Miracle-dz/UniFAR-FTUs huggingface dataset:
Age-related hearing loss is associated with alterations in temporal envelope processing in different neural generators along the auditory pathway

People with age-related hearing loss suffer from speech understanding difficulties, even after correcting for differences in hearing audibility. These problems are not only attributed to deficits in audibility but are also associated with changes in central temporal processing. The goal of this study is to obtain an understanding of potential alterations in temporal envelope processing for middle-aged and older persons with and without hearing impairment. The time series of activity of subcortical and cortical neural generators was reconstructed using a minimum-norm imaging technique. This novel technique allows for reconstructing a wide range of neural generators with minimal prior assumptions regarding the number and location of the generators. The results indicated that the response strength and phase coherence of middle-aged participants with hearing impairment (HI) were larger than for normal-hearing (NH) ones. In contrast, for the older participants, a significantly smaller response strength and phase coherence were observed in the participants with HI than the NH ones for most modulation frequencies. Hemispheric asymmetry in the response strength was also altered in middle-aged and older participants with hearing impairment and showed asymmetry toward the right hemisphere. Our brain source analyses show that age-related hearing loss is accompanied by changes in the temporal envelope processing, although the nature of these changes varies with age.
Quantitative susceptibility mapping as an imaging biomarker for Alzheimer’s disease: The expectations and limitations

Alzheimer’s disease (AD) is the most common type of dementia and a distressing diagnosis for individuals and caregivers. Researchers and clinical trials have mainly focused on β-amyloid plaques, which are hypothesized to be one of the most important factors for neurodegeneration in AD. Meanwhile, recent clinicopathological and radiological studies have shown closer associations of tau pathology rather than β-amyloid pathology with the onset and progression of Alzheimer’s symptoms. Toward a biological definition of biomarker-based research framework for AD, the 2018 National Institute on Aging–Alzheimer’s Association working group has updated the ATN classification system for stratifying disease status in accordance with relevant pathological biomarker profiles, such as cerebral β-amyloid deposition, hyperphosphorylated tau, and neurodegeneration. In addition, altered iron metabolism has been considered to interact with abnormal proteins related to AD pathology thorough generating oxidative stress, as some prior histochemical and histopathological studies supported this iron-mediated pathomechanism. Quantitative susceptibility mapping (QSM) has recently become more popular as a non-invasive magnetic resonance technique to quantify local tissue susceptibility with high spatial resolution, which is sensitive to the presence of iron. The association of cerebral susceptibility values with other pathological biomarkers for AD has been investigated using various QSM techniques; however, direct evidence of these associations remains elusive. In this review, we first briefly describe the principles of QSM. Second, we focus on a large variety of QSM applications, ranging from common applications, such as cerebral iron deposition, to more recent applications, such as the assessment of impaired myelination, quantification of venous oxygen saturation, and measurement of blood– brain barrier function in clinical settings for AD. Third, we mention the relationships among QSM, established biomarkers, and cognitive performance in AD. Finally, we discuss the role of QSM as an imaging biomarker as well as the expectations and limitations of clinically useful diagnostic and therapeutic implications for AD.
Defining the profile of students with low academic achievement: A cross-country analysis through PISA 2018 data

The explanation of underachievement and the search for its associated factors have been of constant interest in educational research. In this regard, the number of variables that have been involved in its description and explanation has increased over the years, as has the number of studies at an international level on this topic. Although much research has focused on identifying the personal, family, and school aspects that exert the greatest influence on students’ low academic performance, the literature shows the need to study the differential effects of said variables according to the countries in which the studies are conducted. The objective of this article is therefore to analyse cross-national differences in the effect of personal, family, and school characteristics on students’ academic underachievement based on data derived from the Programme for International Student Assessment (PISA) 2018. Furthermore, it aims to identify the profile that characterises students with the lowest academic performance and to estimate the importance of the selected variables in explaining low achievement across countries. To reach these goals, the multivariate technique of decision trees through the binary CART (Classification and Regression Trees) algorithm was used, allowing the estimation of both a global model and nine specific models for each of the selected countries. The results show that, despite slight differences between the countries analysed, the variables that define the general profile of students with the lowest achievement and which have shown the strongest predictive capacity for low performance are mainly linked to the students themselves. These variables are followed in importance by family aspects, which present great differences between the territories that compose the sample. Finally, teacher and school variables have shown to have a low explanatory capacity in this study. It can therefore be concluded that, although personal characteristics continue to be those that best explain academic performance, a series of contextual variables, especially related to families, appear to influence academic achievement differentially and may even hide or cancel out certain personal characteristics.
Quantitative ESG disclosure and divergence of ESG ratings

Over the past decade, sustainable finance has been a topic of burgeoning significance for investors, and ESG ratings have become commonly used to implement ESG investment strategies in practice. Strikingly, it is widely documented in both academic literature and investment practices that ESG ratings of a given firm can be extremely different across rating providers. However, despite the disagreement in ESG ratings being subject to a lot of criticism, only few studies have examined the sources and determinants of rating divergence. This study examines whether quantitative ESG disclosure is conducive to rating convergence among agencies. Based on ESG rating data of Chinese A-share listed companies, the author finds that greater quantitative ESG disclosure, especially disclosure on environmental and social pillars, results in greater divergence of ESG ratings. When employing a difference-in-differences design with a quasi-experiment of disclosure guidance introduced by Hong Kong Exchange, the results show that if ESG disclosure is standardized and comparable, more numerical information reduces agencies' rating disagreement instead. Further analyses show that the lack of agreement is related to a low rating in the future. The author also finds that the effect of quantified ESG disclosure on rating divergence is more pronounced when firms are single businesses rather than diversified businesses with poor ESG performance rather than good ESG performance. The results are robust to alternative measures of ESG rating divergence, alternative sample, two-way clustering, and additional control variables. Taken together, the results indicate that quantitative ESG disclosure degenerates rating disagreement.
A Nutrition-Related Factor-Based Risk Stratification for Exploring the Clinical Benefits in the Treatment of Patients With Locally Advanced Esophageal Squamous Cell Carcinoma Receiving Definitive Chemoradiotherapy: A Retrospective Cohort Study

Objective No study has reported the risk stratification of BMI and PNI in patients with locally advanced esophageal squamous cell carcinoma (ESCC) undergoing definitive chemoradiotherapy (dCRT). This study aimed to construct a risk stratification to guide the treatment of ESCC following dCRT. Methods A total of 1,068 patients with locally advanced ESCC who received dCRT were retrospectively analyzed. The impacts of clinicopathological factors on overall survival (OS) and progression-free survival (PFS) were analyzed. Besides, the novel prognostic indices of pre-therapeutic nutritional index (PTNI) and prognostic index (PI) were developed. Results The median follow-up period of OS and PFS were 22.9 and 17.4 months, respectively. The high body mass index (BMI) group had better 5-year OS and PFS (36.4 and 34.0%) than the low BMI group (18.8 and 17.2%). The high prognostic nutritional index (PNI) group also had better 5-year OS and PFS (33.4 and 30.9%) than the low PNI group (17.5 and 17.2%). Multivariate Cox regression analysis showed that BMI and PNI were independent prognostic factors for OS and PFS. Based on nutritional indices, patients were categorized into the low-risk (PTNI = 1), medium-risk (PTNI = 2), and high-risk (PTNI = 3) groups with 5-year OS rates of 38.5, 18.9, 17.5%, respectively (p < 0.001) and 5-year PFS rates of 35.8, 17.6, 16.8%, respectively (p < 0.001). Besides, we also constructed a prognostic index (PI) for OS and PFS which was calculated based on statistically significant factors for predicting OS and PFS. The results revealed that the high-risk group had worse OS and PFS than the low-risk group (p < 0.001). Finally, RCS analysis demonstrated a non-linear relationship between the PNI, BMI, and survival for patients with ESCC. The death hazard of PNI and BMI sharply decreased to 41.8 and 19.7. Conclusion The decreased pre-therapeutic BMI and PNI levels were associated with a worse survival outcome. BMI and PNI are readily available and can be used to stratify risk factors for locally advanced ESCC patients undergoing dCRT. The novel risk stratification may help to evaluate patients’ pre-therapeutic status and guide dCRT for locally advanced ESCC patients.
Multifunctional regulation of VAMP3 in exocytic and endocytic pathways of RBL-2H3 cells

Mast cells (MCs) are inflammatory cells involved in allergic reactions. Crosslinking of the high-affinity receptor for IgE (FcϵRI) with multivalent antigens (Ags) induces secretory responses to release various inflammatory mediators. These responses are largely mediated by soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). Vesicle-associated membrane protein 3 (VAMP3) is a vesicular-SNARE that interacts with targeted SNARE counterparts, driving the fusion of MC secretory granules with the membrane and affecting subsequent assembly of the plasma membrane. However, the role of VAMP3 in FcϵRI-mediated MC function remains unclear. In this study, we comprehensively examined the role of VAMP3 and the molecular mechanisms underlying VAMP3-mediated MC function upon FcϵRI activation. VAMP3 shRNA transduction considerably decreased VAMP3 expression compared with non-target shRNA-transduced (NT) cells. VAMP3 knockdown (KD) cells were sensitized with an anti-DNP IgE antibody and subsequently stimulated with Ag. The VAMP3 KD cells showed decreased degranulation response upon Ag stimulation. Next, we observed intracellular granule formation using CD63-GFP fluorescence. The VAMP3 KD cells were considerably impaired in their capacity to increase the size of granules when compared to NT cells, suggesting that VAMP3 mediates granule fusion and therefore promotes granule exocytosis in MCs. Analysis of FcϵRI-mediated activation of signaling events (FcϵRI, Lyn, Syk, and intracellular Ca2+ response) revealed that signaling molecule activation was enhanced in VAMP3 KD cells. We also found that FcϵRI expression on the cell surface decreased considerably in VAMP3 KD cells, although the amount of total protein did not vary. VAMP3 KD cells also showed dysregulation of plasma membrane homeostasis, such as endocytosis and lipid raft formation. The difference in the plasma membrane environment in VAMP3 KD cells might affect FcϵRI membrane dynamics and the subsequent signalosome formation. Furthermore, IgE/Ag-mediated secretion of TNF-α and IL-6 is oppositely regulated in the absence of VAMP3, which appears to be attributed to both the activation of FcϵRI and defects in VAMP3-mediated membrane fusion. Taken together, these results suggest that enhanced FcϵRI-mediated signal transduction in VAMP3 KD cells occurs due to the disruption of plasma membrane homeostasis. Hence, a multifunctional regulation of VAMP3 is involved in complex secretory responses in MCs.
Quantitative susceptibility mapping and blood neurofilament light chain differentiate between parkinsonian disorders

Objectives We employed quantitative susceptibility mapping (QSM) to assess iron deposition in parkinsonian disorders and explored whether combining QSM values and neurofilament light (NfL) chain levels can improve the accuracy of distinguishing Parkinson’s disease (PD) from multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Materials and methods Forty-seven patients with PD, 28 patients with MSA, 18 patients with PSP, and 28 healthy controls (HC) were enrolled, and QSM data were reconstructed. Susceptibility values in the bilateral globus pallidus (GP), putamen (PUT), caudate nucleus (CN), red nucleus (RN), substantia nigra (SN), and dentate nucleus (DN) were obtained. Plasma NfL levels of 47 PD, 18 MSA, and 14 PSP patients and 22 HC were measured by ultrasensitive Simoa technology. Results The highest diagnostic accuracy distinguishing MSA from PD patients was observed with increased susceptibility values in CN (AUC: 0.740). The susceptibility values in RN yielded the highest diagnostic performance for distinguishing PSP from PD patients (AUC: 0.829). Plasma NfL levels were significantly higher in the MSA and PSP groups than in PD and HC groups. Combining the susceptibility values in the RN and plasma NfL levels improved the diagnostic performance for PSP vs. PD (AUC: 0.904), whereas plasma NfL levels had higher diagnostic accuracy for MSA vs. PD (AUC: 0.877). Conclusion The exploratory study indicates different patterns of iron accumulation in deep gray matter nuclei in Parkinsonian disorders. Combining QSM values with NfL levels may be a promising biomarker for distinguishing PSP from PD, whereas plasma NfL may be a reliable biomarker for differentiating MSA from PD. QSM and NfL measures appeared to have low accuracy for separating PD from controls.
Efficacy and safety of atezolizumab plus bevacizumab combined with hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma

Background Atezolizumab plus bevacizumab has been proved to have promising antitumor activity and tolerable safety in patients with unresectable hepatocellular carcinoma (HCC). Hepatic arterial infusion chemotherapy (HAIC) also demonstrated high response rates and favorable survival for patients with advanced HCC. This study aimed to explore the preliminary clinical efficacy and safety of atezolizumab plus bevacizumab combined with HAIC for patients with treatment-naive advanced HCC. Methods Between October 2020 and September 2021, patients with advanced HCC who initially received atezolizumab plus bevacizumab combined with HAIC of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) from three hospitals in China were reviewed for eligibility. The efficacy was evaluated by tumor response rate and survival, and the safety was evaluated by the frequency of key adverse events (AEs). Results In total, 52 eligible patients with advanced HCC who received triple therapy were included in this study. The objective response rates (ORRs) based on mRECIST and RECIST1.1 criteria were 67.3% and 44.2%, respectively. The median progression-free survival (PFS) of patients was 10.6 months (95% CI, 8.37–13.8), and the overall survival (OS) was not reached. Extrahepatic metastasis was an independent risk factor associated with PFS. All AEs were controlled and no treatment-related deaths occurred. Conclusion Atezolizumab plus bevacizumab combined with HAIC-FOLFOX had a significant therapeutic effect and manageable AEs in patients with advanced HCC, which may be a potential treatment option for advanced HCC.
Perinatal depression screening and prevention: Descriptive findings from a multicentric program in the South of Italy

Introduction Perinatal depression (PD) is a cluster of clinical depressive symptoms occurring globally during pregnancy or after childbirth, with a prevalence of 11.9%. Risk factors for PD among pregnant women may include personality traits of neuroticism, low personal resilience, higher anxiety, avoidance in close relationships, as well as dysfunctional coping strategies. Methods We report on descriptive findings of a screening/prevention program aimed to detect depressive symptoms and associated risk factors in a large sample of women (N = 1,664) accessing the gynecological departments of the Regione Puglia (South of Italy) from July to November 2020. Pregnant women were assessed in their third trimester of pregnancy (T0), after childbirth (T1), and those at risk for PD within 1 year from delivery (T2–T4); The Edinburgh Postnatal Depression Scale (EPDS) has been employed for the screening of PD over time as well as other standardized measures for neuroticism, resilience, coping strategies, and quality of life. Results Of 1,664, n = 1,541 were tested at T1, and 131 scored ≥ 12 at EPDS (14.6 ± 2.95), showing a higher risk for PD. They were followed over time at 1, 6, and 12 months after childbirth (T2–T4), and 15 of them scored ≥ 12 (EPDS) at T4. Women with a higher risk of PD also reported higher levels of neuroticism, lower levels of personal resilience, more anxiety and avoidance in close relationships, higher employment of dysfunctional coping strategies (e.g., denial, self-blame, etc.), and lower quality of life (0.0008 < all p < 0.0001). Conclusion This study confirmed the benefit of screening programs for the early detection of PD among pregnant women. We may suggest a set of risk factors to be considered in the clinical assessment of PD risk as well as the promotion of similar programs to improve depressive outcomes and pathways to care for PD on the basis of a more accurate assessment and referral.
A transmembrane protein family gene signature for overall survival prediction in osteosarcoma

The transmembrane (TMEM) protein family is constituted by a large number of proteins that span the lipid bilayer. Dysregulation of TMEM protein genes widely occurs and is associated with clinical outcomes of patients with multiple tumors. Nonetheless, the significance of TMEM genes in the prognosis prediction of patients with osteosarcoma remains largely unclear. Here, we comprehensively analyzed TMEM protein family genes in osteosarcoma using public resources and bioinformatics methods. Prognosis-related TMEM protein family genes were identified by the univariate Cox regression analysis and were utilized to construct a signature based on six TMEM protein family genes (TMEM120B, TMEM147, TMEM9B, TMEM8A, TMEM59, and TMEM39B) in osteosarcoma. The prognostic signature stratified patients into high- and low-risk groups, and validation in the internal and external cohorts confirmed the risk stratification ability of the signature. Functional enrichment analyses of differentially expressed genes between high- and low-risk groups connected immunity with the prognostic signature. Moreover, we found that M2 and M0 macrophages were the most abundant infiltrated immune cell types in the immune microenvironment, and samples of the high-risk group showed a decreased proportion of M2 macrophages. Single-sample gene set enrichment analysis revealed that the scores of neutrophils and Treg were markedly lower in the high-risk group than these in the low-risk group in The Cancer Genome Atlas and GSE16091 cohorts. As for the related immune functions, APC co-inhibition and cytolytic activity exhibited fewer active levels in the high-risk group than that in the low-risk group in both cohorts. Of the six TMEM genes, the expression of TMEM9B was lower in the high-risk group than in the low-risk group and was positively associated with the overall survival of osteosarcoma patients. In conclusion, our TMEM protein family gene-based signature is a novel and clinically useful prognostic biomarker for osteosarcoma patients, and TMEM9B might be a potential therapeutic target in osteosarcoma.
Latent autoimmune diabetes in adults: a focus on β-cell protection and therapy

Latent autoimmune diabetes in adults (LADA) is a heterogeneous disease sharing some phenotypic, genetic, and immunological features with both type 1 and 2 diabetes. Patients with LADA have a relatively slow autoimmune process and more residual islet β-cell function at onset, allowing a time window to protect residual islet β cells and delay or inhibit disease progression. It is crucial to discover various heterogeneous factors affecting islet β-cell function for precise LADA therapy. In this review, we first describe the natural history of LADA. Thereafter, we summarize β-cell function-related heterogeneous factors in LADA, including the age of onset, body mass index, genetic background, and immune, lifestyle, and environmental factors. In parallel, we evaluate the impact of current hypoglycemic agents and immune intervention therapies for islet β-cell protection. Finally, we discuss the opportunities and challenges of LADA treatment from the perspective of islet β-cell function protection.