bluuebunny/crossref_metadata_2025 huggingface dataset:
A dynamic in vitro model of Down syndrome neurogenesis with trisomy 21 gene dosage correction
Authors: Bansal Prakhar , Banda Erin C. , Glatt-Deeley Heather R. , Stoddard Christopher E. , Linsley Jeremy W. , Arora Neha , Deleschaux Cécile , Ahern Darcy T. , Kondaveeti Yuvabharath , Massey Rachael E. , Nicouleau Michael , Wang Shijie , Sabariego-Navarro Miguel , Dierssen Mara , Finkbeiner Steven , Pinter Stefan F.
Published: June 2024

Excess gene dosage from chromosome 21 (chr21) causes Down syndrome (DS), spanning developmental and acute phenotypes in terminal cell types. Which phenotypes remain amenable to intervention after development is unknown. To address this question in a model of DS neurogenesis, we derived trisomy 21 (T21) human induced pluripotent stem cells (iPSCs) alongside, otherwise, isogenic euploid controls from mosaic DS fibroblasts and equipped one chr21 copy with an inducible
XIST
transgene. Monoallelic chr21 silencing by
XIST
is near-complete and irreversible in iPSCs. Differential expression reveals that T21 neural lineages and iPSCs share suppressed translation and mitochondrial pathways and activate cellular stress responses. When
XIST
is induced before the neural progenitor stage, T21 dosage correction suppresses a pronounced skew toward astrogenesis in neural differentiation. Because our transgene remains inducible in postmitotic T21 neurons and astrocytes, we demonstrate that
XIST
efficiently represses genes even after terminal differentiation, which will empower exploration of cell type–specific T21 phenotypes that remain responsive to chr21 dosage.
Orco-dependent survival of odorant receptor neurons in ants
Authors: Sieriebriennikov Bogdan , Sieber Kayli R. , Kolumba Olena , Mlejnek Jakub , Jafari Shadi , Yan Hua
Published: June 2024

Olfaction is essential for complex social behavior in insects. To discriminate complex social cues, ants evolved an expanded number of
odorant receptor
(
Or
) genes. Mutations in the obligate odorant co-receptor gene
orco
lead to the loss of ~80% of the antennal lobe glomeruli in the jumping ant
Harpegnathos saltator
. However, the cellular mechanism remains unclear. Here, we demonstrate massive apoptosis of odorant receptor neurons (ORNs) in the mid to late stages of pupal development, possibly due to ER stress in the absence of Orco. Further bulk and single-nucleus transcriptome analysis shows that, although most
orco
-expressing ORNs die in
orco
mutants, a small proportion of them survive: They express
ionotropic receptor
(
Ir
) genes that form IR complexes. In addition, we found that some
Or
genes are expressed in mechanosensory neurons and nonneuronal cells, possibly due to leaky regulation from nearby non-
Or
genes. Our findings provide a comprehensive overview of ORN development and
Or
expression in
H. saltator
.
Hydroxylamine production by
Alcaligenes faecalis
challenges the paradigm of heterotrophic nitrification
Authors: Lenferink Wouter B. , Bakken Lars R. , Jetten Mike S. M. , van Kessel Maartje A. H. J. , Lücker Sebastian
Published: June 2024

Heterotrophic nitrifiers continue to be a hiatus in our understanding of the nitrogen cycle. Despite their discovery over 50 years ago, the physiology and environmental role of this enigmatic group remain elusive. The current theory is that heterotrophic nitrifiers are capable of converting ammonia to hydroxylamine, nitrite, nitric oxide, nitrous oxide, and dinitrogen gas via the subsequent actions of nitrification and denitrification. In addition, it was recently suggested that dinitrogen gas may be formed directly from ammonium. Here, we combine complementary high-resolution gas profiles,
15
N isotope labeling studies, and transcriptomics data to show that hydroxylamine is the major product of nitrification in
Alcaligenes faecalis
. We demonstrated that denitrification and direct ammonium oxidation to dinitrogen gas did not occur under the conditions tested. Our results indicate that
A. faecalis
is capable of hydroxylamine production from an organic intermediate. These results fundamentally change our understanding of heterotrophic nitrification and have important implications for its biotechnological application.
Tunable ion energy barrier modulation through aliovalent halide doping for reliable and dynamic memristive neuromorphic systems
Authors: Bae Jongmin , Kwon Choah , Park See-On , Jeong Hakcheon , Park Taehoon , Jang Taehwan , Cho Yoonho , Kim Sangtae , Choi Shinhyun
Published: June 2024

Memristive neuromorphic computing has emerged as a promising computing paradigm for the upcoming artificial intelligence era, offering low power consumption and high speed. However, its commercialization remains challenging due to reliability issues from stochastic ion movements. Here, we propose an innovative method to enhance the memristive uniformity and performance through aliovalent halide doping. By introducing fluorine concentration into dynamic TiO

2−
x

memristors, we experimentally demonstrate reduced device variations, improved switching speeds, and enhanced switching windows. Atomistic simulations of amorphous TiO

2−
x

reveal that fluoride ions attract oxygen vacancies, improving the reversible redistribution and uniformity. A number of migration barrier calculations statistically show that fluoride ions also reduce the migration energies of nearby oxygen vacancies, facilitating ionic diffusion and high-speed switching. The detailed Voronoi volume analysis further suggests design principles in terms of the migrating species’ electrostatic repulsion and migration barriers. This work presents an innovative methodology for the fabrication of reliable memristor devices, contributing to the realization of hardware-based neuromorphic systems.
Epigenetic predictors of species maximum life span and other life-history traits in mammals
Authors: Li Caesar Z. , Haghani Amin , Yan Qi , Lu Ake T. , Zhang Joshua , Fei Zhe , Ernst Jason , Yang X. William , Gladyshev Vadim N. , Robeck Todd R. , Chavez Andreas S. , Cook Joseph A. , Dunnum Jonathan L. , Raj Ken , Seluanov Andrei , Gorbunova Vera , Horvath Steve
Published: June 2024

By analyzing 15,000 samples from 348 mammalian species, we derive DNA methylation (DNAm) predictors of maximum life span (
R
= 0.89), gestation time (
R
= 0.96), and age at sexual maturity (
R
= 0.85). Our maximum life-span predictor indicates a potential innate longevity advantage for females over males in 17 mammalian species including humans. The DNAm maximum life-span predictions are not affected by caloric restriction or partial reprogramming. Genetic disruptions in the somatotropic axis such as growth hormone receptors have an impact on DNAm maximum life span only in select tissues. Cancer mortality rates show no correlation with our epigenetic estimates of life-history traits. The DNAm maximum life-span predictor does not detect variation in life span between individuals of the same species, such as between the breeds of dogs. Maximum life span is determined in part by an epigenetic signature that is an intrinsic species property and is distinct from the signatures that relate to individual mortality risk.
Revitalizing liver function in mice with liver failure through transplantation of 3D-bioprinted liver with expanded primary hepatocytes
Authors: Deng Bo , Ma Yue , Huang Jialyu , He Runbang , Luo Miaomiao , Mao Lina , Zhang Enhua , Zhao Yuanyuan , Wang Xiaoli , Wang Qiangsong , Pang Mingchang , Mao Yilei , Yang Huayu , Liu Lanxia , Huang Pengyu
Published: June 2024

The utilization of three-dimensional (3D) bioprinting technology to create a transplantable bioartificial liver emerges as a promising remedy for the scarcity of liver donors. This study outlines our strategy for constructing a 3D-bioprinted liver, using in vitro–expanded primary hepatocytes recognized for their safety and enhanced functional robustness as hepatic cell sources for bioartificial liver construction. In addition, we have developed bioink biomaterials with mechanical and rheological properties, as well as printing capabilities, tailored for 3D bioprinting. Upon heterotopic transplantation into the mesentery of tyrosinemia or 90% hepatectomy mice, our 3D-bioprinted liver effectively restored lost liver functions, consequently extending the life span of mice afflicted with liver injuries. Notably, the inclusion of an artificial blood vessel in our 3D-bioprinted liver allowed for biomolecule exchange with host blood vessels, demonstrating, in principle, the rapid integration of the bioartificial liver into the host vascular system. This model underscores the therapeutic potential of transplantation for the treatment of liver failure diseases.
The aMPPle differentiation potential of T
H
2 cells in human allergy
Authors: Siddapureddy Sindhura , Eisenbarth Stephanie
Published: June 2024

Single-cell studies of human tissues reveal a stem-like T
H
2 subset as progenitors of key effectors in chronic type 2 inflammation.
Complete genome sequence of a
Pseudomonas fluorescens
bacteriophage UNO-G1W1 isolated from freshwater ice in Nebraska
Authors: Schulze Thomas T. , Neville Andrew J. , Watson Gabrielle F. , Sanford Austin G. , Won Harim I. , Conrin Mackenzie E. , Eastman Connor G. , Lui LeeAnna M. , Alizai M. Yunos , Walters Matthias J. , Davis Paul H. , Tapprich William E.
Published: June 2024

We provide the complete genome sequence for a novel
Pseudomonas fluorescens
bacteriophage named UNO-G1W1. This phage was isolated from a single ice cover sampling. The genome was sequenced on the Nanopore MinION, generated with the direct terminal repeat-phage-pipeline and polished with Illumina short reads. Sequence identity classifies the phage as an
otagovirus
.
High-quality draft genome sequence of
Paenibacillus
sp. RC80, a candidate for biofuel production
Authors: Rizzo Gabriella , Choudoir Mallory , Simoes Rachel , Dayarathne Nipuni , DeAngelis Kristen M.
Published: June 2024

Paenibacillus
sp. RC80 was isolated from temperate deciduous forest soil in New England. The assembled genome is a single contig with 5,977,337 bp and 97.15% estimated completion. RC80 contains features for 2,3-butanediol dehydrogenase production and pathways involved in ethanol production.
Impact of physiotherapy access on health-related quality of life following hip fracture: an observational study on 30 752 hip fractures from the Norwegian Hip Fracture Register 2014–2018
Authors: Kjærvik Cato , Gjertsen Jan-Erik , Stensland Eva , Uleberg Bård , Taraldsen Kristin , Søreide Odd
Published: June 2024

Objectives

The main objective of this study was to investigate the characteristics of patients receiving private community physiotherapy (PT) the first year after a hip fracture. Second, to determine whether utilisation of PT could improve health-related quality of life (HRQoL).

Methods

In an observational cohort study, 30 752 hip fractures from the Norwegian Hip Fracture Register were linked with data from Statistics Norway and the Norwegian Control and Payment of Health Reimbursements Database. Association between covariates and utilisation of PT in the first year after fracture, the association between covariates and EQ-5D index score and the probability of experiencing ‘no problems’ in the five dimensions of the EQ-5D were assessed with multiple logistic regression models.

Results

Median age was 81 years, and 68.4% were females. Most patients with hip fracture (57.7%) were classified as American Society of Anesthesiologists classes 3–5, lived alone (52.4%), and had a low or medium level of education (85.7%). In the first year after injury, 10 838 of 30 752 patients with hip fracture (35.2%) received PT. Lower socioeconomic status (measured by income and level of education), male sex, increasing comorbidity, presence of cognitive impairment and increasing age led to a lower probability of receiving postoperative PT. Among those who used PT, EQ-5D index score was 0.061 points (p<0.001) higher than those who did not. Correspondingly, the probability of having ‘no problems’ in three of the five dimensions of EQ-5D was greater.

Conclusions

A minority of the patients with hip fracture had access to private PT the first year after injury. This may indicate a shortcoming in the provision of beneficial post-surgery rehabilitative care reducing post-treatment HRQoL. The findings underscore the need for healthcare policies that address disparities in PT access, particularly for elderly patients, those with comorbidities and reduced health, and those with lower socioeconomic status.
Quantifying the costs of hospital admission for families of children with a febrile illness in the North East of England
Authors: van der Velden Fabian Johannes Stanislaus , Lim Emma , Smith Holly , Walsh Rebecca , Emonts Marieke
Published: June 2024

Objective

To assess the financial non-medical out-of-pocket costs of hospital admissions for children with a febrile illness.

Design

Single-centre survey-based study conducted between March and November 2022.

Setting

Tertiary level children’s hospital in the North East of England.

Participants

Families of patients with febrile illness attending the paediatric emergency department

Main outcome measures

Non-medical out-of-pocket costs for the admission were estimated by participants including: transport, food and drinks, child care, miscellaneous costs and loss of earnings.

Results

83 families completed the survey. 79 families (95.2%) reported non-medical out-of-pocket costs and 19 (22.9%) reported financial hardship following their child’s admission.

Total costs per day of admission were median £56.25 (IQR £32.10–157.25). The majority of families reported incurring transport (N=75) and food and drinks (N=71) costs.

Conclusions

A child’s hospital admission for fever can incur significant financial costs for their family. One in five participating families reported financial hardship following their child’s admission. Self-employed and single parents were disadvantaged by unplanned hospital admissions and at an increased risk of financial hardship. Local hospital policies should be improved to support families in the current financial climate.
Long-term prognosis of low high-sensitivity cardiac troponin T in the emergency department compared with the general population
Authors: Cyon Love , Kadesjö Erik , Edgren Gustaf , Roos Andreas
Published: June 2024

Background

Long-term prognosis associated with low–high-sensitivity cardiac troponin T (hs-cTnT) concentrations in patients with chest pain is unknown. We investigated these prognostic implications compared with the general population.

Methods

All first visits to seven emergency departments (ED)s in Sweden were included from 9 December 2010 to 31 August, 2017 by patients presenting with chest pain and at least one hs-cTnT measured. Patients with myocardial injury (any hs-cTnT >14 ng/L), including patients with myocardial infarction (MI) were excluded. Standardised mortality ratios (SMRs) and standardised incidence ratios (SIRs) were calculated as the ratio of the number of observed to expected events. The expected number was computed by multiplying the 1-year calendar period-specific, age-specific and sex-specific follow-up time in the cohort with the corresponding incidence in the general population. HRs were calculated for all-cause mortality and major adverse cardiovascular events (MACE), defined as acute MI, heart failure hospitalisation, cerebrovascular stroke or cardiovascular death, between patients with undetectable (<5 ng/L) and low (5–14 ng/L) hs-cTnT.

Results

A total of 1 11 916 patients were included, of whom 69 090 (62%) and 42 826 (38%) had peak hs-cTnT concentrations of <5 and 5–14 ng/L. Patients with undetectable peak hs-cTnT had a lower mortality risk compared with the general Swedish population (SMR 0.83, 95% CI 0.79 to 0.87), with lower risks observed in all patients ≥65 years of age, but a slightly higher risk of being diagnosed with a future MI (SIR 1.39, 95% CI 1.32 to 1.47). The adjusted risk of a first MACE associated with low versus undetectable peak hs-cTnT was 1.6-fold (HR 1.61, 95% CI 1.53 to 1.70).

Conclusion

Patients with chest pain and undetectable hs-cTnT have an overall lower risk of death compared with the general population, with risks being highly age dependent. Detectable hs-cTnT concentrations are still associated with increased long-term cardiovascular risks.
Evaluating health-related behaviours of armed forces personnel in Kuwait: a cross-sectional study
Authors: Alkhezi Eiman
Published: June 2024

Introduction

Evidence is lacking regarding the health-related behaviours of the military force in Kuwait. This study compared health-related behaviours of active-duty armed forces personnel according to their service branch and rank.

Methods

In this cross-sectional descriptive study, an online questionnaire was developed to collect, via text messages, anonymised data from 392 armed forces personnel on their sociodemographics, health status, smoking, physical activity and desire for mental healthcare.

Results

Most of the participants were non-officers (80.35%) from ‘other’ service branch (48.10%), had ≤10 years of military service (64.46%) and were Kuwaitis (79.97%) aged 18–39 years (77.62%) and rated their physical and mental health as ‘good’, with no chronic diseases (93.28%), although 53.13% were overweight and 8.55% were obese, and the prevalence of obesity increased with age. The survey revealed a high prevalence of physical inactivity (65.48%), which increased with age as well as a high prevalence of smoking (82.66%). Almost half of the respondents (46.21%) believed that seeking mental health help could probably damage their military career, this belief significantly increased with age.

Conclusion

Although most of the Kuwaiti armed forces personnel reported having ‘good’ physical and mental health, with no chronic diseases, there was a high prevalence among them of overweight, smoking and low physical activity levels, with no difference between service branches or ranks. Moreover, the stigma of having mental health problems and the fear of the negative effects of seeking mental healthcare on a career were prevalent among the participants. These data are helpful in informing policy and development programmes that meet the needs of armed forces personnel.
Groupoids, Fibrations, and Balanced Colorings of Networks
Authors: Stewart Ian
Published: June 2024

Robust synchrony in network dynamics is governed by balanced colorings and the corresponding quotient network, also formalized in terms of graph fibrations. Dynamics and bifurcations are constrained — often in surprising ways — by the associated synchrony subspaces, which are invariant under all admissible ordinary differential equations (ODEs). The class of admissible ODEs is determined by a groupoid, whose objects are the input sets of nodes and whose morphisms are input isomorphisms between those sets. We define the coloring subgroupoid corresponding to a coloring, leading to groupoid interpretations of colorings and quotient networks. The first half of the paper is mainly tutorial. The second half, which is new, characterizes the structure of the network groupoid and proves that the groupoid of the quotient network is the quotient of the network groupoid by a normal subgroupoid of transition elements.
Beyond ReLU: Unlocking Superior Plant Disease Recognition with Swish
Authors: Bhuvanya R. , Kujani T. , Padmavathy R. , Matheswaran P. , Punitha P.
Published: June 2024

Plant disease identification plays a crucial role in agricultural management, but the traditional methods are time-consuming and imprecise. This work contributes to the ongoing efforts to develop reliable and efficient solutions for automated plant disease diagnosis, ultimately aiding in the timely management and mitigation of agricultural challenges. This study investigated the effectiveness of various deep convolutional neural networks (CNNs) for automated plant disease identification from leaf images. By exploring deep and transfer learning techniques such as CNNs, InceptionNet, DenseNet 121, and ResNet-50, a Deep Convolutional Neural Network (DCNN) is proposed to categorize the leaf disease. Different activation functions, specifically Rectified Linear Unit (ReLU) and Swish, are employed to investigate their impact on model performance. The experiments revealed that the DCNN architecture, when paired with the Swish activation function, demonstrated 96% accuracy in plant disease identification.
Metric dimension of unit graphs
Authors: Pranjali  , Kumar Amit , Sharma Rakshita
Published: June 2024

The notion of the metric dimension of a graph is well-known and its study is well entrenched in the literature. In this paper, we introduce new classes of graphs that exhibit remarkable characteristic: the metric dimension and the diameter of the unit graph are equal. Additionally, we provide a characterization of finite commutative rings [Formula: see text], wherein the metric dimension assumes a value [Formula: see text], where [Formula: see text]. Further, we also demonstrate an exhaustive examination that ascertains the precise finite commutative rings [Formula: see text], in which domination number is equal to metric dimension of unit graph.
The Technological Effects of Renewable and Non-Renewable Energy on Agricultural Productivity in Developed Countries
Authors: Muhamad Goran M.
Published: June 2024

Existing literature confirms both the role of agricultural technology in elevating agricultural productivity and the positive effects of green energy on environmental sustainability; nevertheless, less attention has been paid to agrotechnology’s energy sources and their adaptability to agri-environmental conditions using econometric methods. This study examines the association between renewable and non-renewable energy agrotechnology, and agricultural productivity in 32 developed nations from 2000 to 2021. We apply a difference Generalised Method of Moments (GMM) panel data estimation and Dumitrescu and Hurlin causality test. The findings report a significant and negative coefficient for non-renewable energy agrotechnology indicating that fossil fuel agrotechnology reduces agricultural productivity and thereby causes concerns over sustaining agricultural growth in developed countries. In contrast, the coefficient of renewable energy agrotechnology is positive and highly statistically significant, confirming maximising effects on agricultural productivity. We conduct two robustness checks to assess the credibility of the results. Using panel quantile regression analysis allows for establishing various relationships between the estimated variables at different quantiles of agricultural productivity. Testing for Dumitrescu and Hurlin causality test, we find bidirectional causal links between agricultural productivity and non-renewable energy agrotechnology, renewable energy agrotechnology and FDI, but only a one-way causal relationship between the other variables. This result suggests no integrated policy among the developed countries towards agricultural sustainability, despite their commitments to the Sustainable Development Goals (SDGs). These findings emphasise the employment of sustainable renewable energy agrotechnology as a strategy to tackle the fundamental problems of sustainable agricultural growth.
The Herglotz variational principle for dissipative field theories
Authors: Gaset Jordi , Lainz Manuel , Mas Arnau , Rivas Xavier
Published: June 2024

In the recent years, with the incorporation of contact geometry, there has been a renewed interest in the study of dissipative or non-conservative systems in physics and other areas of applied mathematics. The equations arising when studying contact Hamiltonian systems can also be obtained via the Herglotz variational principle. The contact Lagrangian and Hamiltonian formalisms for mechanical systems has also been generalized to field theories. The main goal of this paper is to develop a generalization of the Herglotz variational principle for first-order and higher-order field theories. In order to illustrate this, we study three examples: the damped vibrating string, the Korteweg–de Vries equation, and an academic example showing that the non-holonomic and the vakonomic variational principles are not fully equivalent.
SCAE: Structural Contrastive Auto-Encoder for Incomplete Multi-View Representation Learning
Authors: Li Mengran , Zhang Ronghui , Zhang Yong , Piao Xinglin , Zhao Shiyu , Yin Baocai
Published: June 2024

Describing an object from multiple perspectives often leads to incomplete data representation. Consequently, learning consistent representations for missing data from multiple views has emerged as a key focus in the realm of Incomplete Multi-view Representation Learning (IMRL). In recent years, various strategies, such as subspace learning, matrix decomposition, and deep learning, have been harnessed to develop numerous IMRL methods. In this article, our primary research revolves around IMRL, with a particular emphasis on addressing two main challenges. Firstly, we delve into the effective integration of intra-view similarity and contextual structure into a unified framework. Secondly, we explore the effective facilitation of information exchange and fusion across multiple views. To tackle these issues, we propose a deep learning approach known as Structural Contrastive Auto-Encoder (SCAE) to solve the challenges of IMRL. SCAE comprises two major components: intra-view structural representation learning and inter-view contrastive representation learning. The former involves capturing intra-view similarity by minimizing the Dirichlet energy of the feature matrix, while also applying spatial dispersion regularization to capture intra-view contextual structure. The latter encourages maximizing the mutual information of inter-view representations, facilitating information exchange and fusion across views. Experimental results demonstrate the efficacy of our approach in significantly enhancing model accuracy and robustly addressing IMRL problems. The code is available at
https://github.com/limengran98/SCAE
.
Toward Long Form Audio-Visual Video Understanding
Authors: Hou Wenxuan , Li Guangyao , Tian Yapeng , Hu Di
Published: June 2024

We live in a world filled with never-ending streams of multimodal information. As a more natural recording of the real scenario, long form audio-visual videos (LFAVs) are expected as an important bridge for better exploring and understanding the world. In this article, we propose the multisensory temporal event localization task in long form videos and strive to tackle the associated challenges. To facilitate this study, we first collect a large-scale LFAV dataset with 5,175 videos and an average video length of 210 seconds. Each collected video is elaborately annotated with diversified modality-aware events, in a long-range temporal sequence. We then propose an event-centric framework for localizing multisensory events as well as understanding their relations in long form videos. It includes three phases in different levels: snippet prediction phase to learn snippet features, event extraction phase to extract event-level features, and event interaction phase to study event relations. Experiments demonstrate that the proposed method, utilizing the new LFAV dataset, exhibits considerable effectiveness in localizing multiple modality-aware events within long form videos. We hope that our newly collected dataset and novel approach serve as a cornerstone for furthering research in the realm of LFAV understanding. Project page:
https://gewu-lab.github.io/LFAV/
.
A Real-Time Parallel Programming Approach for Rust
Authors: Carvalho Tiago , Silva Hugo , Miguel Pinho Luís
Published: June 2024

The development of real-time systems is one of the areas with the highest relevance in computer science, and the number of critical systems has increased significantly. These systems considers several applications running concurrently, and inside each of those applications code might be parallelized to improve their performance and control the priority of each parallelizable task. Several efforts have been done in different programming languages to provide real-time systems with parallel programming models, whether by code extensions or annotations, or with specific features in the actual language core.
Sex-dependent remodeling of right ventricular function in a rat model of pulmonary arterial hypertension
Authors: Kwan Ethan D. , Hardie Becky A. , Garcia Kristen M. , Mu Hao , Wang Tsui-Min , Valdez-Jasso Daniela
Published: June 2024

Combining hemodynamic and morphological measurements from male, female, and ovariectomized female pulmonary arterial hypertension (PAH) rats revealed distinct adaptation mechanisms despite similar pressure overload. Males showed the most diastolic stiffening. Ovariectomized females had enhanced myocyte contractility and calcium transient upregulation. Ovary-intact females primarily responded with hypertrophy, experiencing milder passive myocardial stiffening and no changes in myocyte shortening. These findings suggest potential sex-specific pathways in right ventricular (RV) adaptation to PAH, with implications for targeted interventions.
Machine learning: a new era for cardiovascular pregnancy physiology and cardio-obstetrics research
Authors: Ricci Contessa A. , Crysup Benjamin , Phillips Nicole R. , Ray William C. , Santillan Mark K. , Trask Aaron J. , Woerner August E. , Goulopoulou Styliani
Published: June 2024

The maternal cardiovascular system undergoes functional and structural adaptations during pregnancy and postpartum to support increased metabolic demands of offspring and placental growth, labor, and delivery, as well as recovery from childbirth. Thus, pregnancy imposes physiological stress upon the maternal cardiovascular system, and in the absence of an appropriate response it imparts potential risks for cardiovascular complications and adverse outcomes. The proportion of pregnancy-related maternal deaths from cardiovascular events has been steadily increasing, contributing to high rates of maternal mortality. Despite advances in cardiovascular physiology research, there is still no comprehensive understanding of maternal cardiovascular adaptations in healthy pregnancies. Furthermore, current approaches for the prognosis of cardiovascular complications during pregnancy are limited. Machine learning (ML) offers new and effective tools for investigating mechanisms involved in pregnancy-related cardiovascular complications as well as the development of potential therapies. The main goal of this review is to summarize existing research that uses ML to understand mechanisms of cardiovascular physiology during pregnancy and develop prediction models for clinical application in pregnant patients. We also provide an overview of ML platforms that can be used to comprehensively understand cardiovascular adaptations to pregnancy and discuss the interpretability of ML outcomes, the consequences of model bias, and the importance of ethical consideration in ML use.
Biodiversity Evolution of a Shrub Betula nana L. Populations in the Urals
Authors: Cherepanova Olga , Medvedeva Svetlana , Filippov Evgeniy , Skaptsov Mikhail , Ivchenko Tatyana , Teptina Angelika
Published: June 2024

Genetic polymorphism of B. nana along the Ural ridge is analyzed based on the variability of trnS-trnG, trnL-trnF, trnS-trnT, trnK1-trnK2, and matK1 cpDNA markers with the application of the RFLP method. Specimens of B. pubescens were additionally taken for comparative analysis. The research revealed 12 chlorotypes in B. nana and B. pubescens populations, among which chlorotypes A and B were the most frequent. The Polar Urals populations are characterized by prevailing chlorotype A, significantly decreased genetic polymorphism (He = 0.169), and low divergence (Fst = 0.000–0.050), which are possibly associated with the Pleistocene and Holocene migration processes, the edge effect, and specific ecological conditions of the arctic tundra. The populations of the Middle Urals show prevailing chlorotype B and higher genetic variability (He = 0.296). Reduced gene flow between bog populations of the Middle Urals results in high interpopulation divergence (Gst = 0.701, Nst = 0.764). Shared cpDNA haplotypes and low interspecific differentiation between B. nana and B. pubescens are indicated (Gct = 0.007, Nct = 0.064). Flow cytometry revealed homogeneous DNA content in B. nana and B. pubescens specimen populations (Serebryansky Kamen and Sredneuralsk) with a total 2C DNA content variation range of 0.91–1.09 pg for B. nana and 1.85–2.10 pg for B. pubescens and the absence of triploid hybrids among the studied samples, which suggests a low frequency of occurrence of the latter and, possibly, northern localization of these birch species hybridization zones.
Exploring Insights in Biomass and Waste Gasification via Ensemble Machine Learning Models and Interpretability Techniques
Authors: Bongomin Ocident , Nzila Charles , Mwasiagi Josphat Igadwa , Maube Obadiah
Published: June 2024

This comprehensive review delves into the intersection of ensemble machine learning models and interpretability techniques for biomass and waste gasification, a field crucial for sustainable energy solutions. It tackles challenges like feedstock variability and temperature control, highlighting the need for deeper understanding to optimize gasification processes. The study focuses on advanced modeling techniques like random forests and gradient boosting, alongside interpretability methods like the Shapley additive explanations and partial dependence plots, emphasizing their importance for transparency and informed decision‐making. Analyzing diverse case studies, the review explores successful applications while acknowledging challenges like overfitting and computational complexity, proposing strategies for practical and robust models. Notably, the review finds ensemble models consistently achieve high prediction accuracy (often exceeding R2 scores of 0.9) for gas composition, yield, and heating value. These models (34% of reviewed papers) are the most applied method, followed by artificial neural networks (26%). Heating value (12%) was the most studied performance metric. However, interpretability is often neglected during model development due to the complexity of techniques like permutation and Gini importance. The paper calls for dedicated research on utilizing and interpreting ensemble models, especially for co‐gasification scenarios, to unlock new insights into process synergy. Overall, this review serves as a valuable resource for researchers, practitioners, and policymakers, offering guidance for enhancing the efficiency and sustainability of biomass and waste gasification.
Effects of Injectable Solutions on the Quality of Monocyte‐Derived Dendritic Cells for Immunotherapy
Authors: Teodoro Da Silva Laís , Tiaki Tiyo Bruna , de Jesus Mota Silvia , Mazzilli Ortega Marina , Justamante Handel Schmitz Gabriela , Nosomi Taniwaki Noemi , Mitsue Namiyama Nishina Gislene , José da Silva Duarte Alberto , Miyuki Oshiro Telma
Published: June 2024

Therapeutic vaccines based on monocyte‐derived dendritic cells have been shown to be promising strategies and may act as complementary treatments for viral infections, cancers, and, more recently, autoimmune diseases. Alpha‐type‐1‐polarized dendritic cells (aDC1s) have been shown to induce type‐1 immunity with a high capacity to produce interleukin‐12p70 (IL‐12p70). In the clinical use of cell‐based therapeutics, injectable solutions can affect the morphology, immunophenotypic profile, and viability of cells before delivery and their survival after injection. In this sense, preparing a cell suspension that maintains the quality of aDC1s is essential to ensure effective immunotherapy. In the present study, monocytes were differentiated into aDC1s in the presence of IL‐4 and GM‐CSF. On day 5, the cells were matured by the addition of a cytokine cocktail consisting of IFN‐α, IFN‐γ, IL‐1β, TNF‐α, and Poly I:C. After 48 hr, mature aDC1s were harvested and suspended in two different solutions: normal saline and Ringer’s lactate. The maintenance of cells in suspension was evaluated after 4, 6, and 8 hr of storage. Cell viability, immunophenotyping, and apoptosis analyses were performed by flow cytometry. Cellular morphology was observed by electron microscopy, and the production of IL‐12p70 by aDC1s was evaluated by ELISA. Compared with normal saline, Ringer’s lactate solution was more effective at maintaining DC viability for up to 8 hr of incubation at 4 or 22°C.
Optimization of Bioethanol Production Using Response Surface Methodology for Stress‐Tolerant Wild Yeasts Isolated from Natural Forests
Authors: Tadesse Teshome , Dase Degife , Koricha Anbessa Dabassa , Bacha Ketema
Published: June 2024

Yeasts are essential microorganisms for the ethanol production, and their efficiency depends on the physicochemical characteristics of the fermenting substrate. These microorganisms can be found in various soil and plant sources, such as leaves, bark, and litter of natural forests. The goal of the current study was to assess ethanol production using stress‐tolerant yeasts isolated from leaves, litters, rhizosphere soils, and tree barks collected from three natural forests (Belete‐Gera, Boter‐Becho, and Yayu Biosphere Reserve) in Southwest Ethiopia. Matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS) was used to identify the isolates. Design‐Expert 11.1 (response surface methodology) was used to optimize the fermentation condition for effective ethanol production. A total of 406 yeasts were isolated, of which 67% were capable of ethanol production while 33% were not producers. The strongly fermentative isolates belonged to three genera: Saccharomyces cerevisiae, Meyerozyma guilliermondii, and Candida pelliculosa. S. cerevisiae 9Li2 and 35L1 were excellent candidates for ethanol production, with S. cerevisiae 9Li2 producing the highest ethanol (19.05 g/L) at optimal conditions (pH 5.09, 61.19 hours, and 30°C), while S. cerevisiae 35L1 produced maximum ethanol (19.03 g/L) at pH 4.92 and 30.03°C, within 71.55 hours. On the other hand, S. cerevisiae 9Li2 was able to ferment 40 g/L of glucose to produce 15 g/L of ethanol at 40°C with 73% efficiency at the ideal temperature (40°C), pH (5.167), and duration (72 hours), with a desirability of 0.819. The highest ethanol production (99.5 g/L) was achieved by S. cerevisiae 9Li2 after 48 hours at pH 5.0 and 30°C using 200 g/L of glucose. This work shows that multi‐stress‐tolerant S. cerevisiae isolates can thrive in harsh environments and should be enhanced for industrial bioethanol production exploiting their promising fermentation capacity.
Age-Specific Cancer Mortality in the US During the COVID-19 Pandemic, March to December 2020
Authors: Shiels Meredith S. , Haque Anika T. , Freedman Neal D. , Kim Hae-Rin , Berrington de González Amy , Albert Paul S.
Published: June 2024

Background:

It is important to understand the impact of the COVID-19 pandemic on cancer death rates in 2020 in the US. We estimated whether there were larger-than-expected changes in cancer mortality rates from March to December 2020 after accounting for temporal and seasonal patterns using data from January 2011 to February 2020 by cancer type and age.

Methods:

We obtained death counts and underlying causes of death by cancer type, month/year (2011–2020), and age group from the National Center for Health Statistics and population estimates from the US Census Bureau. Poisson regression was used to test for significant changes in cancer death rates from March to December 2020 compared with prior years.

Results:

After accounting for temporal trends and seasonal patterns, total cancer death rates were significantly lower than expected during March to December 2020 among 55- to 64-year-olds and ≥75-year-olds, but not in other age groups. Cancer death rates were 2% lower than expected from March to June among 55- to 64-year-olds and 2% to 3% lower from March to July and December among ≥75-year-olds. Among ≥75-year-olds, colorectal cancer death rates were lower from March to June [rate ratios (RR) = 0.94–0.96; P < 0.05]; however, lung cancer death rates were 5% lower across each month (all RRs = 0.95; P < 0.05).

Conclusions:

In the US, cancer death rates based on the underlying cause of death were broadly similar to expected rates from March to December 2020. However, cancer death rates were lower than expected among 55- to 64-year-olds and ≥75-year-olds, likely due to COVID-19 as a competing cause of death.

Impact:

Cancer mortality rates from 2020 should be interpreted with caution.
Inhibition of Aberrantly Overexpressed Polo-like Kinase 4 Is a Potential Effective Treatment for DNA Damage Repair–Deficient Uterine Leiomyosarcoma
Authors: Lee Horace H.Y. , Chow Kin Long , Wong Ho Shing , Chong Tsz Yan , Wong Alice S.T. , Cheng Grace H.W. , Ko Jasmine M.K. , Siu Hoi Cheong , Yeung Maximus C.F. , Huen Michael S.Y. , Tse Ka Yu , Bray Mark R. , Mak Tak Wah , Leung Suet Yi , Ip Philip P.C.
Published: June 2024

Purpose:

Uterine leiomyosarcoma (LMS) is an aggressive sarcoma and a subset of which exhibits DNA repair defects. Polo-like kinase 4 (PLK4) precisely modulates mitosis, and its inhibition causes chromosome missegregation and increased DNA damage. We hypothesize that PLK4 inhibition is an effective LMS treatment.

Experimental Design:

Genomic profiling of clinical uterine LMS samples was performed, and homologous recombination (HR) deficiency scores were calculated. A PLK4 inhibitor (CFI-400945) with and without an ataxia telangiectasia mutated (ATM) inhibitor (AZD0156) was tested in vitro on gynecologic sarcoma cell lines SK-UT-1, SKN, and SK-LMS-1. Findings were validated in vivo using the SK-UT-1 xenograft model in the Balb/c nude mouse model. The effects of CFI-400945 were also evaluated in a BRCA2-knockout SK-UT-1 cell line. The mechanisms of DNA repair were analyzed using a DNA damage reporter assay.

Results:

Uterine LMS had a high HR deficiency score, overexpressed PLK4 mRNA, and displayed mutations in genes responsible for DNA repair. CFI-400945 demonstrated effective antitumor activity in vitro and in vivo. The addition of AZD0156 resulted in drug synergism, largely due to a preference for nonhomologous end-joining DNA repair. Compared with wild-type cells, BRCA2 knockouts were more sensitive to PLK4 inhibition when both HR and nonhomologous end-joining repairs were impaired.

Conclusions:

Uterine LMS with DNA repair defects is sensitive to PLK4 inhibition because of the effects of chromosome missegregation and increased DNA damage. Loss-of-function BRCA2 alterations or pharmacologic inhibition of ATM enhanced the efficacy of the PLK4 inhibitor. Genomic profiling of an advanced-stage or recurrent uterine LMS may guide therapy.
EASL-EASD-EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Authors:   European Association for the Study of the Liver (EASL),   European Association for the Study of Diabetes (EASD),   European Association for the Study of Obesity (EASO)
Published: June 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), fibrosis, cirrhosis and MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis and treatment for MASLD. Case-finding strategies for MASLD with liver fibrosis, using non-invasive tests, should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes (T2D) or obesity with additional metabolic risk factor(s). A stepwise approach using blood-based scores (such as FIB-4) and, sequentially, imaging techniques (such as transient elastography) is suitable to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes. In adults with MASLD, lifestyle modification – including weight loss, dietary changes, physical exercise and discouraging alcohol consumption – as well as optimal management of comorbidities – including use of incretin-based therapies (e.g. semaglutide, tirzepatide) for T2D or obesity, if indicated – is advised. Bariatric surgery is also an option in individuals with MASLD and obesity. If locally approved and dependent on the label, adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2) should be considered for a MASH-targeted treatment with resmetirom, which demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile. No MASH-targeted pharmacotherapy can currently be recommended for the cirrhotic stage. Management of MASH-related cirrhosis includes adaptations of metabolic drugs, nutritional counselling, surveillance for portal hypertension and HCC, as well as liver transplantation in decompensated cirrhosis.
Estimativa da distância do disparo de arma de fogo através do exame necroscópico
Authors: Muñoz Daniel Romero , Almeida Marcos de
Published: June 2024

A Justiça solicita, frequentemente, ao médico-legista que realiza a autópsia de um baleado, que avalie a distância do disparo da arma de fogo que atingiu o periciando. Esse diagnóstico exige cautela e um exame acurado. Os autores revisaram a literatura, verificando que os diversos tratadistas que se ocuparam da questão enforcaram-na de modo diferente, isto é, não há uma uniformidade de conceitos e de critérios para sua abordagem e sistematização. Com base nos elementos levantados e na experiência pericial, os autores: a) argumentam que o elemento objetivo que o médico-legista dispõe e no qual deve fundamentar sua conclusões - principalmente em nosso meio - é a lesão e, às vezes, o projétil; b) propõem uma classificação médico-legal das modalidades de disparo de arma de fogo, quanto à distância, tomando por base exclusivamente o que pode ser encontrado no exame da lesão de entrada, na tentativa de sistematizar o estudo pericial dos elementos que permitem essa estimativa.
Implicações médico-legais da indicação de tratamento cirúrgico imediato em episódios de cólica nefrética
Authors: Farhat Omar , Miziara Carmen Silvia Molleis Galego , Muñoz Daniel Romero
Published: June 2024

A crescente disponibilidade de equipamentos de imagem com maior precisão diagnóstica e de instrumentos cirúrgicos com tecnologia avançada levaram ao aumento na indicação de tratamentos intervencionistas imediatos após episódio de cólica nefrética. Em associação, o maior acesso da população a informações sobre as doenças e tratamentos tem sido acompanhado pelo aumento de questionamentos judiciais sobre procedimentos endourológicos em vários países. A revisão de literatura mostra que, apesar da evolução técnica e dos equipamentos disponíveis para tratamento cirúrgico endoscópico de cálculos urinários, permanece incidência previsível de complicações nos procedimentos endourológicos em cálculos ureterais. Ações judiciais e consequentes indenizações devidas a erros médicos decorrentes de procedimentos endourológicos estão progressivamente mais frequentes nos Estados Unidos da América e no Brasil.