bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimal systemic therapy in men with low-volume prostate cancer
Authors: Saxena Akshat , Andrews Jack , Bryce Alan Haruo , Riaz Irbaz Bin 
Published: March 2024

Purpose of review
Low-volume prostate cancer is an established prognostic category of metastatic hormone-sensitive prostate cancer. However, the term is often loosely used to reflect the low burden of disease across different prostate cancer states. This review explores the definitions of low-volume prostate cancer, biology, and current evidence for treatment. We also explore future directions, including the impact of advanced imaging modalities, particularly prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scans, on refining patient subgroups and treatment strategies for patients with low-volume prostate cancer.

Recent findings
Recent investigations have attempted to redefine low-volume disease, incorporating factors beyond metastatic burden. Advanced imaging, especially PSMA PET, offers enhanced accuracy in detecting metastases, potentially challenging the conventional definition of low volume. The prognosis and treatment of low-volume prostate cancer may vary by the timing of metastatic presentation. Biomarker-directed consolidative therapy, metastases-directed therapy, and de-escalation of systemic therapies will be increasingly important, especially in patients with metachronous low-volume disease.

Summary
In the absence of validated biomarkers, the management of low-volume prostate cancer as defined by CHAARTED criteria may be guided by the timing of metastatic presentation. For metachronous low-volume disease, we recommend novel hormonal therapy (NHT) doublets with or without consolidative metastasis-directed therapy (MDT), and for synchronous low-volume disease, NHT doublets with or without consolidative MDT and prostate-directed radiation. Docetaxel triplets may be a reasonable alternative in some patients with synchronous presentation. There is no clear role of docetaxel doublets in patients with low-volume disease. In the future, a small subset of low-volume diseases with oligometastases selected by genomics and advanced imaging like PSMA PET may achieve long-term remission with MDT with no systemic therapy.
Prevention, diagnosis, and treatment of urolithiasis in geriatric patients - differences, similarities and caveats in comparison to the general population
Authors: Schrag Tarek A. , Diarra Danielle , Veser Julian 
Published: March 2024

Purpose of review
Purpose of the review is to address management and prevention of urolithiasis in elderly patients examining the dynamic interplay between general measures, dietary adjustments, lifestyle modifications, and targeted pharmacological and/ or surgical interventions. The goal is to provide understanding of the evolving strategies required for effective urolithiasis prevention in the geriatric population.

Recent findings
Age-specific diagnostic considerations are necessary because urolithiasis in the elderly population is characterized by bigger stones, greater peri-operative risks, and heightened symptom severity. When comorbidities are present, conservative treatments – especially analgesia – provide difficulties. Surgical procedures prove to be safe and effective, with complication rates and practical application comparable to younger cohorts. Prevention approaches that include lifestyle changes and the investigation of novel pharmaceutical options such as sodium-dependent glucose co-transporter 2 (SGLT-2)-inhibitors are promising in the management of urolithiasis in the elderly population.

Summary
Our review offers a thorough investigation of urolithiasis in the elderly population, elucidating distinct clinical manifestations, complex diagnostic issues, and treatment implications. The safety and effectiveness of ureteroscopy in older patients, as well as the possible prophylactic function of SGLT-2-I, offer crucial insights for clinicians. Subsequent studies are necessary to enhance age-specific therapies, addressing the distinct obstacles presented by urolithiasis in the elderly population within this rapidly growing demographic.
Healthcare Burden and Resource Utilization After Pediatric Acute Respiratory Distress Syndrome: A Secondary Analysis of the Collaborative Pediatric Critical Care Research Network Acute Respiratory Distress Syndrome Study
Authors: Ames Stefanie G. , Maddux Aline B. , Burgunder Lauren , Meeks Huong , Fink Erica L. , Meert Kathleen L. , Zinter Matt S. , Mourani Peter M. , Carcillo Joseph A. , Carpenter Todd , Pollack Murray M. , Mareboina Manvita , Notterman Daniel A. , Sapru Anil ,   for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network (CPCCRN)
Published: March 2024

OBJECTIVES:To describe family healthcare burden and health resource utilization in pediatric survivors of acute respiratory distress syndrome (ARDS) at 3 and 9 months.DESIGN:Secondary analysis of a prospective multisite cohort study.SETTING:Eight academic PICUs in the United States (2019–2020).PATIENTS:Critically ill children with ARDS and follow-up survey data collected at 3 and/or 9 months after the event.INTERVENTIONS:None.METHODS AND MEASUREMENT:We evaluated family healthcare burden, a measure of healthcare provided by families at home, and child health resource use including medication use and emergency department (ED) and hospital readmissions during the initial 3- and 9-month post-ARDS using proxy-report. Using multivariable logistic regression, we evaluated patient characteristics associated with family healthcare burden at 3 months.MAIN RESULTS:Of 109 eligible patients, 74 (68%) and 63 patients (58%) had follow-up at 3- and 9-month post-ARDS. At 3 months, 46 families (62%) reported healthcare burden including (22%) with unmet care coordination needs. At 9 months, 33 families (52%) reported healthcare burden including 10 families (16%) with unmet care coordination needs. At month 3, 61 patients (82%) required prescription medications, 13 patients (18%) had ED visits and 16 patients (22%) required hospital readmission. At month 9, 41 patients (65%) required prescription medications, 19 patients (30%) had ED visits, and 16 (25%) required hospital readmission were reported. Medication use was associated with family healthcare burden at both 3 and 9 months. In a multivariable analysis, preillness functional status and chronic conditions were associated with healthcare burden at month 3 but illness characteristics were not.CONCLUSIONS:Pediatric ARDS survivors report high rates of healthcare burden and health resource utilization at 3- and 9-month post-ARDS. Future studies should assess the impact of improved care coordination to simplify care (e.g., medication management) and improve family burden.
Targeting fin whale conservation in the North-Western Mediterranean Sea: insights on movements and behaviour from biologging and habitat modelling
Authors: Panigada Viola , Bodey Thomas W. , Friedlaender Ari , Druon Jean-Noël , Huckstädt Luis A. , Pierantonio Nino , Degollada Eduard , Tort Beatriu , Panigada Simone 
Published: March 2024

Biologging and habitat modelling are key tools supporting the development of conservation measures and mitigating the effects of anthropogenic pressures on marine species. Here, we analysed satellite telemetry data and foraging habitat preferences in relation to chlorophyll-a productivity fronts to understand the movements and behaviour of endangered Mediterranean fin whales (
Balaenoptera physalus)
during their spring–summer feeding aggregation in the North-Western Mediterranean Sea. Eleven individuals were equipped with Argos satellite transmitters across 3 years, with transmissions averaging 23.5 ± 11.3 days. Hidden Markov Models were used to identify foraging behaviour, revealing how individuals showed consistency in their use of seasonal core feeding grounds; this was supported by the distribution of potential foraging habitat. Importantly, tracked whales spent most of their time in areas with no explicit protected status within the study region. This highlights the need for enhanced time- and place-based conservation actions to mitigate the effects of anthropogenic impacts for this species, notably ship strike risk and noise disturbance in an area of exceptionally high maritime traffic levels. These findings strengthen the need to further assess critical habitats and Important Marine Mammal Areas that are crucial for focused conservation, management and mitigation efforts.
Energy input, habitat heterogeneity and host specificity drive avian haemosporidian diversity at continental scales
Authors: Darío Hernandes Córdoba Oscar , Torres-Romero Erik Joaquín , Villalobos Fabricio , Chapa-Vargas Leonardo , Santiago-Alarcon Diego 
Published: March 2024

The correct identification of variables affecting parasite diversity and assemblage composition at different spatial scales is crucial for understanding how pathogen distribution responds to anthropogenic disturbance and climate change. Here, we used a database of avian haemosporidian parasites to test how the taxonomic and phylogenetic diversity and phylogenetic structure of the genera
Plasmodium
,
Haemoproteus
and
Leucocytozoon
from three zoogeographic regions are related to surrogate variables of Earth's energy input, habitat heterogeneity (climatic diversity, landscape heterogeneity, host richness and human disturbance) and ecological interactions (resource use), which was measured by a novel assemblage-level metric related to parasite niche overlap (degree of generalism). We found that different components of energy input explained variation in richness for each genus. We found that human disturbance influences the phylogenetic structure of
Haemoproteus
while the degree of generalism explained richness and phylogenetic structure of
Plasmodium
and
Leucocytozoon
genera. Furthermore, landscape attributes related to human disturbance (human footprint) can filter
Haemoproteus
assemblages by their phylogenetic relatedness. Finally, assembly processes related to resource use within parasite assemblages modify species richness and phylogenetic structure of
Plasmodium
and
Leucocytozoon
assemblages. Overall, our study highlighted the genus-specific patterns with the different components of Earth's energy budget, human disturbances and degree of generalism.
Hospital admissions for acute respiratory tract infections among infants from Nunavut and the burden of respiratory syncytial virus: a 10-year review in regional and tertiary hospitals
Authors: Kinshella Mai-Lei Woo , Allen Jean , Pawa Jasmine , Papenburg Jesse , Jetty Radha , Dwilow Rachel , Embree Joanne , Robinson Joan , Arbour Laura , Sadarangani Manish , Shen Ye , Bone Jeffrey N. , Walker Celia , Kayda Iryna , Sheffield Holden , Scott Darcy , Miners Amber , Goldfarb David M. 
Published: March 2024

AbstractBackgroundNunavut is a northern Canadian territory in Inuit Nunangat (Inuit homeland in Canada). Approximately 85% of the population identifies as Inuit. A high proportion of infants in Nunavut are admitted to hospital with acute respiratory tract infection (ARI) but previous studies have been limited in regional and/or short duration of coverage. This study aimed to estimate the incidence rate, microbiology and outcomes of ARI hospitalizations in Nunavut infants.MethodsWe conducted chart reviews with a retrospective cohort of infants aged <1 year from Nunavut at six Canadian hospitals, including two regional and four tertiary pediatric hospitals January 1, 2010, to June 30, 2020. Descriptive statistics and multivariable logistic regression were performed.ResultsWe identified 1189 ARI admissions of infants during the study period, with an incidence rate of 133.9 per 1000 infants per year (95% confidence interval (CI): 126.8, 141.3). Of these admissions, 56.0% (n=666) were to regional hospitals alone, 72.3% (n=860) involved hospitalization outside of Nunavut, 15.6% (n=185) were admitted into intensive care, and 9.2% (n=109) underwent mechanical ventilation. Of the 730 admissions with a pathogen identified, 45.8% had respiratory syncytial virus (RSV; n=334), for a yearly incidence rate of 37.8 hospitalizations per 1000 infants (95% CI: 33.9, 42.1). Among RSV hospitalizations, 41.1% (n=138) were infants 0-2 months of age and 32.1% (n=108) were > 6months.InterpretationUnderstanding the high burden of ARI among Nunavut infants can inform health policy and serve as a baseline for assessing the impact of any new interventions targeting infant ARIs.
Vividness of Visual Imagery Supported by Intrinsic Structural-Functional Brain Network Dynamics
Authors: Kvamme Timo L. , Lumaca Massimo , Zana Blanka , Paunovic Dunja , Silvanto Juha , Sandberg Kristian 
Published: March 2024

AbstractVividness of visual imagery is subject to individual variability, a phenomenon with largely unexplored neurobiological underpinnings. By analyzing data from 273 participants we explored the link between the structural-functional organization of brain connectomes and the reported intensity of visual imagery (measured with VVIQ-2). Employing graph theory analyses we investigated both the structural (DTI) and functional (rs-fMRI) connectomes within a network of regions often implicated in visual imagery. Our results indicate a relationship between increased local efficiency and clustering coefficients in the structural connectome in individuals who experience more vivid visual imagery. Increased local efficiency and clustering coefficients were mirrored in the functional connectome with increases in left inferior temporal regions, a region frequently identified as a critical hub in the visual imagery literature. Furthermore, individuals with more vivid imagery were found to have lower levels of global efficiency in their functional connectome. We propose that the clarity and intensity of visual imagery are optimized by a network organization characterized by heightened localized information transfer and interconnectedness. Conversely, an excessively globally integrated network might dilute the specific neural activity crucial for generating vivid visual images, leading to less locally concentrated resource allocation in key regions involved in visual imagery vividness.
Development of a Bipyrimidineamide based α-Helix Mimetic Lead Compound for efficient Targeting of MDM2 in Triple-Negative Breast Cancer
Authors: On Jasmin Linh , Woloschin Vitalij , Gier Franziska , Tu Jia-Wey , Bhatia Sanil , Lenz Thomas , Kulik Andrea , Stühler Kai , Niederacher Dieter , Neubauer Hans , Fehm Tanja , Kurz Thomas , Esser Knud 
Published: March 2024

AbstractAbstract FigureTriple-negative breast cancer (TNBC) represents the most aggressive form among breast carcinoma subtypes. Due to limited therapy options, identification of novel active pharmacological compounds is an urgent medical need. A promising approach in cancer treatment is the pharmacological inhibition of murine double minutes 2 (MDM2)-p53/p73 interactions inducing apoptosis in tumors. We here describe a novel bipyrimidineamide based α-helix mimetic9(VWK603) which was designed as a lead candidate to target MDM2.9(VWK603) potently induced cell death in the TNBC cell lines MDA-MB-231, MDA-MB-436 and MDA-MB-468 with IC50values ranging between 3.7 µM and 6.6 µM. The anti-tumor activity was about four more potent higher than determined for the MDM2-specific inhibitor Nutlin-3a. Mechanistic analysis revealed induction of cellular apoptosis as the underlying mode of action of9(VWK603) anti-tumor activity. Since toxicity was observed to be reduced in non-cancerous breast cells, these studies make9(VWK603) a promising candidate for further preclinical MDM2 inhibitor development.
DUAL: deep unsupervised simultaneous simulation and denoising for cryo-electron tomography
Authors: Zeng Xiangrui , Ding Yizhe , Zhang Yueqian , Uddin Mostofa Rafid , Dabouei Ali , Xu Min 
Published: March 2024

AbstractRecent biotechnological developments in cryo-electron tomography allow direct visualization of native sub-cellular structures with unprecedented details and provide essential information on protein functions/dysfunctions. Denoising can enhance the visualization of protein structures and distributions. Automatic annotation via data simulation can ameliorate the time-consuming manual labeling of large-scale datasets. Here, we combine the two major cryo-ET tasks together in DUAL, by a specific cyclic generative adversarial network with novel noise disentanglement. This enables end-to-end unsupervised learning that requires no labeled data for training. The denoising branch outperforms existing works and substantially improves downstream particle picking accuracy on benchmark datasets. The simulation branch provides learning-based cryo-ET simulation for the first time and generates synthetic tomograms indistinguishable from experimental ones. Through comprehensive evaluations, we showcase the effectiveness of DUAL in detecting macromolecular complexes across a wide range of molecular weights in experimental datasets. The versatility of DUAL is expected to empower cryo-ET researchers by improving visual interpretability, enhancing structural detection accuracy, expediting annotation processes, facilitating cross-domain model adaptability, and compensating for missing wedge artifacts. Our work represents a significant advancement in the unsupervised mining of protein structures in cryo-ET, offering a multifaceted tool that facilitates cryo-ET research.
Adult Neurogenesis Reconciles Flexibility and Stability of Olfactory Perceptual Memory
Authors: Sakelaris Bennet , Riecke Hermann 
Published: March 2024

AbstractIn brain regions featuring ongoing plasticity, the task of quickly encoding new information without overwriting old memories presents a significant challenge. In the rodent olfactory bulb, which is renowned for substantial structural plasticity driven by adult neurogenesis and persistent turnover of dendritic spines, we show that by synergistically combining both types of plasticity this flexibility-stability dilemma can be overcome. To do so, we develop a computational model for structural plasticity in the olfactory bulb and show that it is the maturation process of adult-born neurons that enables the bulb to learn quickly and forget slowly. Particularly important are the transient enhancement of the plasticity, excitability, and susceptibility to apoptosis that characterizes young neurons. The model captures many experimental observations and makes a number of testable predictions. Overall, it identifies memory consolidation as an important role of adult neurogenesis in olfaction and exemplifies how the brain can maintain stable memories despite ongoing extensive neurogenesis and synaptic plasticity.
Prevalent fast evolution of genes involved in heterochromatin functions
Authors: Lin Leila , Huang Yuheng , McIntyre Jennifer , Chang Ching-Ho , Colmenares Serafin , Lee Yuh Chwen G. 
Published: March 2024

AbstractHeterochromatin is a gene-poor and repeat-rich genomic compartment universally found in eukaryotes. Despite its low transcriptional activity, heterochromatin plays important roles in maintaining genome stability, organizing chromosomes, and suppressing transposable elements (TEs). Given the importance of these functions, it is expected that the genes involved in heterochromatin regulation would be highly conserved. Yet, a handful of these genes were found to evolve rapidly. To investigate whether these previous findings are anecdotal or general to genes modulating heterochromatin, we compile an exhaustive list of 106 candidate genes involved in heterochromatin functions and investigate their evolution over short and long evolutionary time scales inDrosophila.Our analyses find that these genes exhibit significantly more frequent evolutionary changes, both in the forms of amino acid substitutions and gene copy number change, when compared to genes involved in Polycomb-based repressive chromatin. While positive selection drives amino acid changes within both structured domains with diverse functions and intrinsically disordered regions (IDRs), purifying selection may have maintained the proportions of IDRs of these proteins. Together with the observed negative associations between evolutionary rates of these genes and genomic TE abundance, we propose an evolutionary model where the fast evolution of genes involved in heterochromatin functions is an inevitable outcome of the unique functional roles of heterochromatin, while the rapid evolution of TEs may be an effect rather than cause. Our study provides an important global view of the evolution of genes involved in this critical cellular domain and provides insights into the factors driving the distinctive evolution of heterochromatin.
GDOP: A graph convolutional network-based drug “on-target” pathway prediction algorithm
Authors: Wu Xiaolong , Zhang Lehan , Zheng Mingyue 
Published: March 2024

AbstractSince most compounds do not induce changes in the transcriptomic levels of their target proteins in vivo, traditional gene set enrichment analysis methods can only retrieve downstream differentially expressed genes, which offer little hints to their targets. To address this problem, we proposed a graph convolutional network-based drug “on-target” pathway prediction algorithm, GDOP, which can predict small pathways that contain target gene through the power of deep learning algorithms. Our model receives as input structural information and biological characteristics (gene expression profiles) of molecules. After being trained on the publicly available LINCS data set, GDOP showed better generalization ability, reaching an AUC-ROC of 0.89 and an averaged Top10 accuracy of 0.63 on the test set. Besides, demonstrated that GDOP was able to use RNA-Seq data as input and achieved accuracy prediction results.
Does What You Eat Affect How You Mate? Disentangling the Interactions Between Diet-Induced Phenotypic Plasticity and Adult Reproductive Strategies in Black Soldier Flies
Authors: Zhang Qi-Hui , Ng Keng Hee , Chin Wells Shijian , Tang Yong Jen , Lin Jielin , Puniamoorthy Nalini 
Published: March 2024

AbstractPhenotypic plasticity enables organisms to response to environmental variations by generating a range of phenotypes from a single genotype. In holometabolous insects, traits that influence larval plasticity may hold relevance for adult life history strategies. We present a comprehensive investigation into phenotypic plasticity in black soldier flies, a species known for its efficient waste-to-biomass conversion in the larval stage. Here, we document adult sex-specific plastic responses and reproductive strategies shaped by larval diets. We examined traits including adult body size, reproductive organ development, sperm length, mating behaviours, egg production and other life history parameters across different treatments. Our findings reveal notable sex-specific differences in phenotypic plasticity, with females showing increased plasticity in reproductive investment. Furthermore, males and females differed starkly in allometric growth and weight ratio of reproductive organs. Diets that facilitated longer male lifespans also prompted earlier male emergence suggesting an interplay between lifespan and degree of protandry. This maximizes the overlap of male and female lifespans, thereby enhancing mating success in diverse environmental conditions. Our results reveal plastic responses in mating behaviours, where diets producing smaller adults, smaller reproductive organs, and shorter sperm correlated with significantly enhanced mating effort and performance. This study highlights the complex interactions between nutrition, development, and reproductive strategies, and has significant implications for the insect bioconversion industries.