bluuebunny/crossref_metadata_2025 huggingface dataset:
Women as American Family's health advocate, guide, or guardian: a health communication practitioners' perspective
Authors: Macias Wendy
Published: October 2023

American women are often in the role of being a health advocate, guide, or guardian for family and friends. An examination of gender differences is virtually absent from American-focused health communication literature. I review the topic from an international, professional, and historical perspective and include qualitative data from health communication professional interviews to document and explore this role. Explanatory themes of nature and nurture, as well as collectivism and having the ability to keep track of details, are explored as reasons why women take on these roles to a far greater degree than men. Suggestions for future research are included to encourage more health researchers to add to the academic literature.
Healthcare analytics—A literature review and proposed research agenda
Authors: Elragal Rawan , Elragal Ahmed , Habibipour Abdolrasoul
Published: October 2023

This research addresses the demanding need for research in healthcare analytics, by explaining how previous studies have used big data, AI, and machine learning to identify, address, or solve healthcare problems. Healthcare science methods are combined with contemporary data science techniques to examine the literature, identify research gaps, and propose a research agenda for researchers, academic institutions, and governmental healthcare organizations. The study contributes to the body of literature by providing a state-of-the-art review of healthcare analytics as well as proposing a research agenda to advance the knowledge in this area. The results of this research can be beneficial for both healthcare science and data science researchers as well as practitioners in the field.
High sperm DNA fragmentation: do we have robust evidence to support antioxidants and testicular sperm extraction to improve fertility outcomes? a narrative review
Authors: Romano Massimo , Cirillo Federico , Spadaro Daria , Busnelli Andrea , Castellano Stefano , Albani Elena , Levi-Setti Paolo Emanuele
Published: October 2023

To date, infertility affects 10% to 15% of couples worldwide. A male factor is estimated to account for up to 50% of cases. Oral supplementation with antioxidants could be helpful to improve sperm quality by reducing oxidative damage. At the same time, there is a growing interest in the literature on the use of testicular sperm in patients with high DNA fragmentation index (DFI). This narrative review aims to evaluate the effectiveness of supplementation of oral antioxidants in infertile men with high DFI compared to testicular sperm retrieval. The current evidence is non-conclusive because of serious risk of bias due to small sample sizes and statistical methods. Further large well-designed randomised placebo-controlled trials are still required to clarify the exact role of these to different therapeutic approaches.
Serum metabolomic profiling unveils distinct sex-related metabolic patterns in NAFLD
Authors: Fotakis Charalambos , Kalafati Ioanna-Panagiota , Amanatidou Athina I. , Andreou Vasiliki , Matzapetakis Manolis , Kafyra Maria , Varlamis Iraklis , Zervou Maria , Dedoussis George V.
Published: October 2023

Objective

Obesity poses an increased risk for the onset of Nonalcoholic fatty liver disease (NAFLD). The influence of other factors, such as sex in the incidence and severity of this liver disease has not yet been fully elucidated. Thus, we aimed to identify the NAFLD serum metabolic signatures associated with sex in normal, overweight and obese patients and to associate the metabolite fluctuations across the increasing liver steatosis stages.

Methods and results

Using nuclear magnetic resonance (NMR) serum samples of 210 NAFLD cases and control individuals diagnosed with liver U/S, our untargeted metabolomics enquiry provided a sex distinct metabolic bouquet. Increased levels of alanine, histidine and tyrosine are associated with severity of NAFLD in both men and women. Moreover, higher serum concentrations of valine, aspartic acid and mannose were positively associated with the progression of NAFLD among the male subjects, while a negative association was observed with the levels of creatine, phosphorylcholine and acetic acid. On the other hand, glucose was positively associated with the progression of NAFLD among the female subjects, while levels of threonine were negatively related. Fluctuations in ketone bodies acetoacetate and acetone were also observed among the female subjects probing a significant reduction in the circulatory levels of the former in NAFLD cases. A complex glycine response to hepatic steatosis of the female subjects deserves further investigation.

Conclusion

Results of this study aspire to address the paucity of data on sex differences regarding NAFLD pathogenesis. Targeted circulatory metabolome measurements could be used as diagnostic markers for the distinct stages of NAFLD in each sex and eventually aid in the development of novel sex-related therapeutic options.
The role of the thyroid in polycystic ovary syndrome
Authors: Fan Huanhuan , Ren Qingling , Sheng Zhejin , Deng Ganxiu , Li Limei
Published: October 2023

Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disease in women of childbearing age and can cause metabolic disorder, infertility, and increased anxiety and depression; as a result, it can seriously affect the physical and mental health of fertile women. PCOS is a highly clinically heterogeneous disease with unclear etiology and pathogenesis, which increases the difficulty of treatment. The thyroid gland has complex regulatory effects on metabolism, reproduction, and emotion, and produces hormones that act on almost all cells of the human body. The clinical manifestations of PCOS are similar to some thyroid diseases. Furthermore, some thyroid diseases, such as subclinical hypothyroidism (SCH), not only increase the incidence rate of PCOS, but also exacerbate its associated metabolic abnormalities and reproductive disorders. Interestingly, PCOS also increases the incidence of some thyroid diseases. However, the role of the thyroid in PCOS remains unclear. This review is intended to thoroughly explore the critical role of the thyroid in PCOS by summarizing the comorbidity of PCOS and thyroid diseases and their combined role in metabolic disorders, related metabolic diseases, and reproductive disorders; and by analyzing the potential mechanism through which the thyroid influences the development and progression of PCOS and its symptoms. We hope this review will provide a valuable reference for the role of the thyroid in PCOS.
The connection between tricarboxylic acid cycle enzyme mutations and pseudohypoxic signaling in pheochromocytoma and paraganglioma
Authors: Wang Yuxiong , Liu Bin , Li Faping , Zhang Yanghe , Gao Xin , Wang Yishu , Zhou Honglan
Published: October 2023

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors originating from chromaffin cells, holding significant clinical importance due to their capacity for excessive catecholamine secretion and associated cardiovascular complications. Roughly 80% of cases are associated with genetic mutations. Based on the functionality of these mutated genes, PPGLs can be categorized into distinct molecular clusters: the pseudohypoxia signaling cluster (Cluster-1), the kinase signaling cluster (Cluster-2), and the WNT signaling cluster (Cluster-3). A pivotal factor in the pathogenesis of PPGLs is hypoxia-inducible factor-2α (HIF2α), which becomes upregulated even under normoxic conditions, activating downstream transcriptional processes associated with pseudohypoxia. This adaptation provides tumor cells with a growth advantage and enhances their ability to thrive in adverse microenvironments. Moreover, pseudohypoxia disrupts immune cell communication, leading to the development of an immunosuppressive tumor microenvironment. Within Cluster-1a, metabolic perturbations are particularly pronounced. Mutations in enzymes associated with the tricarboxylic acid (TCA) cycle, such as succinate dehydrogenase (SDHx), fumarate hydratase (FH), isocitrate dehydrogenase (IDH), and malate dehydrogenase type 2 (MDH2), result in the accumulation of critical oncogenic metabolic intermediates. Notable among these intermediates are succinate, fumarate, and 2-hydroxyglutarate (2-HG), which promote activation of the HIFs signaling pathway through various mechanisms, thus inducing pseudohypoxia and facilitating tumorigenesis. SDHx mutations are prevalent in PPGLs, disrupting mitochondrial function and causing succinate accumulation, which competitively inhibits α-ketoglutarate-dependent dioxygenases. Consequently, this leads to global hypermethylation, epigenetic changes, and activation of HIFs. In FH-deficient cells, fumarate accumulation leads to protein succination, impacting cell function. FH mutations also trigger metabolic reprogramming towards glycolysis and lactate synthesis. IDH1/2 mutations generate D-2HG, inhibiting α-ketoglutarate-dependent dioxygenases and stabilizing HIFs. Similarly, MDH2 mutations are associated with HIF stability and pseudohypoxic response. Understanding the intricate relationship between metabolic enzyme mutations in the TCA cycle and pseudohypoxic signaling is crucial for unraveling the pathogenesis of PPGLs and developing targeted therapies. This knowledge enhances our comprehension of the pivotal role of cellular metabolism in PPGLs and holds implications for potential therapeutic advancements.
Beyond apples and pears: sex-specific genetics of body fat percentage
Authors: Roshandel Delnaz , Lu Tianyuan , Paterson Andrew D. , Dash Satya
Published: October 2023

Introduction

Biological sex influences both overall adiposity and fat distribution. Further, testosterone and sex hormone binding globulin (SHBG) influence adiposity and metabolic function, with differential effects of testosterone in men and women. Here, we aimed to perform sex-stratified genome-wide association studies (GWAS) of body fat percentage (BFPAdj) (adjusting for testosterone and sex hormone binding globulin (SHBG)) to increase statistical power.

Methods

GWAS were performed in white British individuals from the UK Biobank (157,937 males and 154,337 females). To avoid collider bias, loci associated with SHBG or testosterone were excluded. We investigated association of BFPAdj loci with high density cholesterol (HDL), triglyceride (TG), type 2 diabetes (T2D), coronary artery disease (CAD), and MRI-derived abdominal subcutaneous adipose tissue (ASAT), visceral adipose tissue (VAT) and gluteofemoral adipose tissue (GFAT) using publicly available data from large GWAS. We also performed 2-sample Mendelian Randomization (MR) using identified BFPAdj variants as instruments to investigate causal effect of BFPAdj on HDL, TG, T2D and CAD in males and females separately.

Results

We identified 195 and 174 loci explaining 3.35% and 2.60% of the variation in BFPAdj in males and females, respectively at genome-wide significance (GWS, p<5x10-8). Although the direction of effect at these loci was generally concordant in males and females, only 38 loci were common to both sexes at GWS. Seven loci in males and ten loci in females have not been associated with any adiposity/cardiometabolic traits previously. BFPAdj loci generally did not associate with cardiometabolic traits; several had paradoxically beneficial cardiometabolic effects with favourable fat distribution. MR analyses did not find convincing supportive evidence that increased BFPAdj has deleterious cardiometabolic effects in either sex with highly significant heterogeneity.

Conclusions

There was limited genetic overlap between BFPAdj in males and females at GWS. BFPAdj loci generally did not have adverse cardiometabolic effects which may reflect the effects of favourable fat distribution and cardiometabolic risk modulation by testosterone and SHBG.
Cellular surface plasmon resonance-based detection of anti-HPA-1a antibody glycosylation in fetal and neonatal alloimmune thrombocytopenia
Authors: Szittner Zoltán , Bentlage Arthur E. H. , Temming A. Robin , Schmidt David E. , Visser Remco , Lissenberg-Thunnissen Suzanne , Mok Juk Yee , van Esch Wim J. E. , Sonneveld Myrthe E. , de Graaf Erik L. , Wuhrer Manfred , Porcelijn Leendert , de Haas Masja , van der Schoot C. Ellen , Vidarsson Gestur
Published: October 2023

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) can occur due to maternal IgG antibodies targeting platelet antigens, causing life-threatening bleeding in the neonate. However, the disease manifests itself in only a fraction of pregnancies, most commonly with anti-HPA-1a antibodies. We found that in particular, the core fucosylation in the IgG-Fc tail is highly variable in anti-HPA-1a IgG, which strongly influences the binding to leukocyte IgG-Fc receptors IIIa/b (FcγRIIIa/b). Currently, gold-standard IgG-glycoanalytics rely on complicated methods (e.g., mass spectrometry (MS)) that are not suited for diagnostic purposes. Our aim was to provide a simplified method to quantify the biological activity of IgG antibodies targeting cells. We developed a cellular surface plasmon resonance imaging (cSPRi) technique based on FcγRIII-binding to IgG-opsonized cells and compared the results with MS. The strength of platelet binding to FcγR was monitored under flow using both WT FcγRIIIa (sensitive to Fc glycosylation status) and mutant FcγRIIIa-N162A (insensitive to Fc glycosylation status). The quality of the anti-HPA-1a glycosylation was monitored as the ratio of binding signals from the WT versus FcγRIIIa-N162A, using glycoengineered recombinant anti-platelet HPA-1a as a standard. The method was validated with 143 plasma samples with anti-HPA-1a antibodies analyzed by MS with known clinical outcomes and tested for validation of the method. The ratio of patient signal from the WT versus FcγRIIIa-N162A correlated with the fucosylation of the HPA-1a antibodies measured by MS (r=-0.52). Significantly, FNAIT disease severity based on Buchanan bleeding score was similarly discriminated against by MS and cSPRi. In conclusion, the use of IgG receptors, in this case, FcγRIIIa, on SPR chips can yield quantitative and qualitative information on platelet-bound anti-HPA-1a antibodies. Using opsonized cells in this manner circumvents the need for purification of specific antibodies and laborious MS analysis to obtain qualitative antibody traits such as IgG fucosylation, for which no clinical test is currently available.
PSGL-1: a novel immune checkpoint driving T-cell dysfunction in obstructive sleep apnea
Authors: Díaz-García Elena , García-Sánchez Aldara , Alfaro Enrique , López-Fernández Cristina , Mañas Eva , Cano-Pumarega Irene , López-Collazo Eduardo , García-Río Francisco , Cubillos-Zapata Carolina
Published: October 2023

Introduction

Although higher incidence of cancer represents a major burden for obstructive sleep apnea (OSA) patients, the molecular pathways driving this association are not completely understood. Recently, the adhesion receptor P-selectin glycoprotein-1 (PSGL 1) has been identified as a novel immune checkpoint, which are recognized major hallmarks in several types of cancer and have revolutionized cancer therapy.

Methods

The expression of PSGL-1 and its ligands VISTA and SIGLEC-5 was assessed in the leucocytes of OSA patients and control subjects exploring the role of intermittent hypoxia (IH) using in vitro models. In addition, PSGL-1 impact on T-cells function was evaluated by ex vivo models.

Results

Data showed PSGL-1 expression is upregulated in the T-lymphocytes from patients with severe OSA, indicating a relevant role of hypoxemia mediated by intermittent hypoxia. Besides, results suggest an inhibitory role of PSGL-1 on T-cell proliferation capacity. Finally, the expression of SIGLEC-5 but not VISTA was increased in monocytes from OSA patients, suggesting a regulatory role of intermittent hypoxia.

Discussion

In conclusion, PSGL-1 might constitute an additional immune checkpoint leading to T-cell dysfunction in OSA patients, contributing to the disruption of immune surveillance, which might provide biological plausibility to the higher incidence and aggressiveness of several tumors in these patients.
Towards modern sustainable construction materials: a bibliographic analysis of engineered geopolymer composites
Authors: Zhang Yin , Li Huihong , Gamil Yaser , Iftikhar Bawar , Murtaza Haseeb
Published: October 2023

Engineered cementitious composites (ECC) exhibits impressive tensile strength but has significant environmental drawbacks due to high cement consumption. Recently, engineered geopolymer composites (EGC) have gained attention as a potential ECC alternative. This comprehensive study reviews the latest EGC advancements, encompassing mix design, design theory, engineering properties, environmental benefits, and durability. It emphasizes how factors like activators, precursors, fibers, additives, and aggregates impact EGC properties, making it a cost-effective material for fire, chemical resistance, and dynamic loads. To address limitations in traditional literature reviews, innovative research methods, including scientometric analysis, were employed to provide a cohesive analysis. This review aims to facilitate knowledge dissemination and collaboration by summarizing EGC advances and highlighting remaining challenges in developing practical applications. It is revealed from the review that various manufacturing methods enhance geopolymers, especially in geopolymer concrete, where replacing 50% of ordinary Portland cement with fly ash boosts strength. Geopolymer concrete excels in pre-cast applications, offering durability and resistance to harsh conditions as an eco-friendly alternative to Portland cement. It suits highway pavement, walls, marine coatings, and tiles, reducing carbon emissions and promoting efficient waste management. EGCs find broad use in construction due to their strong, durable, and eco-friendly qualities, supporting sustainable infrastructure development.
Cognitive decline monitoring through a web-based application
Authors: Sánchez-Vincitore Laura V. , Cubilla-Bonnetier Daniel , Marte-Santana Hugo , Duñabeitia Jon Andoni
Published: October 2023

Cognitive decline usually begins after individuals reach maturity, which is more evident in late adulthood. Rapid and constant cognitive screenings allow early detection of cognitive decline and motivate individuals to participate in prevention interventions. Due to accelerated technological advances, cognitive screening and training are now available to the layperson using electronic devices connected to the internet. Large datasets generated by these platforms provide a unique opportunity to explore cognitive development throughout life and across multiple naturalistic environments. However, such data collection mechanisms must be validated. This study aimed to determine whether the data gathered by commercial visuospatial and phonological working memory tests (CogniFit Inc., San Francisco, USA) confirm the well-established argument that age predicts cognitive decline. Data from 3,212 participants (2,238 females) who were 45 years old or older were analyzed. A linear regression analysis explored the relationship between age and working memory while controlling for gender, sleep quality, and physical activity (variables that are known to affect working memory). We found that age negatively predicts working memory. Furthermore, there was an interaction between age and gender for visuospatial working memory, indicating that although male participants significantly outperformed females, the relationship between age and working memory differs for females and males. Our results suggest that the computerized assessment of visuospatial and phonological working memory is sensible enough to predict cognitive functions in aging. Suggestions for improving the sensitivity of self-reports are discussed. Further studies must explore the nature of gender effects on cognitive aging.
Tempol improves optic nerve histopathology and ultrastructures in cisplatin-induced optic neuropathy in rats by targeting oxidative stress—Endoplasmic reticulum stress—Autophagy signaling pathways
Authors: Alsemeh Amira Ebrahim , Hulail Mohey A. E. , Mokhtar Hanan E. L. , Eldemerdash Reham Talaat , Banatean-Dunea Ioan , Fericean Liana Mihaela , Fathy Maha Abdelhamid , Arisha Ahmed Hamed , Khamis Tarek
Published: October 2023

Introduction

Optic neuropathy is an affection of the optic neurons, which ends with blindness and occurs either primarily due to direct affection of the optic nerve or secondarily as a complication of chronic diseases and/or adverse effects of their therapy. The search for novel therapeutic tools is crucial in addressing the limited therapeutic approaches for optic neuropathy. Therefore, the present study was developed to investigate the possible ameliorative effect of tempol against cisplatin-induced optic neuropathy and its underlying mechanism.

Methods

Forty-eight adult male albino Wistar rats were divided into four equal groups—control, tempol (TEM), cisplatin (CIS), and tempol and cisplatin combined (TEM+CIS). Optic nerve oxidative stress (MDA, SOD, and GPx), gene expression of endoplasmic reticulum stress (ATF-6, XBP-1, BIP, CHOP, and JNK), autophagy 6 (LC3, Beclin-1, and p62) markers, nerve growth factor-1, immunohistochemical expression of (LC3 and p62), histopathological, and electron microscopic examination were performed.

Results

Histopathological and ultrastructure examination validated that cisplatin caused optic neuropathy by inducing oxidative stress, upregulating ER stress markers, and downregulating autophagy markers, and NGF-1 expression. TEM + CIS showed improvement in optic nerve structure and ultrastructure along with oxidative stress, ER stress mRNA, autophagy (immunohistochemical proteins and mRNA) markers, and nerve growth factor mRNA expression.

Conclusions

Based on previous findings, tempol represents a valid aid in cisplatin-induced optic neuropathy by implicating new molecular drug targets (ER stress and autophagy) for optic neuropathy therapy.
Time-course adaptive changes in hippocampal transcriptome and synaptic function induced by simulated microgravity associated with cognition
Authors: Liang Rong , Wang Ling , Yang Qing , Xu Qing , Sun Shufan , Zhou Haichen , Zhao Meiling , Gao Jing , Zheng Chenguang , Yang Jiajia , Ming Dong
Published: October 2023

Introduction

The investigation of cognitive function in microgravity, both short-term and long-term, remains largely descriptive. And the underlying mechanisms of the changes over time remain unclear.

Methods

Behavioral tests, electrophysiological recording, and RNA sequencing were used to observe differences in behavior, synaptic plasticity, and gene expression.

Results

Initially, we measured the performance of spatial cognition exposed to long-term simulated microgravity (SM). Both working memory and advanced cognitive abilities were enhanced. Somewhat surprisingly, the synaptic plasticity of the hippocampal CA3-CA1 synapse was impaired. To gain insight into the mechanism of changing regularity over time, transcriptome sequencing in the hippocampus was performed. The analysis identified 20 differentially expressed genes (DEGs) in the hippocampus after short-term modeling, 19 of which were up-regulated. Gene Ontology (GO) analysis showed that these up-regulated genes were mainly enriched in synaptic-related processes, such as Stxbp5l and Epha6. This might be related to the enhancement of working memory performance under short-term SM exposure. Under exposure to long-term SM, 7 DEGs were identified in the hippocampus, all of which were up-regulated and related to oxidative stress and metabolism, such as Depp1 and Lrg1. Compensatory effects occurred with increased modeling time.

Discussion

To sum up, our current research indicates that the cognitive function under SM exposure is consistently maintained or potentially even being enhanced over both short and long durations. The underlying mechanisms are intricate and potentially linked to the differential expression of hippocampal-associated genes and alterations in synaptic function, with these effects being time-dependent. The present study will lay the experimental and theoretical foundation of the multi-level mechanism of cognitive function under space flight.
Comparison of subthalamic unilateral and bilateral theta burst deep brain stimulation in Parkinson’s disease
Authors: Gülke Eileen , Horn Martin A. , Caffier Julian , Pinnschmidt Hans , Hamel Wolfgang , Moll Christian K. E. , Gulberti Alessandro , Pötter-Nerger Monika
Published: October 2023

High-frequency, conventional deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson’s disease (PD) is usually applied bilaterally under the assumption of additive effects due to interhemispheric crosstalk. Theta burst stimulation (TBS-DBS) represents a new patterned stimulation mode with 5 Hz interburst and 200 Hz intraburst frequency, whose stimulation effects in a bilateral mode compared to unilateral are unknown. This single-center study evaluated acute motor effects of the most affected, contralateral body side in 17 PD patients with unilateral subthalamic TBS-DBS and 11 PD patients with bilateral TBS-DBS. Compared to therapy absence, both unilateral and bilateral TBS-DBS significantly improved (p < 0.05) lateralized Movement Disorder Society-Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS III) scores. Bilateral TBS-DBS revealed only slight, but not significant additional effects in comparison to unilateral TBS-DBS on total lateralized motor scores, but on the subitem lower limb rigidity. These results indicate that bilateral TBS-DBS has limited additive beneficial effects compared to unilateral TBS-DBS in the short term.
Differential gene expression of immunity and inflammation genes in colorectal cancer using targeted RNA sequencing
Authors: Holubekova Veronika , Loderer Dusan , Grendar Marian , Mikolajcik Peter , Kolkova Zuzana , Turyova Eva , Kudelova Eva , Kalman Michal , Marcinek Juraj , Miklusica Juraj , Laca Ludovit , Lasabova Zora
Published: October 2023

Introduction

Colorectal cancer (CRC) is a heterogeneous disease caused by molecular changes, as driver mutations, gene methylations, etc., and influenced by tumor microenvironment (TME) pervaded with immune cells with both pro- and anti-tumor effects. The studying of interactions between the immune system (IS) and the TME is important for developing effective immunotherapeutic strategies for CRC. In our study, we focused on the analysis of expression profiles of inflammatory and immune-relevant genes to identify aberrant signaling pathways included in carcinogenesis, metastatic potential of tumors, and association of Kirsten rat sarcoma virus (KRAS) gene mutation.

Methods

A total of 91 patients were enrolled in the study. Using NGS, differential gene expression analysis of 11 tumor samples and 11 matching non-tumor controls was carried out by applying a targeted RNA panel for inflammation and immunity genes containing 475 target genes. The obtained data were evaluated by the CLC Genomics Workbench and R library. The significantly differentially expressed genes (DEGs) were analyzed in Reactome GSA software, and some selected DEGs were used for real-time PCR validation.

Results

After prioritization, the most significant differences in gene expression were shown by the genes TNFRSF4, IRF7, IL6R, NR3CI, EIF2AK2, MIF, CCL5, TNFSF10, CCL20, CXCL11, RIPK2, and BLNK. Validation analyses on 91 samples showed a correlation between RNA-seq data and qPCR for TNFSF10, RIPK2, and BLNK gene expression. The top differently regulated signaling pathways between the studied groups (cancer vs. control, metastatic vs. primary CRC and KRAS positive and negative CRC) belong to immune system, signal transduction, disease, gene expression, DNA repair, and programmed cell death.

Conclusion

Analyzed data suggest the changes at more levels of CRC carcinogenesis, including surface receptors of epithelial or immune cells, its signal transduction pathways, programmed cell death modifications, alterations in DNA repair machinery, and cell cycle control leading to uncontrolled proliferation. This study indicates only basic molecular pathways that enabled the formation of metastatic cancer stem cells and may contribute to clarifying the function of the IS in the TME of CRC. A precise identification of signaling pathways responsible for CRC may help in the selection of personalized pharmacological treatment.
A plasma miRNA-based classifier for small cell lung cancer diagnosis
Authors: Saviana Michela , Romano Giulia , McElroy Joseph , Nigita Giovanni , Distefano Rosario , Toft Robin , Calore Federica , Le Patricia , Morales Daniel Del Valle , Atmajoana Sarah , Deppen Stephen , Wang Kai , Lee L. James , Acunzo Mario , Nana-Sinkam Patrick
Published: October 2023

Introduction

Small cell lung cancer (SCLC) is characterized by poor prognosis and challenging diagnosis. Screening in high-risk smokers results in a reduction in lung cancer mortality, however, screening efforts are primarily focused on non-small cell lung cancer (NSCLC). SCLC diagnosis and surveillance remain significant challenges. The aberrant expression of circulating microRNAs (miRNAs/miRs) is reported in many tumors and can provide insights into the pathogenesis of tumor development and progression. Here, we conducted a comprehensive assessment of circulating miRNAs in SCLC with a goal of developing a miRNA-based classifier to assist in SCLC diagnoses.

Methods

We profiled deregulated circulating cell-free miRNAs in the plasma of SCLC patients. We tested selected miRNAs on a training cohort and created a classifier by integrating miRNA expression and patients’ clinical data. Finally, we applied the classifier on a validation dataset.

Results

We determined that miR-375-3p can discriminate between SCLC and NSCLC patients, and between SCLC and Squamous Cell Carcinoma patients. Moreover, we found that a model comprising miR-375-3p, miR-320b, and miR-144-3p can be integrated with race and age to distinguish metastatic SCLC from a control group.

Discussion

This study proposes a miRNA-based biomarker classifier for SCLC that considers clinical demographics with specific cut offs to inform SCLC diagnosis.
The value of carcinoembryonic antigen stage in staging, prognosis, and management of colorectal cancer: results from two cohort studies
Authors: Xie Hailun , Wei Lishuang , Liu Mingxiang , Liang Yanren , Wang Qiwen , Tang Shuangyi , Gan Jialiang
Published: October 2023

Background

Combining the carcinoembryonic antigen (CEA) level (C stage) with TNM staging can provide a more comprehensive prognostic assessment of colorectal cancer (CRC). However, the clinical value of incorporating CEA status into the TNM staging system needs to be evaluated.

Methods

We used the SEER database (N = 49,350) and a retrospective cohort from China (N = 1,440). A normal CEA level was staged as C0 and an elevated CEA level was staged as C1. Restricted cubic spline analysis was used to examine the dose-response relationship between the CEA level and survival. The Kaplan-Meier method with the log-rank test was used to plot survival curves. Multivariable Cox proportional hazards regression models with forward stepwise variable selection were used to estimate the hazard ratios and 95% confidence intervals.

Results

Patients with C1 were more likely to have advanced disease than those with C0. CEA on a continuous scale was positively associated with mortality risk. Compared with patients with C0 stage, those with C1 stage had significantly lower survival rates. In the SEER dataset, C1 was independently associated with poor prognosis in patients with CRC, with an approximately 70% increased risk of mortality. Patients with C1 stage had significantly lower survival than those with C0 stage at all clinical stages. Incorporating the C stage into the TNM staging refined the prediction of prognosis of patients with CRC, with a gradual decline in prognosis from stage I C0 to stage IV C1. A similar pattern was observed in the present retrospective cohort study. At each lymph node stage, patients with C1 had significantly lower 5-year survival rates than patients with C0. Compared with lymph node positivity, CEA positivity may have a stronger correlation with a worse prognosis.

Conclusion

Our findings not only validated the independent prognostic significance of CEA in CRC but also demonstrated its enhanced prognostic value when combined with TNM staging. Our study provides evidence supporting the inclusion of C stage in the TNM staging system.
Photobiology: introduction, overview and challenges
Authors: Leister Dario
Published: October 2023

Photobiology is a broad field of research that studies the biological effects of light and has made huge advances in understanding fundamental questions such as how Photosynthesis works and in the area of medicine, which has a direct impact on society. Various specialties of Photobiology have been proposed, and to simplify the overview, six major fields are considered here: Photophysics and Photochemistry, Photosynthesis, Photoreception, Photomedicine, Optogenetics and Optical Bioimaging, and Ecological Photobiology. In this review, an introduction, description and examples are given for each of these major research areas. Current challenges in Photobiology include the understanding of non-visual Photoreception, complex photoreceptive mechanisms and the development of novel therapeutic strategies that may depend on the results of advanced optogenetic approaches. Furthermore, the integration of Photobiology with other fields such as materials science and engineering may lead to artificial photoreceptors and bio-inspired light harvesting and artificial Photosynthesis systems. In an era of global change, understanding the effects of artificial light on organisms and ecosystems is essential to mitigate the ecological disruptions caused by artificial lighting. This non-exhaustive selection of research directions and challenges illustrates the complexity and breadth of Photobiology research.
The ability to induce heat shock transcription factor-regulated genes in response to lethal heat stress is associated with thermotolerance in tomato cultivars
Authors: Mizoi Junya , Todaka Daisuke , Imatomi Tomohiro , Kidokoro Satoshi , Sakurai Tetsuya , Kodaira Ken-Suke , Takayama Hidehito , Shinozaki Kazuo , Yamaguchi-Shinozaki Kazuko
Published: October 2023

Heat stress is a severe challenge for plant production, and the use of thermotolerant cultivars is critical to ensure stable production in high-temperature-prone environments. However, the selection of thermotolerant cultivars is difficult due to the complex nature of heat stress and the time and space needed for evaluation. In this study, we characterized genome-wide differences in gene expression between thermotolerant and thermosensitive tomato cultivars and examined the possibility of selecting gene expression markers to estimate thermotolerance among different tomato cultivars. We selected one thermotolerant and one thermosensitive cultivar based on physiological evaluations and compared heat-responsive gene expression in these cultivars under stepwise heat stress and acute heat shock conditions. Transcriptomic analyses reveled that two heat-inducible gene expression pathways, controlled by the heat shock element (HSE) and the evening element (EE), respectively, presented different responses depending on heat stress conditions. HSE-regulated gene expression was induced under both conditions, while EE-regulated gene expression was only induced under gradual heat stress conditions in both cultivars. Furthermore, HSE-regulated genes showed higher expression in the thermotolerant cultivar than the sensitive cultivar under acute heat shock conditions. Then, candidate expression biomarker genes were selected based on the transcriptome data, and the usefulness of these candidate genes was validated in five cultivars. This study shows that the thermotolerance of tomato is correlated with its ability to maintain the heat shock response (HSR) under acute severe heat shock conditions. Furthermore, it raises the possibility that the robustness of the HSR under severe heat stress can be used as an indicator to evaluate the thermotolerance of crop cultivars.
Chinese cross-cultural adaptation and validation of the Well-being Numerical Rating Scales
Authors: Luo Qing , Liu Chunqin , Zhou Ying , Zou Xiaofang , Song Liqin , Wang Zihan , Feng Xue , Tan Wenying , Chen Jiani , Smith Graeme D. , Chiesi Francesca
Published: October 2023

Introduction

Well-being is a multi-domain concept that involves measuring physical, psychological, social, and spiritual domains. However, there are currently few multi-domain and comprehensive well-being instruments available. In addition, measures that do exist customarily contain a vast number of items that may lead to boredom or fatigue in participants. The Well-being Numerical Rating Scales (WB-NRSs) offer a concise, multi-domain well-being scale. This study aimed to perform the translation, adaptation, and validation of the Chinese version of WB-NRSs (WBNRSs-CV).

Methods

A total of 639 clinical participants and 542 community participants completed the WB-NRSs-CV, the Single-item Self-report Subjective Well-being Scale (SISRSWBS), the World Health Organization Five-item Well-Being Index (WHO-5), the 10-item Perceived Stress Scale (PSS-10), and the Kessler Psychological Distress Scale (K10).

Results

High internal consistency and test-retest reliability were obtained for both samples. Additionally, WB-NRSs-CV was positively associated with SISRSWBS and WHO-5 and negatively associated with PSS-10 and K10. In the item response theory analysis, the model fit was adequate with the discrimination parameters ranging from 2.73 to 3.56. The diffculty parameters ranged from −3.40 to 1.71 and were evenly spaced along the trait, attesting to the appropriateness of the response categories. The invariance tests demonstrated that there was no difference in WB-NRSs-CV across groups by gender or age.

Discussion

The WB-NRSs-CV was translated appropriately and cross-culturally adapted in China. It can be used as a rapid and relevant instrument to assess well-being in both clinical and non-clinical settings, with its utility for well-being measurement and management among the Chinese people.
Network analysis of emotion regulation and reactivity in adolescents: identifying central components and implications for anxiety and depression interventions
Authors: Ruan Qian-Nan , Chen Chun-Mian , Yang Jiang-Shun , Yan Wen-Jing , Huang Zhen-Xing
Published: October 2023

Difficulties in emotion regulation (DER) and emotion reactivity (ER) are important causes and consequences of psychiatric disorders such as depression and anxiety, and previous research suggests that there are many interactions between them. Understanding the structure of their relationship, and which components may play a key role, will help provide insight into emotion disorders in adolescents and provide guidance for clinical interventions. In this study, we collected data from 483 adolescents and used network analysis methods to explore the relationship between DER and ER, specifically looking for core nodes. The results showed that “limited access to emotion regulation strategies” was the most central node in the network. Furthermore, by adding nodes for depression and anxiety to this network, we found that anxiety had the strongest relationship with ER, while depression had a stronger relationship with DER. Thus, our findings suggest that for anxiety disorders, the strong association with ER highlights a potentially promising area for intervention development, whereas for depression, the association with DER points to the possibility of clarifying emotions and exploring coping strategies, acknowledging the complex interplay between depressive and anxious symptoms.
Susceptibility and severity of COVID-19 and risk of psychiatric disorders in European populations: a Mendelian randomization study
Authors: Xue Hua , Zeng Li , Liu Shuangjuan
Published: October 2023

Background

Observational studies have suggested that COVID-19 increases the prevalence of psychiatric disorders, but the results of such studies are inconsistent. This study aims to investigate the association between COVID-19 and the risk of psychiatric disorders using Mendelian randomization (MR) analysis.

Methods

We used summary statistics from COVID-19 Host Genetics Initiative genome-wide association study (GWAS) of COVID-19 involving 2,586,691 participants from European ancestry. Genetic variations of five psychiatric disorders including autism spectrum disorder (ASD) (N = 46,351), bipolar disorder (BID) (N = 51,710), major depressive disorder (MDD) (N = 480,359), anxiety disorder (N = 83,566), and schizophrenia (SCZ) (N = 77,096) were extracted from several GWAS of European ancestry. The inverse-variance weighted (IVW) method as the main MR analysis conducted. We further performed sensitivity analyzes and heterogeneity analyzes as validation of primary MR results.

Results

The IVW analysis found that COVID-19 hospitalization phenotype was the risk factor for BID (OR = 1.320, 95% CI = 1.106–1.576, p = 0.002) and SCZ (OR = 1.096, 95% CI = 1.031–1.164, p = 0.002). Moreover, we detected a significant positive genetic correlation between COVID-19 severity and two psychiatric traits, BID (OR = 1.139, 95% CI = 1.033–1.256, p = 0.008) and SCZ (OR = 1.043, 95% CI = 1.005–1.082, p = 0.024). There was no evidence supporting the causal relationship between COVID-19 susceptibility and psychiatric disorders.

Conclusion

Our results found that the COVID-19 hospitalization phenotype and COVID-19 severity phenotype might be the potential risks of BID and SCZ in European populations. Therefore, patients infected with SARS-CoV-2 should have enhanced monitoring of their mental status.
Wake-up call for HPPP – health promotion, prevention, and preparedness
Authors: Lev Vered , Ron Aviva
Published: October 2023

The latest public health emergencies exposed urgent gaps in health promotion, prevention and preparedness (HPPP). Existing and new infectious diseases have gained far more prevalence than expected, and inequities in access to health care accounted for disturbing differences in the toll of these diseases in different populations. The COVID-19 pandemic not only demonstrated the need to prevent the onset and progression of non-communicable chronic diseases (NCDs) and promote healthy lifestyles, but also the need to prepare for new infectious diseases and their long-term effects on both physical and mental health. Preparedness was previously associated with natural disasters, with activities directed to developing emergency humanitarian action response resources. However, these actions are inadequate for the frequent natural disasters as the climate crisis intensifies. To reach effective actions in HPPP, we take a broad approach to HPPP components, identify the main stakeholders and suggest methods to change allocations for HPPP. We propose a call for action at global and national levels, involving strengthening the United Nations’ Sustainable Development Goals and government commitment to HPPP.
What helps hospital staff in times of crisis: qualitative results of a survey on psychosocial resources and stressors in German hospitals during the COVID-19 pandemic
Authors: Schmidt-Stiedenroth Kira , Guthardt Lisa , Genrich Melanie , Köhne Mara , Stiawa Maja , Erschens Rebecca , Junne Florian , Maatouk Imad ,   The SEEGEN-Consortium, Gündel Harald , Angerer Peter , Müller Andreas
Published: October 2023

Background

Even before the COVID-19 pandemic, hospital workers faced a tremendous workload. The pandemic led to different and additional strain that negatively affected the well-being of employees. This study aims to explore psychosocial resources and strategies that were used by hospital staff.

Methods

In the context of an intervention study, employees of three German hospitals were questioned in writing in summer and fall 2020. Five open-ended questions about the pandemic were asked to capture corresponding effects on daily work routine. Answers of 303 participants were evaluated using structuring qualitative content analysis.

Results

Significant stressors and resources were identified in the areas of work content and task, social relations at work, organization of work, work environment and individual aspects. Stressors included, for example, emotional demands, conflicts, an increased workload, time and performance pressure. Important resources mentioned were, among others, the exchange with colleagues and mutual support. Sound information exchange, clear processes and guidelines and a positive work atmosphere were also important. In addition, the private environment and a positive mindset were perceived as helpful.

Conclusion

This study contributes to a differentiated understanding of existing psychosocial resources of hospital staff in times of crisis. Identifying and strengthening these resources could reduce stress and improve well-being, making hospital staff better prepared for both normal operations and further crisis situations.
Case report: Traumatic hemorrhagic cervical myelopathy in a dog
Authors: Santifort Koen M. , Carrera Ines , Platt Simon
Published: October 2023

A 1.5-year-old female entire French bulldog was referred for neurological evaluation, further diagnostic tests, and treatment 24 h after a road traffic accident. Initial emergency treatment, diagnostic tests, and stabilization had been performed by the referring veterinarian. Neurological examination revealed severe spastic non-ambulatory tetraparesis and was consistent with a C1-5 myelopathy. A magnetic resonance imaging (MRI) study revealed an irregular to elongated ovoid intramedullary lesion centered over the body of C2. The lesion showed marked signal heterogeneity with a central T2W and T2* hyperintense region, surrounded by a hypointense rim on both sequences. The lesion appeared heterogeneously T1W hypointense. The lesion was asymmetric (right-sided), affecting both white and gray matter. The C2-3 intervertebral disk appeared moderately degenerate with a Pfirrmann grade of 3. No evidence of vertebral fracture or luxation was found on radiographs or MRI of the vertebral column. Additional soft tissue abnormalities in the area of the right brachial plexus were suggestive of brachial plexus and muscle injury. A diagnosis of traumatic hemorrhagic myelopathy at the level of C2 and concurrent brachial plexus injury was formed. Conservative treatment was elected and consisted of physiotherapy, bladder care with an indwelling urinary catheter, repeated IV methadone based on pain scoring (0.2 mg/kg), oral meloxicam 0.1 mg/kg q24h, and oral gabapentin 10 mg/kg q8h. The dog was discharged after 4 days, with an indwelling urinary catheter and oral medication as described. The catheter was replaced two times by the referring veterinarian and finally removed after 10 days. Thereafter, voluntary urination was seen. During the 2 months after the road traffic accident, slow recovery of motor function was seen. The right thoracic limb recovery progressed more slowly than the left limb, also showing some lower motor neuron signs during follow-up. This was judged to be consistent with a right-sided brachial plexus injury. The dog was reported ambulatory with mild residual ataxia and residual monoparesis of the right thoracic limb at the last follow-up 3 months post-injury. This case report highlights the MRI-based diagnosis of traumatic hemorrhagic myelopathy in a dog. A fair short-term outcome was achieved with conservative treatment in this case.