower body weight (P = 0.038) as mortality-increasing factors. The 10-year mortality probability after ECMO therapy was 48.5% (95% CI 36.5–62.9%).

CONCLUSIONS
ECMO therapy in critically ill patients after the Norwood operation may significantly improve survival of a patient cohort otherwise forfeited and give the opportunity for successful future-stage operations.
Increased utilization of the hybrid procedure is not associated with improved early survival for newborns with hypoplastic left heart syndrome: a single-centre experience
Authors: Chen Jonathan M , Ittenbach Richard F , Lawrence Kendall M , Hunt Mallory L , Kaplinski Michelle , Mahle Marlene , Fuller Stephanie , Maeda Katsuhide , Nuri Muhammad A K , Gardner Monique M , Mavroudis Constantine D , Mascio Christopher E , Spray Thomas L , Gaynor J William 
Published: April 2024

Abstract

OBJECTIVES
The primary objectives were to examine utilization of the Hybrid versus the Norwood procedure for patients with hypoplastic left heart syndrome or variants and the impact on hospital mortality. The Hybrid procedure was 1st used at our institution in 2004.

METHODS
Review of all subjects undergoing the Norwood or Hybrid procedure between 1 January 1984 and 31 December 2022. The study period was divided into 8 eras: era 1, 1984–1988; era 2, 1989–1993; era 3, 1994–1998; era 4, 1999–2003; era 5, 2004–2008; era 6, 2009–2014; era 7, 2015–2018 and era 8, 2019–2022. The primary outcome was in-hospital mortality. Mortality rates were computed using standard binomial proportions with 95% confidence intervals. Rates across eras were compared using an ordered logistic regression model with and adjusted using the Tukey–Kramer post-hoc procedure for multiple comparisons. In the risk-modelling phase, logistic regression models were specified and tested.

RESULTS
The Norwood procedure was performed in 1899 subjects, and the Hybrid procedure in 82 subjects. Use of the Hybrid procedure increased in each subsequent era, reaching 30% of subjects in era 8. After adjustment for multiple risk factors, use of the Hybrid procedure was significantly and positively associated with hospital mortality.

CONCLUSIONS
Despite the increasing use of the Hybrid procedure, overall mortality for the entire cohort has plateaued. After adjustment for risk factors, use of the Hybrid procedure was significantly and positively associated with mortality compared to the Norwood procedure.
Cardiovascular mortality attributable to dietary risk factors in 54 countries in the WHO European Region from 1990 to 2019: an updated systematic analysis of the Global Burden of Disease Study
Authors: Pörschmann Theresa , Meier Toni , Lorkowski Stefan 
Published: April 2024

Abstract

Aims
This study aimed to estimate the association between single dietary risk factors and cardiovascular diseases (CVDs) in the WHO European Region (WHO ER) by age and sex using the data of the Global Burden of Diseases Study (GBD) from 1990 to 2019.

Methods and results
For this purpose, 13 dietary risks and 13 forms of CVDs were included in the study, and the comparative risk assessment framework of the GBD was used to estimate the deaths attributable to them. The study included four regions, with a total of 54 countries. In 2019, 1.55 million (95 % UI, 1.2-1.9 million) people in the WHO ER died from CVDs attributable to suboptimal diet. Diet-related CVD deaths (DRCDs) accounted for 16.4 % of total deaths and 36.7 % of CVD deaths in 2019. Between 1990 and 2019, there was a DRCDs reduction of 8.1 % and the age-standardized death rate decreased. The deaths were almost equally distributed between women (777 714 deaths) and men (772 519 deaths). The distribution of death numbers between the sexes has changed only slightly over the study period. The largest percentage across the age groups was found in the group 85+ years (32.1 %). Most DRCDs in the WHO ER were caused by a diet low in whole grains (326 755 deaths), followed by a diet low in legumes (232 918 deaths) and a diet high in sodium (193 713 deaths). Overall, 80.3% of deaths were due to ischaemic heart disease, which was the most common cause of death in all countries.

Conclusion
In terms of CVD deaths in the WHO ER, more than every third death is attributable to an unbalanced diet, making the diet one of the most important factors in preventing premature CVD death in the WHO ER.
Physiological and morphological plasticity in response to nitrogen availability of a yeast widely distributed in the open ocean
Authors: Diver Poppy , Ward Ben A , Cunliffe Michael 
Published: April 2024

Abstract
Yeasts are prevalent in the open ocean, yet we have limited understanding of their ecophysiological adaptations, including their response to nitrogen availability, which can have a major role in determining the ecological potential of other planktonic microbes. In this study, we characterized the nitrogen uptake capabilities and growth responses of marine-occurring yeasts. Yeast isolates from the North Atlantic Ocean were screened for growth on diverse nitrogen substrates, and across a concentration gradient of three environmentally relevant nitrogen substrates: nitrate, ammonium, and urea. Three strains grew with enriched nitrate while two did not, demonstrating that nitrate utilization is present but not universal in marine yeasts, consistent with existing knowledge of nonmarine yeast strains. Naganishia diffluens MBA_F0213 modified the key functional trait of cell size in response to nitrogen concentration, suggesting yeast cell morphology changes along chemical gradients in the marine environment. Meta-analysis of the reference DNA barcode in public databases revealed that the genus Naganishia has a global ocean distribution, strengthening the environmental applicability of the culture-based observations. This study provides novel quantitative understanding of the ecophysiological and morphological responses of marine-derived yeasts to variable nitrogen availability in vitro, providing insight into the functional ecology of yeasts within pelagic open ocean environments.
Peripheral Blood Cells From Older Adults Exhibit Sex-Associated Differences in Mitochondrial Function
Authors: Mahapatra Gargi , Gao Zhengrong , Bateman James R , Lockhart Samuel Neal , Bergstrom Jaclyn , Piloso Jemima Elizabeth , Craft Suzanne , Molina Anthony J A 
Published: April 2024

Abstract
Blood-based mitochondrial bioenergetic profiling is a feasible, economical, and minimally invasive approach that can be used to examine mitochondrial function and energy metabolism in human subjects. In this study, we use 2 complementary respirometric techniques to evaluate mitochondrial bioenergetics in both intact and permeabilized peripheral blood mononuclear cells (PBMCs) and platelets to examine sex dimorphism in mitochondrial function among older adults. Employing equal numbers of PBMCs and platelets to assess mitochondrial bioenergetics, we observe significantly higher respiration rates in female compared to male participants. Mitochondrial bioenergetic differences remain significant after controlling for independent parameters including demographic parameters (age, years of education), and cognitive parameters (mPACC5, COGDX). Our study illustrates that circulating blood cells, immune cells in particular, have distinctly different mitochondrial bioenergetic profiles between females and males. These differences should be taken into account as blood-based bioenergetic profiling is now commonly used to understand the role of mitochondrial bioenergetics in human health and aging.
Efficient purging of deleterious mutations contributes to the survival of a rare conifer
Authors: Wang Yi , Yang Yongzhi , Han Zhitong , Li Jialiang , Luo Jian , Yang Heng , Kuang Jingge , Wu Dayu , Wang Shiyang , Tso Sonam , Ju Tsam , Liu Jianquan , Renner Susanne S , Kangshan Mao 
Published: April 2024

Abstract
Cupressaceae is a conifer family rich in plants of horticultural importance, including Cupressus, Chamaecyparis, Juniperus, and Thuja, yet genomic surveys are lacking for this family. Cupressus gigantea, one of the many rare conifers that are threatened by climate change and anthropogenic habitat fragmentation, plays an ever-increasing role in ecotourism in Tibet. To infer how past climate change has shaped the population evolution of this species, we generated a de novo chromosome-scale genome (10.92 Gb) and compared the species’ population history and genetic load with that of a widespread close relative, C. duclouxiana. Our demographic analyses, based on 83 re-sequenced individuals from multiple populations of the two species, revealed a sharp decline of population sizes during the first part of the Quaternary. However, populations of C. duclouxiana then started to recover, while C. gigantea populations continued to decrease until recently. The total genomic diversity of C. gigantea is smaller than that of C. duclouxiana, but contrary to expectations, C. gigantea has fewer highly and mildly deleterious mutations than C. duclouxiana, and simulations and statistical tests support purifying selection during prolonged inbreeding as the explanation. Our results highlight the evolutionary consequences of decreased population size on the genetic burden of a long-lived endangered conifer with large genome size and suggest that genetic purging deserves more attention in conservation management.
Adventures in Lollard Street: An Experimental London Playground, 1955–60
Authors: Highmore Ben 
Published: April 2024

Abstract
This essay situates the emergence of the adventure playground movement in Britain within social and intellectual contexts. It provides a detailed account of the Lollard Adventure Playground, London, which lasted from 1955 to 1960, and describes the general ecology of the playground including indoor activities, the administration of the playground, and its mediation through pamphlets and journalism. It argues that the playground combined a Christian ethos evident in the early playground movement with the growing permissiveness of autonomous play, and shows how adventure playgrounds were a locus for tensions around class and gender.