bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre-hospital glycemia as a biomarker for in-hospital all-cause mortality in diabetic patients - a pilot study
Authors: Greco Salvatore , Salatiello Alessandro , De Motoli Francesco , Giovine Antonio , Veronese Martina , Cupido Maria Grazia , Pedarzani Emma , Valpiani Giorgia , Passaro Angelina 
Published: May 2024

Abstract
Background
Type 2 Diabetes Mellitus (T2DM) presents a significant healthcare challenge, with considerable economic ramifications. While blood glucose management and long-term metabolic target setting for home care and outpatient treatment follow established procedures, the approach for short-term targets during hospitalization varies due to a lack of clinical consensus. Our study aims to elucidate the impact of pre-hospitalization and intra-hospitalization glycemic indexes on in-hospital survival rates in individuals with T2DM, addressing this notable gap in the current literature.

Methods
In this pilot study involving 120 hospitalized diabetic patients, we used advanced machine learning and classical statistical methods to identify variables for predicting hospitalization outcomes. We first developed a 30-day mortality risk classifier leveraging AdaBoost-FAS, a state-of-the-art ensemble machine learning method for tabular data. We then analyzed the feature relevance to identify the key predictive variables among the glycemic and routine clinical variables the model bases its predictions on. Next, we conducted detailed statistical analyses to shed light on the relationship between such variables and mortality risk. Finally, based on such analyses, we introduced a novel index, the ratio of intra-hospital glycemic variability to pre-hospitalization glycemic mean, to better characterize and stratify the diabetic population.

Results
Our findings underscore the importance of personalized approaches to glycemic management during hospitalization. The introduced index, alongside advanced predictive modeling, provides valuable insights for optimizing patient care. In particular, together with in-hospital glycemic variability, it is able to discriminate between patients with higher and lower mortality rates, highlighting the importance of tightly controlling not only pre-hospital but also in-hospital glycemic levels.

Conclusions
Despite the pilot nature and modest sample size, this study marks the beginning of exploration into personalized glycemic control for hospitalized patients with T2DM. Pre-hospital blood glucose levels and related variables derived from it can serve as biomarkers for all-cause mortality during hospitalization.
Direct metagenomics investigation of non-surgical hard-to-heal wounds: a review
Authors: Morsli Madjid , Salipante Florian , Magnan Chloé , Dunyach-Remy Catherine , Sotto Albert , Lavigne Jean-Philippe 
Published: May 2024

Abstract
Background
Non-surgical chronic wounds, including diabetes-related foot diseases (DRFD), pressure injuries (PIs) and venous leg ulcers (VLU), are common hard-to-heal wounds. Wound evolution partly depends on microbial colonisation or infection, which is often confused by clinicians, thereby hampering proper management. Current routine microbiology investigation of these wounds is based on in vitro culture, focusing only on a limited panel of the most frequently isolated bacteria, leaving a large part of the wound microbiome undocumented.

Methods
A literature search was conducted on original studies published through October 2022 reporting metagenomic next generation sequencing (mNGS) of chronic wound samples. Studies were eligible for inclusion if they applied 16 S rRNA metagenomics or shotgun metagenomics for microbiome analysis or diagnosis. Case reports, prospective, or retrospective studies were included. However, review articles, animal studies, in vitro model optimisation, benchmarking, treatment optimisation studies, and non-clinical studies were excluded. Articles were identified in PubMed, Google Scholar, Web of Science, Microsoft Academic, Crossref and Semantic Scholar databases.

Results
Of the 3,202 articles found in the initial search, 2,336 articles were removed after deduplication and 834 articles following title and abstract screening. A further 14 were removed after full text reading, with 18 articles finally included. Data were provided for 3,628 patients, including 1,535 DRFDs, 956 VLUs, and 791 PIs, with 164 microbial genera and 116 species identified using mNGS approaches. A high microbial diversity was observed depending on the geographical location and wound evolution. Clinically infected wounds were the most diverse, possibly due to a widespread colonisation by pathogenic bacteria from body and environmental microbiota. mNGS data identified the presence of virus (EBV) and fungi (Candida and Aspergillus species), as well as Staphylococcus and Pseudomonas bacteriophages.

Conclusion
This study highlighted the benefit of mNGS for time-effective pathogen genome detection. Despite the majority of the included studies investigating only 16 S rDNA, ignoring a part of viral, fungal and parasite colonisation, mNGS detected a large number of bacteria through the included studies. Such technology could be implemented in routine microbiology for hard-to-heal wound microbiota investigation and post-treatment wound colonisation surveillance.
Single-sEV profiling identifies the TACSTD2 + sEV subpopulation as a factor of tumor susceptibility in the elderly
Authors: Ning Nannan , Lu Jianying , Li Qianpeng , Li Mengmeng , Cai Yanling , Wang Hongchun , Li Jingxin 
Published: May 2024

Abstract
Background
Aging is a very complex physiological phenomenon, and sEVs are involved in the regulation of this mechanism. Serum samples from healthy individuals under 30 and over 60 years of age were collected to analyze differences in sEVs proteomics.

Results
Based on PBA analysis, we found that sEVs from the serum of elderly individuals highly express TACSTD2 and identified a subpopulation marked by TACSTD2. Using ELISA, we verified the upregulation of TACSTD2 in serum from elderly human and aged mouse. In addition, we discovered that TACSTD2 was significantly increased in samples from tumor patients and had better diagnostic value than CEA. Specifically, 9 of the 13 tumor groups exhibited elevated TACSTD2, particularly for cervical cancer, colon cancer, esophageal carcinoma, liver cancer and thyroid carcinoma. Moreover, we found that serum sEVs from the elderly (especially those with high TACSTD2 levels) promoted tumor cell (SW480, HuCCT1 and HeLa) proliferation and migration.

Conclusion
TACSTD2 was upregulated in the serum of elderly individuals and patients with tumors, and could serve as a dual biomarker for aging and tumors.
E3 ubiquitin ligase RNF128 negatively regulates the IL-3/STAT5 signaling pathway by facilitating K27-linked polyubiquitination of IL-3Rα
Authors: Yu Jingge , Li Jianguo , Shen Ao , Liu Zhiping , He Tian-Sheng 
Published: May 2024

AbstractIL-3/STAT5 signaling pathway is crucial for the development and activation of immune cells, contributing to the cellular response to infections and inflammatory stimuli. Dysregulation of the IL-3/STAT5 signaling have been associated with inflammatory and autoimmune diseases characterized by inflammatory cell infiltration and organ damage. IL-3 receptor α (IL-3Rα) specifically binds to IL-3 and initiates intracellular signaling, resulting in the phosphorylation of STAT5. However, the regulatory mechanisms of IL-3Rα remain unclear. Here, we identified the E3 ubiquitin ligase RNF128 as a negative regulator of IL-3/STAT5 signaling by targeting IL-3Rα for lysosomal degradation. RNF128 was shown to selectively bind to IL-3Rα, without interacting with the common beta chain IL-3Rβ, which shares the subunit with GM-CSF. The deficiency of Rnf128 had no effect on GM-CSF-induced phosphorylation of Stat5, but it resulted in heightened Il-3-triggered activation of Stat5 and increased transcription of the Id1, Pim1, and Cd69 genes. Furthermore, we found that RNF128 promoted the K27-linked polyubiquitination of IL-3Rα in a ligase activity-dependent manner, ultimately facilitating its degradation through the lysosomal pathway. RNF128 inhibited the activation and chemotaxis of macrophages in response to LPS stimulation, thereby attenuating excessive inflammatory responses. Collectively, these results reveal that RNF128 negatively regulates the IL-3/STAT5 signaling pathway by facilitating K27-linked polyubiquitination of IL-3Rα. This study uncovers E3 ubiquitin ligase RNF128 as a novel regulator of the IL-3/STAT5 signaling pathway, providing potential molecular targets for the treatment of inflammatory diseases.
Integrative analyses of bulk and single-cell transcriptomics reveals the infiltration and crosstalk of cancer-associated fibroblasts as a novel predictor for prognosis and microenvironment remodeling in intrahepatic cholangiocarcinoma
Authors: Zhong Yan-Jie , Luo Xi-Mei , Liu Fei , He Zhi-Qiang , Yang Si-Qi , Ma Wen-Jie , Wang Jun-Ke , Dai Yu-Shi , Zou Rui-Qi , Hu Ya-Fei , Lv Tian-Run , Li Fu-Yu , Hu Hai-Jie 
Published: May 2024

Abstract
Background
Intrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm and characterized by desmoplastic matrix. The heterogeneity and crosstalk of tumor microenvironment remain incompletely understood.

Methods
To address this gap, we performed Weighted Gene Co-expression Network Analysis (WGCNA) to identify and construct a cancer associated fibroblasts (CAFs) infiltration biomarker. We also depicted the intercellular communication network and important receptor-ligand complexes using the single-cell transcriptomics analysis of tumor and Adjacent normal tissue.

Results
Through the intersection of TCGA DEGs and WGCNA module genes, 784 differential genes related to CAFs infiltration were obtained. After a series of regression analyses, the CAFs score was generated by integrating the expressions of EVA1A, APBA2, LRRTM4, GOLGA8M, BPIFB2, and their corresponding coefficients. In the TCGA-CHOL, GSE89748, and 107,943 cohorts, the high CAFs score group showed unfavorable survival prognosis (p < 0.001, p = 0.0074, p = 0.028, respectively). Additionally, a series of drugs have been predicted to be more sensitive to the high-risk group (p < 0.05). Subsequent to dimension reduction and clustering, thirteen clusters were identified to construct the single-cell atlas. Cell-cell interaction analysis unveiled significant enhancement of signal transduction in tumor tissues, particularly from fibroblasts to malignant cells via diverse pathways. Moreover, SCENIC analysis indicated that HOXA5, WT1, and LHX2 are fibroblast specific motifs.

Conclusions
This study reveals the key role of fibroblasts - oncocytes interaction in the remodeling of the immunosuppressive microenvironment in intrahepatic cholangiocarcinoma. Subsequently, it may trigger cascade activation of downstream signaling pathways such as PI3K-AKT and Notch in tumor, thus initiating tumorigenesis. Targeted drugs aimed at disrupting fibroblasts-tumor cell interaction, along with associated enrichment pathways, show potential in mitigating the immunosuppressive microenvironment that facilitates tumor progression.
Oroxin A alleviates early brain injury after subarachnoid hemorrhage by regulating ferroptosis and neuroinflammation
Authors: Chen Junhui , Shi Zhonghua , Zhang Chunlei , Xiong Kun , Zhao Wei , Wang Yuhai 
Published: May 2024

Abstract
Background
Subarachnoid hemorrhage (SAH), a severe subtype of stroke, is characterized by notably high mortality and morbidity, largely due to the lack of effective therapeutic options. Although the neuroprotective potential of PPARg and Nrf2 has been recognized, investigative efforts into oroxin A (OA), remain limited in preclinical studies.

Methods
SAH was modeled in vivo through filament perforation in male C57BL/6 mice and in vitro by exposing HT22 cells to hemin to induce neuronal damage. Following the administration of OA, a series of methods were employed to assess neurological behaviors, brain water content, neuronal damage, cell ferroptosis, and the extent of neuroinflammation.

Results
The findings indicated that OA treatment markedly improved survival rates, enhanced neurological functions, mitigated neuronal death and brain edema, and attenuated the inflammatory response. These effects of OA were linked to the suppression of microglial activation. Moreover, OA administration was found to diminish ferroptosis in neuronal cells, a critical factor in early brain injury (EBI) following SAH. Further mechanistic investigations uncovered that OA facilitated the translocation of nuclear factor erythroid 2-related factor 2 (Nrf-2) from the cytoplasm to the nucleus, thereby activating the Nrf2/GPX4 pathway. Importantly, OA also upregulated the expression of FSP1, suggesting a significant and parallel protective effect against ferroptosis in EBI following SAH in synergy with GPX4.

Conclusion
In summary, this research indicated that the PPARg activator OA augmented the neurological results in rodent models and diminished neuronal death. This neuroprotection was achieved primarily by suppressing neuronal ferroptosis. The underlying mechanism was associated with the alleviation of cellular death through the Nrf2/GPX4 and FSP1/CoQ10 pathways.
Severe morbidity and hospital-based mortality from Rift Valley fever disease between November 2017 and March 2020 among humans in Uganda
Authors: Anywaine Zacchaeus , Hansen Christian , Warimwe George M. , Abu-Baker Mustapher Ggayi , Nyakarahuka Luke , Balinandi Stephen , Ario Alex Riolexus , Lutwama Julius J. , Elliott Alison , Kaleebu Pontiano 
Published: May 2024

Abstract
Background
Rift Valley fever (RVF) is a zoonotic viral disease of increasing intensity among humans in Africa and the Arabian Peninsula. In Uganda, cases reported prior to 2016 were mild or not fully documented. We report in this paper on the severe morbidity and hospital-based mortality of human cases in Uganda.

Methods
Between November 2017 and March 2020 human cases reported to the Uganda Virus Research Institute (UVRI) were confirmed by polymerase chain reaction (PCR). Ethical and regulatory approvals were obtained to enrol survivors into a one-year follow-up study. Data were collected on socio-demographics, medical history, laboratory tests, potential risk factors, and analysed using Stata software.

Results
Overall, 40 cases were confirmed with acute RVF during this period. Cases were not geographically clustered and nearly all were male (39/40; 98%), median age 32 (range 11–63). The median definitive diagnosis time was 7 days and a delay of three days between presumptive and definitive diagnosis. Most patients (31/40; 78%) presented with fever and bleeding at case detection. Twenty-eight (70%) cases were hospitalised, out of whom 18 (64%) died. Mortality was highest among admissions in regional referral (11/16; 69%) and district (4/5; 80%) hospitals, hospitalized patients with bleeding at case detection (17/27; 63%), and patients older than 44 years (9/9; 100%). Survivors mostly manifested a mild gastro-intestinal syndrome with nausea (83%), anorexia (75%), vomiting (75%), abdominal pain (50%), and diarrhoea (42%), and prolonged symptoms of severe disease including jaundice (67%), visual difficulties (67%), epistaxis (50%), haemoptysis (42%), and dysentery (25%). Symptom duration varied between two to 120 days.

Conclusion
RVF is associated with high hospital-based mortality, severe and prolonged morbidity among humans that present to the health care system and are confirmed by PCR. One-health composite interventions should be developed to improve environmental and livestock surveillance, prevent infections, promptly detect outbreaks, and improve patient outcomes.
Age-related enhancement of the association between episodic memory and gray matter volume in medial temporal and frontal lobes
Authors: Zhao Shaokun , Sang Feng , Liu Chen , Wang Fei , Liu Jiawen , Chen Chuansheng , Wang Jun , Li Xin , Zhang Zhanjun 
Published: May 2024

Abstract
Background
Episodic memory (EM) deteriorates as a result of normal aging as well as Alzheimer’s disease. The neural underpinnings of such age-related memory impairments in older individuals are not well-understood. Although previous research has unveiled the association between gray matter volume (GMV) and EM in the elderly population, such findings exhibit variances across distinct age cohorts. Consequently, an investigation into the dynamic evolution of this relationship with advancing age is imperative.

Result
The present study utilized a sliding window approach to examine how the correlation between EM and GMV varied with age in a cross-sectional sample of 926 Chinese older adults. We found that both verbal EM (VEM) and spatial EM (SEM) exhibited positive correlations with GMV in extensive areas primarily in the temporal and frontal lobes and that these correlations typically became stronger with older age. Moreover, there were variations in the strength of the correlation between EM and GMV with age, which differed based on sex and the specific type of EM. Specifically, the association between VEM and GMVs in the insula and parietal regions became stronger with age for females but not for males, whereas the association between SEM and GMVs in the parietal and occipital regions became stronger for males but not for females. At the brain system level, there is a significant age-related increase in the correlations between both types of EM and the GMV of both the anterior temporal (AT) system and the posterior medial (PM) system in male group. In females, both types of EM show stronger age-related correlations with the GMV of the AT system compared to males.

Conclusions
Our study revealed a significant positive correlation between GMV in most regions associated with EM and age, particularly in the frontal and temporal lobes. This discovery offers new insights into the connection between brain structure and the diminishing episodic memory function among older individuals.
Implementation of early essential neonatal care for newborns delivered by cesarean section in Jiaxing: a single-center prospective randomized controlled trial
Authors: Xu Jianping , Zhang Min , Li Yi , Gu Shuiqin 
Published: May 2024

Abstract
Background
As an essential part of Early Essential Newborn Care, 90 minutes of mother-infant skin-to-skin contact is significant in improving maternal and infant outcomes. However, due to human resource constraints and the consideration of maternal and infant safety, it is difficult to achieve continuous uninterrupted skin-to-skin contact for at least 90 minutes during and after cesarean delivery. The aim of this study was to investigate the efficacy and safety of the continuous uninterrupted skin-to-skin contact for at least 90 minutes during and after cesarean section for exclusive breastfeeding rate during hospitalization and maternal and infant health indicators during and after cesarean delivery.

Methods
This is a single-center, prospective randomized controlled trial conducted in one tertiary care hospital in China. We selected 280 cases of elective cesarean delivery in a tertiary maternal and child specialty hospital in Zhejiang Province from September 2018 to August 2022, which were randomly divided into two groups: in the conventional group, doulas performed at least 30 minutes for early continuous SSC within 10–30 minutes during and after cesarean delivery. In the EENC group, with immediate continuous SSC within 5–10 minutes of neonatal delivery until surgery is completed and continued SSC after returning to the ward. Exclusive breastfeeding rate during hospitalization and maternal and infant health indicators were compared between the groups.

Results
A total of 258 cases were analyzed. Compared with the control group, the EENC group had earlier first breastfeeding initiation (13.7 ± 3.6 vs 62.8 ± 6.5 minutes, P < 0.001), longer duration of first breastfeeding (42.6 ± 9.0 vs 17.9 ± 7.5 minutes, P < 0.001), earlier onset of lactogenesis II (73.7 ± 3.6 vs 82.5 ± 7.4 hours, P < 0.001), higher breastfeeding self-efficacy score (128.6 ± 8.9 vs 104.4 ± 8.5, P < 0.001), higher Exclusive breastfeeding rate during hospitalization (88% vs 81%, P = 0.018), higher maternal satisfaction scores (18.9 ± 1.1 vs 14.0 ± 2.7, P < 0.001). Meanwhile the EENC group showed lower incidence of neonatal hypothermia (0% vs 4.6%, P = 0.014), lower neonatal hypoglycemia (0% vs 5.4%, P = 0.007) and less cumulative blood loss within 24 hours postpartum (254.2 ± 43.6 vs 282.8 ± 63.8 ml, P < 0.001).

Conclusion
The implementation of EENC up to 90 minutes by caesarean doula company nurses is feasible and beneficial to maternal and infant health.

Trial Registration
ChiCTR1800018195(2018-09-04).
Trauma exposure across the lifespan among individuals engaged in treatment with medication for opioid use disorder: differences by gender, PTSD status, and chronic pain
Authors: Rodríguez Monique N. , Colgan Dana D. , Leyde Sarah , Pike Kenneth , Merrill Joseph O. , Price Cynthia J. 
Published: May 2024

Abstract
Background
There is little study of lifetime trauma exposure among individuals engaged in medication treatment for opioid use disorder (MOUD). A multisite study provided the opportunity to examine the prevalence of lifetime trauma and differences by gender, PTSD status, and chronic pain.

Methods
A cross-sectional study examined baseline data from participants (N = 303) enrolled in a randomized controlled trial of a mind–body intervention as an adjunct to MOUD. All participants were stabilized on MOUD. Measures included the Trauma Life Events Questionnaire (TLEQ), the Brief Pain Inventory (BPI), and the Posttraumatic Stress Disorder Checklist (PCL-5). Analyses involved descriptive statistics, independent sample t-tests, and linear and logistic regression.

Results
Participants were self-identified as women (n = 157), men (n = 144), and non-binary (n = 2). Fifty-seven percent (n = 172) self-reported chronic pain, and 41% (n = 124) scored above the screening cut-off for PTSD. Women reported significantly more intimate partner violence (85%) vs 73%) and adult sexual assault (57% vs 13%), while men reported more physical assault (81% vs 61%) and witnessing trauma (66% vs 48%). Men and women experienced substantial childhood physical abuse, witnessed intimate partner violence as children, and reported an equivalent exposure to accidents as adults. The number of traumatic events predicted PTSD symptom severity and PTSD diagnostic status. Participants with chronic pain, compared to those without chronic pain, had significantly more traumatic events in childhood (85% vs 75%).

Conclusion
The study found a high prevalence of lifetime trauma among people in MOUD. Results highlight the need for comprehensive assessment and mental health services to address trauma among those in MOUD treatment.

Trial registration
NCT04082637.