bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of white blood cell parameters with metabolic syndrome: A systematic review and meta-analysis of 168,000 patients
Authors: Mahmood Aysal , Haider Hoorain , Samad Saba , Kumar Danisha , Perwaiz Aimen , Mushtaq Rabeea , Ali Abraish , Farooq Muhammad Zain , Farhat Hadi 
Published: March 2024

Background:
Leukocyte parameters are predicted to be affected in patients with metabolic syndrome (MetS). We conducted a systematic review and meta-analysis to study the association between white blood cell parameters (WBC) in people with and without MetS.

Methods:
PubMed, EMBASE, Scopus and Cochrane Library databases were searched according to the study protocol. The standardized mean difference (SMD) and 95% confidence intervals (CI) of leukocyte markers between individuals with and without MetS were pooled using an inverse variance model. Additionally, a subgroup analysis by sex was performed where possible. Methodological quality assessment was conducted using the Newcastle-Ottawa scale (NOS) for observational studies and the Cochrane Risk of Bias tool 2.0 for Randomized Controlled Trials (RCTs).

Results:
Of 6068 articles identified, 63 were eligible for the study. Compared to controls, individuals with MetS showed significantly higher concentrations of total leukocyte count (SMD [95% CI]: 0.60 [0.55–0.65]; P < .00001; I
2 = 100%), neutrophil counts (0.32 [0.28–0.37]; P < .00001; I
2 = 99%), lymphocyte counts (0.15 [0.07–0.23]; P = .0004; I
2 = 100%), basophil counts (0.01 [0.00–0.02]; P = .02; I
2 = 98%), monocyte counts (0.05 [0.02–0.09]; P = .003; I
2 = 99%), and neutrophil-to-lymphocyte ratio (0.24 [0.15–0.33]; P < .00001; I
2 = 98%). There were no significant differences in the eosinophil count (0.02 [−0.01 to 0.05]; P = .19; I
2 = 96%) and monocyte-to-lymphocyte ratio (0.06 [−0.05 to 0.17]; P = .27; I
2 = 100%) between patients with and without MetS, however, the lymphocyte-to-monocyte ratio (0.52 [−0.81 to −0.23]; P = .0005; I
2 = 52%) tended to be significantly lower in patients with MetS.

Conclusion:
Biomarkers such as total leukocyte count, neutrophil count, lymphocyte count, basophil count, monocyte count and neutrophil-to-lymphocyte ratio are associated with higher levels in patients in MetS and thus can potentially be used for early detection of MetS.
Chronological change of left ventricular global longitudinal strain in patients with maternally inherited diabetes and deafness: A case series
Authors: Seo Jeong-Sook 
Published: March 2024

Rationale:
Maternally inherited diabetes and deafness (MIDD) is a rare genetic disorder arising from mitochondrial DNA mutations, characterized by a combination of diabetes mellitus and sensorineural deafness. It is known that MIDD patients with cardiomyopathy have a poor prognosis, but there are no established guidelines for the diagnosis and follow-up of cardiomyopathy in MIDD patients.

Patient concerns:
Patient 1 was a 48-year-old woman who visited the hospital with cardiomegaly and had been taking oral hypoglycemic agents for 8 years. Patient 2 was a 21-year-old man, the son of patient 1, who visited the hospital for genetic screening. Patient 2 was also diagnosed diabetes mellitus 2 years ago.

Diagnosis:
Patient 1 was found to have restrictive cardiomyopathy on echocardiography and underwent endomyocardial biopsy and genetic testing to determine the etiology. The m.3243A>G mutation was confirmed and she was diagnosed with MIDD accompanied with diabetes and hearing loss. Additionally, patient 2 had m.3243 A>G mutation and was diagnosed with MIDD due to diabetes and hearing loss.

Interventions:
Because MIDD does not have a specific treatment, patient 1 took ubidecarenone (coenzyme Q10), acetylcarnitine, and multivitamin along with the treatment for diabetes control and heart failure. Patient 2 was taking ubidecarenone (coenzyme Q10), acetylcarnitine, and multivitamin along with treatment for diabetes.

Outcomes:
She subsequently underwent routine transthoracic echocardiography, and a progressive decline in global longitudinal strain (GLS) was first observed, followed by a worsening of the patient’s clinical situation. Patient 2 had concentric remodeling and decreased GLS. On periodic echocardiography, GLS decreased at a very slow rate, and the patient’s clinical course was stable.

Lessons:
The findings of this report contribute to the understanding of the clinical course of MIDD-associated cardiomyopathy and highlight the potential of GLS as a sensitive marker for disease progression.
Hepatic hemangiomatosis: a case report from Morocco
Authors: Hamdaoui Yassine , Harouachi Abdelhakim , Kharkhach Ayoub , Bouhout Tariq , Serji Badr 
Published: March 2024

Introduction:
Hepatic hemangiomas are benign liver tumors comprising clusters of blood-filled cavities, lined by endothelial cells, and supplied by the hepatic artery. The vast majority of hepatic hemangiomas (HH) are asymptomatic, often discovered incidentally during imaging studies for unrelated pathologies.

Case Report:
We present the clinical case of a 72-year-old patient admitted to our department due to a suspicious mass that emerged in the right hypochondrium a few months earlier. Laboratory studies were within normal limits, and diagnostic findings supported hepatic hemangiomatosis. Therapeutic abstention (with symptomatic treatment and close monitoring) was recommended.

Discussion:
Diffuse hepatic hemangiomatosis (DHH) is rare with an unclear etiology. In many cases, HH are small and asymptomatic at diagnosis with a stable progression. Asymptomatic patients typically undergo bservation with long-term follow-up, and imaging is generally unnecessary for lesions smaller than 5 cm, unless there is rapid growth or diagnostic uncertainty. Surgical resection may be considered for symptomatic patients or those with hemangiomas causing mass effects, after excluding other causes of pain.

Conclusion:
Ensuring an accurate diagnosis of hepatic hemangiomas is essential to differentiate them from other focal hepatic lesions, considering the possibility of coexisting diagnoses. While the majority of cases are asymptomatic and non-progressive, a subset may exhibit rapid growth or complications, requiring specific therapeutic approaches.
Impact of Hospital Affiliation With a Flagship Hospital System on Surgical Outcomes
Authors: Ramadan Omar I. , Rosenbaum Paul R. , Reiter Joseph G. , Jain Siddharth , Hill Alexander S. , Hashemi Sean , Kelz Rachel R. , Fleisher Lee A. , Silber Jeffrey H. 
Published: March 2024

Objective:To compare general surgery outcomes at flagship systems, flagship hospitals, and flagship hospital affiliates versus matched controls.Summary Background Data:It is unknown whether flagship hospitals perform better than flagship hospital affiliates for surgical patients.Methods:Using Medicare claims for 2018 to 2019, we matched patients undergoing inpatient general surgery in flagship system hospitals to controls who underwent the same procedure at hospitals outside the system but within the same region. We defined a “flagship hospital” within each region as the major teaching hospital with the highest patient volume that is also part of a hospital system; its system was labeled a “flagship system.” We performed 4 main comparisons: patients treated at any flagship system hospital versus hospitals outside the flagship system; flagship hospitals versus hospitals outside the flagship system; flagship hospital affiliates versus hospitals outside the flagship system; and flagship hospitals versus affiliate hospitals. Our primary outcome was 30-day mortality.Results:We formed 32,228 closely matched pairs across 35 regions. Patients at flagship system hospitals (32,228 pairs) had lower 30-day mortality than matched control patients [3.79% vs. 4.36%, difference=−0.57% (−0.86%, −0.28%),P<0.001]. Similarly, patients at flagship hospitals (15,571/32,228 pairs) had lower mortality than control patients. However, patients at flagship hospital affiliates (16,657/32,228 pairs) had similar mortality to matched controls. Flagship hospitals had lower mortality than affiliate hospitals [difference-in-differences=−1.05% (−1.62%, −0.47%),P<0.001].Conclusions:Patients treated at flagship hospitals had significantly lower mortality rates than those treated at flagship hospital affiliates. Hence, flagship system affiliation does not alone imply better surgical outcomes.
Can We Predict Kidney Graft Function and Graft Survival Using Hypothermic Machine Perfusion Parameters From Donors After Circulatory Death?
Authors: Offerni Juliano C. M. , Ai Li Erica , Matti Danny , Luke Grant , Luke Patrick P. , Sener Alp 
Published: March 2024

Background.
Hypothermic machine perfusion (HMP) reduces renal injury in donation after circulatory death donors with a high Kidney Donor Profile Index (KDPI). This study aims to characterize the correlation between KDPI, HMP parameters, and donor vitals during the withdrawal period in predicting short- and long-term graft outcomes.

Methods.
ANOVA with Tukey’s honestly significant difference tests compared the relationship between average flow, average resistance, peak resistance, flow slope, and resistance slope on day 30, 1-y, and 3-y eGFR, and days of delayed graft function. Graft and recipient survival rates were assessed using Kaplan-Meier analysis.

Results.
The data for 72 grafts were suitable for analysis. Kidneys with KDPI >50% had a significantly higher day 30, and 1-y posttransplant eGFR, if HMP average flow was >150 mL/min, or the average resistance was <0.15 mm Hg/mL/min, compared with kidneys with also KDPI >50% but had not achieved the same pump parameters. There were no significant differences in the Kaplan-Meier analysis, considering recipient or graft survival, regardless of the KPDI score with 3- or 5-y outcomes.

Conclusions.
Use of average resistance and average flow from a HMP, in conjunction with KDPI, may be predictive of the short- and long-term function of donation after circulatory death kidney transplants.
DCAF16-Based Covalent Handle for the Rational Design of Monovalent Degraders
Authors: Lim Melissa , Cong Thang Do , Orr Lauren M. , Toriki Ethan S. , Kile Andrew C. , Papatzimas James W. , Lee Elijah , Nomura Daniel K. 
Published: March 2024

AbstractTargeted protein degradation with monovalent molecular glue degraders is a powerful therapeutic modality for eliminating disease causing proteins. However, rational design of molecular glue degraders remains challenging. In this study, we sought to identify a transplantable and linker-less covalent handle that could be appended onto the exit vector of various protein-targeting ligands to induce the degradation of their respective targets. Using the BET family inhibitor JQ1 as a testbed, we synthesized and screened a series of covalent JQ1 analogs and identified a vinylsulfonyl piperazine handle that led to the potent and selective degradation of BRD4 in cells. Through chemoproteomic profiling, we identified DCAF16 as the E3 ligase responsible for BRD4 degradation—an E3 ligase substrate receptor that has been previously covalently targeted for molecular glue-based degradation of BRD4. Interestingly, we demonstrated that this covalent handle can be transplanted across a diverse array of protein-targeting ligands spanning many different protein classes to induce the degradation of CDK4, the androgen receptor, BTK, SMARCA2/4, and BCR-ABL/c-ABL. Our study reveals a DCAF16-based covalent degradative and linker-less chemical handle that can be attached to protein-targeting ligands to induce the degradation of several different classes of protein targets.
Genetic susceptibility to acute viral bronchiolitis
Authors: Pasanen Anu , Karjalainen Minna K. ,   FinnGen, Korppi Matti , Hallman Mikko , Rämet Mika 
Published: March 2024

AbstractAcute viral bronchiolitis is a major cause of infant hospitalizations worldwide. Childhood bronchiolitis is considered a risk factor for asthma, suggesting shared genetic factors and biological pathways. Genetic risk loci may provide new insights into disease pathogenesis. Here, we examined the genetic contributions to bronchiolitis susceptibility by analyzing 1,465 infants hospitalized for bronchiolitis and 356,404 individuals without a history of acute lower respiratory tract infections in the FinnGen project data. Genome-wide analysis identified associations (p<5×10-8) for variants in gasdermin B (GSDMB) and a missense variant in cadherin-related family member 3 (CDHR3). Children with bronchiolitis in infancy were more likely to develop asthma later in life compared to controls. The two associated loci were previously linked to asthma and susceptibility to wheezing illness by other causative agents than RSV. Our analysis discovered associations with overall bronchiolitis, with larger effects in non-RSV than RSV-induced infection. Our results suggest that genetic variants inCDHR3andGSDMBmodulate susceptibility to bronchiolitis, especially when caused by viruses other than RSV, and that severe bronchiolitis in infancy may trigger the development of asthma in genetically susceptible individuals determined by these loci.
WITHDRAWN: Radiation-induced non-neoplastic cells senescence promoting the proliferation and invasiveness of GBM through SASP/JAK2-STAT3 Pathway
Authors: Nie Pan , Chen Jincao , Zhang Jibo 
Published: March 2024

Withdrawal statementThe authors have withdrawn their manuscript owing to [The authors have conducted further in-depth research on this study and updated the previous data.]. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Unravelling the effects of individual heterogeneity on connectivity estimates: Insights from Spatial Capture-Recapture modelling
Authors: Kervellec Maëlis , Gimenez O. , Vanpé C. , Quenette P.-Y. , Sentilles J. , Palazón S. , Jordana I. Afonso , Jato R. , Irurtia M. M. Elósegui , Milleret C. 
Published: March 2024

AbstractSpatial Capture-Recapture (SCR) models, parametrized with least cost path distance, provide a unifying framework for explicitly estimating landscape connectivity and population size from individual detection data. However, we frequently encounter individuals with larger apparent space use than the rest of the population. To avoid biased population size estimates, it is common practice to remove these outliers from the analysis. Yet such individuals are likely to be very important when the aim is to estimate connectivity. We therefore investigated how unmodelled individual heterogeneity in space use affects population size and connectivity estimates from SCR models.We first conducted a simulation study. We varied the proportion of the population whose space use is most constrained by landscape structure. We fit four SCR models, increasing the degree of modelled individual heterogeneity to assess its effect on parameter estimates. Secondly, we applied these models to the Pyrenean brown bear population, examining the effects of removing outliers or modelling explicitly heterogeneity on parameter estimates.Our simulation study showed that population size was underestimated when no individual heterogeneity was modelled and increased with increasing the level of individual heterogeneity modelled. Moreover, unmodeled individual heterogeneity led to biased connectivity estimates towards the group, which is the most detected. In our case study, modelling individual heterogeneity was key to unravel the patterns in population space use. Female brown bear movements were restricted by road density (estimated resistance:α2= 0.27 [0.01, 0.43]), whereas a small group of males were not affected by road density (α2= - 0.16 [-0.64, 0.24]).Our study provides valuable insights for optimizing the application of SCR models. When the primary objective is to accurately estimate population size, we recommend removing outlier individuals with larger home range sizes to avoid the risk of underestimating population size. Conversely, when the aim is to assess landscape population-level connectivity, modelling individual heterogeneity is essential. Our findings underscore the importance of tailoring the SCR model to the specific research goal, ensuring more precise and meaningful ecological inferences.
Intrinsically linked lineage-specificity of transposable elements and lncRNAs reshapes transcriptional regulation species- and tissue-specifically
Authors: Lin Jie , Wu Yijin , He Sha , Xiong Wei , Pontarotti Pierre , Zhu Hao 
Published: March 2024

AbstractLineage-specificity of transcriptional regulation by lncRNAs critically determines whether mouse models reliably mimic human diseases. To address this question, we identified human/mouse-specific lncRNAs from GENCODE-annotated human and mouse lncRNAs, predicted their DNA binding domains (DBDs) and binding sites (DBSs), analysed transposable elements (TEs) in DBDs and DBSs, and analysed functional enrichment of target genes. 84%/98% of human/mouse-specific lncRNAs, 61%/95% of their DBDs, and 46%/73% of their DBSs contain TEs almost exclusively originated from simians/rodents, indicating intrinsically linked lineage-specificity of TEs, lncRNAs, and lncRNAs’ DBSs. We then revealed how transcriptional regulation is lineage-specifically rewired by co-opted lncRNAs and DBSs by analysing distributions of target genes in signalling pathways and expression of target genes in multiple tissues in humans and mice. Transcriptional regulation is greatly rewired species-specifically and tissue-specifically. We further analysed transcriptomic data of Alzheimer’s disease and tumours from human patients and mouse models, with results supporting the above conclusions. Our results reveal the intrinsically linked lineage-specificity of transposable elements, lncRNAs, and transcriptional regulation, provide data and tool for analysing and differentiating transcriptional regulation in humans and mice, and suggest that many evolutionary novelties may be destined to be lineage-specific.
A theoretical basis for cell deaths
Authors: Himeoka Yusuke , Horiguchi Shuhei A. , Kobayashi Tetsuya J. 
Published: March 2024

AbstractUnderstanding deaths and life-death boundaries of cells is a fundamental challenge in biological sciences. In this study, we present a theoretical framework for investigating cell death. We conceptualize cell death as a controllability problem within dynamical systems, and compute the life-death boundary through the development of “stoichiometric rays”. This method utilizes enzyme activity as control parameters, exploiting the inherent property of enzymes to enhance reaction rates without affecting thermodynamic potentials. This approach facilitates the efficient evaluation of the global controllability of models. We demonstrate the utility of our framework using its application to a toy metabolic model, where we delineate the life-death boundary. The formulation of cell death through mathematical principles provides a foundation for the theoretical study of cellular mortality.SIGNIFICANCE STATEMENTWhat is death? This fundamental question in biology lacks a clear theoretical framework despite numerous experimental studies. In this study, we present a new way to understand cell death by looking at how cells can or cannot control their states. We define a “dead state” as a state from which a cell cannot return to being alive. Our method, called “Stoichiometric Rays”, helps determine if a cell’s state is dead based on enzymatic reactions. By using this method, we can quantify the life-death boundary in metabolic models. The present framework provides a theoretical basis and a tool for understanding cell death.
Zinc Alpha-2-Glycoprotein (ZAG/AZGP1) secreted by triple-negative breast cancer promotes tumor microenvironment fibrosis
Authors: Verma Surbhi , Giagnocavo Stephanie Dudics , Curtin Meghan C. , Arumugam Menusha , Osburn-Staker Sandra M. , Wang Guoying , Atkinson Aaron , Nix David A. , Lum David H. , Cox James E. , Hilgendorf Keren I. 
Published: March 2024

SummaryObesity is a predisposition factor for breast cancer, suggesting a localized, reciprocal interaction between breast cancer cells and the surrounding mammary white adipose tissue. To investigate how breast cancer cells alter the composition and function of adipose tissue, we screened the secretomes of ten human breast cancer cell lines for the ability to modulate the differentiation of adipocyte stem and progenitor cells (ASPC). The screen identified a key adipogenic modulator, Zinc Alpha-2-Glycoprotein (ZAG/AZGP1), secreted by triple-negative breast cancer (TNBC) cells. TNBC-secreted ZAG inhibits adipogenesis and instead induces the expression of fibrotic genes. Accordingly, depletion of ZAG in TNBC cells attenuates fibrosis in white adipose tissue and inhibits tumor growth. Further, high expression of ZAG in TNBC patients, but not other clinical subtypes of breast cancer, is linked to poor prognosis. Our findings suggest a role of TNBC-secreted ZAG in promoting the transdifferentiation of ASPCs into cancer-associated fibroblasts to support tumorigenesis.
Persistent Behavioral and Physiological Effects of Dietary Protein Restriction
Authors: Soto Paul L. , Morrison Christopher D. 
Published: March 2024

AbstractProtein provides essential amino acids critical for survival. Recent research has identified that dietary protein restriction induces physiological and behavioral adaptations and that those adaptations are mediated by liver-produced fibroblast growth factor 21 (FGF21) that acts in the brain. Most of the research on adaptations to dietary protein restriction and the biological factors that mediate those adaptations carries an implicit assumption that the effects of dietary protein restriction are reversible. Rarely is the assumption of reversibility directly examined by varying dietary protein content within animals. Recently collected data on preference for protein versus carbohydrate solutions indicates that when mice are placed on a low (5%) protein diet, preference for protein is rapidly increased. However, when mice are switched from a low to normal (20%) protein diet, relative consumption of protein decreases but preference for protein persists. Re-analysis of published data suggests, similarly, that preference for protein-rich food sources remains elevated following exposure to dietary protein restriction and that calcium influx in the ventral tegmental area of the brain in response to protein consumption also remains persistently elevated following dietary protein restriction. Together, the data suggest that prior protein restriction can exert long-lasting effects on protein preference and on brain activity associated with protein consumption. The finding that the effects of protein restriction do not rapidly reverse implies that protein choice may be a function, not only of current nutritional state, but of historical nutritional conditions. Further, these results suggest that a full understanding of the environmental and biological determinants of protein choice requires studies in which dietary protein intake is varied within subjects.