Miracle-dz/UniFAR-FTUs huggingface dataset:
Aging affects GABAergic function and calcium homeostasis in the mammalian central clock

Introduction Aging impairs the function of the central circadian clock in mammals, the suprachiasmatic nucleus (SCN), leading to a reduction in the output signal. The weaker timing signal from the SCN results in a decline in rhythm strength in many physiological functions, including sleep–wake patterns. Accumulating evidence suggests that the reduced amplitude of the SCN signal is caused by a decreased synchrony among the SCN neurons. The present study was aimed to investigate the hypothesis that the excitation/inhibition (E/I) balance plays a role in synchronization within the network. Methods Using calcium (Ca2+) imaging, the polarity of Ca2+ transients in response to GABA stimulation in SCN slices of old mice (20–24 months) and young controls was studied. Results We found that the amount of GABAergic excitation was increased, and that concordantly the E/I balance was higher in SCN slices of old mice when compared to young controls. Moreover, we showed an effect of aging on the baseline intracellular Ca2+ concentration, with higher Ca2+ levels in SCN neurons of old mice, indicating an alteration in Ca2+ homeostasis in the aged SCN. We conclude that the change in GABAergic function, and possibly the Ca2+ homeostasis, in SCN neurons may contribute to the altered synchrony within the aged SCN network.
The adoption and impacts of improved parboiling technology for rice value chain upgrading on the livelihood of women rice parboilers in Benin

Food insecurity and child malnutrition remain persistent problems in sub-Saharan Africa. Rice is a staple food for more than half of the world’s population. However, white rice is poor in micronutrients and records higher glycemic values compared to parboiled rice. An improved parboiling system called “Grain quality enhancer, Energy-efficient and durable Material” (GEM in short) allows the processing of quality rice with better physical and nutritional properties compared to traditional systems. This paper assessed the drivers and impact of the adoption of the GEM system on women’s livelihoods. A total of 822 rice women parboilers were randomly sampled and interviewed in Benin, in regions where the GEM system was introduced. We employed the endogenous switching regression model (ESR) to assess the impact of the GEM system. We found evidence that adoption of the GEM system increased women parboilers’ rice output rate (dehulling return), income and food security and reduced poverty. The impact of the GEM system is estimated at 14.38 kg of milled rice per 100 kg of paddy (21.46%), equivalent to US$ 7.25 of additional income (17.77%). A significantly lower poverty rate of 26% was found among households due to the adoption of the GEM system. These results are supported by women’s perceptions that the output rate, better nutritional value and reduction of broken rice during dehulling are major advantages of the improved parboiling system. Policy actions such as training of local fabricators and credit options are required for out-scaling and sustainability of the improved parboiling system.
Big Five personality traits and coping strategies of Italian university students during the COVID-19 pandemic first wave

Introduction Little is known about the role personality traits may have played for university students in diminishing and compensating for the negative impact of COVID-19 in its early phases, promoting adaptive coping. University students represent a population which was consistently obliged to follow social distance rules due to the early shift of many organizations from face-to-face to online learning. Therefore, it is worth exploring whether the Big Five traits acted as risk or protective factors after the outbreak of a disaster such as the COVID-19 pandemic for Italian university students. Methods We involved a sample of 2,995 university students who completed an online survey in March 2020. We measured the Big Five personality traits through the Big Five Inventory-2-XS and their coping strategies through the Robust—Pandemic Coping Scale. The latter assessed four COVID-19-related coping dimensions, namely Despair (e.g., including helplessness and feeling lack of control), Aversion (e.g., referring to oppositive strategies), Proactivity (e.g., comprising problem solving and information seeking), and Adjustment (e.g., concerning reappraisal and assertiveness). Results Preliminarily, two Linear Mixed Models indicated that university students had higher scores in Conscientiousness, followed by Open-Mindedness, and then Agreeableness. These three traits were, in turn, higher than Extraversion and Negative Emotionality, which did not differ among them. Concerning coping, university students reacted more frequently utilizing adaptive strategies (with Proactivity used more frequently than Adjustment) rather than maladaptive strategies (with Despair higher than Aversion). A Path Analysis examining the relations between the Big Five traits and the four coping dimensions showed that Negative Emotionality can be considered as a risk factor, and that Agreeableness, Conscientiousness, and Open-Mindedness can be conceptualized as protective factors. More interestingly, we found that Extraversion entailed both a risk and a protective role for Italian university students after the outbreak of the COVID-19 pandemic. Discussion Notwithstanding limitations, these findings can be the basis for developing disaster preparation and prevention actions, aiming at promoting students’ positive coping towards current and future disasters.
Respiratory Complex I Regulates Dendritic Cell Maturation in Explant Model of Human Tumor Immune Microenvironment

Combining cytotoxic chemotherapy or novel anticancer drugs with T-cell modulators holds great promise in treating advanced cancers. However, the response varies depending on the tumor immune microenvironment (TIME). Therefore, there is a clear need for pharmacologically tractable models of the TIME to dissect its influence on mono- and combination treatment response at the individual level. Here we establish a Patient-Derived Explant Culture (PDEC) model of breast cancer, which retains the immune contexture of the primary tumor, recapitulating cytokine profiles and CD8+ T cell cytotoxic activity. We explored the immunomodulatory action of a synthetic lethal BCL2 inhibitor venetoclax + metformin drug combination ex vivo, discovering metformin cannot overcome the lymphocyte-depleting action of venetoclax. Instead, metformin promotes dendritic cell maturation through inhibition of mitochondrial complex I, increasing their capacity to co-stimulate CD4+ T cells and thus facilitating anti-tumor immunity. Our results establish PDECs as a feasible model to identify immunomodulatory functions of anticancer drugs in the context of patient-specific TIME.
Gut microbiome profiling of neonates using Nanopore MinION and Illumina MiSeq sequencing

This study aimed to evaluate the difference in gut microbiomes between preterm and term infants using third-generation long-read sequencing (Oxford Nanopore Technologies, ONT) compared with an established gold standard, Illumina (second-generation short-read sequencing). A total of 69 fecal samples from 51 term (T) and preterm (P) infants were collected at 7 and 28 days of life. Gut colonization profiling was performed by 16S rRNA gene sequencing using ONT. We used Illumina to validate and compare the patterns in 13 neonates. Using bioinformatic analysis, we identified features that differed between P and T. Both T1 and P1 microbiomes were dominated by Firmicutes (Staphylococcus and Enterococcus), whereas sequentially showed dominant transitions to Lactobacillus (p < 0.001) and Streptococcus in T2 (p = 0.001), and pathogenic bacteria (Klebsiella) in P2 (p = 0.001). The abundance of beneficial bacteria (Bifidobacterium and Lactobacillus) increased in T2 (p = 0.026 and p < 0.001, respectively). These assignments were correlated with the abundance at the species-level. Bacterial α-diversity increased in T (p = 0.005) but not in P (p = 0.156), and P2 showed distinct β-diversity clustering than T2 (p = 0.001). The ONT reliably identified pathogenic bacteria at the genus level, and taxonomic profiles were comparable to those identified by Illumina at the genus level. This study shows that ONT and Illumina are highly correlated. P and T had different microbiome profiles, and the α- and β-diversity varied. ONT sequencing has potential for pathogen detection in neonates in clinical settings.
Adjuvant capecitabine in triple negative breast cancer patients with residual disease after neoadjuvant treatment: real-world evidence from CaRe, a multicentric, observational study

Background In triple negative breast cancer patients treated with neoadjuvant chemotherapy, residual disease at surgery is the most relevant unfavorable prognostic factor. Current guidelines consider the use of adjuvant capecitabine, based on the results of the randomized CREATE-X study, carried out in Asian patients and including a small subset of triple negative tumors. Thus far, evidence on Caucasian patients is limited, and no real-world data are available. Methods We carried out a multicenter, observational study, involving 44 oncologic centres. Triple negative breast cancer patients with residual disease, treated with adjuvant capecitabine from January 2017 through June 2021, were recruited. We primarily focused on treatment tolerability, with toxicity being reported as potential cause of treatment discontinuation. Secondarily, we assessed effectiveness in the overall study population and in a subset having a minimum follow-up of 2 years. Results Overall, 270 patients were retrospectively identified. The 50.4% of the patients had residual node positive disease, 7.8% and 81.9% had large or G3 residual tumor, respectively, and 80.4% a Ki-67 >20%. Toxicity-related treatment discontinuation was observed only in 10.4% of the patients. In the whole population, at a median follow-up of 15 months, 2-year disease-free survival was 62%, 2 and 3-year overall survival 84.0% and 76.2%, respectively. In 129 patients with a median follow-up of 25 months, 2-year disease-free survival was 43.4%, 2 and 3-year overall survival 78.0% and 70.8%, respectively. Six or more cycles of capecitabine were associated with more favourable outcomes compared with less than six cycles. Conclusion The CaRe study shows an unexpectedly good tolerance of adjuvant capecitabine in a real-world setting, although effectiveness appears to be lower than that observed in the CREATE-X study. Methodological differences between the two studies impose significant limits to comparability concerning effectiveness, and strongly invite further research.
Effects of excitatory transcranial magnetic stimulation over the different cerebral hemispheres dorsolateral prefrontal cortex for post-stroke cognitive impairment: a systematic review and meta-analysis

Background Post-stroke cognitive impairment (PSCI) is a significant health concern. Transcranial magnetic stimulation (TMS) is considered a promising rehabilitation therapy for improving cognition, and the effects of excitatory TMS on PSCI have received much attention in recent years. However, the effects of different cerebral hemispheres on excitatory TMS treatment of cognitive impairment have not been studied. This review aimed to study the effects of excitatory TMS over the dorsolateral prefrontal cortex (DLPFC) of different cerebral hemispheres on the cognitive function of patients with PSCI. Methods Literature published in PubMed, Web of Science, Embase, Cochrane Library, Scopus, and Wiley from inception to September 30, 2022, were searched. Two researchers independently performed literature screening, data extraction, and quality assessment. Furthermore, we conducted a meta-analysis using RevMan software (version 5.4) and rated the strength of evidence using GRADEpro. Results A total of 19 studies were included in this meta-analysis. The results showed that excitatory TMS over the left hemisphere DLPFC was significantly better in improving global cognition (SMD = 2.26, 95% CI 1.67–2.86, P < 0.00001; vs. SMD = 2.53, 95% CI 1.86–3.20, P < 0.00001), memory (SMD = 1.29, 95% CI 0.72–1.87, P < 0.0001), attention (SMD = 2.32, 95% CI 1.64–3.01, P < 0.00001), executive (SMD = 0.64, 95% CI 0.21–1.07, P = 0.004), P300 latency (SMD = 2.69, 95% CI 2.13–3.25, P < 0.00001), and depression (SMD = 0.95, 95% CI 0.26–1.63, P = 0.007) than that of the control group, but the effect on improving activities of daily living (ADL) was unclear (P = 0.03 vs. P = 0.17). Subgroup analysis further showed that excitatory TMS over the right hemisphere DLPFC was effective in improving the global cognition of PSCI patients (P < 0.00001), but the stimulation effect over the ipsilateral hemisphere DLPFC was unclear (P = 0.11 vs. P = 0.003). Additionally, excitatory TMS over the ipsilateral hemisphere DLPFC showed no statistical difference in improving ADL between the two groups (P = 0.25). Conclusions Compared to other hemispheric sides, excitatory TMS over the left hemisphere DLPFC was a more effective stimulation area, which can significantly improved the global cognitive function, memory, attention, executive, P300 latency, and depression in patients with PSCI. There was no apparent therapeutic effect on improving activities of daily living (ADL). In the future, more randomized controlled trials with large-sample, high quality, and follow-up are necessary to explore a usable protocol further. Systematic review registration https://www.crd. york.ac. uk/PROSPERO/, identifier: CRD42022369096.
Peripheral skin cooling during hyper-gravity: hemodynamic reactions

Introduction: Orthostatic dysregulation occurs during exposure to an increased gravitational vector and is especially common upon re-entering standard Earth gravity (1 g) after an extended period in microgravity (0 g). External peripheral skin cooling (PSC) has recently been described as a potent countermeasure against orthostatic dysregulation during heat stress and in lower body negative pressure (LBNP) studies. We therefore hypothesized that PSC may also be an effective countermeasure during hyper-gravity exposure (+Gz). Methods: To investigate this, we designed a randomized short-arm human centrifuge (SAHC) experiment (“Coolspin”) to investigate whether PSC could act as a stabilizing factor in cardiovascular function during +Gz. Artificial gravity between +1 g and +4 g was generated by a SAHC. 18 healthy male volunteers completed two runs in the SAHC. PSC was applied during one of the two runs and the other run was conducted without cooling. Each run consisted of a 10-min baseline trial followed by a +Gz step protocol marked by increasing g-forces, with each step being 3 min long. The following parameters were measured: blood pressure (BP), heart rate (HR), stroke volume (SV), total peripheral resistance (TPR), cardiac output (CO). Furthermore, a cumulative stress index for each subject was calculated. Results: +Gz led to significant changes in primary as well as in secondary outcome parameters such as HR, SV, TPR, CO, and BP. However, none of the primary outcome parameters (HR, cumulative stress-index, BP) nor secondary outcome parameters (SV, TPR, CO) showed any significant differences—whether the subject was cooled or not cooled. Systolic BP did, however, tend to be higher amongst the PSC group. Conclusion: In conclusion, PSC during +Gz did not confer any significant impact on hemodynamic activity or orthostatic stability during +Gz. This may be due to lower PSC responsiveness of the test subjects, or an insufficient level of body surface area used for cooling. Further investigations are warranted in order to comprehensively pinpoint the exact degree of PSC needed to serve as a useful countermeasure system during +Gz.
Hedonic and eudaimonic well-being for sustainable development in university students: personality traits or acceptance of change?

Introduction The psychology of sustainability and sustainable development aims to contribute to the establishment of a culture of sustainability regarding the 2030 Agenda and its 17 sustainable development goals. Methods In this framework, this study examined the associations between acceptance of change and well-being (hedonic and eudaimonic sides), controlling for the effects of personality traits, in 284 Italian university students. Results Acceptance of change explained additional variance over personality traits regarding hedonic and eudaimonic well-being. Discussion Acceptance of change could thus represent a promising well-being resource from the perspective of strength-based prevention, opening future perspectives to face the challenges of sustainable development, particularly concerning Goal 3 of the 2030 Agenda: “Good health and well-being. ”
Long-term trends of HIV/AIDS incidence in India: an application of joinpoint and age–period–cohort analyses: a gendered perspective

Background Monitoring the transmission patterns of human immunodeficiency virus (HIV) in a population is fundamental for identifying the key population and designing prevention interventions. In the present study, we aimed to estimate the gender disparities in HIV incidence and the age, period, and cohort effects on the incidence of HIV in India for identifying the predictors that might have led to changes in the last three decades. Data and methods This study utilizes data from the Global Burden of Disease Study for the period 1990–2019. The joinpoint regression analysis was employed to identify the magnitude of the changes in age-standardized incidence rates (ASIRs) of HIV. The average annual percentage changes in the incidence were computed, and the age–period–cohort analysis was performed. Results A decreasing trend in the overall estimates of age-standardized HIV incidence rates were observed in the period 1990–2019. The joinpoint regression analysis showed that the age-standardized incidence significantly declined from its peak in 1997 to 2019 (38.0 and 27.6 among males and females per 100,000 in 1997 to 5.4 and 4.6, respectively, in 2019). The APC was estimated to be 2.12 among males and 1.24 among females for the period 1990–2019. In recent years, although the gender gap in HIV incidence has reduced, females were observed to bear a proportionately higher burden of HIV incidence. Age effect showed a decline in HIV incidence by 91.1 and 70.1% among males and females aged between 15–19 years and 75–79 years. During the entire period from 1990–1994 to 2015–2019, the RR of HIV incidence decreased by 36.2 and 33.7% among males and females, respectively. Conclusion India is experiencing a decline in new HIV infections in recent years. However, the decline is steeper for males than for females. Findings highlight the necessity of providing older women and young women at risk with effective HIV prevention. This study emphasizes the need for large-scale HIV primary prevention efforts for teenage girls and young women.
Women's experiences with implementation of the physiologic birth program in Iran: a qualitative content analysis study

Introduction Increased rate of caesarean section (CS) without medical indication is a global concern. According to the guidelines of the World Health Organization (WHO), the physiologic birth program is one of the strategies for reducing the rate of unnecessary caesarean sections. The aim of this study is to explain women's experiences with the implementation of the physiologic birth program in Iran. Materials and methods This study is a part of a mixed-method study involving 15 targeted semi-structured interviews individually conducted with women attending physiologic birth classes between January 2022 and June 2022. Interviews continued until data saturation was achieved. Data were analyzed using conventional content analysis approach based on the criteria proposed by Graneheim and Lundman, using MAXQDA10 software. Results Analysis of the findings of the study led to the emergence of 2 themes, 4 categories, and 10 subcategories. The first theme was the positive experiences of the women (“satisfaction with pregnancy” and “making the childbirth process pleasant”), and the second theme was their negative experiences with physiologic birth (“challenges and limitation of physiologic birth program” and “lack of high-quality obstetric services in the public health system”). Conclusion The results of this study showed that childbirth preparation classes reduced women's fear and stress and enhanced their positive attitude toward vaginal delivery by preparing them for childbirth. Also, effective communication with midwives and their support along with efficient implementation of physiologic birth techniques led to successful pain management and satisfaction with the birth process. Policymakers should implement strategies to remove limitations and make this program accessible to all women.
Treatment of loco-regional recurrence of nasopharyngeal carcinoma in a non-endemic area: oncologic outcomes, morbidity, and proposal of a prognostic nomogram

Introduction The study assessed outcomes and toxicities of different treatment modalities for local and/or regional recurrent nasopharyngeal carcinoma (NPC) in a non-endemic area. Methods Patients treated with curative intent for recurrent NPC with salvage surgery, photon-based radiotherapy, proton therapy (PT), with or without chemotherapy, at different Italian referral centers between 1998 and 2020 were included. Adverse events and complications were classified according to the Common Terminology Criteria for Adverse Events. Characteristics of the patients, tumors, treatments, and complications are presented along with uni- and multivariate analysis of prognostic factors. A survival predictive nomogram is also provided. Results A total of 140 patients treated from 1998 to 2020 were retrospectively assessed. Cases with lower age, comorbidity rate, stage, and shorter disease-free interval (DFI) preferentially underwent endoscopic surgery. More advanced cases underwent re-irradiation, fairly distributed between photon-based radiotherapy and PT. Age and DFI were independent factors influencing overall survival. No independent prognostic effect of treatment modality was observed. No significant difference in the morbidity profile of treatments was observed, with 40% of patients experiencing at least one adverse event classified as G3 or higher. Conclusion Recurrent NPC in a non-endemic area has dissimilar aspects compared to its endemic counterpart, suggesting the need for further studies that can guide the choice of the best treatment modality.