bluuebunny/crossref_metadata_2025 huggingface dataset:
(‐)‐Epigallocatechin‐3‐O‐Gallate Regulates Muscle Growth, Antioxidant Status, and Nutritional Composition of Juvenile Common Carp (Cyprinus carpio L.)
Authors: Mi Jiali , Liu Dan , Zhi Shaoyang , Yan Xiao , Qin Chaobin , Xu Xinxin , Wang Luming , Nie Guoxing
Published: March 2024

Among the polyphenolic compounds commonly found in green tea, (‐)‐epigallocatechin‐3‐gallate (EGCG) is known to have various functions, including the promotion of antioxidant and myofiber growth in mammals. However, the effect of EGCG on common carp (Cyprinus carpio L.) remains poorly understood. To evaluate the role of EGCG on juvenile common carp, 255 fish (initial weight 17.33 ± 0.34 g) were fed with five experimental diets containing 0, 0.05, 0.25, 0.5, and 1 g/kg EGCG. The results showed that diet supplementation with 0.05–0.5 g/kg EGCG supplementation significantly enhanced the specific growth rate (SGR) and reduced the feed conversion ratio (FCR). Weight gain rate (WGR) was significantly enhanced in the 0.25 and 0.5 g/kg EGCG groups. As for antioxidants, 0.25–1 g/kg EGCG significantly reduced protein carbonyl (PC) content and upregulated superoxide dismutase (sod) gene expression in the muscle. As for muscle nutritional composition, 0.05–0.5 g/kg EGCG increased total amino acid (TAA) and flavor amino acid (FAA) contents, likely via the rapamycin (mTOR) signaling pathway. Muscle n‐3 polyunsaturated fatty acids (n‐3 PUFA) content was increased with 0.5 g/kg EGCG, presumably owing to the upregulation of fatty acyl elongase 5 (elovl5), long‐chain fatty acyl‐CoA synthetase 6 (acsl6), and peroxisome proliferator‐actiated receptor α (pparα). Dietary EGCG (0.05–1 g/kg) significantly increased muscle hardness and chewiness, accompanied by an increase in myofiber density. EGCG supplementation (0.25–1 g/kg) increased the pH value and reduced lactate contents in the muscle. However, muscle crude lipid and hydroxyproline contents significantly decreased with 1 g/kg EGCG. Overall, quadratic regression analysis of WGR, SGR, TAA, and FAA showed that optimal EGCG (0.46–0.52 g/kg) dietary supplementation improved the growth and nutritional composition of juvenile common carp.
Plasma microRNA-320c as a Potential Biomarker for the Severity of Knee Osteoarthritis and Regulates cAMP Responsive Element Binding Protein 5 (CREB5) in Chondrocytes
Authors: Zhou Rongwei , Zhao Like , Wang Qian , Cheng Yongjing , Song Miao , Huang Cibo
Published: March 2024

Objective. Osteoarthritis (OA) is a commonly known prevalent joint disease, with limited therapeutic methods. This study aimed to investigate the expression of plasma microRNA-320c (miR-320c) in patients with knee OA and to explore the clinical value and potential mechanism of miR-320c in knee OA. Methods. Forty knee OA patients and 20 healthy controls were enrolled. The levels of plasma miR-320c and plasma inflammatory cytokines were measured by real-time PCR or ELISA. Correlations of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and cytokine levels with the miR-320c expression level were evaluated by Pearson correlation analysis. Then, a receiver operating characteristic (ROC) curve was drawn to analyse the diagnostic value of miR-320c in OA. Finally, the interaction of miR-320c and cAMP responsive element binding protein 5 (CREB5) was determined using a luciferase reporter assay, and the effect of CREB5 on the cAMP pathway was assessed. Results. The expression level of plasma miR-320c was significantly higher in OA patients than in healthy controls (p <0.05). The increased plasma miR-320c level was positively correlated with the WOMAC score (r = 0.796, p <0.001) and the plasma interleukin (IL)-1β (r = 0.814, p <0.001) and IL-6 (r = 0.695, p <0.001) levels in patients with OA. ROC curve analysis demonstrated the relatively high diagnostic accuracy of plasma miR-320c for OA. Furthermore, the luciferase reporter assay results showed that miR-320c regulates CREB5 expression by binding to the CREB5 3′-untranslated region. Moreover, suppression of CREB5 significantly reduced the expression levels of c-fos and c-jun. Conclusion. Our results indicate that plasma miR-320c may serve as a potential novel predictor of the severity of knee OA and that miR-320c may play an important role in the pathogenesis of OA through inhibiting the cAMP pathway by targeting CREB5.
A Subpopulation of Luminal Progenitors Secretes Pleiotrophin to Promote Angiogenesis and Metastasis in Inflammatory Breast Cancer
Authors: Zhang Mengmeng , Zhou Kaiwen , Wang Zilin , Liu Ting , Stevens Laura E. , Lynce Filipa , Chen Wendy Y. , Peng Sui , Xie Yubin , Zhai Duanyang , Chen Qianjun , Shi Yawei , Shi Huijuan , Yuan Zhongyu , Li Xiaoping , Xu Juan , Cai Zhenhai , Guo Jianping , Shao Nan , Lin Ying
Published: March 2024

Inflammatory breast cancer (IBC) is a highly aggressive subtype of breast cancer characterized by rapidly arising diffuse erythema and edema. Genomic studies have not identified consistent alterations and mechanisms that differentiate IBC from non-IBC tumors, suggesting that the microenvironment could be a potential driver of IBC phenotypes. Here, using single-cell RNA sequencing, multiplex staining, and serum analysis in patients with IBC, we identified enrichment of a subgroup of luminal progenitor (LP) cells containing high expression of the neurotropic cytokine pleiotrophin (PTN) in IBC tumors. PTN secreted by the LP cells promoted angiogenesis by directly interacting with the NRP1 receptor on endothelial tip cells located in both IBC tumors and the affected skin. NRP1 activation in tip cells led to recruitment of immature perivascular cells in the affected skin of IBC, which are correlated with increased angiogenesis and IBC metastasis. Together, these findings reveal a role for cross-talk between LPs, endothelial tip cells, and immature perivascular cells via PTN–NRP1 axis in the pathogenesis of IBC, which could lead to improved strategies for treating IBC.

Significance:

Nonmalignant luminal progenitor cells expressing pleiotrophin promote angiogenesis by activating NRP1 and induce a prometastatic tumor microenvironment in inflammatory breast cancer, providing potential therapeutic targets for this aggressive breast cancer subtype.
FIGURE 1 from Pain and Its Association with Survival for Black and White Individuals with Advanced Prostate Cancer in the United States
Authors: Rencsok Emily M. , Slopen Natalie , McManus Hannah D. , Autio Karen A. , Morgans Alicia K. , McSwain Lawrence , Barata Pedro , Cheng Heather H. , Dreicer Robert , Gerke Travis , Green Rebecca , Heath Elisabeth I. , Howard Lauren E. , McKay Rana R. , Nowak Joel , Pileggi Shannon , Pomerantz Mark M. , Rathkopf Dana E. , Tagawa Scott T. , Whang Young E. , Ragin Camille , Odedina Folakemi T. , Kantoff Philip W. , Vinson Jake , Villanti Paul , Haneuse Sebastien , Mucci Lorelei A. , George Daniel J.
Published: March 2024

Distributions of pain at study enrollment by race. A, Distributions of scores on the EORTC pain scale by race. B, Distributions of scores on the average pain scale by race. C, Distributions of scores on the worst pain scale by race. D, Distributions of scores on the bone pain scale by race.
Supplementary Figure 6 from Autophagy Inhibition–induced Cytosolic DNA Sensing Combined with Differentiation Therapy Induces Irreversible Myeloid Differentiation in Leukemia Cells
Authors: Baba Tomohisa , Tomaru Utano , Hirao Atsushi , Mukaida Naofumi , Johmura Yoshikazu
Published: March 2024

Fig. S6 and its legend
Supplementary Figure 5 from Autophagy Inhibition–induced Cytosolic DNA Sensing Combined with Differentiation Therapy Induces Irreversible Myeloid Differentiation in Leukemia Cells
Authors: Baba Tomohisa , Tomaru Utano , Hirao Atsushi , Mukaida Naofumi , Johmura Yoshikazu
Published: March 2024

Fig. S5 and its legend
Supplementary Figure 10 from Autophagy Inhibition–induced Cytosolic DNA Sensing Combined with Differentiation Therapy Induces Irreversible Myeloid Differentiation in Leukemia Cells
Authors: Baba Tomohisa , Tomaru Utano , Hirao Atsushi , Mukaida Naofumi , Johmura Yoshikazu
Published: March 2024

Fig. S10 and its legend
Cross-Cultural Adaptation and Validation of the Greek Cypriot Montreal Children’s Hospital Feeding Scale
Authors: Papaleontiou Andri , Voniati Louiza , Gryparis Alexandros , Georgiou Rafaella , Siafaka Vassiliki , Tafiadis Dionysios
Published: March 2024

Introduction: Assessing pediatric feeding disorders (PFD) is essential for a child’s development to prevent severe consequences. The assessment procedures for PFD may include parents’ questionnaires such as the Montreal Children’s Hospital Feeding Scale (MCH-FS). The aim of this study was the cross-cultural adaptation of the MCH-FS to the Greek language. Methods: One hundred parents of Greek Cypriot children with PFD (clinical group) and 100 parents of healthy Greek Cypriot children (control group) aged 6 months to 16 years old participated in the study and completed the MCH-FS. World Health Organization (WHO) guidelines were implemented for translation and cultural adaptation. Results: The internal consistency was excellent, α = 0.85 (ICC: 0.817–0.891). Content validity was significant (S-CVI = 1) with an agreement equal to 14. A strong and significant correlation of MCH-FS was computed according to principal component analysis (14 items ranging between −0.6 and 0.7). The Kaiser-Meyer-Olkin factor analysis was equal to 0.91 with substantial correlations (Bartlett’s test = 0.001, 654,804). The MCH-FS cut-off point between the two groups was 38.00 (AUC: 0.901 [95% CI: 0.859–0.942], p < 0.001; sensitivity = 0.800 and 1-specificity = 0.630). A statistically significant difference between the two groups was observed for the MCH-FS total score, with the clinical group scoring higher (U = 992.00, p < 0.001). Likewise, the same differences were observed among children with different PFD, H (3) = 96.715, p < 0.001. Conclusion: The MCH-FS had good psychometric properties in its current form in Greek. It is suggested that the MCH-FS can be used as a valid tool for children with PFD in the Greek Cypriot population.
“Negros mágicos” e a evolução da representação de negritudes em Jojo’s Bizarre Adventure: os casos de Avdol e Pucci
Authors: Felipe Anna Luiza Diniz , Silva Michele Delbon
Published: March 2024

It examines the representation of black characters in Jojo's Bizarre Adventure, highlighting how the series addresses issues of black identity and diversity in Japanese culture, albeit in a problematic way. It discusses the importance of representation and explore the social and cultural implications of this representation, focusing on characters such as Muhammad Avdol and Father Pucci to question racial stereotypes.
Assimetria informacional no processo orçamentário hospitalar: reflexos dos problemas de agência sobre a eficiência técnica e a qualidade dos serviços prestados
Authors: Souza Vitor , Abbas Katia , Faia Valter da Silva , Ferreira Marcelo Marchine
Published: March 2024

The study looks at the dichotomy between Technical Efficiency and Quality in the provision of hospital services, placing Informational Asymmetry within the Budget Process as an interactive part of this relationship in order to explain the behavior of both performance measures. The goal is therefore to analyze the effects that information asymmetries in the budget process exert on the Technical Efficiency and Quality of services performed in hospitals funded by public resources. The research strategy employed was a multiple case study, investigating two hospitals in Brazil’s South Region: one public and one nonprofit private. Three data collection techniques were used: direct observation, semi-structured interviews, and documentary analysis. As to analyzing the obtained data, content analysis using thematic topics was the adopted technique. Results indicate that Information Asymmetry in the Budget Process between the state and the hospitals, respectively Principal and Agents, when related to the budget planning stage, results in harmful effects for Technical Efficiency and beneficial ones for Quality; however, when related to a lack of financial alignment in the budget execution stage, that information asymmetry results in opposite effects, i.e., favorable for Technical Efficiency and harmful for Quality. The study’s conclusions contribute to extant discussions on the dichotomy between Technical Efficiency and Quality in services performed in hospital contexts, analyzing this phenomenon through the effects that Information Asymmetry in the Budget Process exerts on both performance measures.
A Deep Learning Approach to Analyzing Continuous-Time Cognitive Processes
Authors: Shain Cory , Schuler William
Published: March 2024

The dynamics of the mind are complex. Mental processes unfold continuously in time and may be sensitive to a myriad of interacting variables, especially in naturalistic settings. But statistical models used to analyze data from cognitive experiments often assume simplistic dynamics. Recent advances in deep learning have yielded startling improvements to simulations of dynamical cognitive processes, including speech comprehension, visual perception, and goal-directed behavior. But due to poor interpretability, deep learning is generally not used for scientific analysis. Here, we bridge this gap by showing that deep learning can be used, not just to imitate, but to analyze complex processes, providing flexible function approximation while preserving interpretability. To do so, we define and implement a nonlinear regression model in which the probability distribution over the response variable is parameterized by convolving the history of predictors over time using an artificial neural network, thereby allowing the shape and continuous temporal extent of effects to be inferred directly from time series data. Our approach relaxes standard simplifying assumptions (e.g., linearity, stationarity, and homoscedasticity) that are implausible for many cognitive processes and may critically affect the interpretation of data. We demonstrate substantial improvements on behavioral and neuroimaging data from the language processing domain, and we show that our model enables discovery of novel patterns in exploratory analyses, controls for diverse confounds in confirmatory analyses, and opens up research questions in cognitive (neuro)science that are otherwise hard to study.
Interreligious Interaction in the Ilorin Metropolis
Authors: Akande Lydia Bosede , Ogunbiyi Olatunde Oyewole , Fahm AbdulGafar Olawale
Published: March 2024

This study explores interreligious interactions in Ilorin, Nigeria, with a focus on Sobi Hill. Employing a phenomenological approach, it examines how different religious groups interpret and engage with this symbol of unity. Through historical analysis, site visits, observations, questionnaires, and interviews, the research identifies three key factors that contributes to peaceful coexistence: influential figures, evolving generational attitudes, and Sobi Hill’s religious significance. The study concludes that Ilorin’s harmonious coexistence is epitomized by Sobi Hill, where residents from various faiths gather for joint celebrations that emphasize the city’s commitment to unity.
Second-step lectotypification of Stobaea rigida and reassessment of heterotypic synonyms of Berkheya rigida (Asteraceae, Arctotideae)
Authors: KARIS PER OLA , MCKENZIE ROBERT J.
Published: March 2024

As part of a taxonomic reassessment of species that were classified in Berkheya series Rigidae in the most recent monograph of Berkheya, the type material for Berkheya rigida and its putative heterotypic synonyms is reassessed. The original material for the basionym, Stobaea rigida, is heterospecific. Therefore, a second-step lectotype is designated consistent with predominant usage of the name Berkheya rigida. The name Apuleia rigida and its replacement name Stobaea gaertneri apply to a conspicuously radiate species and are excluded from the synonymy of Berkheya rigida. The morphological variability of Berkheya rigida is discussed.
Four new species and new records of the genus Paulianidia of Madagascar (Coleoptera: Staphylinidae: Paederinae)
Authors: JANÁK JIŘÍ , BAŇAŘ PETR
Published: March 2024

Four new species of the genus Paulianidia Jarrige, 1978, P. densepunctata Janák & Baňař, sp. nov., P. tanala Janák & Baňař, sp. nov., P. valohoaka Janák & Baňař, sp. nov., and P. vohimana Janák & Baňař, sp. nov. of Madagascar are described and illustrated. New records of seven additional species are added. A key to all Paulianidia species with illustration of important characters is presented.
Modeling the Subgrid-Scale Scalar Variance: A Priori Tests and Application to Supersaturation in Cloud Turbulence
Authors: Salesky Scott T. , Gillis Kendra , Anderson Jesse , Helman Ian , Cantrell Will , Shaw Raymond A.
Published: March 2024

The subgrid-scale (SGS) scalar variance represents the “unmixedness” of the unresolved small scales in large-eddy simulations (LES) of turbulent flows. Supersaturation variance can play an important role in the activation, growth, and evaporation of cloud droplets in a turbulent environment, and therefore efforts are being made to include SGS supersaturation fluctuations in microphysics models. We present results from a priori tests of SGS scalar variance models using data collected in turbulent Rayleigh–Bénard convection in the Michigan Tech Pi chamber for Rayleigh numbers Ra ∼ 108–109. Data from an array of 10 thermistors were spatially filtered and used to calculate the true SGS scalar variance, a scale-similarity model, and a gradient model for dimensionless filter widths of h/Δ = 25, 14.3, and 10 (where h is the height of the chamber and Δ is the spatial filter width). The gradient model was found to have fairly low correlations (ρ ∼ 0.2), with the most probable values departing significantly from the one-to-one line in joint probability density functions (JPDFs). However, the scale-similarity model was found to have good behavior in JPDFs and was highly correlated (ρ ∼ 0.8) with the true SGS variance. Results of the a priori tests were robust across the parameter space considered, with little dependence on Ra and h/Δ. The similarity model, which only requires an additional test filtering operation, is therefore a promising approach for modeling the SGS scalar variance in LES of cloud turbulence and other related flows.
Ghosted: Challenges to Conducting Qualitative Research in the Digital Era
Authors: Sackett Blair
Published: March 2024

Electronic forms of communication—including email, texting, and social media platforms—have increased the speed and ease of communication. Yet, a rise in non-response and ghosting (when someone ceases communication without an explanation) has been documented across contexts, from romantic dating to quantitative research studies. Surprisingly, the rise of electronic communication has received little attention in the methodological literature for qualitative researchers. Based on an analysis of virtual and face-to-face recruitment in two qualitative studies I conducted, I find that ghosting is a routine feature of digital recruitment. There are situational contexts in which ghosting is more common, including lags in the timing of communication and requests that are too overwhelming. “Old-school” methods, such as seeking sponsorship, strategizing outreach, and building rapport, can be adapted to help researchers capitalize on the benefits of electronic communication technologies in recruitment.
Topline/Final Diagnostic Inclusion of Relevant Histologic Findings in Surgical Pathology Reporting of Carcinoma in Prostate Biopsies
Authors: Mullane Patrick , Williamson Sean R. ,   The Prostate Biopsy Reporting Panel *, Sangoi Ankur R.
Published: March 2024

Introduction

As the list of histologic parameters to include in surgical pathology reports of prostate cancer biopsies grows, some pathologists include this information in the microscopic description or summary sections of the report, whereas others include it in the “topline” or final diagnosis section. This prompted us to develop a multi-institutional survey to assess reporting trends among genitourinary (GU) pathologists.

Methods

A survey instrument was shared among 110 GU pathologists via surveymonkey.com. Anonymized respondent data was analyzed.

Results

Eighty-four (76%) participants completed the survey across four continents. Most participants report tumor volume quantitation (88%), number of cores involved (89%), and both Gleason grade and Grade group (93%) in their topline; 71% include percent of pattern 4, with another 16% including it depending on cancer grade; 58% include the presence of cribriform growth pattern 4, with another 11% including it depending on cancer grade. When present, most include extraprostatic extension (90%), prostatic intraductal carcinoma (77%), and perineural invasion (77%). Inclusion of atypical intraductal proliferation (AIP) in the topline diagnosis was cancer grade-dependent, with 74% including AIP in Grade group 1, 61% in Grade group 2, 45% in Grade group 3, 30% in Grade group 4, and 26% in Grade group 5 cancers.

Conclusion

Certain histologic features such as Gleason grade and tumor volume/cores involved are frequently included in the topline diagnosis, whereas the incorporation of other findings are more variably included. Prostate biopsy reporting remains a dynamic process with stylistic similarities and differences existing among GU pathologists.
Patient and caregiver satisfaction of a palliative care chronic diseases clinic during COVID lockdowns
Authors: Sim Xiang Rong , Hudson Jade , Parker Catriona , Runacres Fiona , Poon Peter
Published: March 2024

Objectives

To assess the quality assurance of a specialist palliative care clinic focused on chronic diseases and explore the satisfaction and acceptability of the telemedicine model amongst patients and caregivers.

Methods

A cross-sectional 23-item survey was developed by the clinical team, approved by ethics and distributed to patients and caregivers. Data collection ran between September 2021 and February 2022, and SPSS was used for data analysis. Demographics were collected from hospital records.

Results

Thirty-five surveys were returned. The cohort had a median age of 82 years, and the most common primary diagnosis was renal failure. Participants rated telemedicine as easier to access than face-to-face appointments due to convenience. Telemedicine was rated highly for future utility, with video consultations being perceived as more useful than telephone consultations. Participants responded overwhelmingly well towards the clinic.

Discussion

Findings demonstrated high levels of satisfaction with the Supportive Care Clinic model and for telemedicine. However, logistical challenges and the desire for face-to-face appointments were also identified. The study highlights the importance of offering a range of modalities for patient engagement in healthcare services and suggests that telemedicine should complement, rather than replace, face-to-face consultations. Future investigations should explore patient and caregiver sentiment towards telemedicine platforms alongside patient deterioration.
Prevalence and correlates of diabetes and impaired fasting glucose among adults in Afghanistan: Insights from a national survey
Authors: Dadras Omid , Nyaboke Ongosi Anita , Wang Chia-Wen
Published: March 2024

Objectives:

Afghanistan is experiencing an escalating burden of noncommunicable diseases, with diabetes and impaired fasting glucose being of particular concern. To explore the prevalence of diabetes and impaired fasting glucose and associated factors among adult Afghans.

Methods:

This cross-sectional study used secondary data from a nationally representative survey, conducted in 2018 in Afghanistan. A blood sample was collected from the fingertip and tested through a strip to measure blood glucose. The complex sampling design and sampling weights were accounted for in all analyses to produce representative estimates of the target population in Afghanistan.

Results:

Of 3890 Afghan adults aged 18–69 years who participated in this survey, 11.07% and 10.32% had diabetes and impaired fasting glucose, respectively. For overweight individuals with abdominal obesity, the risk for diabetes became significantly elevated, with an adjusted relative risk ratio of 2.12 (95% CI: 1.10–4.09). However, the most pronounced effect was observed among individuals classified as having obesity with abdominal obesity with an adjusted relative risk ratio of 2.54 (95% CI: 1.37–4.70). Moreover, high cholesterol level was significantly associated with both impaired fasting glucose (ARRR: 2.52, 95% CI: 1.55–4.12) and diabetes (ARRR: 4.12, 95% CI: 2.59–6.56), whereas high blood pressure was significantly associated with only diabetes (ARRR: 1.82, 95% CI: 1.16–2.86).

Conclusions:

This investigation provides critical insight into the prevalence of diabetes and IFG among Afghan adults aged 18–69 years. Relative to the global average, the higher prevalence observed calls for specifically designed interventions targeting individuals with cardiometabolic risk factors, such as elevated body mass index, abdominal obesity, hypertension, and hypercholesterolemia.
The nitric oxide–soluble guanylate cyclase–cGMP pathway in pulmonary hypertension: from PDE5 to soluble guanylate cyclase
Authors: Benza Raymond L. , Grünig Ekkehard , Sandner Peter , Stasch Johannes-Peter , Simonneau Gérald
Published: March 2024

The nitric oxide (NO)–soluble guanylate cyclase (sGC)–cyclic guanosine monophosphate (cGMP) pathway plays a key role in the pathogenesis of pulmonary hypertension (PH). Targeted treatments include phosphodiesterase type 5 inhibitors (PDE5i) and sGC stimulators. The sGC stimulator riociguat is approved for the treatment of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). sGC stimulators have a dual mechanism of action, enhancing the sGC response to endogenous NO and directly stimulating sGC, independent of NO. This increase in cGMP productionviaa dual mechanism differs from PDE5i, which protects cGMP from degradation by PDE5, rather than increasing its production. sGC stimulators may therefore have the potential to increase cGMP levels under conditions of NO depletion that could limit the effectiveness of PDE5i. Such differences in mode of action between sGC stimulators and PDE5i could lead to differences in treatment efficacy between the classes. In addition to vascular effects, sGC stimulators have the potential to reduce inflammation, angiogenesis, fibrosis and right ventricular hypertrophy and remodelling. In this review we describe the evolution of treatments targeting the NO–sGC–cGMP pathway, with a focus on PH.
20 years of neuromuscular electrical stimulation in COPD
Authors: LoMauro Antonella , Gervasoni Fabrizio
Published: March 2024

Although a lung disease, COPD is also associated with extrapulmonary manifestations including, among others, limb muscle dysfunction. Limb muscle dysfunction is a key systemic consequence of COPD that impacts patients' physical activity, exercise tolerance, quality of life and survival. Deconditioning is the main mechanism underlying the development of limb muscle dysfunction in COPD, which can be partially improved with exercise. However, some patients may not be able to tolerate exercise because of incapacitating breathlessness or unwillingness to undertake whole-body exercise. Alternative training modalities that do not give rise to dyspnoea, such as neuromuscular electrical stimulation (NMES), are urged. Over the past 20 years, NMES in COPD has presented conflicting conclusions in meta-analysis. In this review, we try to understand the reason for this result by analysing possible biases and factors that brought conflicting conclusions. We discuss the population (the intervention group, but also the control group), the outcome measures, the frequency of stimulation, the rehabilitation protocol (i.e.NMES aloneversusstandard care/rehabilitation or NMES plus conventional exercise trainingversusconventional exercise training alone or NMESversussham treatment) and the trial design. The main reason for this discrepancy is the lack of dedicated guidelines for NMES. Further research is urged to determine the optimal parameters for an NMES programme. Despite this, NMES appears to be an effective means of enhancing quadriceps strength and exercise capacity in COPD with the potential to break the vicious circle induced by the disease and COPD patients’ lifestyle.
Endoplasmic reticulum stress and therapeutic strategies in metabolic, neurodegenerative diseases and cancer
Authors: Yuan Siqi , She Dan , Jiang Shangming , Deng Nan , Peng Jiayi , Ma Ling
Published: March 2024

The accumulation of unfolded or misfolded proteins within the endoplasmic reticulum (ER), due to genetic determinants and extrinsic environmental factors, leads to endoplasmic reticulum stress (ER stress). As ER stress ensues, the unfolded protein response (UPR), comprising three signaling pathways—inositol-requiring enzyme 1, protein kinase R-like endoplasmic reticulum kinase, and activating transcription factor 6 promptly activates to enhance the ER’s protein-folding capacity and restore ER homeostasis. However, prolonged ER stress levels propels the UPR towards cellular demise and the subsequent inflammatory cascade, contributing to the development of human diseases, including cancer, neurodegenerative disorders, and diabetes. Notably, increased expression of all three UPR signaling pathways has been observed in these pathologies, and reduction in signaling molecule expression correlates with decreased proliferation of disease-associated target cells. Consequently, therapeutic strategies targeting ER stress-related interventions have attracted significant research interest. In this review, we elucidate the critical role of ER stress in cancer, metabolic, and neurodegenerative diseases, offering novel therapeutic approaches for these conditions.
Do changes in the frailty score differ by the type of group sports and exercises participated in? A 3-year longitudinal study
Authors: Tsuji Taishi , Kanamori Satoru , Watanabe Ryota , Yokoyama Meiko , Miyaguni Yasuhiro , Saito Masashige , Kondo Katsunori
Published: March 2024

Background

Older adults who engage in group sports and exercises achieve greater health benefits than those who exercise by themselves. The benefits of group participation may vary depending on the type of sports/exercise they engage in. The present study aimed to identify the association between specific sports and exercise types performed in groups and evaluate the longitudinal changes in multidimensional frailty scores among community-dwelling older adults in Japan.

Methods

We used 3-year follow-up data from the Japan Gerontological Evaluation Study and analyzed 33,746 men and 36,799 women aged ≥ 65 years. To elucidate the relationship between participation in 20 types of group sports/exercises in 2016 (baseline) and the change in frailty score (using the Kihon Checklist, KCL) from 2016 to 2019, we performed linear regression analyses through multivariate adjustments for age group, self-rated health, marital status, living alone, occupational status, years of education, alcohol drinking status, smoking status, equivalent income, and disease status using an inverse probability weighting method. P < 0.05 was considered statistically significant.

Results

The mean change in KCL scores over 3 years was + 0.62 and + 0.61 points in men and women, respectively, implying the degree of frailty worsened. The sports/exercise types that significantly prevented increments in KCL scores for both sexes compared to non-participants were hiking (men: B, − 0.36; women: B, − 0.29), walking (men: B, − 0.26; women: B, − 0.24), tennis (men: B, − 0.23; women: B, − 0.24), ground golf (men: B, − 0.21; women: B, − 0.19), and weight exercises (men: B, − 0.19; women: B, − 0.16).

Conclusion

Participation in specific sports and exercise groups offer significant physical and psychological benefits for frailty prevention among older adults in Japan. The results of this study may offer substantive evidence to encourage older adults to participate in group activities for the prevention of multidimensional frailty. It will also help public health stakeholders to decide which type of sports and exercise groups to promote in a community.
Quantitative proteomic analysis of HER2 protein expression in PDAC tumors
Authors: Randall Jamie , Hunt Allison L. , Nutcharoen Aratara , Johnston Laura , Chouraichi Safae , Wang Hongkun , Winer Arthur , Wadlow Raymond , Huynh Jasmine , Davis Justin , Corgiat Brian , Bateman Nicholas W. , Deeken John F. , Petricoin Emanuel F. , Conrads Thomas P. , Cannon Timothy L.
Published: March 2024

Metastatic pancreatic adenocarcinoma (PDAC) is the third leading cause of cancer-related death in the United States, with a 5-year survival rate of only 11%, necessitating identification of novel treatment paradigms. Tumor tissue specimens from patients with PDAC, breast cancer, and other solid tumor malignancies were collected and tumor cells were enriched using laser microdissection (LMD). Reverse phase protein array (RPPA) analysis was performed on enriched tumor cell lysates to quantify a 32-protein/phosphoprotein biomarker panel comprising known anticancer drug targets and/or cancer-related total and phosphorylated proteins, including HER2Total, HER2Y1248, and HER3Y1289. RPPA analysis revealed significant levels of HER2Total in PDAC patients at abundances comparable to HER2-positive (IHC 3+) and HER2-low (IHC 1+ /2+ , FISH−) breast cancer tissues, for which HER2 screening is routinely performed. These data support a critical unmet need for routine clinical evaluation of HER2 expression in PDAC patients and examination of the utility of HER2-directed antibody–drug conjugates in these patients.
A non-negative spike-and-slab lasso generalized linear stacking prediction modeling method for high-dimensional omics data
Authors: Shen Junjie , Wang Shuo , Dong Yongfei , Sun Hao , Wang Xichao , Tang Zaixiang
Published: March 2024

Background

High-dimensional omics data are increasingly utilized in clinical and public health research for disease risk prediction. Many previous sparse methods have been proposed that using prior knowledge, e.g., biological group structure information, to guide the model-building process. However, these methods are still based on a single model, offen leading to overconfident inferences and inferior generalization.

Results

We proposed a novel stacking strategy based on a non-negative spike-and-slab Lasso (nsslasso) generalized linear model (GLM) for disease risk prediction in the context of high-dimensional omics data. Briefly, we used prior biological knowledge to segment omics data into a set of sub-data. Each sub-model was trained separately using the features from the group via a proper base learner. Then, the predictions of sub-models were ensembled by a super learner using nsslasso GLM. The proposed method was compared to several competitors, such as the Lasso, grlasso, and gsslasso, using simulated data and two open-access breast cancer data. As a result, the proposed method showed robustly superior prediction performance to the optimal single-model method in high-noise simulated data and real-world data. Furthermore, compared to the traditional stacking method, the proposed nsslasso stacking method can efficiently handle redundant sub-models and identify important sub-models.

Conclusions

The proposed nsslasso method demonstrated favorable predictive accuracy, stability, and biological interpretability. Additionally, the proposed method can also be used to detect new biomarkers and key group structures.
The mediating effect of nutrition on oral frailty and fall risk in community-dwelling elderly people
Authors: Song Huizi , Wei Yulian , Wang Yan , Zhang Jiahui
Published: March 2024

Background

Population aging is accelerating, particularly in Asian countries. Falls are the leading cause of unintentional injuries in the elderly over 60 years old in China. Hence, it is crucial to anticipate the risk factors associated with fall risk. We aimed to explore whether oral frailty and fall risk were reciprocally related and whether nutrition mediated their association.

Methods

From October 2022 to March 2023, a total of 409 elderly individuals from the Yangzhou community were selected using the convenience sampling method. Cross-sectional data on older adults’ oral frailty, nutrition, and fall risk were collected using questionnaires. Data analysis was performed using SPSS 27.0 and PROCESS macro.

Results

The fall risk score was 1.0 (ranging from 0 to 4.0), with 107 cases (26.2%) identified as being at risk of falling. Spearman correlation analysis revealed a positive correlation between oral frailty and the risk of falls (rs = 0.430, P < 0.01). Nutrition was found to have a negative correlation with both oral frailty and fall risk (rs=-0.519、-0.457, P < 0.01). When controlling for covariates, it was observed that nutrition mediated the relationship between oral frailty and falls. The mediating effect value accounted for 48.8% of the total effect (P < 0.01).

Conclusions

Oral frailty was significantly associated with fall risk, and nutrition might be a mediating factor for adverse effects of oral frailty and fall risk. Enhancing the nutrition of older individuals is a vital approach to mitigating fall risk among those with oral frailty.
Comparing the efficacy of fluconazole and cryotherapy Versus cryotherapy alone on treating cutaneous leishmaniasis: a triple-blind randomized clinical trial
Authors: Parhizkar Ahmad Reza , Sharafi Mehdi , Mansuri Susan , Hadibarhaghtalab Maryam , Afrashteh Sima , Fatemian Hossein , Chijan Mahsa Rostami
Published: March 2024

Objective

Cutaneous Leishmaniasis (CL) is one of the highly prevalent endemic diseases in the Middle East. The disease is a complex skin infection imposing a heavy burden on many developing countries. This study aimed to evaluate the impact of adding oral fluconazole to topical cryotherapy on the treatment efficacy and time to achieve complete recovery of CL lesions.

Method

This triple-blind randomized clinical trial included 52 participants with CL. Participants were allocated to receive either weekly cryotherapy with liquid nitrogen and oral fluconazole at a dose of 6 mg/kg daily at a maximum of 400 mg for 6 weeks as the interventional arm or weekly cryotherapy with liquid nitrogen plus the placebo for the same period of 6 weeks as the control arm.

Results

Fifty-two eligible participants enrolled the study, with a CL lesion count of 1 to 8 (mean 1.96), and served as the interventional (n = 28) and control (n = 24) arms. The trend of the mean surface area of the lesions was significantly decreasing in both arms (P < 0.001), with no statistically significant difference between arms (P = 0.133) or all assessed time point pairwise comparisons (P > 0.05). There was no significant difference between the treatment arms in terms of the end-point recovery status (P = 0.491) or the frequency of post-treatment secretion (P = 0.437). No adverse effect was observed.

Conclusion

Despite a slightly higher reduction in the lesion surface in the cryotherapy and fluconazole treatment arm, the addition of fluconazole did not provide statistically significant therapeutic value to cryotherapy in the treatment of CL. However, with adjustment for the initial lesion size, the efficacy of the regimen in the interventional arm was more pronounced, though it was still insignificant.
Improving dengue fever predictions in Taiwan based on feature selection and random forests
Authors: Kuo Chao-Yang , Yang Wei-Wen , Su Emily Chia-Yu
Published: March 2024

Background

Dengue fever is a well-studied vector-borne disease in tropical and subtropical areas of the world. Several methods for predicting the occurrence of dengue fever in Taiwan have been proposed. However, to the best of our knowledge, no study has investigated the relationship between air quality indices (AQIs) and dengue fever in Taiwan.

Results

This study aimed to develop a dengue fever prediction model in which meteorological factors, a vector index, and AQIs were incorporated into different machine learning algorithms. A total of 805 meteorological records from 2013 to 2015 were collected from government open-source data after preprocessing. In addition to well-known dengue-related factors, we investigated the effects of novel variables, including particulate matter with an aerodynamic diameter < 10 µm (PM10), PM2.5, and an ultraviolet index, for predicting dengue fever occurrence. The collected dataset was randomly divided into an 80% training set and a 20% test set. The experimental results showed that the random forests achieved an area under the receiver operating characteristic curve of 0.9547 for the test set, which was the best compared with the other machine learning algorithms. In addition, the temperature was the most important factor in our variable importance analysis, and it showed a positive effect on dengue fever at < 30 °C but had less of an effect at > 30 °C. The AQIs were not as important as temperature, but one was selected in the process of filtering the variables and showed a certain influence on the final results.

Conclusions

Our study is the first to demonstrate that AQI negatively affects dengue fever occurrence in Taiwan. The proposed prediction model can be used as an early warning system for public health to prevent dengue fever outbreaks.
A new classification allowing assessment of instrumental vaginal-birth practices
Authors: Schaeffer Marine , Faisant Marie-Caroline , Buisson Alexandre , Vanneaux Manon , Hoffmann Pascale , Riethmuller Didier
Published: March 2024

Background

Instrumental vaginal birth, a very common intervention in obstetrics, concerns nearly one in eight women in France. Instrumentally assisted vaginal childbirth can be for maternal and/or fetal indications. Although it reduces recourse to caesarean section, it is subject to risks. Practices concerning instrumental birth are disparate, varying among different practitioners, maternity units and countries, and it is essential to be able to evaluate them. Our objective was to create a classification tool of women requiring instrumental birth to facilitate the analysis of practices within our maternity unit as well as to enable temporal and geographical comparisons.

Materials and methods

We propose a simple and robust classification based on the same principles as Robson's classification. It is made up of seven totally inclusive and mutually exclusive groups. Our classification was refined and validated using the Delphi method by a panel of 14 experts from throughout France, and tested in our maternity unit using data from throughout 2021.

Results

The seven clinically relevant groups are based on five obstetric criteria (multiplicity, presentation, gestational age, previous type of birth, induction of labor). To classify each woman in a group, five successive questions are posed in a predefined order. The classification has been validated by the experts with highly satisfactory overall agreement.

Conclusion

In order to improve the quality of care, we propose a tool to standardize the evaluation of instrumental vaginal birth practice (called the “Isère classification”, after the county where we work in south-eastern France). It will also facilitate the comparison the practices among different maternity units in a network, a country or even among different countries.
Transgelin-2, a novel cancer stem cell-related biomarker, is a diagnostic and therapeutic target for biliary tract cancer
Authors: Jo Jung Hyun , Park Soo Been , Chung Joowon , Oh Taeyun , Lee Hee Seung , Chung Moon Jae , Park Jeong Youp , Bang Seungmin , Park Seung Woo , Jung Dawoon E. , Song Si Young
Published: March 2024

Background

Biliary tract cancer (BTC) is a relatively rare but aggressive gastrointestinal cancer with a high mortality rate. Cancer stem cell (CSC) populations play crucial roles in tumor biology and are responsible for the low response to anti-cancer treatment and the high recurrence rate. This study investigated the role of Transgelin-2 (TAGLN2), overexpressed in CSC in BTC cells, and analyzed its expression in patient tissues and serum to identify potential new targets for BTC.

Methods

TAGLN2 expression was suppressed by small-interfering or short hairpin RNAs, and its effects on tumor biology were assessed in several BTC cell lines. Furthermore, the effects of TAGLN2 silencing on gemcitabine-resistant BTC cells, differentially expressed genes, proteins, and sensitivity to therapeutics or radiation were assessed. TAGLN2 expression was also assessed using western blotting and immunohistochemistry in samples obtained from patients with BTC to validate its clinical application.

Results

Suppression of TAGLN2 in BTC cell lines decreased cell proliferation, migration, invasion, and tumor size, in addition to a reduction in CSC features, including clonogenicity, radioresistance, and chemoresistance. TAGLN2 was highly expressed in BTC tissues, especially in cancer-associated fibroblasts in the stroma. Patients with a low stromal immunohistochemical index had prolonged disease-free survival compared to those with a high stromal immunohistochemical index (11.5 vs. 7.4 months, P = 0.013). TAGLN2 expression was higher in the plasma of patients with BTC than that in those with benign diseases. TAGLN2 had a higher area under the curve (0.901) than CA19-9, a validated tumor biomarker (0.799; P < 0.001).

Conclusion

TAGLN2 plays a critical role in promoting BTC cell growth and motility and is involved in regulating BTC stemness. Silencing TAGLN2 expression enhanced cell sensitivity to radiation and chemotherapeutic drugs. The expression of TAGLN2 in patient tissue and plasma suggests its potential to serve as a secretory biomarker for BTC. Overall, targeting TAGLN2 could be an appropriate therapeutic strategy against advanced cancer following chemotherapy failure.
Tumor burden score and carcinoembryonic antigen predict outcomes in patients with intrahepatic cholangiocarcinoma following liver resection: a multi‑institutional analysis
Authors: Fu Jun , Zheng Lifang , Tang Shicuan , Lin Kongying , Zheng Shuguo , Bi Xinyu , Wang Jianming , Guo Wei , Li Fuyu , Wang Jian , Wang Kui , Li Haitao , Zeng Yongyi
Published: March 2024

Background

The prognostic significance of tumor burden score (TBS) in relation to carcinoembryonic antigen (CEA) has not been investigated among patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC). This study aimed to develop and validate a simplified model, a combination of TBS and CEA (CTC grade), for predicting the long-term outcomes of postoperative ICC patients.

Methods

Patients who underwent curative − intent resection of ICC between 2011 and 2019 were identified from a large multi − institutional database. The impact of TBS, CEA, and the CTC grade on overall survival (OS) and recurrence − free survival (RFS) was evaluated in both the derivation and validation cohorts. The receiver operating characteristic curve was utilized for assessing the predictive accuracy of the model. Subgroup analyses were performed across 8th TNM stage system stratified by CTC grade to assess the discriminatory capacity within the same TNM stage.

Results

A total of 812 patients were included in the derivation cohort and 266 patients in the validation cohort. Survival varied based on CEA (low: 36.7% vs. high: 9.0%) and TBS (low: 40.3% vs. high: 17.6%) in relation to 5 − year survival (both p < 0.001). As expected, patients with low CTC grade (i.e., low TBS/low CEA) were associated with the best OS as well as RFS, while high CTC grade (i.e., high TBS/high CEA) correlated to the worst outcomes. The model exhibited well performance in both the derivation cohort (area under the curve of 0.694) and the validation cohort (0.664). The predictive efficacy of the CTC grade system remains consistently stable across TNM stages I and III/IV.

Conclusion

The CTC grade, a composite parameter derived from the combination of TBS and CEA levels, served as an easy − to − use tool and performed well in stratifying patients with ICC relative to OS and RFS.