bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery of (R)-2-amino-3-triazolpropanoic acid derivatives as NMDA receptor glycine site agonists with GluN2 subunit-specific activity
Authors: Zhao Fabao , Mazis Georgios , Yi Feng , Lotti James S. , Layeux Michael S. , Schultz Eric P. , Bunch Lennart , Hansen Kasper B. , Clausen Rasmus P.
Published: November 2022

N-Methyl-d-aspartate (NMDA) receptors play critical roles in central nervous system function and are involved in variety of brain disorders. We previously developed a series of (R)-3-(5-furanyl)carboxamido-2-aminopropanoic acid glycine site agonists with pronounced variation in activity among NMDA receptor GluN1/2A-D subtypes. Here, a series of (R)-2-amino-3-triazolpropanoic acid analogues with a novel chemical scaffold is designed and their pharmacological properties are evaluated at NMDA receptor subtypes. We found that the triazole can function as a bioisostere for amide to produce glycine site agonists with variation in activity among NMDA receptor subtypes. Compounds 13g and 13i are full and partial agonists, respectively, at GluN1/2C and GluN1/2D with 3- to 7-fold preference in agonist potency for GluN1/2C-D over GluN1/2A-B subtypes. The agonist binding mode of these triazole analogues and the mechanisms by which the triazole ring can serve as a bioisostere for amide were further explored using molecular dynamics simulations. Thus, the novel (R)-2-amino-3-triazolpropanoic acid derivatives reveal insights to agonist binding at the GluN1 subunit of NMDA receptors and provide new opportunities for the design of glycine site agonists.
Electrical storm refractory multiple antiarrhythmic medications was stopped by interatrial shunting procedure—A case report
Authors: Han Caiping , Qiu Rujie , Li Lei , Han Min , Xu Chengyi , Liu Li , Liu Chengwei
Published: November 2022

Electrical storm (ES) remains a major dilemma for clinicians, often presenting as a medical emergency associated with significant adverse outcomes. The mechanisms behind triggering ES are complex. Although the increased activation of the sympathetic nervous system was widely accepted as a major mechanism in initiating and maintaining ES, it's thought that the interaction between mechanical and electrical substrates may play an important role in some situations. Here we present a case of ES that was refractory to multiple antiarrhythmic medications but was stopped by interatrial shunting. We aim to highlight the importance of mechano-electric feedback (MEF) as the pathophysiological mechanisms of some types of ES and the utility of interatrial shunting as an alternative therapeutic strategy for patients with ES initially refractory to antiarrhythmic medications when there is evidence to indicate increased left ventricular filling pressure or left atrial pressure.
Two genetic variants in NEXN and ABCC6 genes found in a patient with right coronary artery to right ventricle fistula combined with giant coronary aneurysm and patent ductus arteriosus
Authors: Peng Yongxuan , Ye Jiajun , Xu Yuejuan , Huang Jihong , Wu Yurong , Liu Wei , Bai Kai , Chen Sun , Lu Yanan
Published: November 2022

Objective

Coronary artery fistula, defined as communication between a coronary artery and a great vessel or a cardiac chamber, is a relatively rare anomaly with an estimated incidence of 0.002% in the general population. It could be combined with a giant coronary artery aneurysm, with an incidence of 5.9% of the total incidence rate of CAF in the general population. The pathogenesis of these two combined anomalies is not clear, and we aimed to detect whether genetic abnormalities underlie the pathogenesis of these rarely combined anomalies.

Materials and methods

A 6-year-old patient with a diagnosis of the right coronary artery to right ventricle fistula combined with a giant right coronary artery aneurysm and patent ductus arteriosus underwent a surgical repair at our center. The diagnosis was confirmed by echocardiography, CT, and surgery. DNA was extracted from the peripheral venous blood samples of the patient and his mother after informed consent was obtained. Hematoxylin and Eosin (HE) and Alizarin red staining were performed on the excised coronary artery aneurysm. Exome sequencing and in silico analyses were performed to detect detrimental genetic variants.

Results

No obvious abnormalities were found in the excised coronary artery aneurysm. A heterozygous truncated variant (NM_144573: c.G298T; p.G100X) in the NEXN gene and a missense variant (NM_001171: c.G1312A; p.V438M) in the ABCC6 gene were carried by the patient but not by his mother.

Conclusion

The NEXN-truncated variant, NEXN-G100X, is associated with the development of coronary arteries and congenital coronary artery anomalies.
Identification and verification of immune-related biomarkers and immune infiltration in diabetic heart failure
Authors: Zhong Zuoquan , Zhang Hanlin , Xu Ting , Hao Jinjin , Chen Xing , Sun Shimin , Yang Jinjin , Sun Jing , Lin Hui , Guo Hangyuan
Published: November 2022

Purpose

Diabetic heart failure (DHF) or cardiomyopathy is a common complication of diabetes; however, the underlying mechanism is not clear. In the present study, the authors searched for differentially expressed genes associated with DHF and the molecular types of immune cells based on bioinformatics.

Methods

The RNA expression dataset of DHF was obtained from the NCBI Gene Expression Omnibus (GEO) database. After preprocessing the data, the differentially expressed genes (DEGs) between the DHF group and the non-diabetic heart failure (NHF) group were screened and intersected with immune-related genes (IRGs) in the ImmPort database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the DAVID tool. The ssGSEA algorithm was used to evaluate immune infiltration of the heart tissue in each group. In addition, the protein-protein interaction (PPI) network and miRNA-mRNA network were constructed using the STRING online website and Cytoscape program. Finally, validation analysis was performed using animal models.

Results

Eight immune-related core genes were identified. GO and KEGG showed that core genes were mainly enriched in angiogenesis and cytokine-cytokine receptor interaction. Immune infiltration results showed that activated dendritic cells, central memory CD4 T cells, central memory CD8 T cells, myeloid-derived suppressor cells (MDSCs), neutrophils, and regulatory T cells may be involved in DHF. Neutrophils may play a key role in the pathogenesis of HF in diabetes.

Conclusion

Immune-related core genes and immune infiltrating cells provide a new perspective on the pathogenesis of DHF.
EPick: Attention-based multi-scale UNet for earthquake detection and seismic phase picking
Authors: Li Wei , Chakraborty Megha , Fenner Darius , Faber Johannes , Zhou Kai , Rümpker Georg , Stöcker Horst , Srivastava Nishtha
Published: November 2022

Earthquake detection and seismic phase picking play a crucial role in the travel-time estimation of P and S waves, which is an important step in locating the hypocenter of an event. The phase-arrival time is usually picked manually. However, its capacity is restricted by available resources and time. Moreover, noisy seismic data present an additional challenge for fast and accurate phase picking. We propose a deep learning-based model, EPick, as a rapid and robust alternative for seismic event detection and phase picking. By incorporating the attention mechanism into UNet, EPick can address different levels of deep features, and the decoder can take full advantage of the multi-scale features learned from the encoder part to achieve precise phase picking. Experimental results demonstrate that EPick achieves 98.80% accuracy in earthquake detection over the STA/LTA with 80% accuracy, and for phase arrival time picking, EPick reduces the absolute mean errors of P- and S- phase picking from 0.072 s (AR picker) to 0.030 s and from 0.189 s (AR picker) to 0.083 s, respectively. The result of the model generalization test shows EPick’s robustness when tested on a different seismic dataset.
Effects of rheological stratification and elasticity of lithosphere on subduction initiation
Authors: Katayama Ikuo , Yoshida Masaki , Hirauchi Ken-ichi
Published: November 2022

The breaking and bending of rigid and elastic lithosphere was probably essential for the initiation of plate subduction, although how this occurred is still poorly understood. Here we test effects of rheological stratification and elasticity of lithosphere on subduction initiation, which are possibly resulting from thermal cracking and seawater penetration into the lithosphere. In addition to the strong influence of water on rheological behavior, the material rigidity is also sensitive to the development of crack and fluid saturation. Numerical modeling indicates that water-weakening and a low-rigidity lithosphere are essential for the initiation of plate subduction, and such conditions are likely to have arisen on the early Earth due to extensive thermal contraction of the planet. Our results indicate that the formation of thermal cracks and penetration of seawater play an important role on subduction initiation, and are likely to have operated on planets other than Earth. However, if the ocean is disappeared, fluid penetration is likely to cease and plate tectonics would have stopped due to increasing the strength and rigidity of the lithosphere.
Prognostic value of 18F-FDG PET/CT in patients with advanced or metastatic non-small-cell lung cancer treated with immune checkpoint inhibitors: A systematic review and meta-analysis
Authors: Ling Tao , Zhang Lianghui , Peng Rui , Yue Chao , Huang Lingli
Published: November 2022

Purpose

This study aimed to investigate the value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in predicting early immunotherapy response of immune checkpoint inhibitors (ICIs) in patients with advanced or metastatic non-small-cell lung cancer (NSCLC).

Methods

A comprehensive search of PubMed, Web of science, Embase and the Cochrane library was performed to examine the prognostic value of 18F-FDG PET/CT in predicting early immunotherapy response of ICIs in patients with NSCLC. The main outcomes for evaluation were overall survival (OS) and progression-free survival (PFS). Detailed data from each study were extracted and analyzed using STATA 14.0 software.

Results

13 eligible articles were included in this systematic review. Compared to baseline 18F-FDG PET/CT imaging, the pooled hazard ratios (HR) of maximum and mean standardized uptake values SUVmax, SUVmean, MTV and TLG for OS were 0.88 (95% CI: 0.69-1.12), 0.79 (95% CI: 0.50-1.27), 2.10 (95% CI: 1.57-2.82) and 1.58 (95% CI: 1.03-2.44), respectively. The pooled HR of SUVmax, SUVmean, MTV and TLG for PFS were 1.06 (95% CI: 0.68–1.65), 0.66 (95% CI: 0.48-0.90), 1.50 (95% CI: 1.26-1.79), 1.27 (95% CI: 0.92-1.77), respectively. Subgroup analysis showed that high MTV group had shorter OS than low MTV group in both first line group (HR: 1.97, 95% CI: 1.39-2.79) and undefined line group (HR: 2.11, 95% CI: 1.61-2.77). High MTV group also showed a shorter PFS in first line group (HR: 1.85, 95% CI: 1.28-2.68), and low TLG group had a longer OS in undefined group (HR: 1.37, 95% CI: 1.00-1.86). No significant differences were in other subgroup analysis.

Conclusion

Baseline MTV and TLG may have predictive value and should be prospectively studied in clinical trials. Baseline SUVmax and SUVmean may not be appropriate prognostic markers in advanced or metastatic NSCLC patients treated with ICIs.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=323906, identifier CRD42022323906.
Immuno-cardio-oncology: Killing two birds with one stone?
Authors: Van Linthout Sophie , Volk Hans-Dieter
Published: November 2022

Inflammation and a dysregulated immune system are common denominators of cancer and cardiovascular disease (CVD). Immuno-cardio-oncology addresses the interconnected immunological aspect in both cancer and CVD and the integration of immunotherapies and anti-inflammatory therapies in both distinct disease entities. Building on prominent examples of convergent inflammation (IL-1ß biology) and immune disbalance (CD20 cells) in cancer and CVD/heart failure, the review tackles both the roadblocks and opportunities of repurposed use of IL-1ß drugs and anti-CD20 antibodies in both fields, and discusses the use of advanced therapies e.g. chimeric antigen receptor (CAR) T cells, that can address the raising burden of both cancer and CVD. Finally, it is discussed how inspired by precision medicine in oncology, the use of biomarker-driven patient stratification is needed to better guide anti-inflammatory/immunomodulatory therapeutic interventions in cardiology.
Maka Niu: A low-cost, modular imaging and sensor platform to increase observation capabilities of the deep ocean
Authors: Novy Dan , Kawasumi Lui , Ferguson Jon , Sullivan Margaret , Bell Peter , Chow Jennifer S. , de Sousa João Borges , Cantner Kat A. , Woodward Benjamin , Adams Allan , Bell Katherine L.C.
Published: November 2022

The deep sea (>200 m) is vast, covering 92.6% of the seafloor and largely unexplored. Imaging and sensor platforms capable of surviving the immense pressures at these depths are expensive and often engineered by individuals and institutions in affluent countries as unique, monolithic vehicles that require significant expertise and investment to build, operate, and maintain. Maka Niu was co-designed with a global community of deep-sea researchers. It is a low-cost, modular imaging and sensor platform that leverages off-the-shelf commodity hardware along with the efficiencies of mass production to decrease the price per unit and allow more communities to explore previously unseen regions of the deep ocean. Maka Niu combines a Raspberry Pi single-board computer, a Pi Camera Module V2, and a novel pressure housing and viewport combination capable of withstanding 1,500 m water depth. Other modules, including high-lumen LEDs, can be engineered to use the same battery charging and control system and form factor, allowing for an ever-increasing number of capabilities to be added to the system. After deployment, imagery and sensor data are wirelessly uploaded to Tator, an integrated media management and machine learning backend for automated analysis and classification. Maka Niu’s mobile mission programming and data management systems are designed to be user-friendly. Here, Maka Niu is described in detail along with data and imagery recorded from deployments around the world.
Proteomic analysis of urinary extracellular vesicles of kidney transplant recipients with BKV viruria and viremia: A pilot study
Authors: Bruschi Maurizio , Granata Simona , Candiano Giovanni , Petretto Andrea , Bartolucci Martina , Ghiggeri Gian Marco , Stallone Giovanni , Zaza Gianluigi
Published: November 2022

Introduction

To better define the biological machinery associated with BK virus (BKV) infection, in kidney transplantation, we performed a proteomics analysis of urinary extracellular vesicles (EVs).

Methods

Twenty-nine adult kidney transplant recipients (KTRs) with normal allograft function affected by BKV infection (15 with only viremia, 14 with viruria and viremia) and 15 controls (CTR, KTRs without BKV infection) were enrolled and randomly divided in a training cohort (12 BKV and 6 CTR) used for the mass spectrometry analysis of the EVs (microvesicles and exosomes) protein content and a testing cohort (17 BKV and 9 CTR) used for the biological validation of the proteomic results by ELISA. Bioinformatics and functional analysis revealed that several biological processes were enriched in BKV (including immunity, complement activation, renal fibrosis) and were able to discriminate BKV vs. CTR. Kinase was the only gene ontology annotation term including proteins less abundant in BKV (with SLK being the most significantly down-regulated protein). Non-linear support vector machine (SVM) learning and partial least squares discriminant analysis (PLS-DA) identified 36 proteins (including DNASE2, F12, AGT, CTSH, C4A, C7, FABP4, and BPNT1) able to discriminate the two study groups. The proteomic profile of KTRs with BKV viruria alone vs. viremia and viruria was quite similar. Enzyme-linked immunosorbent assay (ELISA) for SLK, BPNT1 and DNASE2, performed on testing cohort, validated proteomics results.

Discussions

Our pilot study demonstrated, for the first time, that BKV infection, also in the viruric state, can have a negative impact on the allograft and it suggested that, whether possible, an early preventive therapeutic strategy should be undertaken also in KTRs with viruria only. Our results, then, revealed new mechanistic insights into BKV infection and they selected potential biomarkers that should be tested in future studies with larger patients’ cohorts.
Potential biomarkers of atopic dermatitis
Authors: Yu Ling , Li Linfeng
Published: November 2022

Atopic dermatitis (AD) is a chronic, recurrent inflammatory skin disease with a wide range of heterogeneity. Accurate biomarkers or predictors are the keys to instructing personalized tailored precise treatment. The development of technology such as transcriptomics, genomics, and proteomics provides novel insights into the possibility to find potential biomarkers. Meanwhile, emerging minimally invasive methods such as tape stripping were used to reveal different profiles of patients’ skin without biopsy. Several potential biomarkers or predictors have been found. In this review, we summarized the current development of potential biomarkers of AD. Nitric oxide synthase 2/inducible nitric oxide synthase (NOS2/iNOS), human beta-defensin-2 (hBD-2), and matrix metalloproteinases 8/9 (MMP8/9) may be the candidate biomarkers for AD diagnosis. Filaggrin (FLG) gene mutation increased the occurrence risk of AD. Fatty-acid-binding protein 5 (FABP5) may serve as an effective biomarker for the atopic march (AM). Squamous cell carcinoma antigen 2 (SCCA2), serum thymus and activation-regulated chemokine (TARC), cutaneous T-cell-attracting chemokine (CTACK), eosinophil-derived neurotoxin (EDN), macrophage-derived chemokine (MDC), lactate dehydrogenase (LDH), and interleukin (IL)-18 can be the candidate biomarkers for disease severity monitoring. IL-17, IL-23, IL-33, and indoleamine 2,3-dioxygenase (IDO1) can be used as predictive biomarkers for AD comorbidities. LDH, TARC, pulmonary and activation-regulated chemokine (PARC), periostin, IL-22, eotaxin-1/3, and IL-8 may be the candidate biomarkers for monitoring treatment effects. There are still unmet needs and a long way to go for more convenient, non-invasive, and effective predictors and biomarkers to better guide personalized precise treatment.
Risk factors of lymph node metastasis or lymphovascular invasion for superficial esophageal squamous cell carcinoma: A practical and effective predictive nomogram based on a cancer hospital data
Authors: Tao Yali , Chen Shengsen , Yu Jiangping , Shen Qiwen , Ruan Rongwei , Wang Shi
Published: November 2022

Background

Lymphovascular invasion (LVI) is mostly used as a preoperative predictor to establish lymph node metastasis (LNM) prediction models for superficial esophageal squamous cell carcinoma (SESCC). However, LVI still needs to be confirmed by postoperative pathology. In this study, we combined LNM and LVI as a unified outcome and named it LNM/LVI, and aimed to develop an LNM/LVI prediction model in SESCC using preoperative factors.

Methods

A total of 512 patients who underwent radical resection of SESCC were retrospectively collected. Logistic regression and least absolute shrinkage and selection operator (LASSO) regression were adopted to identify the predictive factors of LNM/LVI. Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were calculated to select the potential predictive factors from the results of LASSO and logistic regression. A nomogram for predicting LNM/LVI was established by incorporating these factors. The efficacy, accuracy, and clinical utility of the nomogram were, respectively, assessed with the area under the curve (AUC), calibration curve, and decision curve analysis (DCA). Finally, the random forest (RF) algorithm was used to further evaluate the impact of these factors included in the nomogram on LNM/LVI.

Results

Tumor size, tumor location, tumor invasion depth, tumor differentiation, and macroscopic type were confirmed as independent risk factors for LNM/LVI according to the results of logistic regression, LASSO regression, IDI, and NRI analyses. A nomogram including these five variables showed a good performance in LNM/LVI prediction (AUC = 0.776). The calibration curve revealed that the predictive results of this nomogram were nearly consistent with actual observations. Significant clinical utility of our nomogram was demonstrated by DCA. The RF model with the same five variables also had similar predictive efficacy with the nomogram (AUC = 0.775).

Conclusion

The nomogram was adopted as a final tool for predicting LNM/LVI because its risk score system made it more user-friendly and clinically useful than the random forest model, which can help clinicians make optimal treatment decisions for patients with SESCC.
The survey of soil-transmitted helminth species abundance in Slovakia with an emphasis on parameters important for their distribution
Authors: Ihnacik Lukáš , Šmigová Júlia , Šoltys Jindřich , Bobíková Diana , Kuzevičová Žofia , Kuzevič Štefan , Schusterová Ingrid , Papajová Ingrid
Published: November 2022

Soil-transmitted helminths (STH) can be easily dispensable in socially disadvantaged groups. The Roma people represent the group most at risk in Slovakia. This study aimed to investigate the occurrence of STH infections in minorities living with animals under low hygienic conditions and on contaminated soil. Subsequently, we identified the risk assessment factors of the STH transmissions based on parasitological results. In our study, STHs were predominantly found among the Roma communities living in unsanitary conditions. The prevalence of Ascaris lumbricoides among the majority was 0.79%, and Trichuris trichiura was 0.05 %. On the contrary, a community-based cross-sectional survey across eastern Slovakia also found a prevalence of 22.28 and 3.47% for A. lumbricoides and T. trichiura among the Roma population. Inhabitants that belong to the Roma minority had a 37.12 infection OR times higher than non-Roma inhabitants. The Roma people living in the countryside have a 2.23-fold higher chance of getting infected with STH than Roma living in the city. Therefore, soil and domestic animals were also examined for the presence of the STH eggs to show the environmental burden. In general, the presence of STH eggs was confirmed in 26.26% of the soil examined samples. The detailed description is as follows: eggs of Toxocara spp., Trichuris spp., eggs from the family Ancylostomatidae, and Toxascaris leonina. Ascaris eggs were detected only in the soil from localities with low hygienic standards. The probability of contracting the STH eggs in segregated settlements was 15.94 times higher compared to urban or rural areas. In addition to humans, dogs can also be a source of STH eggs in the soil. The STH eggs were confirmed in 43.55% of dog droppings. The most interesting finding was that the eggs of the genus Ascaris were up to 7.93% of dog droppings from localities with a low hygienic standard were positive. This study revealed that climatic factors and the WASH conditions influenced the distribution of STHs to variable degrees. In addition, ethnicity and sanitation were crucial factors in the distribution of STH infection in eastern Slovakia.
Multiple sexually transmitted co-infections are associated with adverse reproductive outcomes in asymptomatic adolescent pregnant women; A Prospective cohort study
Authors: Wasnik Kirti , Mittal Pratima , Ghope Priti , Sonkar Subash C. , Arora Geetika , Saluja Daman
Published: November 2022

Background

A prospective cohort was conducted to assess the prevalence of seven RTIs/STIs in adolescent asymptomatic pregnant women to find a significant correlation between infection and pregnancy.

Methods

The study was restricted to 18–19 years of asymptomatic adolescent pregnant women attending Ante-Natal Care and the health status of the pregnant women were followed up to parturition. The health status of the infant was followed till 6 months post-delivery. The prevalence of the concerning pathogens and the significance of their association with adverse outcomes of pregnancy were determined.

Results

Among 279 subjects, the most significant co-infections were observed for M. hominis with U. parvum (9.31%; p-value–0.0071/OR−2.6421) and U. urealyticum (7.88%; p-value–0.0119/OR−2.6455). Statistically significant associations were found between C. trachomatis [(p-value-0.0439); OR−2.9902] and M. genitalium [(p-value−0.0284); OR−3.442] with PTB, N. gonorrhoeae with LBW <2.5 kg [(p-value−0.0052);OR−4.9017], U. urealyticum with VLBW <2 kg [(p-value-0.0262);OR−3.0207], M. genitalium [(p-value-0.0184); OR−11.7976] and T. vaginalis with PROM [(p-value 0.0063); OR−19.4275] while M. genitalium [(p-value 0.0190); OR–12.9230] and U. urealyticum [(p-value 0.0063); OR-14.5149] with PPROM with 95% CI respectively.

Conclusions

Asymptomatic adolescents are at high risk of adverse pregnancy outcomes if infected with the concerned pathogens.
Consciousness and inward electromagnetic field interactions
Authors: MacIver M. Bruce
Published: November 2022

Electromagnetic field (EMF) theories of mind/brain integration have been proposed to explain brain function for over seventy years. Interest in this theory continues to this day because it explains mind-brain integration and it offers a simple solution to the “binding problem” of our unified conscious experience. Thus, it addresses at least in part the “hard problem” of consciousness. EMFs are easily measured and many corelates have been noted for field activity; associated with loss and recovery of consciousness, sensory perceptions, and behavior. Unfortunately, the theory was challenged early on by experiments that were thought to have ruled out a role of EMFs in brain activity, and the field of neuroscience has since marginalized EMF theories. Here I explain why early evidence against EMFs contributing to consciousness was misinterpreted and offer an alternative view to help direct future research.
Impact of low skeletal muscle mass and quality on clinical outcomes in patients with head and neck cancer undergoing (chemo)radiation
Authors: Bardoscia Lilia , Besutti Giulia , Pellegrini Massimo , Pagano Maria , Bonelli Candida , Bonelli Efrem , Braglia Luca , Cozzi Salvatore , Roncali Massimo , Iotti Cinzia , Pinto Carmine , Pattacini Pierpaolo , Ciammella Patrizia
Published: November 2022

The study aimed to explore the impact of low skeletal muscle mass and quality on survival outcomes and treatment tolerance in patients undergoing radical chemo-radiation therapy for head and neck cancer (HNC). This is significant given the growing interest in sarcopenia as a possible negative predictive/prognostic factor of disease progression and survival. From 2010 to 2017, 225 patients were included in the study. Pre-treatment computed tomography (CT) scans of HNC patients undergoing (chemo)radiation therapy were retrospectively reviewed. The skeletal muscle area, normalized for height to obtain the skeletal muscle index (SMI), the skeletal muscle density (SMD) and the intramuscular adipose tissue area (IMAT) were measured at the level of the L3 vertebra. Low SMD and low SMI were defined according to previously reported thresholds, while high IMAT was defined using population-specific cut-point analysis. SMI, SMD, and IMAT were also measured at the proximal thigh (PT) level and tested as continuous variables. Clinical morpho-functional parameters, baseline nutritional markers with a known or suspected impact on HNC treatment, clinical outcomes and sarcopenia were also collected. In multivariate analyses, adjusted by age, sex, stage, diabetes, body mass index (BMI), and weight loss, L3-SMI was not significantly associated with survival, while poor muscle quality was negatively associated with overall survival (OS) (HR = 1.88, 95% CI = 1.09–3.23, p = 0.022 and HR = 2.04, 95% CI = 1.27–3.27, p = 0.003, for low L3-SMD and high L3-IMAT, respectively), progression-free survival (PFS) (HR = 2.26, 95% CI = 1.39–3.66, p = 0.001 and HR = 1.97, 95% CI = 1.30–2.97, p = 0.001, for low L3-SMD and high L3-IMAT, respectively) and cancer-specific survival (CSS) (HR = 2.40, 95% CI = 1.28–4.51, p = 0.006 and HR = 1.81, 95% CI = 1.04–3.13, p = 0.034, for low L3-SMD and high L3-IMAT, respectively). Indices at the PT level, tested as continuous variables, showed that increasing PT-SMI and PT-SMD were significant protective factors for all survival outcomes (for OS: HR for one cm2/m2 increase in PT-SMI 0.96; 95% CI = 0.94–0.98; p = 0.001 and HR for one HU increase in PT-SMD 0.90; 95% CI = 0.85–0.94; p < 0.001, respectively). PT-IMAT was a significant risk factor only in the case of CSS (HR for one cm2 increase 1.02; 95% CI = 1.00–1.03; p = 0.046). In conclusion, pre-treatment low muscle quality is a strong prognostic indicator of death risk in patients affected by HNC and undergoing (chemo)radiotherapy with curative intent.
The clinical implications of circulating microRNAs as potential biomarkers in screening oral squamous cell carcinoma
Authors: Gao Huan , Shen Yi , Feng Zhengyang , Cai Yuxing , Yang Jianxin , Zhu Yaqun , Peng Qiliang
Published: November 2022

Background

Recent studies have highlighted the biomarker role of circulating miRNAs in oral squamous cell carcinoma (OSCC), indicating their potential application as early diagnostic markers for OSCC. However, the diagnostic results have proven inconclusive. This study was conducted to evaluate the diagnostic value of circulating miRNAs for OSCC diagnosis.

Methods

Eligible published studies were identified by a literature search carried out in several databases by using combinations of keywords associated with OSCC, circulating miRNAs, and diagnosis. The bivariate meta-analysis model was adopted to summarize the pooled parameters. Afterwards, we thoroughly explored the sources of heterogeneity after evaluating the risk of bias.

Results

A total of 60 studies focusing on 41 circulating miRNAs were included. The pooled sensitivity, specificity, and AUC were 0.75 (95%CI: 0.69-0.80), 0.76 (0.70-0.81), 0.82 (0.79-0.85), respectively. Subgroup analyses showed that miRNA combinations were more accurate than single miRNAs. Additionally, plasma may be a better matrix for miRNAs assays in OSCC diagnosis as the plasma-based miRNA assay had a higher level of diagnostic accuracy than serum-based miRNA assay. Subgroup analyses also suggested that using circulating miRNAs for OSCC diagnosis is more effective in Caucasians than in Asian ethnic groups. Finally, circulating miRNA assays based on large sample sizes have superior diagnostic accuracy than small sample sizes.

Conclusion

Circulating miRNAs might be applied as effective surrogate biomarkers for early diagnosis of OSCC. Nevertheless, future larger-scale prospective studies should be performed to enhance the diagnostic efficiency and investigate the miRNA combinations with more pronounced accuracy.
Distinct care trajectories among persons living with arthritic conditions: A two-year state sequence analysis
Authors: Nguena Nguefack Hermine Lore , Pagé M. Gabrielle , Choinière Manon , Vanasse Alain , Deslauriers Simon , Angarita-Fonseca Adriana , Blanchette Marc-André , Lacasse Anaïs
Published: November 2022

Objectives

Developing solutions to optimize care trajectories (CareTs) requires examining patient journeys through the health care system. This study aimed to describe CareTs among people living with arthritis and evaluate their association with self-reported health outcomes.

Methods

Analyses were conducted using the TorSaDE Cohort (n = 102,148), which connects the 2007 to 2016 Canadian Community Health Surveys (CCHS) with Quebec administrative databases (longitudinal claims). CareTs of participants living with arthritis according to CCHS (n = 16,631), over the two years before CCHS completion, were clustered using state sequence analysis (months as a time unit). CareT group membership was then put in association with self-reported outcomes (pain intensity and interference, self-perceived general and mental health).

Results

The analysis revealed five CareT groups characterized predominantly by: (1) arthritis-related visits to a specialist (n = 2,756; 16.6%), (2) arthritis-related emergency department visits (n = 2,928; 17.6%), (3) very high all-cause health care utilization and arthritis-related hospitalizations (n = 1,570; 9.4%), (4) arthritis-related medical visits to general practitioners and specialists (n = 2,708; 16.3%), (5) low all-cause health care utilization (n = 6,669; 40.1%). Multivariable results revealed that CareT group membership was associated with higher levels of pain interference (CareT group #3 vs. #5: OR: 1.4, 95%CI: 1.1–1.8) and fair/poor self-perceived general health (CareT group #1 vs. #5: OR: 1.551, 95%CI: 1.319–1.824; #2 vs. #5: OR: 1.244, 95%CI: 1.062–1.457; #3 vs. #5: OR: 1.771, 95%CI: 1.451–2.162; #4 vs. #5: OR: 1.481, 95%CI: 1.265–1.735).

Discussion

Sate sequence analysis is an innovative method of studying CareTs and valuable for making evidence-based decisions taking into account inter- and intra-individual variability.
Assessment of choroidal vascularity and choriocapillaris blood perfusion in Chinese preschool-age anisometropic hyperopic amblyopia children
Authors: Hui Wang , Xiaofeng Hu , Hua Xin , Yihan Dong , Yong Tao
Published: November 2022

Purpose

To determine the macular and peripapillary area choroid microstructure parameters of hyperopic anisometropic amblyopia eyes and compare to fellow and age-matched control eyes. To assess the correlation between the axial length (AL), choroidal thickness (CT) and choroid microstructure parameters.

Methods

This cross-sectional comparative, non-interventional study involved 52 hyperopic anisometropic amblyopia children and 48 age-matched heathy controls. 52 eyes with hyperopic anisometropic amblyopia and 48 age-matched control eyes were studied. The peripapillary and subfoveal CT were determined. The total choroidal area (TCA), luminal area (LA), and stromal area (SA) of the subfoveal and peripapillary choroid were measured. In addition, the correlation between the AL, CT and choroid microstructure parameters were calculated.

Results

The peripapillary and subfoveal CT of the amblyopic eyes was significantly thicker than the fellow and control eyes (all P < 0.05). The subfoveal and peripapillary choroidal SA, LA and TCA of the amblyopic eyes were significantly increased than that of the fellow and control eyes (all P < 0.05). The choroidal vascularity index (CVI) values of the amblyopic eye were significantly different among the three groups (P < 0.05). There was a statistically significant negative correlation between AL and subfoveal CT (SFCT), LA and TCA levels (P < 0.001, P = 0.039, P = 0.027, respectively). Spherical equivalent (SE) was positive correlated with SFCT, LA and TCA levels (P = 0.456, 0.229 and 0.240, respectively; all P < 0.05). There was a statistically significant positive correlation between SFCT, SE, LA, SA, TCA and CVI levels (all P < 0.05).

Conclusion

The subfoveal and peripapillary CT of amblyopic children abnormally increased and correlated with shorter AL and higher SE. The choroidal structure of the amblyopic eyes was different from the fellow and control eyes, the hyperopic anisometropic amblyopic eyes had significantly thicker sub-foveal choroid, higher LA, SA, and TCA. AL and CT affect choroidal structure and vascular density. Choroidal blood flow may be increased in amblyopic eyes. The larger LA, SA, TCA, and lower CVI were characteristic of the amblyopic eye.
Primary health care, access to legal abortion and the notion of ideal victim among medical practitioners: The case of Chile
Authors: Casas Lidia C. , Álvarez Juan J. , Vivaldi Lieta V. , Montero Adela R. , Bozo Natalia , Babul Jorge
Published: November 2022

In 2017, Chile enacted new legislation allowing access to legal abortion on three grounds, including rape. This article summarizes a qualitative, exploratory study that examined the role of primary healthcare services in the treatment of rape survivors in order to identify challenges and strengths in accessing legal abortion. The relevant data was collected through 19 semi-structured interviews conducted with key informants. The angry legislative debate that preceded enactment of the 2017 abortion bill evidenced the presence of strong biases against survivors of sexual violence. At the time, abortion opponents sought, inter alia, to discredit women who report rape, arguing that such claims would be misused to secure illicit abortions. In actual fact, however, rape has turned out to be the least used of all grounds for abortion, with girls and teens making up the smallest group of seekers. This article presents our findings on rape-related issues, notably the biases and shortcomings of medical practitioners regarding the new abortion law. We noted with concern their failure to screen for sexual violence and propensity to stigmatize the victims, a phenomenon that becomes exacerbated when it involves particularly vulnerable populations, such as girls and women who are poor, homeless, migrant, or who abuse alcohol or drugs. We further noted that prevalent stereotypes based on the notion of the ideal victim can revictimize girls and women and work to defeat the intent of the law. In Chile, the primary healthcare system is a key point of entry for abortion. In this highly charged arena, however, lack of political will, compounded by the COVID-19 pandemic, have kept health care practitioners from undergoing timely, gender-sensitive training on the new law, a key requirement for ensuring dignified care and respect for women’s rights. We conclude that if government policy is to prevent multiple, intersectional discrimination, it must recognize the diversity of women and adapt to their specific contexts and singularities.
Bringing social interaction at the core of organizational neuroscience
Authors: Boukarras Sarah , Ferri Donato , Frisanco Althea , Farnese Maria Luisa , Consiglio Chiara , Alvino Ilario , Bianchi Francesco , D’Acunto Andrea , Borgogni Laura , Aglioti Salvatore Maria
Published: November 2022

Organizations are composed of individuals working together for achieving specific goals, and interpersonal dynamics do exert a strong influence on workplace behaviour. Nevertheless, the dual and multiple perspective of interactions has been scarcely considered by Organizational Neuroscience (ON), the emerging field of study that aims at incorporating findings from cognitive and brain sciences into the investigation of organizational behaviour. This perspective article aims to highlight the potential benefits of adopting experimental settings involving two or more participants (the so-called “second person” approach) for studying the neural bases of organizational behaviour. Specifically, we stress the idea that moving beyond the individual perspective and capturing the dynamical relationships occurring within dyads or groups (e.g., leaders and followers, salespersons and clients, teams) might bring novel insights into the rising field of ON. In addition, designing research paradigms that reliably recreate real work and life situations might increase the generalizability and ecological validity of its results. We start with a brief overview of the current state of ON research and we continue by describing the second-person approach to social neuroscience. In the last paragraph, we try and outline how this approach could be extended to ON. To this end, we focus on leadership, group processes and emotional contagion as potential targets of interpersonal ON research.
The relationship between childhood adversity and problem behavior of new street corner youth on campus: A moderate mediation model
Authors: Fan LinLin , Meng WeiJie
Published: November 2022

To explore the impact mechanism of childhood adversity on problem behaviors of new street corner youth on campus, we surveyed 637 new street corner youth on campus and completed the Strengths and Difficulties Questionnaire, the Childhood Environment Scale, the Life History Strategies Scale, and the Dark Triad Scale. After controlling for gender and age of new street corner youth on campus, results revealed that childhood adversity was significantly and positively associated with problem behaviors. Mediation analysis showed that life history strategy mediated the association between childhood adversity and problem behaviors. Moreover, moderated mediation analysis further indicated that dark triad moderated the association between childhood adversity and life history strategy, as well as the association between life history strategy and problem behaviors. These findings suggest that interventions of life history strategy and dark triad may be effective means to affect problem behaviors of new street corner youth on campus.
Parent–child interaction during a home STEM activity and children’s handwashing behaviors
Authors: Sobel David M. , Stricker Laura W.
Published: November 2022

We examined correlations between a home-based STEM activity illustrating the importance of soap use during handwashing and children’s (4-to 7-year-olds, N = 81, 42 girls, 39 boys) use of soap when washing their hands. Parents and children either participated in or watched the activity. Children reflected on the activity immediately afterward and a week later. Parent–child interaction during participation related to the frequency of unprompted soap use during handwashing, controlling for performance on other, related cognitive measures. Children whose parents were more goal-directed, and set goals for the interaction, were less likely to use soap spontaneously when handwashing in the subsequent week. The amount of causal knowledge children generated when they reflected on the experience immediately afterward also influenced whether children used soap when washing their hands. Reducing the autonomy children believe they have during a STEM-based activity potentially leads them to not engage in a behavior related to the activity on their own. Overall, these data suggest that parent–child interaction during STEM activities can influence the ways children encode and engage with those activities in their everyday lives. Given that the ways children wash their hands might mitigate the spread of disease, interventions that focus on providing children with the belief that STEM activities are for them might be broadly beneficial to society.
Filling the gaps in the research about second primary malignancies after bladder cancer: Focus on race and histology
Authors: Othmane Belaydi , Yi Zhenglin , Zhang Chunyu , Chen Jinbo , Zu Xiongbing , Fan Benyi
Published: November 2022

Purpose

Previous research has shown that bladder cancer has one of the highest incidences of developing a second primary malignancy. So, we designed this study to further examine this risk in light of race and histology.

Patients and methods

Using the surveillance, epidemiology, and end results (SEER) 18 registry, we retrospectively screened patients who had been diagnosed with bladder cancer between 2000 and 2018. We then tracked these survivors until a second primary cancer diagnosis, the conclusion of the trial, or their deaths. In addition to doing a competing risk analysis, we derived standardized incidence ratios (SIRs) and incidence rate ratios (IRRs) for SPMs by race and histology.

Results

A total of 162,335 patients with bladder cancer were included, and during follow-ups, a second primary cancer diagnosis was made in 31,746 of these patients. When the data were stratified by race, SIRs and IRRs for SPMs showed a significant difference: Asian/Pacific Islanders (APIs) had a more pronounced increase in SPMs (SIR: 2.15; p 0.05) than White and Black individuals who had an SIRs of 1.69 and 1.94, respectively; p 0.05. In terms of histology, the epithelial type was associated with an increase in SPMs across all three races, but more so in APIs (IRR: 3.51; 95% CI: 2.11–5.85; p 0.001).

Conclusion

We found that race had an impact on both the type and risk of SPMs. Additionally, the likelihood of an SPM increases with the length of time between the two malignancies and the stage of the index malignancy.
Excess mortality in Poland during the first and second wave of the COVID-19 pandemic in 2020
Authors: Pikala Małgorzata , Krzywicka Małgorzata , Burzyńska Monika
Published: November 2022

Purpose

The aim of the study was to analyse excess deaths by major causes of death and associated changes in the mortality pattern of the Polish population in 2020 due to the impact of the COVID-19 pandemic.

Methods

The study used data on all deaths in Poland which occurred between 2010 and 2020 (N = 3,912,237). 10-year mortality trends for 2010–2019 were determined. An analysis of time trends has been carried out with joinpoint models and Joinpoint Regression Program. Based on the determined regression models, the number of deaths expected in 2020 and the number of excess deaths due to selected causes were calculated.

Results

The crude death rates of all-cause deaths increased from 2000 to 2019 at an average annual rate of 1% (p = 0.0007). The determined regression model revealed that the number of deaths in 2020 should have been 413,318 (95% CI: 411,252 to 415,385). In reality, 477,355 people died in Poland that year. The number of excess deaths was therefore 64,037 (15.5%). According to data from Statistics Poland the number of COVID-19-related deaths was 40,028, the number of non-COVID-19 deaths was 24,009. The largest percentage increase over the expected number of deaths was observed for suicide (12.5%), mental and behavioral disorders (7.2%) and diseases of circulatory system (5.9%). A lower than expected number of deaths was observed for malignant neoplasms (−3.2%) and transport accidents (−0.1%).

Conclusion

The difference between expected and observed non-COVID-19 deaths in 2020 indicates a need for further analysis of the causes of excess mortality.
Living alone is associated with a higher prevalence of psychiatric morbidity in a population-based cross-sectional study
Authors: Chen Te-Yu , Geng Jiun-Hung , Chen Szu-Chia , Lee Jia-In
Published: November 2022

Background

Living alone has been linked to poor mental health, however large-scale epidemiological studies on the association between living alone and psychiatric morbidity including depression and anxiety are lacking. The aim of this study was to investigate this issue in a large Taiwanese cohort.

Methods

In this cross-sectional study, we enrolled 121,601 volunteers from 29 community recruitment stations in Taiwan and divided them into two groups based on whether or not they lived alone. Psychiatric morbidity was defined as a Generalized Anxiety Disorder 2-item score ≥ 3, Patient Health Questionnaire 2-item score ≥ 3, or self-reported depression. Logistic regression was used to explore the associations between living alone and psychiatric morbidity.

Results

The participants who lived alone had a higher prevalence of psychiatric morbidity [odds ratio (OR) = 1.608, 95% confidence interval (CI) = 1.473 to 1.755] after adjusting for potential confounders. In a subgroup analysis, married subjects who lived alone and divorce/separation (OR = 2.013, 95% CI = 1.763 to 2.299) or widowing (OR = 1.750, 95% CI = 1.373 to 2.229) were more likely to have psychiatric morbidity than those who were married and not living alone.

Conclusions

Our findings suggest that living alone is a risk factor for psychiatric morbidity, especially for married subjects who live alone in concordance with divorce, separation, or the death of a spouse.