Miracle-dz/UniFAR-FTUs huggingface dataset:
Sirtuins and Neuropeptide y downregulation in Flinders Sensitive Line Rat Model of Depression.

OBJECTIVE Since the NAD+-dependent histone deacetylases sirtuin-1 (SIRT1) and sirtuin-2 (SIRT2) are critically involved in epigenetics, endocrinology and immunology and affect the longevity in model organisms, we investigated their expression in brains of 3 month old and 14-15 month old rat model of depression Flinders Sensitive Line (FSL) and control Flinders Resistant Line (FRL) rats. In view of the dysregulated NPY system in depression we also studied NPY in young and old FSL to explore the temporal trajectory of depressive-like-ageing interaction. METHODS Sirt1, Sirt2 and Npy mRNA were determined using qRT-PCR in prefrontal cortex (PFC) from young and old FSL and FRL, and in hippocampi from young FSL and FRL. RESULTS PFC. Sirt1 expression was decreased in FSL (p=0.001). An interaction between age and genotype was found (p=0.032); young FSL had lower Sirt1 with respect to both age (p=0.026) and genotype (p=0.001). Sirt2 was lower in FSL (p=0.003). Npy mRNA was downregulated in FSL (p=0.001) but did not differ between the young and old rat groups. Hippocampus.Sirt1 was reduced in young FSL compared to young FRL (p=0.005). There was no difference in Sirt2 between FSL and FRL. Npy levels were decreased in hippocampus of young FSL compared to young FRL (p=0.003). Effects of ageing could not be investigated due to loss of samples. CONCLUSIONS i. This is the first demonstration that SIRT1 and SIRT2 are changed in brain of FSL, a rat model of depression ; ii. The changes are age dependent; iii. Sirtuins are potential targets for treatment of age-related neurodegenerative diseases.
Phenotypic plasticity drives phenological changes in a Mediterranean blue tit population

Earlier phenology induced by climate change, such as the passerines' breeding time, is observed in many natural populations. Understanding the nature of such changes is key to predict the responses of wild populations to climate change. Genetic changes have been rarely investigated for laying date, though it has been shown to be heritable and under directional selection, suggesting that the trait could evolve. In a Corsican blue tit population, the birds' laying date has significantly advanced over 40 years, and we here determine whether this response is of plastic or evolutionary origin, by comparing the predictions of the breeder's and the Robertson‐Price (STS) equations, to the observed genetic changes. We compare the results obtained for two fitness proxies (fledgling and recruitment success), using models accounting for their zero inflation. Because the trait appears heritable and under directional selection, the breeder's equation predicts that genetic changes could drive a significant part of the phenological change observed. We, however, found that fitness proxies and laying date are not genetically correlated. The STS, therefore, predicts no evolution of the breeding time, predicting correctly the absence of trend in breeding values. Our results also emphasize that when investigating selection on a plastic trait under fluctuating selection, part of the fitness‐trait phenotypic covariance can be due to within individual covariance. In the case of repeated measurements, splitting within and between individual covariance can shift our perspective on the actual intensity of selection over multiple selection episodes, shedding light on the potential for the trait to evolve.
Islet cell encapsulation – Application in diabetes treatment

In this minireview, we briefly outline the hallmarks of diabetes, the distinction between type 1 and type 2 diabetes, the global incidence of diabetes, and its associated comorbidities. The main goal of the review is to highlight the great potential of encapsulated pancreatic islet transplantation to provide a cure for type 1 diabetes. Following a short overview of the different approaches to islet encapsulation, we provide a summary of the merits and demerits of each approach of the encapsulation technology. We then discuss various attempts to clinical translation with each model of encapsulation as well as the factors that have mitigated the full clinical realization of the promise of the encapsulation technology, the progress that has been made and the challenges that remain to be overcome. In particular, we pay significant attention to the emerging strategies to overcome these challenges. We believe that these strategies to enhance the performance of the encapsulated islet constructs discussed herein provide good platforms for additional work to achieve successful clinical translation of the encapsulated islet technology.
(Dis)Connecting Through COVID-19: Experiences of Older Persons in the Context of a Volunteer–Client Relationship

Abstract The coronavirus (COVID-19) pandemic and mandated physical distancing requirements significantly impacted volunteer programs for older persons with many long-standing programs either ceasing altogether or pivoting to connecting through virtual technologies. In this study, we collected qualitative interview data from 23 clients and 33 volunteers to investigate their experiences during the COVID-19 pandemic and the effects on the volunteer–client relationship. Three themes were identified: pandemic emotions, negotiating social interactions, and growing through the COVID-19 pandemic. These findings provide important insights into the experiences of hospice organizations and their volunteers and clients during the COVID 19 pandemic, further highlighting the importance of acknowledging both older persons’ vulnerability and their resilience, of building in compassionate community approaches to care, and of finding innovative ways to foster volunteer–client relationships during times when physical visiting is not possible.
Diet quality and disease activity in rheumatoid arthritis

Objective:This study examined associations between diet quality and disease activity in adults with rheumatoid arthritis (RA). Perceived stress was also compared to diet and disease activity. Methods: In a cross-sectional design, 50 adults with RA were recruited. The Arizona Food Frequency Questionnaire was used to measure dietary intake (four weeks) and diet quality scores were calculated with the Healthy Eating Index – 2015. Perceived stress was measured with the Perceived Stress Scale. Disease activity was measured with the Health Assessment Questionnaire-Disability Index and Pain Scale, erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein, and Disease Activity Score Including 28 Joints-ESR. Results: Diet quality (56; SD ± 12) in participants was lower than the national mean (59). Age (p = 0.015) and gender (p = 0.003) were associated with higher diet quality. The belief that diet affects RA disease activity was reported by 44% of the participants, and these participants were significantly more likely to report dietary changes (p < 0.0001). Higher educational level (at least some college) was associated with this belief (B = −1.535, p = 0.023). Participants with lower diet quality also had significantly higher pain (B = −0.396, p = 0.022) and ESR scores (p = 0.019). Women were more likely to have higher HAQ-DI scores (B = 0.570, p = 0.001). Perceived stress was significantly associated with HAQ-DI and pain scores (B = 0.445, p = 0.001 and B = 0.289, p = 0.042, respectively). Medical cannabis was reportedly used by 8% of participants. Conclusion: In RA patients, lower diet quality may be associated with more pain and inflammation, and perceived stress may be associated with higher disability and disease activity.
Surgical Treatment of Postinfarction Ventricular Septal Rupture

Key Points Question What are the early outcomes of surgical treatment of postinfarction ventricular septal rupture? Findings In this cohort study of 475 patients from 26 different centers worldwide, the early mortality rate for surgically treated ventricular septal rupture was 40.4%, mostly due to low cardiac output, and it did not improve in the last 2 decades. Meaning The findings of this study suggest that patient-tailored preoperative and perioperative management of postinfarction ventricular septal rupture should be addressed to improve the current suboptimal survival rates.
Involving medical students in the planning and delivery of a vaccination and health screening outreach clinic

ABSTRACT Improving access to healthcare for people experiencing homelessness can be achieved via outreach clinics. Involving medical students in homeless healthcare projects leads to increased understanding of the social determinants of health and positive changes in student perception of this vulnerable patient group. Projects such as this can increase the social accountability of medical schools, with the potential to have a positive effect on health in the local community. Third-year medical students on GP placement were given the opportunity to design and deliver temporary clinics to the homeless population in Corby with the support of Public Health Northamptonshire. The study aimed to evaluate this educational intervention by exploring the students’ motivation, experience and ideas on sustainability of the project via a focus group. Humanitarianism and the opportunity to meet patients face-to-face during the pandemic were motivating factors for joining the project. Students felt the educational experience was valuable, providing exposure to a patient group not often encountered in medical school. They gained an understanding of some of the challenges faced by this population. Some said this project forced them to address their unconscious biases and cited that to be a reason why projects like this should be mandatory. The learning experience made students consider funding and the organisation of healthcare. This study found that hands-on learning can provide educational and rewarding experiences for medical students. Positive experiences in the GP setting may impact career choices and allow them consider leadership and public health.
Aged healthy mice acquire clonal hematopoiesis mutations

Chin and colleagues used detailed mutational analysis of aged mice and transplantation to evaluate the mouse as a model of clonal hematopoiesis (CH). Their data suggest that while murine hematopoietic stem cells acquire mutations in CH-associated genes when aged and CH clones can expand after transplantation (as in humans), these are rare events. Nevertheless, genetically manipulated murine models mimicking human CH are feasible and may prove useful in the future.
Differentiating brain function of punishment versus reward processing in conduct disorder with and without attention deficit hyperactivity disorder

Abstract Objectives Conduct disorder (CD) and attention-deficit/hyperactivity disorder (ADHD) are reported to co-occur in about 30–50% of affected individuals. Research suggests that poor reinforcement-based decision-making may contribute to impaired social functioning in both youths with CD and ADHD. Considering its frequent co-occurrence this raises the question whether decision-making deficits in both disorders have a disorder-specific and/or shared neurobiological basis. Methods 138 participants with CD, ADHD, or CD + ADHD, and typically developing controls (TDCs) aged 9–18 years (48% girls) were included in the study. Participants completed a reinforcement-based decision-making task in the fMRI scanner, investigating decision-making capabilities under different reinforcement contingencies (i.e. punishment vs. reward). Whole-brain and ROI analyses were used to test for potential group differences. Results For punishment versus reward contingencies, relative to TDCs, youths with CD + ADHD displayed lower brain activity in dorsal striatum (incl. caudate), middle temporal gyrus (MTG), inferior frontal gyrus (IFG) and lateral occipital cortex, and they showed lower activity in dorsal striatum (incl. putamen), orbitofrontal cortex (OFC) and IFG relative to participants with ADHD. All other group comparisons were found to be non-significant. Conclusions Participants with comorbid CD + ADHD are neurobiologically the most severely impaired group regarding reinforcement-based decision-making, particularly in response to punishment.
Systematic analysis of authorship demographics in global surgery

Background Global surgery has recently gained prominence as an academic discipline within global health. Authorship inequity has been a consistent feature of global health publications, with over-representation of authors from high-income countries (HICs), and disenfranchisement of researchers from low-income and middle-income countries (LMICs). In this study, we investigated authorship demographics within recently published global surgery literature. Methods We performed a systematic analysis of author characteristics, including gender, seniority and institutional affiliation, for global surgery studies published between 2016 and 2020 and indexed in the PubMed database. We compared the distribution of author gender and seniority across studies related to different topics; between authors affiliated with HICs and LMICs; and across studies with different authorship networks. Results 1240 articles were included for analysis. Most authors were male (60%), affiliated only with HICs (51%) and of high seniority (55% were fully qualified specialist or generalist clinicians, Principal Investigators, or in senior leadership or management roles). The proportion of male authors increased with increasing seniority for last and middle authors. Studies related to Obstetrics and Gynaecology had similar numbers of male and female authors, whereas there were more male authors in studies related to surgery (69% male) and Anaesthesia and Critical care (65% male). Compared with HIC authors, LMIC authors had a lower proportion of female authors at every seniority grade. This gender gap among LMIC middle authors was reduced in studies where all authors were affiliated only with LMICs. Conclusion Authorship disparities are evident within global surgery academia. Remedial actions to address the lack of authorship opportunities for LMIC authors and female authors are required.
Loss of major nutrient sensing and signaling pathways suppresses starvation lethality in electron transport chain mutants

The electron transport chain (ETC) is a well-studied and highly conserved metabolic pathway that produces ATP through generation of a proton gradient across the inner mitochondrial membrane coupled to oxidative phosphorylation. ETC mutations are associated with a wide array of human disease conditions and to aging-related phenotypes in a number of different organisms. In this study, we sought to better understand the role of the ETC in aging using a yeast model. A panel of ETC mutant strains that fail to survive starvation was used to isolate suppressor mutants that survive. These suppressors tend to fall into major nutrient sensing and signaling pathways, suggesting that the ETC is involved in proper starvation signaling to these pathways in yeast. These suppressors also partially restore ETC-associated gene expression and pH homeostasis defects, though it remains unclear whether these phenotypes directly cause the suppression or are simply effects. This work further highlights the complex cellular network connections between metabolic pathways and signaling events in the cell and their potential roles in aging and age-related diseases.
Brain Responses to Surprising Stimulus Offsets: Phenomenology and Functional Significance

Abstract Abrupt increases of sensory input (onsets) likely reflect the occurrence of novel events or objects in the environment, potentially requiring immediate behavioral responses. Accordingly, onsets elicit a transient and widespread modulation of ongoing electrocortical activity: the Vertex Potential (VP), which is likely related to the optimisation of rapid behavioral responses. In contrast, the functional significance of the brain response elicited by abrupt decreases of sensory input (offsets) is more elusive, and a detailed comparison of onset and offset VPs is lacking. In four experiments conducted on 44 humans, we observed that onset and offset VPs share several phenomenological and functional properties: they (1) have highly similar scalp topographies across time, (2) are both largely comprised of supramodal neural activity, (3) are both highly sensitive to surprise and (4) co-occur with similar modulations of ongoing motor output. These results demonstrate that the onset and offset VPs largely reflect the activity of a common supramodal brain network, likely consequent to the activation of the extralemniscal sensory system which runs in parallel with core sensory pathways. The transient activation of this system has clear implications in optimizing the behavioral responses to surprising environmental changes.
Effective methods for isolation and purification of extracellular vesicles from plants.

Plant extracellular vesicles (EVs) play critical roles in the cross-kingdom trafficking of molecules from hosts to interacting microbes, most notably in plant defense responses. However, the isolation of pure, intact EVs from plants remains challenging. A variety of methods have been utilized to isolate plant EVs from apoplastic washing fluid (AWF). Here, we compare published plant EV isolation methods, and provide our recommended method for the isolation and purification of plant EVs. This method includes a detailed protocol for clean AWF collection from Arabidopsis thaliana leaves, followed by EV isolation via differential centrifugation. To further separate and purify specific subclasses of EVs from heterogeneous vesicle populations, density gradient ultracentrifugation and immunoaffinity capture are then utilized. We found that immunoaffinity capture is the most precise method for specific EV subclass isolation when suitable specific EV biomarkers and their corresponding antibodies are available. Overall, this study provides a guide for the selection and optimization of EV isolation methods for desired downstream applications. This article is protected by copyright. All rights reserved.
Spanish Society of Hematology and Hemotherapy expert consensus opinion for SARS-CoV-2 vaccination in onco-hematological patients

Abstract In the midst of the COVID-19 pandemic, different vaccines in front of SARS-CoV-2 have been approved and administered in different vulnerable populations. As patients with cancer were excluded from pivotal trials of vaccination, little is known on their immunogenic response to these vaccines, particularly in patients with severely impaired immune system. In response to that uncertainty, the Spanish Society of Hematology and Hemotherapy launched an initiative aimed to provide recommendations for vaccination of the main hematological conditions. This document is based on the available information on COVID-19 outcomes, prior knowledge on vaccination in hematological patients, recent published data on serological response in oncohematological patients and expert opinions. New information about SARS-CoV-2 vaccination will be gathered in the near future, providing new scientific grounds to delineate the most adequate management of vaccination in patients with hematological diseases. The current limited data on SARS-CoV-2 vaccines in hematological patients represents a major limitation of this expert consensus opinion. In fact, the speed in which this field evolves may reduce their validity in the near future.
Comparison of Sodium Lactate Infusion and Carbon Dioxide Inhalation Panic Provocation Tests: A Meta-analysis

Abstract Background Sodium lactate (NaL) infusion and carbon dioxide (CO2) inhalation are proven to provoke acute panic attacks (PAs) in patients with panic disorder (PD). A systematic literature search and meta-analysis were performed to compare the effect sizes of these methods. Methods Odds ratios were calculated for each of the original studies and were pooled using the random-effects model. Results Either NaL or CO2 provocations significantly increased the rates of PAs in individuals with PD compared to those in healthy controls. However, the effect size of NaL infusion (OR=25.13, 95% CI=15.48–40.80) was significantly greater than that of CO2 inhalation (OR=10.58, 95%CI=7.88–14.21). Conclusion The evidence for the efficacy of the two panic provocation tests is very strong. Yet, the results support the superiority of NaL infusion over CO2 inhalation challenge as a panic provocation test. Thus, lactate seems a much stronger stimulus than CO2 for the brain suffocation detector.
Plasma Proneurotensin and Prediction of Cause-Specific Mortality in a Middle-aged Cohort During Long-term Follow-up

Abstract Context Neurotensin is associated with cardiometabolic diseases but its role with mortality risk in humans is unknown. Objective This work aims to examine the prediction of proneurotensin (Pro-NT) with respect to total and cause-specific mortality in a middle-aged cohort. Methods In the population-based middle-aged cohort (n = 4632; mean age, 57 years) of the Malmö Diet and Cancer Study, Pro-NT was assessed and total as well as cause-specific mortality was studied. Main cause of death was based on the International Classification of Diseases. Results During a mean follow-up of 20 ± 3 years, 950 men and 956 women died. There was significantly increased mortality risk in individuals belonging to the highest quartile (Q) of Pro-NT (Q4, Pro-NT ≥ 149 pmol/L) compared with Qs 1 to 3 (Pro-NT < 149 pmol/L), hazard ratio (HR), 95% CI of 1.29 (1.17-1.42; P < .001). Data were adjusted for sex and age. No significant interaction was observed between Pro-NT and sex on mortality risk. Individuals within Q4 vs Qs 1 to 3 had an HR of 1.41 (95% CI, 1.18-1.68; P < .001) for death due to cardiovascular disease (n = 595/4632); 2.53 (95% CI, 1.37-4.67; P = .003), due to digestive tract disease (n = 42/4632), 1.62 (95% CI, 1.04-2.52; P = .032) due to mental and behavioral disease (n = 90/4632); and 1.91 (95% CI, 1.15-3.19; P = .013) due to unspecific causes (n = 64/4632). There was no significant relationship between Pro-NT and deaths due to cancer, infections, neurological, or other causes. Adjustment for cardiovascular risk factors only marginally changed these results. Conclusion The relationship between Pro-NT and total mortality risk was mainly driven by cardiovascular mortality, but high Pro-NT also predicts death from digestive, mental, and behavioral disease and deaths attributed to unspecific causes.