bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical teaching in applied health science: effects of a student-led journal club on aging and physical activity
Authors: Fleiner Tim , Trumpf Rieke , Schnorr Thiemo , Buchner Theresa , Haussermann Peter , Zijlstra Wiebren , Morat Tobias
Published: October 2023

Background

This project aims to investigate the effects of a student-led journal club on students’ critical thinking and clinical application skills in the academic field of aging and physical activity.

Methods

A pre-post design analysis with data collected in four successive cohorts of the program M.Sc. Sport and Movement Gerontology was conducted. Each student assigned himself/herself to a study, and then led the journal club discussion and published a summary of the journal club via graphical abstract on social media. The students rated their perceived confidence in the beginning (T0) and after the semester (T1) via questionnaire and 5-point Likert scales addressing their ability to review and summarize the evidence, to present it in a journal club and to lead the discussion.

Results

41 students (32 women, M = 25 years SD 1.9 years) were included. The journal club was rated as “very good” (median 2, IQR 1). Students’ confidence on participating, leading the journal club and transferring the results into clinical practice improved significantly (r ≥ 0.6, p < 0.01) – e.g.: “I feel confident in leading a discussion on the literature presented”, T0: “undecided” (median 3, IQR 2) to T1: “rather agree” (median 4, IQR 1, Z= -5.41, r = 0.85, p < 0.01).

Discussion

The student-led journal club shows to be an effective teaching approach for the field of aging and physical activity within applied health science education. Especially the students’ self-assignment to the studies and involving the scientific community via social media was rated as useful and highly motivating for students and lecturers.
Relationship between craving to drugs, emotional manipulation and interoceptive awareness for social acceptance: the addictive perspective
Authors: Khedr Mahmoud Abdelwahab , El-Ashry Ayman Mohamed , Ali Eman Abdeen , Eweida Rasha Salah
Published: October 2023

Background

Drug addiction (DA) is a global psychiatric worldwide problem. Patients with substance use disorder are more likely to use the numerous defenses at their disposal to control their surroundings emotionally. This could virtually cause a tidal wave of social rejection of them in the community. The study aims to investigate drug craving, emotional manipulation, and interoceptive awareness for social acceptance among patients with substance use disorder.

Methods

This study followed a descriptive correlational design on a sample of 110 patients with substance use disorder who were recruited to complete the Penn Alcohol Craving Scale, the Emotion Manipulation Questionnaire, and the Perceived Acceptance Scale.

Results

Most respondents recorded high levels of PACS and emotional manipulation ability. A highly positive and significant correlation was found between scores on emotional manipulation ability and PACS.

Conclusion

Craving for drugs was a significant predictor of emotional manipulation ability. Incorporation of effective nursing interventions to enable patients with substance use disorder to engage in self-reflection related to how their cravings for drugs may lead them to prioritize their needs over others.
Forkhead box transcription factors (FOXOs and FOXM1) in glioma: from molecular mechanisms to therapeutics
Authors: Tabnak Peyman , Hasanzade Bashkandi Aysa , Ebrahimnezhad Mohammad , Soleimani Mahdieh
Published: October 2023

Glioma is the most aggressive and malignant type of primary brain tumor, comprises the majority of central nervous system deaths, and is categorized into different subgroups according to its histological characteristics, including astrocytomas, oligodendrogliomas, glioblastoma multiforme (GBM), and mixed tumors. The forkhead box (FOX) transcription factors comprise a collection of proteins that play various roles in numerous complex molecular cascades and have been discovered to be differentially expressed in distinct glioma subtypes. FOXM1 and FOXOs have been recognized as crucial transcription factors in tumor cells, including glioma cells. Accumulating data indicates that FOXM1 acts as an oncogene in various types of cancers, and a significant part of studies has investigated its function in glioma. Although recent studies considered FOXO subgroups as tumor suppressors, there are pieces of evidence that they may have an oncogenic role. This review will discuss the subtle functions of FOXOs and FOXM1 in gliomas, dissecting their regulatory network with other proteins, microRNAs and their role in glioma progression, including stem cell differentiation and therapy resistance/sensitivity, alongside highlighting recent pharmacological progress for modulating their expression.
Elderly patients with stage II gastric cancer do not benefit from adjuvant chemotherapy
Authors: Guo Jianping , Xiong Zhizhong , Yin Shi , Wen Yue’e , Jin Longyang , Wang Caiqin , Chen Huaxian , Luo Dandong , Deng Zijian , Huang Dayin , Li Xianzhe , Yi Biying , Mao Chaobin , Lian Lei
Published: October 2023

Background

With the aging of the population, the burden of elderly gastric cancer (EGC) increases worldwide. However, there is no consensus on the definition of EGC and the efficacy of adjuvant chemotherapy in patients with stage II EGC. Here, we investigated the effectiveness of adjuvant chemotherapy in defined EGC patients.

Methods

We enrolled 5762 gastric cancer patients of three independent cohorts from the Sixth Affiliated Hospital of Sun Yat-sen University (local), the Surveillance, Epidemiology, and End Results (SEER), and the Asian Cancer Research Group (ACRG). The optimal age cutoff for EGC was determined using the K-adaptive partitioning algorithm. The defined EGC group and the efficacy of adjuvant chemotherapy for them were confirmed by Cox regression and Kaplan–Meier survival analyses. Furthermore, gene set variation analyses (GSVA) were performed to reveal pathway enrichment between groups.

Results

The optimal age partition value for EGC patients was 75. In the local, SEER, and ACRG cohorts, the EGC group exhibited significantly worse overall survival and cancer-specific survival than the non-EGC group (P < 0.05) and was an independent risk factor. Stratified analyses based on chemotherapy showed that EGC patients derived little benefit from adjuvant chemotherapy. Furthermore, GSVA analysis revealed the activation of DNA repair-related pathways and downregulation of the p53 pathway, which may partially contribute to the observed findings.

Conclusion

In this retrospective, international multi-center study, 75 years old was identified as the optimal age cutoff for EGC definition, and adjuvant chemotherapy proved to be unbeneficial for stage II EGC patients.
The effect of an app-based dietary intervention on diet-related greenhouse gas emissions – results from a randomized controlled trial
Authors: Pitt Stephanie , Sjöblom Linnea , Bälter Katarina , Trolle Lagerros Ylva , Bonn Stephanie E
Published: October 2023

Background

Dietary change towards a diet low in greenhouse gas emissions (GHGEs) can reduce climate impact and improve individual-level health. However, there is a lack of understanding if diet interventions can achieve low-GHGE diets.

Methods

A randomized controlled trial was conducted to assess the effects of an app-based intervention. The intervention was designed to improve dietary intake of people with Type 2 diabetes, and was delivered via an app over 12 weeks, with each week covering one diet-related topic. Dietary intake was assessed at baseline and 3-month follow up by a 95-item food frequency questionnaire and linked to GHGE values. A total of n = 93 participants (n = 46 and n = 47 for the intervention and control group, respectively) were included in the analysis. Changes to GHGEs within and between the groups were analysed with inferential statistics.

Results

The majority (60%) of participants were male, with a mean age of 63.2 years and body mass index of 30 kg/m2. At baseline, diet-related GHGEs were 4.8 and 4.9 kg CO2-eq/day in the intervention and control group, respectively. At 3-month follow up the corresponding GHGEs were 4.7 and 4.9 kg CO2-eq/day. We found no statistically significant changes to diet-related GHGEs within or between groups, or within food categories, from baseline to 3-month follow up.

Conclusion

No evidence was found for the effectiveness of the app-based intervention to generate changes to diet-related GHGEs in a population of people with Type 2 diabetes. However, future interventions that target reducing meat consumption specifically may have the potential to result in a reduction of individual-level diet-related GHGEs.

Trial registration

ClinicalTrials.gov, NCT03784612. Registered 24 December 2018. www.clinicaltrials.gov/ct2/show/NCT03784612.
Prediction of clinically significant prostate cancer through urine metabolomic signatures: A large-scale validated study
Authors: Huang Hsiang-Po , Chen Chung-Hsin , Chang Kai-Hsiung , Lee Ming-Shyue , Lee Cheng-Fan , Chao Yen-Hsiang , Lu Shih-Yu , Wu Tzu-Fan , Liang Sung-Tzu , Lin Chih-Yu , Lin Yuan Chi , Liu Shih-Ping , Lu Yu-Chuan , Shun Chia-Tung , Huang William J. , Lin Tzu-Ping , Ku Ming-Hsuan , Chung Hsiao-Jen , Chang Yen-Hwa , Liao Chun-Hou , Yu Chih-Chin , Chung Shiu-Dong , Tsai Yao-Chou , Wu Chia-Chang , Chen Kuan-Chou , Ho Chen-Hsun , Hsiao Pei-Wen , Pu Yeong-Shiau
Published: October 2023

Purpose

Currently, there are no accurate markers for predicting potentially lethal prostate cancer (PC) before biopsy. This study aimed to develop urine tests to predict clinically significant PC (sPC) in men at risk.

Methods

Urine samples from 928 men, namely, 660 PC patients and 268 benign subjects, were analyzed by gas chromatography/quadrupole time-of-flight mass spectrophotometry (GC/Q-TOF MS) metabolomic profiling to construct four predictive models. Model I discriminated between PC and benign cases. Models II, III, and GS, respectively, predicted sPC in those classified as having favorable intermediate risk or higher, unfavorable intermediate risk or higher (according to the National Comprehensive Cancer Network risk groupings), and a Gleason sum (GS) of ≥ 7. Multivariable logistic regression was used to evaluate the area under the receiver operating characteristic curves (AUC).

Results

In Models I, II, III, and GS, the best AUCs (0.94, 0.85, 0.82, and 0.80, respectively; training cohort, N = 603) involved 26, 24, 26, and 22 metabolites, respectively. The addition of five clinical risk factors (serum prostate-specific antigen, patient age, previous negative biopsy, digital rectal examination, and family history) significantly improved the AUCs of the models (0.95, 0.92, 0.92, and 0.87, respectively). At 90% sensitivity, 48%, 47%, 50%, and 36% of unnecessary biopsies could be avoided. These models were successfully validated against an independent validation cohort (N = 325). Decision curve analysis showed a significant clinical net benefit with each combined model at low threshold probabilities. Models II and III were more robust and clinically relevant than Model GS.

Conclusion

This urine test, which combines urine metabolic markers and clinical factors, may be used to predict sPC and thereby inform the necessity of biopsy in men with an elevated PC risk.
Insulin-degrading enzyme (IDE) as a modulator of microglial phenotypes in the context of Alzheimer’s disease and brain aging
Authors: Corraliza-Gomez Miriam , Bermejo Teresa , Lilue Jingtao , Rodriguez-Iglesias Noelia , Valero Jorge , Cozar-Castellano Irene , Arranz Eduardo , Sanchez Diego , Ganfornina Maria Dolores
Published: October 2023

The insulin-degrading enzyme (IDE) is an evolutionarily conserved zinc-dependent metallopeptidase highly expressed in the brain, where its specific functions remain poorly understood. Besides insulin, IDE is able to cleave many substrates in vitro, including amyloid beta peptides, making this enzyme a candidate pathophysiological link between Alzheimer's disease (AD) and type 2 diabetes (T2D). These antecedents led us to address the impact of IDE absence in hippocampus and olfactory bulb. A specific induction of microgliosis was found in the hippocampus of IDE knockout (IDE-KO) mice, without any effects in neither hippocampal volume nor astrogliosis. Performance on hippocampal-dependent memory tests is influenced by IDE gene dose in 12-month-old mice. Furthermore, a comprehensive characterization of the impact of IDE haploinsufficiency and total deletion in metabolic, behavioral, and molecular parameters in the olfactory bulb, a site of high insulin receptor levels, reveals an unambiguous barcode for IDE-KO mice at that age. Using wildtype and IDE-KO primary microglial cultures, we performed a functional analysis at the cellular level. IDE absence alters microglial responses to environmental signals, resulting in impaired modulation of phenotypic states, with only transitory effects on amyloid-β management. Collectively, our results reveal previously unknown physiological functions for IDE in microglia that, due to cell-compartment topological reasons, cannot be explained by its enzymatic activity, but instead modulate their multidimensional response to various damaging conditions relevant to aging and AD conditions.
Obesity drives adipose-derived stem cells into a senescent and dysfunctional phenotype associated with P38MAPK/NF-KB axis
Authors: Grun L K , Maurmann R M , Scholl J N , Fogaça M E , Schmitz C R R , Dias C K , Gasparotto J , Padoin A V , Mottin C C , Klamt F , Figueiró F , Jones M H , Filippi-Chiela E C , Guma F C R , Barbé-Tuana F M
Published: October 2023

Background

Adipose-derived stem cells (ADSC) are multipotent cells implicated in tissue homeostasis. Obesity represents a chronic inflammatory disease associated with metabolic dysfunction and age-related mechanisms, with progressive accumulation of senescent cells and compromised ADSC function. In this study, we aimed to explore mechanisms associated with the inflammatory environment present in obesity in modulating ADSC to a senescent phenotype. We evaluated phenotypic and functional alterations through 18 days of treatment. ADSC were cultivated with a conditioned medium supplemented with a pool of plasma from eutrophic individuals (PE, n = 15) or with obesity (PO, n = 14), and compared to the control.

Results

Our results showed that PO-treated ADSC exhibited decreased proliferative capacity with G2/M cycle arrest and CDKN1A (p21WAF1/Cip1) up-regulation. We also observed increased senescence-associated β-galactosidase (SA-β-gal) activity, which was positively correlated with TRF1 protein expression. After 18 days, ADSC treated with PO showed augmented CDKN2A (p16INK4A) expression, which was accompanied by a cumulative nuclear enlargement. After 10 days, ADSC treated with PO showed an increase in NF-κB phosphorylation, while PE and PO showed an increase in p38MAPK activation. PE and PO treatment also induced an increase in senescence-associated secretory phenotype (SASP) cytokines IL-6 and IL-8. PO-treated cells exhibited decreased metabolic activity, reduced oxygen consumption related to basal respiration, increased mitochondrial depolarization and biomass, and mitochondrial network remodeling, with no superoxide overproduction. Finally, we observed an accumulation of lipid droplets in PO-treated ADSC, implying an adaptive cellular mechanism induced by the obesogenic stimuli.

Conclusions

Taken together, our data suggest that the inflammatory environment observed in obesity induces a senescent phenotype associated with p38MAPK/NF-κB axis, which stimulates and amplifies the SASP and is associated with impaired mitochondrial homeostasis.
DENV-2 NS1 promotes AMPK-LKB1 interaction to activate AMPK/ERK/mTOR signaling pathway to induce autophagy
Authors: Wu Ning , Ji Jinzhong , Gou Xiaoqin , Hu Pan , Cheng Yao , Liu Yuhang , Wang Yuanying , Zhang Qilong , Zuo Li
Published: October 2023

The global incidence of dengue fever has gradually increased in recent years, posing a serious threat to human health. In the absence of specific anti-dengue drugs, understanding the interaction of Dengue virus (DENV) with the host is essential for the development of effective therapeutic measures. Autophagy is often activated during DENV infection to promote viral replication, but the mechanism of how DENV's own proteins induce autophagy has not been clarified. In this study, we first preliminarily identified DENV-2 NS1 as the most likely viral protein for DENV-2-induced autophagy with the help of molecular docking techniques. Further experimental results confirmed that DENV-2 NS1 regulates DENV-2 infection of HUVEC-induced autophagy through the AMPK/ERK/mTOR signaling pathway. Mechanistically, DENV-2 NS1 mainly interacted with AMPK by means of its Wing structural domain, and NS1 bound to all three structural domains on the AMPKα subunit. Finally, the experimental results showed that DENV-2 NS1 promoted the interaction between LKB1 and AMPKα1 and thus activated AMPK by both increasing the expression of LKB1 and binding LKB1. In conclusion, the results of this study revealed that DENV-2 NS1 protein served as a platform for the interaction between AMPK and LKB1 after DENV-2 infection with HUVEC, and pulled AMPK and LKB1 together to form a complex. LKB1 to form a complex, promoting LKB1 action on the kinase structural domain of AMPKα1, which in turn promotes phosphorylation of the Thr172 site on the AMPK kinase structural domain and activates AMPK, thereby positively regulating the AMPK/ERK/mTOR signaling pathway and inducing autophagy. The present discovery improves our understanding of DENV-2-induced host autophagy and contributes to the development of anti-dengue drugs.
Tumor removal limits prostate cancer cell dissemination in bone and osteoblasts induce cancer cell dormancy through focal adhesion kinase
Authors: Liu Ruihua , Su Shang , Xing Jing , Liu Ke , Zhao Yawei , Stangis Mary , Jacho Diego P. , Yildirim-Ayan Eda D. , Gatto-Weis Cara M. , Chen Bin , Li Xiaohong
Published: October 2023

Background

Disseminated tumor cells (DTCs) can enter a dormant state and cause no symptoms in cancer patients. On the other hand, the dormant DTCs can reactivate and cause metastases progression and lethal relapses. In prostate cancer (PCa), relapse can happen after curative treatments such as primary tumor removal. The impact of surgical removal on PCa dissemination and dormancy remains elusive. Furthermore, as dormant DTCs are asymptomatic, dormancy-induction can be an operational cure for preventing metastases and relapse of PCa patients.

Methods

We used a PCa subcutaneous xenograft model and species-specific PCR to survey the DTCs in various organs at different time points of tumor growth and in response to tumor removal. We developed in vitro 2D and 3D co-culture models to recapitulate the dormant DTCs in the bone microenvironment. Proliferation assays, fluorescent cell cycle reporter, qRT-PCR, and Western Blot were used to characterize the dormancy phenotype. We performed RNA sequencing to determine the dormancy signature of PCa. A drug repurposing algorithm was applied to predict dormancy-inducing drugs and a top candidate was validated for the efficacy and the mechanism of dormancy induction.

Results

We found DTCs in almost all mouse organs examined, including bones, at week 2 post-tumor cell injections. Surgical removal of the primary tumor reduced the overall DTC abundance, but the DTCs were enriched only in the bones. We found that osteoblasts, but not other cells of the bones, induced PCa cell dormancy. RNA-Seq revealed the suppression of mitochondrial-related biological processes in osteoblast-induced dormant PCa cells. Importantly, the mitochondrial-related biological processes were found up-regulated in both circulating tumor cells and bone metastases from PCa patients’ data. We predicted and validated the dormancy-mimicking effect of PF-562,271 (PF-271), an inhibitor of focal adhesion kinase (FAK) in vitro. Decreased FAK phosphorylation and increased nuclear translocation were found in both co-cultured and PF-271-treated C4-2B cells, suggesting that FAK plays a key role in osteoblast-induced PCa dormancy.

Conclusions

Our study provides the first insights into how primary tumor removal enriches PCa cell dissemination in the bones, defines a unique osteoblast-induced PCa dormancy signature, and identifies FAK as a PCa cell dormancy gatekeeper.
Risk prediction for liver injury in Epstein-Barr virus infection in pediatric respiratory tract infections
Authors: Mao Song , Wu Liangxia , Shi Wenjing
Published: October 2023

Background

Epstein-Barr virus (EBV) infection is likely to co-occur in pediatric respiratory tract infections (RTIs). Liver injury is the common complication of EBV infection. The detailed risk factors for liver injury in EBV infection remain elusive. We aimed to investigate the incidence, characteristics and potential risk factors for liver injury in EBV infection for early risk prediction.

Methods

We retrospectively recruited the pediatric RTIs cases with EBV infection according to a predefined criteria from our hospital between January 2015 and December 2017. We extracted the clinical and laboratory data from the electronical medical records. The impact of age, gender, and various parameters on the liver injury risk was investigated. Univariate logistic regression analysis was performed to analyse the association between clinical/laboratory parameters and liver injury. The related indexes were enrolled in the multivariate logistic regression analysis. Decision curve analysis was used to yield the value of related parameters in predicting liver injury. Receiver operating curve (ROC) analysis was applied to produce the C-index of white blood cell (WBC) count for liver injury. We also tested the non-linear association between WBC count and alanine aminotransferase (ALT).

Results

A total of 216 pediatric RTIs with EBV infection were enrolled. EBV infection is more likely to occur during the winter season. Cytomegalovirus infection was independently associated with liver injury in EBV infection (OR = 6.972, 95% CI = 1.648–29.490, p = 0.008). WBC count was independently associated with liver injury in EBV infection (OR = 1.169, 95% CI = 1.051–1.301, p = 0.004). The P interaction value between WBC count and cytomegalovirus was 0.149. The decision curve analysis showed that WBC count had larger area under curve compared with platelet (PLT) and birthweight (BW). ROC analysis yielded the c-index of WBC count: 0.75 and cut-point of 8.3. The turning point of WBC count in its association with ALT was 16.8. The p value before and after the turning point was < 0.001 and 0.123, respectively.

Conclusions

Cytomegalovirus co-infection demonstrated 5.972 more times of liver injury risk in EBV infection. WBC count was an independent biomarker for liver injury before the turning point of 16.8 in EBV infection. More attention should be paid to the risk of EBV infection in the winter. Cytomegalovirus infection and WBC count merit attention in the monitoring of possible liver injury in EBV infection among pediatric RTIs.
System inflammation response index: a novel inflammatory indicator to predict all-cause and cardiovascular disease mortality in the obese population
Authors: Kong Fanliang , Huang Junhao , Xu Chunhua , Huang Tingyuan , Wen Grace , Cheng Wenke
Published: October 2023

Aim

This study aims to investigate the relationship between two novel inflammatory markers, namely, the Systemic Inflammatory Response Index (SIRI) and the Systemic Immune Inflammatory Index (SII), as well as the all-cause and cardiovascular disease (CVD) mortality in the obese population.

Materials and methods

We conducted a prospective cohort study based on the data of 13,026 obese adults (age ≥ 18 years) from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014 and followed until December 2019. SIRI was calculated by the formula: (neutrophil count × monocyte count) / lymphocyte count, while that of SII was: (platelet count × neutrophil count)/lymphocyte count. The association of SIRI and SII with all-cause and CVD mortality was evaluated using Cox regression. In addition, the nomogram was performed to predict 10-year survival probability.

Results

During a median follow-up of 137 months, 1959 and 553 all-cause and CVD deaths were recorded, respectively. Spearman correlation analysis indicated that SIRI and SII were unrelated to almost all baseline characteristics (r < 0.15). Multivariate Cox regression models displayed that each standard deviation (SD) increase in SIRI was associated with a 16% (HR 1.16; 95% CI 1.09–1.24) and 22% (HR 1.22; 95% CI 1.10–1.36) increase in the risk of all-cause and CVD mortality, respectively. Likewise, every SD increase in SII was correlated with a 9% (HR 1.09; 95% CI 1.02–1.16) and 14% (HR 1.14; 95% CI 1.04–1.26) increase in the risk of all-cause and CVD mortality, respectively. The predictive value of SIRI for all-cause and CVD mortality (AUC = 0.601 and 0.624) exceeded that of SII (AUC = 0.528 and 0.539). Moreover, the nomogram displayed a substantial predictive value for 10-year survival (AUC = 0.847) with sensitivity and specificity exceeding 75%.

Conclusions

In the obese population, SIRI and SII are independent risk factors for all-cause and CVD mortality. Notably, the predictive ability of SIRI for both all-cause and CVD mortality significantly outperforms that of SII, suggesting that SIRI is a more valuable marker of inflammation.
The relevance of the non-invasive biomarkers lncRNA GAS5/miR-21 ceRNA regulatory network in the early identification of diabetes and diabetic nephropathy
Authors: Sun He , Chen Tong , Li Xin , Zhu Yonghong , Zhang Shuang , He Ping , Peng Yali , Fan Qiuling
Published: October 2023

Background

To investigate the diagnostic value of serum lncRNA growth arrest-specific transcript 5 (lncRNA GAS5) and microRNA-21 (miR-21) in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN), and elucidate their roles in the pathogenesis.

Methods

A microarray technology was used asses lncRNA GAS5 and miR-21 expression profiles in non-anticoagulant blood from 44 patients including T2DM without DN group (DM), T2DM with DN group (DN), and healthy controls group (N), followed by real-time PCR validation. Logistic regression and receiver operating characteristic (ROC) curves were applied to evaluate the clinical indicators among normal, T2DM, and DN patients.

Results

The serum lncRNA GAS5 expression in T2DM and DN patients was significantly down-regulated compared with the N group, while the expression of miR-21 was significantly up-regulated (all P < 0.05). Fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) were negatively correlated with serum lncRNA GAS5, and FBG was independently correlated with serum lncRNA GAS5. Urinary microalbumin, total cholesterol (TC), creatinine (Cr), urea, and systolic blood pressure (SBP) were significantly positively correlated with serum miR-21. Glomerular filtration rate (GFR) and albuminuria (ALB) were negatively correlated with serum miR-21, and ALB was independently correlated with serum miR-21. Serum lncRNA GAS5, miR-21 and lncRNA GAS5/miR-21 showed good diagnostic efficiency as the “diagnostic signature” of T2DM and DN.

Conclusion

The lncRNA GAS5/miR-21 diagnostic signature may be a more effective non-invasive biomarker for detecting T2DM. In addition, miR-21 alone may be a more accurate serum biomarker for the early screening of DN patients.
Single-cell sequencing technology applied to epigenetics for the study of tumor heterogeneity
Authors: Hu Yuhua , Shen Feng , Yang Xi , Han Tingting , Long Zhuowen , Wen Jiale , Huang Junxing , Shen Jiangfeng , Guo Qing
Published: October 2023

Background

Previous studies have traditionally attributed the initiation of cancer cells to genetic mutations, considering them as the fundamental drivers of carcinogenesis. However, recent research has shed light on the crucial role of epigenomic alterations in various cell types present within the tumor microenvironment, suggesting their potential contribution to tumor formation and progression. Despite these significant findings, the progress in understanding the epigenetic mechanisms regulating tumor heterogeneity has been impeded over the past few years due to the lack of appropriate technical tools and methodologies.

Results

The emergence of single-cell sequencing has enhanced our understanding of the epigenetic mechanisms governing tumor heterogeneity by revealing the distinct epigenetic layers of individual cells (chromatin accessibility, DNA/RNA methylation, histone modifications, nucleosome localization) and the diverse omics (transcriptomics, genomics, multi-omics) at the single-cell level. These technologies provide us with new insights into the molecular basis of intratumoral heterogeneity and help uncover key molecular events and driving mechanisms in tumor development.

Conclusion

This paper provides a comprehensive review of the emerging analytical and experimental approaches of single-cell sequencing in various omics, focusing specifically on epigenomics. These approaches have the potential to capture and integrate multiple dimensions of individual cancer cells, thereby revealing tumor heterogeneity and epigenetic features. Additionally, this paper outlines the future trends of these technologies and their current technical limitations.
Is the clinical phenotype impact the prognosis in dementia with Lewy bodies?
Authors: Aveneau Clément , Wallon David , Degos Bertrand , Obadia Alexandre , Hourregue Claire , Benisty Sarah , Garcin Béatrice , Dumurgier Julien , Paquet Claire
Published: October 2023

Introduction

The first predominant clinical symptoms of dementia with Lewy bodies (DLB) are highly variable; however, the prognosis based on initial predominant symptoms remains poorly understood.

Methods

Multicenter retrospective study in 4 French expert neurological centers. Patients were categorized in 3 groups according to their first more predominant symptoms: cognitive, psychiatric, or motor.

Results

Analysis of 310 DLB patients. The mean age was 73.5 years old (SD 7.5) including 32.3% of women. The mean follow-up was 7.25 years (SD 3.6). We observed that the full clinical picture was more frequent in the motor group than in the cognitive group (p = 0.01); male gender and age at onset were associated with a significant excess risk of instantaneous mortality (p = 0.01).

Conclusion

Initial symptoms may affect the clinical course of patients, but no significant difference in mortality was observed.
Readthrough isoform of aquaporin-4 (AQP4) as a therapeutic target for Alzheimer’s disease and other proteinopathies
Authors: Mohaupt Pablo , Vialaret Jérôme , Hirtz Christophe , Lehmann Sylvain
Published: October 2023

The glymphatic system is a crucial component in preserving brain homeostasis by facilitating waste clearance from the central nervous system (CNS). Aquaporin-4 (AQP4) water channels facilitate the continuous interchange between cerebrospinal fluid and brain interstitial fluid by convective flow movement. This flow is responsible for guiding proteins and metabolites away from the CNS. Proteinopathies are neurological conditions characterized by the accumulation of aggregated proteins or peptides in the brain. In Alzheimer’s disease (AD), the deposition of amyloid-β (Aβ) peptides causes the formation of senile plaques. This accumulation has been hypothesized to be a result of the imbalance between Aβ production and clearance. Recent studies have shown that an extended form of AQP4 increases Aβ clearance from the brain. In this mini-review, we present a summary of these findings and explore the potential for future therapeutic strategies aiming to boost waste clearance in AD.
Barriers to penicillin allergy de-labeling in the inpatient and outpatient settings: a qualitative study
Authors: Alagoz Esra , Saucke Megan , Balasubramanian Prakash , Lata Paul , Liebenstein Tyler , Kakumanu Sujani
Published: October 2023

Background

Penicillin allergy is the most commonly reported drug allergy in the US. Despite evidence demonstrating that up to 90% of labels are incorrect, scalable interventions are not well established. As part of a larger mixed methods investigation, we conducted a qualitative study to describe the barriers to implementing a risk-based penicillin de-labeling protocol within a single site Veteran’s hospital.

Methods

We conducted individual and group interviews with multidisciplinary inpatient and outpatient healthcare teams. The interview guides were developed using the Theoretical Domains Framework (TDF) to explore workflows and contextual factors influencing identification and evaluation of patients with penicillin allergy. Three researchers iteratively developed the codebook based on TDF domains and coded the data using thematic analysis.

Results

We interviewed 20 clinicians. Participants included three hospitalists, five inpatient pharmacists, one infectious disease physician, two anti-microbial stewardship pharmacists, four primary care providers, two outpatient pharmacists, two resident physicians, and a nurse case manager for the allergy service. The factors that contributed to barriers to penicillin allergy evaluation and de-labeling were classified under six TDF domains; knowledge, skills, beliefs about capabilities, beliefs about consequences, professional role and identity, and environmental context and resources. Participants from all groups acknowledged the importance of penicillin de-labeling. However, they lacked confidence in their skills to perform the necessary evaluations, such as test dose challenges. The fear of inducing an allergic reaction and adding further complexity to patient care exacerbated their reluctance to de-label patients. The lack of ownership of de-labeling initiative was another significant obstacle in establishing consistent clinical workflows. Additionally, heavy workloads, competing priorities, and ease of access to alternative antibiotics prevented the prioritization of tasks related to de-labeling. Space limitations and nursing staff shortages added to challenges in outpatient settings.

Conclusion

Our findings demonstrated that barriers to penicillin allergy de-labeling fall under multiple behavioral domains. Better role clarification, opportunities to develop necessary skills, and dedicated resources are needed to overcome these barriers. Future interventions will need to employ a systemic approach that addresses each of the behavioral domains influencing penicillin allergy de-labeling with stakeholder engagement of the inpatient and outpatient health care teams.
A fault diagnosis method for rolling bearings based on graph neural network with one-shot learning
Authors: Gao Yan , Wu Haowei , Liao Haiqian , Chen Xu , Yang Shuai , Song Heng
Published: October 2023

The manuscript proposes a fault diagnosis method based on graph neural network (GNN) with one-shot learning to effectively diagnose rolling bearings under variable operating conditions. In this proposed method, the convolutional neural network is utilized for feature extraction, reducing loss in the process. Subsequently, GNN applies an adjacency matrix to generate codes for one-shot learning. Experimental verification is conducted using open data from Case Western Reserve University Rolling Bearing Data Center, where four different working conditions with six types of typical faults are selected as input signals. The classification accuracy of the proposed method reaches 98.02%. To further validate its effectiveness, traditional single-learning neural networks such as Siamese, Matching Net, Prototypical Net and (Stacked Auto Encoder) SAE are introduced as comparisons. Simulation results that the proposed method outperforms all chosen methods.
The temporal association between suicide and comorbid mental disorders in people treated for substance use disorders: a National registry study
Authors: Myhre Martin Ø. , Walby Fredrik A. , Bramness Jørgen G. , Mehlum Lars
Published: October 2023

Background

The time after contact with specialized health services for mental health and substance use is associated with an increased risk of suicide, where temporal aspects of suicide and comorbid mental disorders in patients with substance use disorders could be associated. This study aimed to examine the temporal association between time from last treatment contact to suicide and comorbid mental disorders in patients with substance use disorders.

Methods

This study is a historical prospective case series using nationwide registry data. It included 946 individuals registered the year before suicide with a substance use disorder (F10-F19) in Norway's specialized health services for treating substance use and mental health disorders between 2010 and 2020. The outcome was the number of weeks from the last contact with services to suicide. The exposure was comorbid mental disorders divided into 'no comorbid mental disorder’; ‘psychosis or bipolar disorders’ (F20−F31), ‘depressive or anxiety disorders' (F32−F49); and 'personality disorders' (F60-F69). Covariates included gender, age, last diagnosed substance use disorder, registered deliberate self-harm last year, and the number of in- and outpatient contacts the previous year.

Results

The number of weeks from last service contact to suicide differed (p =  < 0.001) between patients with no comorbid mental disorders (Median = 7; IQR 2–23), psychosis or bipolar disorders (Median = 2; IQR = 1–7), depressive or anxiety disorders (Median = 3; IQR = 1–11) and personality disorders (Median = 1; IQR = 1–5.5). Significantly decreased adjusted incidence rate ratios (aIRR) were found for psychosis or bipolar disorders [aIRR = 0.67 (95% CI 0.53–0.85)] and personality disorders [aIRR = 0.56 (0.42–0.77)] compared to no comorbid mental disorder when adjusted for individual characteristics and service contact. For depressive and anxiety disorders compared to no comorbid mental disorder, the association was significant when adjusted for individual characteristics [aIRR = 0.55 (0.46–0.66)].

Conclusions

While patients with substance use disorders generally died by suicide a short time after contact with services, patients with comorbid mental disorders died an even shorter time after such contact and significantly shorter than patients without such comorbidities.
Comparison of trimodality therapy and neoadjuvant chemotherapy combined with radical cystectomy for the survival of muscle-invasive bladder cancer: a population-based analysis
Authors: Zhou Yi-Xin , Hu Qian-Cheng , Zhu Ya-Juan , Mu Xiao-Li , Liu Ji-Yan , Chen Ye
Published: October 2023

Background

Trimodality therapy (TMT) is a mature alternative to radical cystectomy (RC) for patients with muscle-invasive bladder cancer (MIBC) who seek to preserve their primary bladder or are inoperable due to comorbidities. To date, there has been increasing evidence of the effectiveness of TMT as an alternative to RC. In contrast, no literature has stated the effectiveness of neoadjuvant chemotherapy combined with RC (NAC + RC) compared with TMT.

Objective

We aimed to compare the prognosis between patients receiving TMT and NAC + RC.

Methods

The clinicopathological characteristics of patients with T2-4aN0M0 MIBC were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox proportional hazards regression models and Kaplan‒Meier survival curves were used for the survival analysis. Propensity-score matching (PSM) was applied to determine the differences between the two groups. The primary outcome was cancer-specific survival (CSS), and the secondary outcome was overall survival (OS).

Results

In total, 1,175 patients with MIBC who underwent TMT (n = 822) or NAC + RC (n = 353) were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. After 1:1 PSM, the final patient sample included 303 pairs. The prognosis of patients receiving NAC + RC was significantly better than that of patients receiving TMT in both unmatched and matched cohorts (5-year CSS: before PSM, 75.4% vs. 50.6%, P < 0.0001; after PSM, 76.3% vs. 49.5%, P < 0.0001; 5-year OS: before PSM, 71.7% vs. 37.4%, P < 0.0001; after PSM, 71.7% vs. 31.4%, P < 0.0001). The survival advantages of NAC + RC remained remarkable in the stratified analysis of most factors after PSM. Multivariate Cox regression analysis showed that being older than 68 years old, unmarried, grade III/IV, T3-4a stage, and undergoing TMT independently correlated with poor OS.

Conclusion

Thus, in this study, patients with MIBC receiving NAC + RC presented with a better prognosis than those receiving TMT.
Unraveling the effects of import bans on domestic poultry production: a case study of Senegal
Authors: Zamani Omid , Chibanda Craig , Pelikan Janine
Published: October 2023

Senegal banned all imports of uncooked poultry meat in 2006 in response to Avian Influenza outbreaks in many exporting countries. This paper investigates the effects of the import ban on domestic chicken meat production and the performance of Senegal's broiler farms. To do so, we employ various comparative analyses at the farm and macro levels. We use the synthetic control method to estimate the effects on total production, which shows that Senegal’s chicken meat production increased more than it would have without the import ban. This may imply, in line with the infant-industry argument, that the ban has had a positive impact on chicken meat production. In addition, we use a farm-level analysis to evaluate the performance of typical Senegalese broiler farms. The comparison with Ghana shows that Senegalese farms are performing better and have lower costs of production. An opening of the markets should only be implemented gradually, by replacing the ban with tariffs because local industries must have the opportunity to adapt to the competition of the international market step by step.
Imprinting at the KBTBD6 locus involves species-specific maternal methylation and monoallelic expression in livestock animals
Authors: Ahn Jinsoo , Hwang In-Sul , Park Mi-Ryung , Hwang Seongsoo , Lee Kichoon
Published: October 2023

Background

The primary differentially methylated regions (DMRs) which are maternally hypermethylated serve as imprinting control regions (ICRs) that drive monoallelic gene expression, and these ICRs have been investigated due to their implications in mammalian development. Although a subset of genes has been identified as imprinted, in-depth comparative approach needs to be developed for identification of species-specific imprinted genes. Here, we examined DNA methylation status and allelic expression at the KBTBD6 locus across species and tissues and explored potential mechanisms of imprinting.

Results

Using whole-genome bisulfite sequencing and RNA-sequencing on parthenogenetic and normal porcine embryos, we identified a maternally hypermethylated DMR between the embryos at the KBTBD6 promoter CpG island and paternal monoallelic expression of KBTBD6. Also, in analyzed domesticated mammals but not in humans, non-human primates and mice, the KBTBD6 promoter CpG islands were methylated in oocytes and/or allelically methylated in tissues, and monoallelic KBTBD6 expression was observed, indicating livestock-specific imprinting. Further analysis revealed that these CpG islands were embedded within transcripts in porcine and bovine oocytes which coexisted with an active transcription mark and DNA methylation, implying the presence of transcription-dependent imprinting.

Conclusions

In this study, our comparative approach revealed an imprinted expression of the KBTBD6 gene in domesticated mammals, but not in humans, non-human primates, and mice which implicates species-specific evolution of genomic imprinting.
Targeting CD22 for B-cell hematologic malignancies
Authors: Xu Jia , Luo Wenjing , Li Chenggong , Mei Heng
Published: October 2023

CD19-targeted chimeric receptor antigen (CAR)-T cell therapy has shown remarkable clinical efficacy in the treatment of relapsed or refractory (R/R) B-cell malignancies. However, 30%–60% of patients eventually relapsed, with the CD19-negative relapse being an important hurdle to sustained remission. CD22 expression is independent of CD19 expression in malignant B cells. Consequently, CD22 is a potential alternative target for CD19 CAR-T cell-resistant patients. CD22-targeted therapies, mainly including the antibody–drug conjugates (ADCs) and CAR-T cells, have come into wide clinical use with acceptable toxicities and promising efficacy. In this review, we explore the molecular and physiological characteristics of CD22, development of CD22 ADCs and CAR-T cells, and the available clinical data on CD22 ADCs and CAR-T cell therapies. Furthermore, we propose some perspectives for overcoming tumor escape and enhancing the efficacy of CD22-targeted therapies.
The relationship between social support, coping strategies and psychological distress and positive mental well-being in carers of people with borderline personality disorder
Authors: Hayes Aoife , Dempsey Maria , Kells Mary , Murphy Mike
Published: October 2023

Background

Informal carers of people with BPD experience high levels of burden and psychological distress relative to other populations. There is a scarcity of research evidencing the influence of modifiable factors on carer outcomes to inform interventions. This study aimed to investigate the relationship between social support, coping strategies and psychological distress and positive mental well-being in this carer population.

Methods

In this cross-sectional study, 1207 carers completed the McLean Screening Instrument for BPD-Carer Version, the Brief COPE, the Multidimensional Scale of Perceived Social Support, the Kessler Psychological Distress scale, the WHO-5 Well-being Index, and the Coronavirus Anxiety Scale. Data for 863 participants who met the inclusion criteria were analysed.

Results

Carers reported low positive mental well-being and high psychological distress. Perceived social support and several coping strategies were significant unique predictors of psychological distress and positive mental well-being. Perceived social support and positive reframing were the strongest predictors of higher positive mental well-being and lower psychological distress. Self-blame, behavioural disengagement and substance use were the strongest predictors of adverse outcomes.

Conclusions

The findings evidence modifiable factors that may be used to improve informal carer outcomes and indicate that carer interventions may be improved by focusing on reducing the use of self-blame, behavioural disengagement and substance use, and development of quality social support and skills to positively reframe caregiving situations.