bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of toileting behavior on daytime non-sedentary behavior in nursing home residents
Authors: Nakano Yuri , Kubota Satoshi , Furudate Takuya
Published: March 2024

Nursing home residents engage in lower levels of physical activity, primarily remaining seated or lying down, except for routine activities of daily living (ADLs). Since ADLs, particularly toileting, require effort. This study investigated the relationship between physical activity and toileting activity during the daytime among elderly nursing home residents.
The study involved 30 participants, including a group of healthy community-dwelling elderly individuals and two groups of nursing home residents with independent and non-independent toileting behavior, respectively. The physical activity of participants was measured with an accelerometer, and estimated metabolic equivalents, duration, and amount of physical activity were calculated.
The amount of physical activity associated with toileting was significantly higher in the independent and non-independent groups than in the community group. Moreover, the amount of non-sedentary physical activity associated with toileting positively affected the amount of non-sedentary physical activity during the daytime. These findings suggest that toileting activity can contribute significantly to the physical activity of elderly nursing home residents.
Interventions focusing on improving toileting behavior among nursing home residents may positively impact overall physical activity and functional abilities.
Electric transmission value and its drivers in United States power markets
Authors: Kemp Julie , Millstein Dev , Gorman Will , Jeong Seongeun , Wiser Ryan
Published: March 2024

Electric transmission infrastructure serves a critical role during extreme weather and supply disruptions and can enable low-cost, low-carbon electricity systems. This paper contributes to a more complete understanding of transmission’s value, cost-effectiveness, and market barriers. By studying wholesale energy market prices in the United States during 2012-2022, we find that additional transfer capacity between regions was especially valuable (median of $116M/GW-year) and directionally balanced. Transmission’s market value was highly influenced by a small fraction of time: 5% of hours typically capture at least 45% of value. These peak periods were driven primarily by unforeseen changes in conditions within one day of operations. Transmission infrastructure cost estimates were less than market values for most studied locations, including all links crossing regional seams where value-to-cost ratios were frequently above 4, suggesting barriers to the development of valuable infrastructure. These results complement forward-looking modeling studies and aid efforts to improve modeling practices.
Global projection of terrestrial vertebrate food webs under future climate and land-use changes
Authors: Yan Chuan , Hao Xiyang , Holyoak Marcel , Zhang Zhicheng
Published: March 2024

Food webs represent an important nexus between biodiversity, ecological communities and ecosystem functioning, and they could be radically changed by anthropogenic climate change and habitat loss. Considering changes in food webs around the world has been limited by data availability, we systematically amassed information about species’ diet, traits, distributions, habitat use, and phylogenetics and used machine learning to predict changes in global and local meta-food webs of terrestrial vertebrates. Terrestrial vertebrate food webs are expected to be greatly changed by the end of this century. Future food webs will be smaller and more densely connected, with systematic declines in predator generality and diversity across trophic groups. Decreases in food-web modularity and connectance will make terrestrial vertebrate communities vulnerable to the propagation of extinctions. Increased species' dispersal could ameliorate these trends. Overall, terrestrial food webs will face increased risks of collapse from climate and land-use change, posing significant challenges to biodiversity conservation.
Streptococcus strain D19 T antibacterial protein reverses the inflammatory damage of respiratory cells induced by Acinetobacter baumannii through ferroptosis
Authors: sun ye , Li Shuyin , Che Yuchen , Liang Hao , Guo Yi , Xiao Chunling
Published: March 2024

Background
Microecological equilibrium is essential for human health. Previous research has demonstrated that Streptococcus strain A, the main bacterial group in the respiratory tract, can suppress harmful microbes and protect the body. In this study, Streptococcus strain D19T was isolated from the oral and pharyngeal cavities of healthy children. Its antibacterial mechanism against Acinetobacter baumannii was examined, as well as its potential to prevent inflammatory damage to cells. We evaluated the effect of the fermentation conditions of D19T on inhibition of Acinetobacter baumannii growth; Isolation and purification of antibacterial active components of strain D19T and molecular mechanism of inhibition of Acinetobacter baumannii; Molecular mechanism of D19T bacteriostatic protein reversing cellular inflammatory injury induced by Acinetobacter baumannii.
Results
The supernatant of fermentation broth of Streptococcus D19T was the active component against Acinetobacter baumannii, but the bacteria had no antibacterial activity. The supernatant of D19T fermentation broth was precipitated by (NH4)2SO4 solution, and the protein was the active antibacterial component. After gel filtration chromatography and anion gel filtration chromatography, the molecular weight of antibacterial protein was 53kD. D19T antibacterial protein can improve cell membrane permeability, limit extracellular soluble protein release, inhibit Acinetobacter baumannii biofilm formation, and prevent Acinetobacter baumannii adhesion. Acinetobacter baumannii induces inflammatory damage to respiratory cells via ferroptosis, and the D19T antibacterial protein can counteract this damage, protecting the respiratory tract.
Conclusion
Streptococcus strain D19T, as a potential probiotic, inhibits the growth of Acinetobacter baumannii and the inflammatory damage of respiratory cells, playing a protective role in human respiratory health.
Subsurface Flow Pathway and Hydrochemistry of a Geographically Isolated Depression Wetland in the Serra Geral Diabase Formation, São Paulo State, Brazil
Authors: Franco Isabella , Sardinha Diego Souza , Furlan Lucas Moreira , Casagrande Matheus Felipe Stanfoca , Moreira César Augusto , Rosolen Vania
Published: March 2024

Connectivity among water bodies is a key of important hydrological and ecological processes and fundamental to water management. Hydrochemistry and potentiometric studies applied on an isolated wetland allow to assess the landscape influence in water, flow pathways, and subsurface connection. This study focus on an isolated wetland developed over diabase on a topographic depression with no visible connection with river and aims to determine the influence of rainfall and landscape on its water composition and to investigate the existence of subsurface flow toward the Santa Gertrudes stream. Water level was monitored, and water samples were collected in the four wells during the wet and dry seasons. Physical and chemical water parameters were measured, and it was determined the concentration of ions of interest. Pearson’s correlations were applied to understand the codependence between physical and chemical parameters and ions and Piper’s diagram allowed to classify the water composition. Six potentiometric maps were generated based on hydraulic loads interpolation derived from each monitoring event. The findings indicate that water levels fluctuate between rainy and dry periods, suggesting direct rainwater influence on water availability. The water composition was categorized as Sodium Bicarbonate, exhibiting seasonal concentration variations. The strong positive correlation between sodium, bicarbonate and carbonate, and sulfate with the electrical conductivity (Ce) and among themselves suggests that these ions are being released simultaneously into water due to the alteration of the rock and soil minerals. Potentiometric data reinforce the hypothesis of a subsurface connection between the studied area and the Santa Gertrudes stream.
Geographic inequalities, and social-demographic determinants of reproductive, maternal and child health at sub-national levels in Kenya.
Authors: Karimi Janette , Cherono Anitah , Alegana Victor , Mutua Martin , Kiarie Hellen , Muthee Rose , Temmerman Marleen , Gichangi Peter
Published: March 2024

Background
Global initiatives have emphasized tracking indicators to monitor progress, particularly in countries with the highest maternal and child mortality. Routine data can be used to monitor indicators for improved targeting. Our objective was to assess the geographic inequalities in estimates of reproductive, maternal and child health indicators from routine data at the subnational level in Kenya.
Methods
Monthly data from 47 counties clustered in 8 regions, from January 2018 to December 2021 were assembled from the District Health Information Software version 2 (DHIS2) in Kenya. This included women of reproductive age receiving family planning commodities, pregnant women completing four antenatal care visits, deliveries conducted by skilled birth attendants, fully immunized children at 1 year and number of maternal deaths at health facilities, from which five indicators were constructed with denominators. A hierarchical Bayesian model was used to generate estimates of the five indicators the at sub-national levels(counties and sub counties), adjusting for four determinants of health. A reproductive, maternal, and child health (RMCH) index was generated from the 5 indicators to compare overall performance across the continuum of care in reproductive, maternal and child health across the different counties.
Results
The DHIS2 data quality for the selected 5 indicators was acceptable with detection of less than 3% outliers for the FMMR and less than 1% for the other indicators. Overall, counties in the north-eastern, eastern and coastal regions had the lowest RMCH index due to low service coverage and high facility maternal mortality. Full immunization coverage at 1 year (FIC) had the highest estimate (79.3% BCI: 77.8–80.5%), while Women of Reproductive age receiving FP commodities had the lowest estimate (38.6% BCI: 38.2–38.9%). Health facility density was an important determinant in estimating all five indicators. Maternal education was positively correlated with higher FIC coverage, while wealthier sub counties had higher FMMR.
Conclusions
Tracking of RMCH indicators revealed geographical inequalities at the County and subcounty level, often masked by national-level estimates. These findings underscore the value of routine monitoring indicators as a potential for evidence-based sub-national planning and precision targeting of interventions to marginalized populations.
A CMOS-integrated terahertz near-field sensor based on an ultra-strongly coupled meta-atom
Authors: Chernyadiev Alexander , But Dmytro , Ivonyak Yurii , Ikamas Kęstutis , Lisauskas Alvydas
Published: March 2024

Recently, plasmonic-based sensors operating in the terahertz frequency range have emerged as perspective tools for rapid and efficient label-free biosensing applications. In this work, we present a fully electronic approach allowing us to achieve state-of-the-art sensitivity by utilizing a near-field-coupled electronic sensor. We demonstrate that the proposed concept enables the efficient implementation and probing of a so-called ultra-strongly coupled sub-wavelength meta-atom as well as a single resonant circuit, allowing to limit the volume of material under test down to a few picoliter range. The sensor has been monolithically integrated into a cost-efficient silicon-based CMOS technology. Our findings are supported by both numerical and analytical models and validated through experiments. They lay the groundwork for near-future developments, outlining the perspectives for a terahertz microfluidic lab-on-chip dielectric spectroscopy sensor.
Clinical subtypes of older adults starting long-term care in Japan and their association with prognoses: a data-driven cluster analysis
Authors: Ito Yuji , Iwagami Masao , Komiyama Jun , Hamasaki Yoko , Kuroda Naoaki , Suzuki Ai , Ito Tomoko , Goto Tadahiro , Wan Eric Y F , Lai Francisco T T , Tamiya Nanako
Published: March 2024

We aimed to identify the clinical subtypes in individuals starting long-term care in Japan and examined their association with prognoses. Using linked medical insurance claims data and survey data for care-need certification in a large city, we identified participants who started long-term care. Grouping them based on 22 diseases recorded in the past 6 months using fuzzy c-means clustering, we examined the longitudinal association between clusters and death or care-need level deterioration within 2 years. We analyzed 4,648 participants (median age 83 [interquartile range 78–88] years, female 60.4%) between October 2014 and March 2019 and categorized them into (i) musculoskeletal and sensory, (ii) cardiac, (iii) neurological, (iv) respiratory and cancer, (v) insulin-dependent diabetes, and (vi) unspecified subtypes. The results of clustering were replicated in another city. Compared with the musculoskeletal and sensory subtype, the adjusted hazard ratio (95% confidence interval) for death was 1.22 (1.05–1.42), 1.81 (1.54–2.13), and 1.21 (1.00–1.46) for the cardiac, respiratory and cancer, and insulin-dependent diabetes subtypes, respectively. The care-need levels more likely worsened in the cardiac, respiratory and cancer, and unspecified subtypes than in the musculoskeletal and sensory subtype. In conclusion, distinct clinical subtypes exist among individuals initiating long-term care.
DAF-16/FOXO and HLH-30/TFEB comprise a cooperative regulatory axis controlling tubular lysosome induction in C. elegans
Authors: Ricaurte-Perez Cristian , Wall P. , Dubuisson Olga , Bohnert K. , Johnson Alyssa E.
Published: March 2024

Although life expectancy has increased, longer lifespans do not always align with prolonged healthspans and, as a result, the occurrence of age-related degenerative diseases continues to increase. Thus, biomedical research has been shifting focus to strategies that enhance both lifespan and healthspan concurrently. Two major transcription factors that have been heavily studied in the context of aging and longevity are DAF-16/FOXO and HLH-30/TFEB; however, how these two factors coordinate to promote longevity is still not fully understood. In this study, we reveal a new facet of their cooperation that supports healthier aging in C. elegans. Namely, we demonstrate that the combinatorial effect of daf-16 and hlh-30 is required to trigger robust lysosomal tubulation, which contributes to systemic health benefits in late age by enhancing cross-tissue proteostasis mechanisms. Remarkably, this change in lysosomal morphology can be artificially induced via overexpression of SVIP, a previously characterized tubular lysosome stimulator, even when one of the key transcription factors, DAF-16, is absent. This adds to growing evidence that SVIP could be utilized to employ tubular lysosome activity in adverse conditions or disease states. Mechanistically, intestinal overexpression of SVIP leads to nuclear accumulation of HLH-30 in gut and non-gut tissues and triggers global gene expression changes that promotes systemic health benefits. Collectively, our work reveals a new cellular process that is under the control of DAF-16 and HLH-30 and provides further insight into how these two transcription factors may be exerting their pro-health effects.
Chromium supplementation and type 2 diabetes mellitus: An extensive systematic review
Authors: Georgaki Maria-Nefeli , Tsokkou Sophia , Keramas Antonios , Papamitsou Theodora , Karachrysafi Sofia , Kazakis Nerantzis
Published: March 2024

Diabetes is a global public health concern with increasing prevalence worldwide. Chromium (Cr), a trace element found in soil, water, and food, has been proposed to have a possible positive effect in glucose metabolism and diabetes mellitus prevention. However, the relationship between trivalent chromium (Cr (III)) exposure, mainly through the consumption of diet supplements, and type 2 diabetes mellitus (T2DM) remains controversial. An extensive systematic review of the current literature on randomized controlled studies (RCTs) was conducted, using the databases, PubMed, Scopus, ScienceDirect, and Cochrane, with specific keywords and inclusion as well as exclusion criteria. After close screening of the research studies retrieved from the mentioned websites was conducted, the most related studies were included in the final systematic review. The studies were evaluated for the degree og relevance, quality, and risk bias, using appropriate quality assessment tools. Several of the included RCT studies reported possible benefits of Cr (III) supplementation, mainly in the form of chromium picolinate (CrPic), chromium yeast (CY), chromium chloride (CrCl3), and chromium nicotinate (CrN). The dosage of chromium was between 50 and 1000 μg/day and it was consumed from 2 to 6 months. Glycemic control markers, including FPG, insulin, HbA1C, and HOMA-IR levels, significantly decrease following chromium supplementation, mainly in studies with a longer intervention period. Supplementing with chromium (Cr) indicated that could significantly improve lipid profile by raising high-density lipoprotein (HDL) and lowering triglyceride (TG) and total cholesterol (TC) while having little effect on low-density lipoprotein (LDL). However, most research findings include significant limitations, such as inconsistent dosage and type of chromium, formulation of supplements, and study duration. Further well-designed and high-quality research is needed to fully understand the role of chromium dietary supplementation and the potential risks related to its mechanisms of action, type, and dose, in the prevention and treatment of type 2 diabetes mellitus (T2DM).
Exploring the Influence of Urbanization on Gut Mycobiota through Dietary Changes in Burkina Faso
Authors: Renzi Sonia , Meriggi Niccolò , Paola Monica Di , Bacci Giovanni , Cerasuolo Benedetta , Gori Agnese , Casari Silene , Banci Elena , de Blasi Alessia , Diallo Salou , Kaborè Berenger , Derra Karim , Tinto Halidou , Filippo Carlotta , De Mast Quirijn , Lionetti Paolo , Cavalieri Duccio
Published: March 2024

Background
How the evolution of dietary habits has impacted the yeasts associated with our gut is largely unknown. The impact of urbanization and globalization on human nutrition and the composition of gut microbial communities are considered driving forces behind the rise in non-communicable diseases. While previous studies in developing countries have investigated changes in the bacterial component of the gut microbiota during the transition from rural to urban areas, the modifications in the intestinal fungal communities are completely unexplored. In this study, we examined the impact of urbanization and dietary shifts on the composition of the gut mycobiota in families residing in rural, semi-urbanized, and urban areas in Burkina Faso. We compared these findings with families living in the urban area of Florence (Italy) as a reference for a globalized lifestyle.
Results
Our research revealed a significant reduction in the alpha diversity of the intestinal mycobiota as individuals transitioned from rural to urban areas. Members of rural households exhibited greater fungal richness and biodiversity compared to those in urban households, including affluent families in the capital city, Ouagadougou. We observed that the fungal diversity varied in households as a function of the rural-to-urban transition gradient, and we identified 33 fungal amplicon sequence variants (ASVs), including 12 fungal species, as associated with distinct areas with specific lifestyle and dietary patterns as indicators of the rural-to-urban transition.
Conclusion
The household-level survey of rural and urban communities in Burkina Faso highlighted the effect of urbanization on the lifestyle and subsequent composition of the participants' intestinal mycobiota. A greater diversity of fungal taxa emerged in the rural cohort, along with the presence of distinct species with potential pathogenic traits. This finding suggests that the continuous exposure to pathogenic fungi and the ensuing interaction with the immune system may contribute to the maintenance of lower incidence and severity of non-communicable diseases (NCDs) in non-globalized communities. In agreement with the “hygiene hypothesis”, the lack of yeast diversity could provide a potential explanation for the higher prevalence of inflammatory and immune-related disorders in urbanized regions across the world.
Directional selection, not the direction of selection, affects telomere length and copy number at ribosomal RNA loci
Authors: Sadler Daniel , Watts Phillip C. , Uusi-Heikkilä Silva
Published: March 2024

Many fisheries exert directional selection on traits such as body size and growth rate. Whether directional selection impacts regions of the genome associated with traits related to growth is unknown. To address this issue, we characterised copy number variation in three regions of the genome associated with cell division, (1) telomeric DNA, (2) loci transcribed as ribosomal RNA (rDNA), and (3) mitochondrial DNA (mtDNA), in three selection lines of zebrafish reared at three temperatures (22°C, 28°C, and 34°C). Selection lines differed in (1) the direction of selection (two lines experienced directional selection for large or small body size) and (2) whether they experienced any directional selection itself. Lines that had experienced directional selection were smaller, had lower growth rate, shorter telomeres, and lower rDNA copy number than the line that experiencing no directional selection. Neither telomere length nor rDNA copy number were affected by temperature. In contrast, mtDNA content increased at elevated temperature but did not differ among selection lines. Though directional selection impacts rDNA and telomere length, direction of such selection did not matter, whereas mtDNA acts as a stress marker for temperature. Future work should examine the consequences of these genomic changes in natural fish stocks.
A Cross-cultural Comparative Study between Chinese and Japanese Preschool Educators’ Use of Mental State Language in Interactions With Children
Authors: Li Hongxin , Lu Zhongjie , Liu Yelin , Han Feifei , Hu Jiangbo
Published: March 2024

Mental state language (MSL) is a language used to describe individual internal states including one’s desire, emotion, perception and cognition. This study compared Chinese and Japanese preschool educators’ use of MSL in interactions with preschool children. Based on ecological systems of educator-child interactions, it analyzed 12 Chinese and 12 Japanese native preschool educators’ use of MSL in interactions with children considering the contextual factors (e.g. educator-child ratio and activity settings). The corpus analysis involved 8453 clauses from spontaneous 30-mintute spontaneous interactions during free play. The findings reveled that Japanese educators used a significantly higher proportion MSL compared to the Chinese educators. Among the four types of MSL, the Chinese educators uttered Cognition with higher frequency and more diverse cognitive terms, while the Japanese cohort used more Desire and Emotion with abundant emotional expressions. Child age is identified as a significant factor influencing educators’ use of MSL. The study discussed how Japanese and Chinese preschool educators provide distinct language experiences for children in different cultural-linguistic contexts, which has implications for worldwide preschool education in multicultural contexts.
Spatiotemporal dynamics of the CD11c+ microglial population in the mouse brain and spinal cord from developmental to adult stages
Authors: Nomaki Kohei , Fujikawa Risako , Masuda Takahiro , Tsuda Makoto
Published: March 2024

CD11c-positive (CD11c+) microglia have attracted considerable attention because of their potential implications in central nervous system (CNS) development, homeostasis, and disease. However, the spatiotemporal dynamics of the proportion of CD11c+ microglia in individual CNS regions are poorly understood. Here, we investigated the proportion of CD11c+ microglia in six CNS regions (forebrain, olfactory bulb, diencephalon/midbrain, cerebellum, pons/medulla, and spinal cord) from the developmental to adult stages by flow cytometry and immunohistochemical analyses using a CD11c reporter transgenic mouse line, Itgax-Venus. We found that the proportion of CD11c+ microglia in total microglia varied between CNS regions during postnatal development. Specifically, the proportion was high in the olfactory bulb and cerebellum at postnatal day P(4) and P7, respectively, and approximately half of the total microglia were CD11c+. The proportion declined sharply in all regions to P14, and the low percentage persisted over P56. In the spinal cord, the proportion of CD11c+ microglia was also high at P4 and declined to P14, but increased again at P21 and thereafter. Interestingly, the distribution pattern of CD11c+ microglia in the spinal cord markedly changed from gray matter at P4 to white matter at P21. Collectively, our findings reveal the differences in the spatiotemporal dynamics of the proportion of CD11c+ microglia among CNS regions from early development to adult stages in normal mice. These findings improve our understanding of the nature of microglial heterogeneity and its dynamics in the CNS.
A quarter century of pollinator research in Cameroon: achievements and opportunities
Authors: Drager Andrea P. , Dounia Dounia
Published: March 2024

Pollinator research is important for supporting food security and ecosystem health. Reviews assessing global or continental-scale trends often find that data from most African countries is lacking. Yet, over the last 25 years, pollination research has grown rapidly in Cameroon, the ecologically diverse “breadbasket” of Central Africa. In this review, we synthesize pollinator research in Cameroon to date, with the aim of informing future research and policy. We summarize work along several axes (research areas, author affiliation, journal type, agroecological zone, crop coverage, and pollinator taxonomic focus) and then discuss the applied plant-pollinator work in greater detail. We find that nationally led research (133/194; 69% of studies) has focused mainly on crop pollinators and their impacts on yield, on melliferous plants and on apiculture. Research has been carried out in all five agroecological zones in the country, with the greatest concentration in the High Guinean savannah. Bees, particularly Apis mellifera, are the most studied pollinator group. International research has focused on eco-evolutionary questions in natural montane systems and along elevational gradients; main taxa studied have been Lepidoptera and sunbirds. Pollinators of wild harvested and plantation tree crops are little studied, as is pollinator health, and the influence of natural areas on pollination services. We suggest how existing work can be leveraged and/or what data is lacking to address key policy-related questions such as: pollinator trends assessments, the importance of natural areas for sustaining pollinator populations, and the impacts of pollination deficits on production.
Unveiling the Lived Experiences of Sexual and Gender Diverse Individuals in Guyana: A Qualitative Investigation into Wellbeing
Authors: Kanhai Gregory , James Drexler
Published: March 2024

Background
While there have been notable improvements in the social conditions of sexual and gender identity minority individuals in Guyana, recent research has identified the persistence of structural heterosexism and discrimination, including the reluctance of the Guyanese government to repeal colonial-era “anti-gay” laws that govern sexual behavior. In this qualitative study, we employed a theoretical framework integrating the Social Determinants of Health, Well-being Domains Theory, and Intersectional Minority Stress Theory to explore the positive and negative experiences of individuals from sexual and gender identity minority groups residing in Guyana.
Methods
Four focus groups were convened that included adult non-heterosexual men, women and transgender persons (Total N = 45). The focus groups prompted discussions about participants’ experiences in various life domains, including social, interpersonal, vocational, healthcare, housing, public spaces, socio-political contexts, significant life events, and personal successes. We used thematic analysis to identify recurring patterns and themes in the participants’ discussions, providing a structured framework for understanding and interpreting their experiences in the specified life domains.
Results
Major positive themes included non-governmental organization support, family acceptance and healthy habit adoption to cope with stress. Negative themes included transportation inaccessibility, job discrimination, and lack of governmental support.
Conclusion
The Guyanese sexual and gender identity minority community is resilient and productive, despite enduring centuries-old social norms in Guyana that ostracize them. They have developed community resilience through the support of NGOs and past government initiatives, yet there remains a significant need for further efforts to achieve social parity. Collaborative initiatives involving both governmental and civil society organizations can play a vital role in dismantling the barriers.
ATM inhibition enhance antitumor immunity of CRC by activating cGAS/STING and NFκB/IRF1/NLRC5 pathway
Authors: Li Chunya , Wang Boyu , Tu Jingyao , Liu Chaofan , Wang Yuan , Chen Junjie , Huang Yongbiao , Liu Bo , Yuan Xianglin
Published: March 2024

Backgroud
Accumulating evidence supports the concept that DNA damage response (DDR) targeted therapies can improve antitumor immune response by increasing the immunogenicity of tumor cells and improving the tumor immune microenvironment. Ataxia telangiectasia mutated (ATM) is a core component of the DNA repair system. Although ATM gene has a significant mutation rate in many human cancers including colorectal, prostate, lung, and breast, it remains understudied compared with other DDR-involved molecules such as PARP and ATR. There is still a vast research opportunity for ATM targeted inhibition in tumors.
Methods
ATM knockout and knockdown colorectal cancer cell lines were used to construct animal models and perform in vitro experiments. KU60019 targets ATM as a drug control. Immunohistochemistry and flow cytometry were used to examine the frequency and functional properties of immune cells in the tumor tissue and tumor-draining lymph nodes. The mechanism was investigated by siRNA, Western blot, immunofluorescence, real-time quantitative PCR and flow cytometry.
Results
Here, we found that either gene knockout or drug intervention, ATM inhibition activated the cGAS/STING pathway in cancer cells, and this effect could be amplified by radiation. In addition, ATM inhibition augmented MHC class I expression in cancer cells and this effect was amplified by radiation and IFNγ, thereby promoting CD8+ T cells to active and kill cancer cells. We found that ATM inhibition in CRC cells leads to activation of canonical NFκB pathway and non-canonical NFκB pathway. Activation of the NFκB pathway in ATM-inhibited cells activated IRF1/NLRC5 pathway, leading to upregulation of MHC class I expression, which was STING independent.
Conclusions
This work indicated that ATM nonsense mutation predicted the clinical benefits of radiotherapy combined with immune checkpoint blockade for patients with CRC. It also provides a molecular mechanism rationale for ATM-targeted agents for patients with CRC.
The effect of smoking on breast cancer screening results in female population:a study in Wu wei, China
Authors: Sun Qian , Hu Junguo , Ye Yancheng , Ma Li , Zhang Xiaoqian , Yang Rui , Huang Yue
Published: March 2024

Objective To construct a pathway analysis model of breast cancer screening population in this region based on Anderson model theory, and explore the influencing factors and pathways of screening results of breast cancer screening population in this region, in order to provide reference for refining breast cancer screening strategies and programs.
Methods Firstly, the distribution of each variable in the detection of breast related diseases was described by single factor analysis, and then a pathway analysis model for screening results of female breast cancer screening population in 2021-2023 was constructed according to the results of factor screening, so as to clarify the influence path and influence coefficient of each factor.
Results A total of 1792 female residents participated in breast cancer screening between 2021 and 2023, and 353 were detected with breast related diseases, with a detection rate of 19.7%. Single factor analysis showed that: Exposure to harmful substances, age, highest education, marital status, family history of breast cancer, menopause, weekly intake of fresh vegetables and fruits, weekly intake of processed foods, weekly intake of meat, eggs and milk, taste preference, preferred food or drink temperature, smoking, alcohol consumption, regular physical exercise, history of breast biopsy or breast benign Variables such as history of surgery and history of chest radiotherapy were different in whether breast related disease was detected. The result of path analysis model shows that the overall model fits well. The most significant variable of propensity characteristic dimension is the highest education; The significant variable in the dimension of medical behavior was smoking. The path coefficient indicates that the female population with lower education and smoking is more likely to detect mamma-related lesions in the screening population. In addition to the direct effect, the highest degree of education also had an indirect effect on whether breast related lesions were detected in the female screening population through the mediating variable of smoking.
Conclusion The results of this study confirm the importance of a healthy lifestyle. We should further strengthen the publicity and education on smoking cessation, and persuade smokers, especially pay attention to the promotion of smoking cessation behavior in the female population with low education level.
Towards quantitative cognitive-behavioural models of psychopathology: An active inference account of social anxiety disorder
Authors: Jin Frances , Zhang Yinghao , Hedley Friederike , Zhang Ru-Yuan
Published: March 2024

Understanding the mechanisms underlying psychopathology is a central goal in clinical science. While existing theories have demonstrated high clinical utility, they have provided limited quantitative and experimentally falsifiable explanations of psychopathological mechanisms. Previous computational modelling studies have primarily focused on isolated factors, posing challenges for advancing clinical theories. To address this gap and leverage the strengths of clinical theories and computational modelling in a synergetic manner, it is crucial to develop a quantitative model that integrates major vulnerability factors within a comprehensive psychopathological model. In this study, using social anxiety disorder (SAD) as an example, we present a novel approach by combining active inference modelling, an innovative computational approach that elucidates human cognition and action, with cognitive-behavioural theory (CBT), a well-established clinical framework. This CBT-informed quantitative account integrates multiple vulnerability factors to elucidate the psychopathology of SAD. Through a series of simulations, we systematically delineate their effects on pathological behaviours. This resultant model inherits the conceptual comprehensiveness of CBT and the quantitative rigor of active inference modelling, revealing previously elusive pathogenetic pathways and enabling the formulation of specific predictions for empirical studies. Furthermore, this resultant model provides a strong theoretical foundation for precision medicine in SAD by allowing for individual differences in the symptom development trajectory. Overall, this research presents the first quantitative model of SAD that unifies major pathogenesis factors proposed by CBT. It highlights the feasibility and potential of integrating clinical theory and computational modelling to advance our understanding of psychopathology.
Significance of Liquid-Liquid Phase Separation-related Genes in the Prognostic Assessment of Oral Squamous Cell Carcinoma: A Multi-omics Analysis
Authors: Luo Ding , Li Huan , Jing Jie
Published: March 2024

Background
Liquid-liquid phase separation (LLPS) is implicated in tumorigenesis and progression, yet its role in oral squamous cell carcinoma (OSCC) remains unexplored. This study aims to identify LLPS-associated genes in OSCC and develop a prognostic assessment model.
Methods
We analyzed 334 OSCC and 32 normal samples from the TCGA-HNSC cohort. Inclusion criteria encompassed histologically verified primary OSCC, mRNA profiles, and pertinent clinical data, while samples with no survival status or survival time less than 30 days were excluded. The final cohort consisted of 297 OSCC patients with complete data on age, gender, TNM staging, and grading. We utilized single-cell sequencing data from GEO (GSE103322), with GSE42743 as the validation cohort. LLPS-related genes from DrLLPS were employed, and key genes were identified through weighted co-expression network and clustering analysis. Prognostic models were developed using Coxboost, Lasso regression, and Stepcox regression. Additionally, immune infiltration analysis was conducted to study the immune microenvironment of OSCC.
Results
The study established a predictive model based on eight LLPS-related genes in OSCC (VRK1, PLK1, POLE2, ESCO2, NEIL3, CENPI, GAS2L3, STIL). OSCC patients were stratified into two groups: high-risk and low-risk, with the high-risk group exhibiting significantly poorer prognosis (p < 0.05). Furthermore, notable differences in the immune environment were also observed between the groups.
Conclusions
This study identified eight LLPS-associated genes critical for OSCC prognosis and immune status, leading to the development of a predictive model. This research holds significance for advancing OSCC diagnosis and treatment strategies.
Vaulting Further: Cranial Vault Expansion for Craniocerebral Disproportion without Primary Craniosynostosis
Authors: Ng Jinggang J. , Saikali Linda M. , Zapatero Zachary D. , Massenburg Benjamin B. , Wu Meagan , Romeo Dominic J. , Heuer Gregory G. , Bartlett Scott P. , Taylor Jesse A. , Swanson Jordan W. , Lang Shih-Shan
Published: March 2024

Purpose:
Treatment of subjects with refractory idiopathic intracranial hypertension (IIH) or shunted hydrocephalus with chronic shunt complications is challenging. What is the role for cranial vault expansion, particularly utilizing posterior vault distraction osteogenesis (PVDO), in these cases? This study assesses medium-term efficacy of cranial vault expansion in this unique patient population.
Methods:
A retrospective review was conducted of patients who underwent cranial vault expansion from 2008 to 2023 at the Children’s Hospital of Philadelphia. Subjects who did not have a diagnosis of primary craniosynostosis were included in the study. Demographic information, medical history, and perioperative details were collected from medical records. Primary outcomes were the rate of CSF diversion procedures and resolution of presenting signs and symptoms. Secondary outcomes were perioperative and 90-day complications and reoperation requirement.
Results:
Among 13 included subjects, nine (69.2%) patients had a primary diagnosis of shunted hydrocephalus and 4 (30.8%) patients had IIH. Twelve (92.3%) subjects underwent posterior vault distraction osteogenesis (PVDO) and one (7.7%) underwent posterior vault remodeling (PVR). All 4 patients with IIH demonstrated symptomatic improvement following PVDO, including resolution of headaches, vomiting, and/or papilledema. Among 9 patients with shunted hydrocephalus, CSF diversion requirement decreased from 2.7 ± 1.6 procedures per year preoperatively to 1.2 ± 1.8 per year following cranial vault expansion (p=0.030). The mean postoperative follow-up was 4.1 ± 2.1 years and four (30.8%) patients experienced complications within 90 days of surgery, including infection (n=2), CSF leak (n=1), and elevated ICP requiring lumbar puncture (n=1). Four (30.8%) patients underwent repeat cranial vault expansion for recurrence of ICP-related symptoms. At most recent follow-up, 7 of 9 patients with shunted hydrocephalus demonstrated symptomatic improvement.
Conclusion:
Cranial vault expansion reduced intracranial hypertension-related symptomology as well as the rate of CSF diversion-related procedures in patients with refractory IIH and shunted hydrocephalus without craniosynostosis, and should be considered in those who have significant shunt morbidity.
Investigating the Roles of YWHAB in Breast Cancer
Authors: Winstone Lacey , Gatien Beatrice G , GOPAUL VAISHNAVI L , NAULT BRAYDON DARRYL , Sujit Maiti , OPPERMAN REID MORGAN , Majumder Mousumi
Published: March 2024

Background: miR-526b and miR-655 have been shown to promote aggressive breast cancer phenotypes. Analysis of cell-free secretions of MCF7-miRNA-high cells identified eight differentially secreted proteins, including 14-3-3 Beta (YWHAB). Here, we investigated the roles of YWHAB in breast cancer and tested its potential as a biomarker.
Methods: Breast tumor cell lines MCF7, SKBR3, Hs578T, MCF7-COX2 and stable miRNA-overexpressing MCF7-miR526b, MCF7-miR655, SKBR3-526b cells were used in vitro assays including mRNA, protein expression, and functional assays. In silico data was used to support our findings by identifying potential links between miRNAs and YWHAB and to test diagnostic and prognostic biomarker potential. Biomarker potential was validated using breast tumor biopsy tissue and plasma samples.
Results:
YWHAB expression is significantly upregulated in miRNA-overexpressing cell lines both at total RNA and secretory RNA levels. These miRNAs have previously been shown to increase cell migration. Following YWHAB-KD cell migration and proliferation decreased, E-Cad expression increased, and Vimentin decreased, evidently showing YWHAB involved in EMT. In silico data showed increased expression of YWHAB mRNA in breast cancer biopsy tissue and blood plasma and increased YWHAB protein in breast tumors. High expression of YWHAB is associated with poor breast cancer patient survival. YWHAB expression was measured in breast tissues and blood plasma and found to be significantly high in all advanced stages and hormonal subtypes of tumors, compared to control tissue. YWHABshowed high sensitivity as a tumour biomarker (AUC of 0.7340, p = 0.0012) and in combination with pri-miR526b showed strong potential as a blood biomarker (AUC of 0.711, p = 0.032).
Conclusion:
High expression of YWHAB is associated with poor survival. It can be used as a prognostic marker, and therapeutic target in aggressive cancers to mitigate cell migration. In combination with pri-miR526b, YWHAB is a promising blood biomarker for breast cancer detection.
Characteristic alterations of dynamic amplitude of low-frequency fluctuation in patients with post-stroke depression
Authors: Lu Qiuhong , Lu Shunzu , Wang Xue , Huang Yanlan , Liu Jie , Huang Qiuhui , Huang Hua , Liang Zhijian
Published: March 2024

The abnormalities in static brain activity in patients with post-stroke depression (PSD) have been widely reported. However, the dynamics of neural activity in PSD remain enigmatic. We investigated the abnormalities in dynamic neural activity in patients with PSD with the dynamic amplitude of low-frequency fluctuation (dALFF) method. Imaging and clinical data from 25 patients with PSD and 28 without PSD collected from April 2020 to June 2023 were evaluated. The between-group comparisons of dALFF variance and state properties were conducted using a combined approach of sliding window and clustering analysis. The correlation coefficients between abnormal dALFF variance and ALFF in the distinguished regions (DRs) and depression severity of PSD were calculated. Compared with that in patients without PSD, decreased dALFF variance in patients with PSD was mainly located in lower dALFF variance in multiple emotion-related brain regions. The dALFF was clustered into four states in all patients. In particular, state 3 was the remarkably distinct state that dwelled for more time in the PSD group. There was a negative correlation between decreased dALFF variance in the right parietal cortex and Hamilton Rating Scale for Depression (HAMD) scores in patients with PSD. ALFF values in the DRs showed no correlation with the HAMD score. Our results suggest that patients with PSD showed characteristic alterations in dynamic regional neural activity, which might be regarded as potential neural mechanisms of PSD. This study demonstrates the dynamic features of neural activity in PSD, which may advance future neuroimaging studies.
Association between Hematocrit in the First Two Hours of Life and Retinopathy during Prematurity: A Retrospective Study from DRYAD
Authors: Kong Xiaohui , Wang Huabin , Yang Ru , Zhang Min , Li Chengshuai , Zhang Rui , Wei Lihua , Xu Jing , Xueyun Ren
Published: March 2024

Introduction:
Our study investigated the association between hematocrit in the first two hours (HCT2h) of life and retinopathy of prematurity (ROP).
Methods
Data were obtained from an observational study of the DRYAD database. The study was conducted at the Santa Clara Valley Medical Center (SCVMC). Data on preterm babies whose gestational age (GA) was < 34 weeks were collected prospectively from January 2008 to February 2014. Logistic regression was applied to explore the association between HCT2h and ROP.
Results
A total of 326 very preterm infants born at or earlier than 34 weeks were included. The incidence of any ROP was 23.9%, and the incidence of severe ROP was 4.6%. The HCT2h, birth weight, GA, Apgar1 min, and Apgar5 min of any ROP group were significantly lower than those of preterm babies without ROP (p < 0.001). Sex differences, the rate of multiples, and delivery mode between the two groups were not statistically significant (p > 0.05). We classified HCT2h into three levels, and after multivariate logistic regression, we found that high HCT2h remained a significant protective factor against ROP (p < 0.001). Through subgroup analysis, we observed that among preterm infants with a GA of 28 weeks or more, there was a significant inverse association between a 1% increase in HCT2h and a 17% reduction in the occurrence of ROP.
Conclusion
We found that a greater HCT2h was associated with a lower incidence of ROP among preterm infants born between 28 and 34 weeks of gestation.
Trial registration:
This was a retrospective study and the data were from the DRYAD database. Santa Clara Valley Medical Center’s (SCVMC) ethical committee reviewed and approved the studies involving human participants. The participants provided their written informed consent to participate in this study. We did not perform any extra interventions.