bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of non-insulin-based insulin resistance indices with disease severity and adverse outcome in idiopathic pulmonary arterial hypertension: a multi-center cohort study
Authors: Zhang Sicheng , Gao Luyang , Li Sicong , Luo Manqing , Chen Lichuan , Xi Qunying , Zhao Zhihui , Zhao Qing , Yang Tao , Zeng Qixian , Li Xin , Huang Zhihua , Duan Anqi , Wang Yijia , Luo Qin , Guo Yansong , Liu Zhihong
Published: May 2024

Background

Insulin resistance (IR) plays an important role in the pathophysiology of cardiovascular disease. Recent studies have shown that diabetes mellitus and impaired lipid metabolism are associated with the severity and prognosis of idiopathic pulmonary arterial hypertension (IPAH). However, the relationship between IR and pulmonary hypertension is poorly understood. This study explored the association between four IR indices and IPAH using data from a multicenter cohort.

Methods

A total of 602 consecutive participants with IPAH were included in this study between January 2015 and December 2022. The metabolic score for IR (METS-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride and glucose (TyG) index, and triglyceride-glucose-body mass index (TyG-BMI) were used to quantify IR levels in patients with IPAH. The correlation between non-insulin-based IR indices and long-term adverse outcomes was determined using multivariate Cox regression models and restricted cubic splines.

Results

During a mean of 3.6 years’ follow-up, 214 participants experienced all-cause death or worsening condition. Compared with in low to intermediate-low risk patients, the TG/HDL-C ratio (2.9 ± 1.7 vs. 3.3 ± 2.1, P = 0.003) and METS-IR (34.5 ± 6.7 vs. 36.4 ± 7.5, P < 0.001) were significantly increased in high to intermediate-high risk patients. IR indices correlated with well-validated variables that reflected the severity of IPAH, such as the cardiac index and stroke volume index. Multivariate Cox regression analyses indicated that the TyG-BMI index (hazard ratio [HR] 1.179, 95% confidence interval [CI] 1.020, 1.363 per 1.0-standard deviation [SD] increment, P = 0.026) and METS-IR (HR 1.169, 95% CI 1.016, 1.345 per 1.0-SD increment, P = 0.030) independently predicted adverse outcomes. Addition of the TG/HDL-C ratio and METS-IR significantly improved the reclassification and discrimination ability beyond the European Society of Cardiology (ESC) risk score.

Conclusions

IR is associated with the severity and long-term prognosis of IPAH. TyG-BMI and METS-IR can independently predict clinical worsening events, while METS-IR also provide incremental predictive performance beyond the ESC risk stratification.
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

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

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

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

IL-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

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

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

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

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

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

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.
Export priority technique for Uni-portal thoracoscopic left upper lobectomy
Authors: Yang Yanhui , Li Ji , Cheng Xin , Cheng Sipeng , Xie Xiaoyang
Published: May 2024

Background

Further explore the safety and feasibility of Uni-portal video assisted thoracoscopic (UVATS) left upper lobectomy by optimizing the treatment of incisions and blood vessels.

Methods

We conducted a retrospective analysis of data from 32 patients who underwent UVATS left upper lobectomy and systematic mediastinal lymph node dissection utilizing the Export priority technique between January 2021 and December 2022. We documented perioperative indicators, including surgical time, intraoperative blood loss, the number of lymph nodes dissected, and postoperative pathological staging.

Results

All surgeries were conducted utilizing the Export priority technique in UVATS. The mean surgical duration was (98.93 ± 14.98) minutes, with an average intraoperative blood loss of (79.53 ± 37.96) ml. The mean count of dissected lymph nodes was (13.96 ± 2.69). The length of hospital Stay averaged (5.62 ± 1.81) days. On the first postoperative day, the thoracic drainage volume was (101.87 ± 49.46) ml. The mean duration of postoperative thoracic tube insertion was (3.1 ± 1.84) days. No occurrences of postoperative hoarseness, pulmonary infection, or complications such as bronchopleural fistula were observed.

Conclusion

The application of the Export priority technique improves the safety and feasibility of UVATS left upper lobectomy.
The effectiveness of an online short-format Recovery College model: a co-learning model to support mental health
Authors: Briand Catherine , Giguère Charles-Édouard , Macario de Medeiros Julio , Vallée Catherine , Luconi Francesca , Vachon Brigitte , Drolet Marie-Josée , Monthuy-Blanc Johana , Mahroug Amani , Hakin Régis
Published: May 2024

Background

Our societies are facing mental health challenges, which have been compounded by the Covid-19. This event led people to isolate themselves and to stop seeking the help they needed. In response to this situation, the Health and Recovery Learning Center, applying the Recovery College (RC) model, modified its training program to a shorter online format. This study examines the effectiveness of a single RC training course delivered in a shortened online format to a diverse population at risk of mental health deterioration in the context of Covid-19.

Methods

This quasi-experimental study used a one-group pretest-posttest design with repeated measures. Three hundred and fifteen (n = 315) learners agreed to take part in the study and completed questionnaires on wellbeing, anxiety, resilience, self-management, empowerment and stigmatizing attitudes and behaviors.

Results

Analyses of variance using a linear mixed models revealed that attending a RC training course had, over time, a statistically significant effect on wellbeing (p = 0.004), anxiety (p < 0.001), self-esteem/self-efficacy (p = 0.005), disclosure/help-seeking (p < 0.001) and a slight effect on resilience (p = 0.019) and optimism/control over the future (p = 0.01).

Conclusions

This study is the first to measure participation in a single online short-format RC training course, with a diversity of learners and a large sample. These results support the hypothesis that an online short-format training course can reduce psychological distress and increase self-efficacy and help-seeking.

Trial registration

This study was previously approved by two certified ethics committees: Comité d’éthique de la recherche du CIUSSS EMTL, which acted as the committee responsible for the multicenter study, reference number MP-12-2021-2421, and Comité d’éthique avec les êtres humains de l’UQTR, reference number CER-20-270-07.01.
Elimination disorders and associated factors among children and adolescents age 5–14 year-old attending paediatric outpatient clinic at Wolaita Sodo University comprehensive specialized hospital, South Ethiopia
Authors: Berhanu Tamene , Abera Mubarek , Girma Shimelis , Tesfaye Yonas
Published: May 2024

Background

Elimination disorder occurs in children over the age of normal toileting who continue to have an inability to control urination or feces, either during the day, at night, or both. Paediatric elimination disorders are not well understood by parents, teachers, medical professionals, mental health practitioners, and researchers. Hence, this study aimed to assess the magnitude of elimination disorder and associated factors among children and Adolescents aged 5–14 years old at Wolaita Sodo University Comprehensive Specialized Hospital, South Ethiopia, in 2022.

Method

A hospital-based cross-sectional study was conducted from September 22 to November 22, 2022, at Wolaita Sodo University Comprehensive Specialized Hospital. A systematic random sampling technique was employed to select 423 study subjects. The data were gathered using a structured, face-to-face interviewer-administered questionnaire. The development of the symptom score for dysfunctional elimination syndrome of Vancouver questionnaires was used to screen for elimination disorders. Logistic regression model was used to determine the association between the outcome and independent variables. A 95% CI and Odds ratio with corresponding p-value < 0.05 were used to determine the predictors of the outcome variable.

Result

The overall magnitude of elimination disorder among children and Adolescents age 5–14 in this study was (n 70, 16.8%); in boys (n 47, 17.3%) and girls (n 23, 15.75%). The prevalence of enuresis was (n 64, 15.3%), encopresis (n 15, 3.6%), both enuresis and encopresis, or combined elimination disorder (n 9, 2.2%). Age 9–11 years (AOR = 3.2, 95%CI:1.09, 9.43), family size four and above (AOR = 3.4, 95%CI:1.78, 6.56), family history of elimination disorder (AOR = 3.9, 95%CI:2.12, 7.45), emotional problem (AOR = 2.2, 95%CI:1.18, 4.05), hyperactive problem (AOR = 3.8, 95%CI:1.83, 7.83), low toilet training skills (AOR = 5.9, 95%CI:2.61, 13.33), bad parenting practices, were poor supervision (AOR = 4.4, 95%CI 1.29, 14.69) were significantly associated with elimination disorder.

Conclusion and recommendation

In this study, approximately one in five children and adolescents had an elimination disorder. Younger age, family size four and above, positive family history of elimination disorder, presence of emotional and hyperactive problems, bad parenting practices, and low toilet training skills were factors associated with elimination disorders. Therefore, preventative, etiological, and therapeutic measure, early toilet training, supportive parenting practices, screening for children’s and adolescents’ behavioral problems, and elimination disorders need attention to reduce the effect of the problem.
TRPS1 maintains luminal progenitors in the mammary gland by repressing SRF/MRTF activity
Authors: Tollot-Wegner Marie , Jessen Marco , Kim KyungMok , Sanz-Moreno Adrián , Spielmann Nadine , Gailus-Durner Valerie , Fuchs Helmut , Hrabe de Angelis Martin , von Eyss Björn
Published: May 2024

The transcription factor TRPS1 is a context-dependent oncogene in breast cancer. In the mammary gland, TRPS1 activity is restricted to the luminal population and is critical during puberty and pregnancy. Its function in the resting state remains however unclear. To evaluate whether it could be a target for cancer therapy, we investigated TRPS1 function in the healthy adult mammary gland using a conditional ubiquitous depletion mouse model where long-term depletion does not affect fitness. Using transcriptomic approaches, flow cytometry and functional assays, we show that TRPS1 activity is essential to maintain a functional luminal progenitor compartment. This requires the repression of both YAP/TAZ and SRF/MRTF activities. TRPS1 represses SRF/MRTF activity indirectly by modulating RhoA activity. Our work uncovers a hitherto undisclosed function of TRPS1 in luminal progenitors intrinsically linked to mechanotransduction in the mammary gland. It may also provide new insights into the oncogenic functions of TRPS1 as luminal progenitors are likely the cells of origin of many breast cancers.
Two-point immobilization of M3 muscarinic receptor: a method for recognizing receptor antagonists in natural products
Authors: Huang Xiaomin , Wang Ting , Wang Ludan , Sun Yantao , Zhang Ziru , Zhang Yajun
Published: May 2024

In the investigation of active ingredients from natural products, current technologies relying on drug–target affinity recognition analysis face significant challenges. This is primarily due to their limited specificity and inability to provide downstream pharmacodynamic information, such as agonistic or antagonistic activity. In this study, a two-point method was developed by immobilizing M3 acetylcholine receptor (M3R) through the combination of the conformation-specific peptide BJ-PRO-13a and the HaloTag trap system. We systematically assessed the specificity of the immobilized M3R using known M3R antagonists (pirenzepine and atropine) and agonists (cevimeline and pilocarpine). By frontal analysis and nonlinear chromatography, the performance of immobilized M3R was evaluated in terms of binding kinetics and thermodynamics of four drugs to the immobilized M3R. Additionally, we successfully identified two M3R antagonists within an extract from Daturae Flos (DF), specifically hyoscyamine and scopolamine. Our findings demonstrate that this immobilization method effectively captures receptor-ligand binding interactions and can discern receptor agonists from antagonists. This innovation enhances the efficiency of receptor chromatography to determine binding-affinity in the development of new drugs, offering promise for the screening and characterization of active compounds, particularly within complex natural products.
Health-related quality of life and its predictors among hypertensive patients on follow up at public hospitals in Addis Ababa, Ethiopia: application of Tobit regression model
Authors: Megerssa Yordanos , Kune Guta , Nigatu Mamo
Published: May 2024

Background

Health-related quality of life and its associated factors among hypertensive patients living in Ethiopia are not well studied. Therefore, this study aims to assess the level of health-related quality of life and its associated factors in hypertensive patients on follow-up in Public Hospitals in Addis Ababa, Ethiopia.

Methods

A facility-based cross-sectional study was conducted among 339 hypertensive patients on follow-up at Yekatit 12 &Zewditu Hospitals. Data were collected through face-to-face interviews using Euro Quality of Life Groups 5 Dimensions 5 Levels (EQ-5D-5L) in combination with Euro Quality of Life Groups Visual Analog Scale (EQ-VAS). A multivariable Tobit regression model was employed to assess the association between EQ-5D-5L index, EQ-VAS, and potential predicting factors.

Results

The median index value and EQ-VAS Scales score was 0.86 (IQR = 0.74, 0.94) and 69 (IQR = 55, 80) respectively.

The proportion of participants reporting anxiety/depression and pain/discomfort problems was highest, while the fewest patients reported problems in the self-care dimension. Older, rural residents, low income, higher stages of hypertension, increased use of antihypertensive medications, and patients with an increased hospitalization rate scored lower on health-related quality of life than others.

Conclusion

Health-related quality of life among hypertensive patients attending public health hospitals in Addis Ababa is unacceptably poor. Emphasis should be given to patients with higher stages of hypertension, increased use of antihypertensive medications, and an increased hospitalization rate giving due focus to older, rural residents, and low-income patients to promote their health-related quality of life.
Deep Reinforcement Learning techniques for dynamic task offloading in the 5G edge-cloud continuum
Authors: Nieto Gorka , de la Iglesia Idoia , Lopez-Novoa Unai , Perfecto Cristina
Published: May 2024

The integration of new Internet of Things (IoT) applications and services heavily relies on task offloading to external devices due to the constrained computing and battery resources of IoT devices. Up to now, Cloud Computing (CC) paradigm has been a good approach for tasks where latency is not critical, but it is not useful when latency matters, so Multi-access Edge Computing (MEC) can be of use. In this work, we propose a distributed Deep Reinforcement Learning (DRL) tool to optimize the binary task offloading decision, this is, the independent decision of where to execute each computing task, depending on many factors. The optimization goal in this work is to maximize the Quality-of-Experience (QoE) when performing tasks, which is defined as a metric related to the battery level of the UE, but subject to satisfying tasks’ latency requirements. This distributed DRL approach, specifically an Actor-Critic (AC) algorithm running on each User Equipment (UE), is evaluated through the simulation of two distinct scenarios and outperforms other analyzed baselines in terms of QoE values and/or energy consumption in dynamic environments, also demonstrating that decisions need to be adapted to the environment’s evolution.
The protective role of prebiotics and probiotics on diarrhea and gut damage in the rotavirus-infected piglets
Authors: Yang Heng , Fan Xiangqi , Mao Xiangbing , Yu Bing , He Jun , Yan Hui , Wang Jianping
Published: May 2024

Rotavirus is one of the pathogenic causes that induce diarrhea in young animals, especially piglets, worldwide. However, nowadays, there is no specific drug available to treat the disease, and the related vaccines have no obvious efficiency in some countries. Via analyzing the pathogenesis of rotavirus, it inducing diarrhea is mainly due to disturb enteric nervous system, destroy gut mucosal integrity, induce intracellular electrolyte imbalance, and impair gut microbiota and immunity. Many studies have already proved that prebiotics and probiotics can mitigate the damage and diarrhea induced by rotavirus infection in hosts. Based on these, the current review summarizes and discusses the effects and mechanisms of prebiotics and probiotics on rotavirus-induced diarrhea in piglets. This information will highlight the basis for the swine production utilization of prebiotics and probiotics in the prevention or treatment of rotavirus infection in the future.
Characterizing OXPHOS inhibitor-mediated alleviation of hypoxia using high-throughput live cell-imaging
Authors: Beerkens Anne P. M. , Boreel Daan F. , Nathan James A. , Neuzil Jiri , Cheng Gang , Kalyanaraman Balaraman , Hardy Micael , Adema Gosse J. , Heskamp Sandra , Span Paul N. , Bussink Johan
Published: May 2024

Background

Hypoxia is a common feature of many solid tumors and causes radiotherapy and immunotherapy resistance. Pharmacological inhibition of oxidative phosphorylation (OXPHOS) has emerged as a therapeutic strategy to reduce hypoxia. However, the OXPHOS inhibitors tested in clinical trials caused only moderate responses in hypoxia alleviation or trials were terminated due to dose-limiting toxicities. To improve the therapeutic benefit, FDA approved OXPHOS inhibitors (e.g. atovaquone) were conjugated to triphenylphosphonium (TPP+) to preferentially target cancer cell’s mitochondria. In this study, we evaluated the hypoxia reducing effects of several mitochondria-targeted OXPHOS inhibitors and compared them to non-mitochondria-targeted OXPHOS inhibitors using newly developed spheroid models for diffusion-limited hypoxia.

Methods

B16OVA murine melanoma cells and MC38 murine colon cancer cells expressing a HIF-Responsive Element (HRE)-induced Green Fluorescent Protein (GFP) with an oxygen-dependent degradation domain (HRE-eGFP-ODD) were generated to assess diffusion-limited hypoxia dynamics in spheroids. Spheroids were treated with IACS-010759, atovaquone, metformin, tamoxifen or with mitochondria-targeted atovaquone (Mito-ATO), PEGylated mitochondria-targeted atovaquone (Mito-PEG-ATO) or mitochondria-targeted tamoxifen (MitoTam). Hypoxia dynamics were followed and quantified over time using the IncuCyte Zoom Live Cell-Imaging system.

Results

Hypoxic cores developed in B16OVA.HRE and MC38.HRE spheroids within 24 h hours after seeding. Treatment with IACS-010759, metformin, atovaquone, Mito-PEG-ATO and MitoTam showed a dose-dependent reduction of hypoxia in both B16OVA.HRE and MC38.HRE spheroids. Mito-ATO only alleviated hypoxia in MC38.HRE spheroids while tamoxifen was not able to reduce hypoxia in any of the spheroid models. The mitochondria-targeted OXPHOS inhibitors demonstrated stronger anti-hypoxic effects compared to the non-mito-targeted OXPHOS inhibitors.

Conclusions

We successfully developed a high-throughput spheroid model in which hypoxia dynamics can be quantified over time. Using this model, we showed that the mitochondria-targeted OXPHOS inhibitors Mito-ATO, Mito-PEG-ATO and MitoTam reduce hypoxia in tumor cells in a dose-dependent manner, potentially sensitizing hypoxic tumor cells for radiotherapy.
Head-to-head comparison of [68Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT for the evaluation of tonsil cancer and lymph node metastases: a single-centre retrospective study
Authors: Ji Mengjing , Ma Guang , Liu Cheng , Gu Bingxin , Du Xinyue , Ou Xiaomin , Xu Xiaoping , Song Shaoli , Yang Zhongyi
Published: May 2024

Background

This study aimed to compare the diagnostic value of [68 Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT imaging for primary lesions and metastatic lymph nodes in patients with tonsil cancer.

Method

Twenty-one tonsil cancer patients who underwent [68 Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT scans within two weeks in our centre were retrospectively enrolled. The maximum standardized uptake value (SUVmax) and tumor-to-background ratio (TBR) of the two tracers were compared by using the Mann‒Whitney U test. In addition, the sensitivity, specificity, and accuracy of the two methods for diagnosing metastatic lymph nodes were analysed.

Results

In detecting primary lesions, the efficiency was higher for [68 Ga]Ga-DOTA-FAPI-04 PET/CT (20/22) than for [18F]FDG PET/CT (9/22). Although [68 Ga]Ga-DOTA-FAPI-04 uptake (SUVmax, 5.03 ± 4.06) was lower than [18F]FDG uptake (SUVmax, 7.90 ± 4.84, P = 0.006), [68 Ga]Ga-DOTA-FAPI-04 improved the distinction between the primary tumor and contralateral normal tonsillar tissue. The TBR was significantly higher for [68 Ga]Ga-DOTA-FAPI-04 PET/CT (3.19 ± 2.06) than for [18F]FDG PET/CT (1.89 ± 1.80) (p < 0.001). In lymph node analysis, SUVmax and TBR were not significantly different between [68 Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT (7.67 ± 5.88 vs. 8.36 ± 6.15, P = 0.498 and 5.56 ± 4.02 vs. 4.26 ± 3.16, P = 0.123, respectively). The specificity and accuracy of [68 Ga]Ga-DOTA-FAPI-04 PET/CT were higher than those of [18F]FDG PET/CT in diagnosing metastatic cervical lymph nodes (all P < 0.05).

Conclusion

The availability of [68 Ga]Ga-DOTA-FAPI-04 complements the diagnostic results of [18F]FDG by improving the detection rate of primary lesions and the diagnostic accuracy of cervical metastatic lymph nodes in tonsil cancer compared to [18F]FDG.
High insertion torque versus regular insertion torque: early crestal bone changes on dental implants in relation to primary stability—a retrospective clinical study
Authors: Ruppin Jörg-Martin , Stimmelmayr Michael
Published: May 2024

The aim of the presented retrospective study was to evaluate the early crestal bone changes around an implant type designed for high primary stability. A total number of 111 implants placed clinically were evaluated regarding insertion torque, bone density, implant stability quotient (ISQ) and early crestal bone loss from standardized digital radiographs. The implants were allocated in two groups: the „regular torque “ group contained all implants that achieved less than 50 Ncm as final insertion torque (n = 63) and the „high torque“ group contained the implants that achieved 50–80 Ncm (n = 48). To avoid possible damage either to the implant´s inner connection or to the bone by application of excessive force, a limit of 80 Ncm was set for all surgeries. All implants underwent submerged healing for three months. ISQ measurements and standardized digital radiographs were taken at day of insertion and at day of second stage surgery. The bone loss was measured on the mesial and distal aspect of the implant. The data evaluation showed the following results: Mean bone loss was 0.27 ± 0.30 mm for the high torque group and 0.24 ± 0.27 mm for the regular torque group. The difference was not statistically significant (p = 0.552). In the two groups, no complications nor implant loss occurred. For the evaluated implant type, there was no significant difference in crestal bone changes and complication rate between high and regular insertion torque in the early healing period.

Graphical Abstract