Miracle-dz/UniFAR-FTUs huggingface dataset:
Aberrant Maturation of the Uncinate Fasciculus Follows Exposure to Unpredictable Patterns of Maternal Signals

Across species, unpredictable patterns of maternal behavior are emerging as novel predictors of aberrant cognitive and emotional outcomes later in life. In animal models, exposure to unpredictable patterns of maternal behavior alters brain circuit maturation and cognitive and emotional outcomes. However, whether exposure to such signals in humans alters the development of brain pathways is unknown. Across species, unpredictable patterns of maternal behavior are emerging as novel predictors of aberrant cognitive and emotional outcomes later in life. In animal models, exposure to unpredictable patterns of maternal behavior alters brain circuit maturation and cognitive and emotional outcomes. However, whether exposure to such signals in humans alters the development of brain pathways is unknown. In mother–child dyads, we tested the hypothesis that exposure to more unpredictable maternal signals in infancy is associated with aberrant maturation of corticolimbic pathways. We focused on the uncinate fasciculus, the primary fiber bundle connecting the amygdala to the orbitofrontal cortex and a key component of the medial temporal lobe–prefrontal cortex circuit. Infant exposure to unpredictable maternal sensory signals was assessed at 6 and 12 months. Using high angular resolution diffusion imaging, we quantified the integrity of the uncinate fasciculus using generalized fractional anisotropy (GFA). Higher maternal unpredictability during infancy presaged greater uncinate fasciculus GFA in children 9–11 years of age (n = 69, 29 female). In contrast to the uncinate, GFA of a second corticolimbic projection, the hippocampal cingulum, was not associated with maternal unpredictability. Addressing the overall functional significance of the uncinate and cingulum relationships, we found that the resulting imbalance of medial temporal lobe–prefrontal cortex connectivity partially mediated the association between unpredictable maternal sensory signals and impaired episodic memory function. These results suggest that unbalanced maturation of corticolimbic circuits is a mechanism by which early unpredictable sensory signals may impact cognition later in life. SIGNIFICANCE STATEMENT Our prior work across species demonstrated that unpredictable patterns of maternal care are associated with compromised memory function. However, the neurobiological mechanisms by which this occurs in humans remain unknown. Here, we identify an association of exposure to unpredictable patterns of maternal sensory signals with the integrity of corticolimbic circuits involved in emotion and cognition using state-of-the-art diffusion imaging techniques and analyses. We find that exposure to early unpredictability is associated with higher integrity of the uncinate fasciculus with no effect on a second corticolimbic pathway, the cingulum. The resulting imbalance of corticolimbic circuit development is a novel mediator of the association between unpredictable patterns of maternal care and poorer episodic memory.
Comparative molecular dynamics study of the receptor-binding domains in SARS-CoV-2 and SARS-CoV and the effects of mutations on the binding affinity

Abstract Here, we report on a computational comparison of the receptor-binding domains (RBDs) on the spike proteins of severe respiratory syndrome coronavirus‐2 (SARS-CoV-2) and SARS-CoV in free forms and as complexes with angiotensin-converting enzyme 2 (ACE2) as their receptor in humans. The impact of 42 mutations discovered so far on the structure and thermodynamics of SARS-CoV-2 RBD was also assessed. The binding affinity of SARS-CoV-2 RBD for ACE2 is higher than that of SARS-CoV RBD. The binding of COVA2-04 antibody to SARS-CoV-2 RBD is more energetically favorable than the binding of COVA2-39, but also less favorable than the formation of SARS-CoV-2 RBD-ACE2 complex. The net charge, the dipole moment and hydrophilicity of SARS-CoV-2 RBD are higher than those of SARS-CoV RBD, producing lower solvation and surface free energies and thus lower stability. The structure of SARS-CoV-2 RBD is also more flexible and more open, with a larger solvent-accessible surface area than that of SARS-CoV RBD. Single-point mutations have a dramatic effect on distribution of charges, most prominently at the site of substitution and its immediate vicinity. These charge alterations alter the free energy landscape, while X→F mutations exhibit a stabilizing effect on the RBD structure through π stacking. F456 and W436 emerge as two key residues governing the stability and affinity of the spike protein for its ACE2 receptor. These analyses of the structural differences and the impact of mutations on different viral strains and members of the coronavirus genera are an essential aid in the development of effective therapeutic strategies. Communicated by Ramaswamy H. Sarma Graphical abstract
Short- versus long-term dual antiplatelet therapy after second-generation drug-eluting stent implantation in patients with diabetes mellitus: A meta-analysis of randomized controlled trials

Background Diabetes is considered to be a high-risk factor for thromboembolic events. However, available data about the optimal dual antiplatelet therapy (DAPT) in patients with diabetes mellitus (DM) after second-generation drug-eluting stent (DES) implantation are scant. Objective The purpose of this study was to compare the impact of various DAPT durations on clinical outcomes in patients with DM after second-generation DES implantation. Methods We searched PubMed, Embase, and the Cochrane Library for studies that compared short-term (≤ 6 months) and long-term (≥ 12 months) DAPT in patients with DM. The primary endpoints were late (31–365 days) and very late (> 365 days) stent thrombosis (ST). The secondary endpoints included myocardial infarction (MI), target vessel recanalization (TVR), all-cause death, and major bleeding. Results Six randomized controlled trials, with a total of 3,657 patients with DM, were included in the study. In terms of the primary endpoint, there was no significant difference between the two groups in late (OR 1.15, 95% CI: 0.42–3.19, P = 0.79) or very late (OR 2.18, 95% CI: 0.20–24.18; P = 0.53) ST. Moreover, there was no significant difference in the secondary endpoints, including MI (OR 1.11, 95% CI: 0.72–1.71, P = 0.63), TVR (OR 1.31, 95% CI: 0.82–2.07, P = 0.26), all-cause death (OR 1.03, 95% CI: 0.61–1.75, P = 0.90) and major bleeding (OR 1.07, 95% CI: 0.34–3.40, P = 0.90) between the two groups. Conclusion Our study demonstrated that compared with long-term DAPT, short-term DAPT had no significant difference in the clinical outcomes of patients with DM implanted with second-generation DES.
The Evolving Knowledge on T and NK Cells in Classic Hodgkin Lymphoma: Insights into Novel Subsets Populating the Immune Microenvironment

Simple Summary In classic Hodgkin lymphoma, T and NK cells constitute a significant fraction of the reactive microenvironment established by malignant Hodgkin Reed–Sternberg cells. Despite their abundance, T and NK cells remain largely ineffective because of two coordinated levels of immune evasion. The first is based on the acquisition of regulatory properties or exhausted phenotypes that cripple their antitumor activity. The second is represented by their peculiar spatial distribution, with the most immunosuppressive subpopulations lying in close proximity of neoplastic cells. Recent discoveries about the functional role and the spatial orientation of T and NK cells in classic Hodgkin lymphoma are the focus of this review. Abstract Classic Hodgkin lymphoma (cHL) is a unique lymphoid neoplasm characterized by extensive immune infiltrates surrounding rare malignant Hodgkin Reed–Sternberg (HRS) cells. Different subsets of T and NK cells have long been recognized in the cHL microenvironment, yet their distinct contribution to disease pathogenesis has remained enigmatic. Very recently, novel platforms for high dimensional analysis of immune cells, such as single-cell RNA sequencing and mass cytometry, have revealed unanticipated insights into the composition of T- and NK-cell compartments in cHL. Advances in imaging techniques have better defined specific T-helper subpopulations physically interacting with neoplastic cells. In addition, the identification of novel cytotoxic subsets with an exhausted phenotype, typically enriched in cHL milieu, is shedding light on previously unrecognized immune evasion mechanisms. This review examines the immunological features and the functional properties of T and NK subsets recently identified in the cHL microenvironment, highlighting their pathological interplay with HRS cells. We also discuss how this knowledge can be exploited to predict response to immunotherapy and to design novel strategies to improve PD-1 blockade efficacy.
Independent and combined associations of sugar-sweetened beverage consumption, TV viewing, and physical activity with severe depressive symptoms among 59,402 adults

Objective: Our aim was to analyze the association between sugar-sweetened beverage consumption and depressive symptoms, as well as the extent to which TV viewing and physical activity moderate this association. Methods: We used cross-sectional data from the 2013 Brazilian National Survey (Pesquisa Nacional de Saúde) of 59,402 adults (33,482 women, mean age = 42.9 years, 95%CI 42.7-43.2 years). Depressive symptoms (Patient Health Questionnaire-9), physical activity, TV viewing, and sugar-sweetened beverage consumption, as well as potential confounders (chronological age, ethnicity, consumption of candy/sweets and fruit, multimorbidity, education, and employment status) were self-reported. Poisson regression models were used for association analyses. Results: The consumption of 16 or more glasses/week of sugar-sweetened beverages was associated with higher levels of severe depressive symptoms among women compared to no consumption (prevalence ratio [PR] 1.71 [95%CI 1.38-2.11]). Consistent interactions were observed between 1-5 glasses and TV viewing (PR 2.09 [95%CI 1.06-4.12]) and between 11-15 glasses and TV viewing (PR 2.90 [95%CI 1.29-6.50]) among men compared to no consumption, given that the co-occurrence of sugar-sweetened beverage consumption and elevated TV viewing was associated with higher odds of severe depressive symptoms. Sugar-sweetened beverage consumption did not interact with physical activity, only presenting an independent association. Conclusion: Sugar-sweetened beverage consumption was independently associated with severe depressive symptoms among women and interacted with TV viewing, but not with physical activity among men.
Understanding adaptive teamwork in health care: Progress and future directions

Health care teamwork is a vital part of clinical work and patient care but is poorly understood. Despite poor teamwork being cited as a major contributory factor to adverse events, we lack vital knowledge about how teamwork can be improved. Teams in health care are diverse in structure and purpose, and most patient care depends on the ability of different professionals to coordinate their actions. Research in this area has narrowly defined health care teams, focused mainly on a small range of settings and activities and addressed a limited range of research questions. We argue that a new approach to teamwork research is needed and make three recommendations. First, the temporal and dynamic features of teamwork should be studied to understand how teamwork unfolds sequentially. Second, contextual influences should be integrated into study designs, including the organization of work, tasks, patients, organisational structures, and health care system factors. Finally, exploratory, rather than confirmatory, research designs are needed to analyse the complex patterns of social interaction inherent in health care work, to build our theoretical understanding of health care teams and their work, and ultimately to develop effective interventions to support better teamwork for the benefit of patients.
Corrected and Republished from: A Nonfunctional Opsonic Antibody Response Frequently Occurs after Pneumococcal Pneumonia and Is Associated with Invasive Disease

Numerous reports on the dynamics of antipneumococcal immunity in relation to immunization with pneumococcal vaccines and on the prevalence of naturally acquired immunity in various populations have been published. In contrast, studies on the dynamics of the humoral immune response triggered by pneumococcal infection are scarce. ABSTRACT Naturally acquired opsonic antipneumococcal antibodies are commonly found in nonvaccinated adults and confer protection against infection and colonization. Despite this, only limited data exist regarding the adaptive immune response after pneumococcal exposure. To investigate the dynamics of naturally acquired antipneumococcal immunity in relation to an episode of infection, opsonic antibody activity was studied with paired acute-phase and convalescent-phase sera obtained from 54 patients with pneumococcal community-acquired pneumonia (CAP) using an opsonophagocytic assay (OPA). Results were compared with clinical characteristics and anticapsular immunoglobulin (Ig) concentrations. Interestingly, a nonfunctional opsonic antibody response (characterized by a decreased convalescent-phase serum OPA titer compared to that of the acute-phase serum or undetectable titers in both sera) was observed in 19 (35%) patients. The remaining individuals exhibited either an increased convalescent-phase OPA titer (n = 24 [44%]) or a detectable, but unchanged, titer at both time points (n = 11 [20%]). Invasive pneumococcal disease (i.e., bacteremia) was significantly more common among patients with a nonfunctional convalescent-phase response than in patients with other convalescent-phase responses. Anticapsular Ig concentrations were higher among patients with detectable convalescent-phase OPA titers (P = 0.003), and the greatest Ig concentration increase was observed among patients with an increased convalescent-phase response (P = 0.002). Our findings indicate that an episode of pneumococcal infection may act as an immunizing event. However, in some cases when patients with CAP also suffer from bacteremia, a nonfunctional opsonic antibody response may occur. Furthermore, the results suggest that factors other than anticapsular Ig concentrations determine opsonic antibody activity in serum. IMPORTANCE Numerous reports on the dynamics of antipneumococcal immunity in relation to immunization with pneumococcal vaccines and on the prevalence of naturally acquired immunity in various populations have been published. In contrast, studies on the dynamics of the humoral immune response triggered by pneumococcal infection are scarce. This study provides valuable information that will contribute to fill this knowledge gap. Our main results indicate that a functional immune response may fail after CAP, predominantly among patients with simultaneous bacteremia.
Effect of Surgical Mask on Setup Error in Head and Neck Radiotherapy

Purpose: With the widespread prevalence of Corona Virus Disease 2019 (COVID-19), cancer patients are suggested to wear a surgical mask during radiation treatment. In this study, cone beam CT (CBCT) was used to investigate the effect of surgical mask on setup errors in head and neck radiotherapy. Methods: A total of 91 patients with head and neck tumors were selected. CBCT was performed to localize target volume after patient set up. The images obtained by CBCT before treatment were automatically registered with CT images and manually fine-tuned. The setup errors of patients in 6 directions of Vrt, Lng, Lat, Pitch, Roll and Rotation were recorded. The patients were divided into groups according to whether they wore the surgical mask, the type of immobilization mask used and the location of the isocenter. The setup errors of patients were calculated. A t-test was performed to detect whether it was statistically significant. Results: In the 4 groups, the standard deviation in the directions of Lng and Pitch of the with surgical mask group were all higher than that in the without surgical mask group. In the head-neck-shoulder mask group, the mean in the Lng direction of the with surgical mask group was larger than that of the without surgical mask group. In the lateral isocenter group, the mean in the Lng and Pitch directions of the with surgical mask group were larger than that of the without surgical mask group. The t-test results showed that there was significant difference in the setup error between the 2 groups (p = 0.043 and p = 0.013, respectively) only in the Lng and Pitch directions of the head-neck-shoulder mask group. In addition, the setup error of 6 patients with immobilization open masks exhibited no distinguished difference from that of the patients with regular immobilization masks. Conclusion: In the head and neck radiotherapy patients, the setup error was affected by wearing surgical mask. It is recommended that the immobilization open mask should be used when the patient cannot finish the whole treatment with a surgical mask.
Piscine Orthoreovirus-1 Isolates Differ in Their Ability to Induce Heart and Skeletal Muscle Inflammation in Atlantic Salmon (Salmo salar)

Piscine orthoreovirus 1 (PRV-1) is the causative agent of heart and skeletal muscle inflammation (HSMI) in farmed Atlantic salmon (Salmo salar). The virus is widespread in Atlantic salmon and was present in Norway long before the first description of HSMI in 1999. Furthermore, in Canada the virus is prevalent in farmed Atlantic salmon but HSMI is not and Canadian isolates have failed to reproduce HSMI experimentally. This has led to the hypothesis that there are virulence differences between PRV-1 isolates. In this study we performed a dose standardized challenge trial, comparing six PRV-1 isolates, including two Norwegian field isolates from 2018, three historical Norwegian isolates predating the first report of HSMI and one Canadian isolate. The Norwegian 2018 isolates induced lower viral protein load in blood cells but higher plasma viremia. Following peak replication in blood, the two Norwegian 2018 isolates induced histopathological lesions in the heart consistent with HSMI, whereas all three historical Norwegian and the Canadian isolates induced only mild cardiac lesions. This is the first demonstration of virulence differences between PRV-1 isolates and the phenotypic differences are linked to viral proteins encoded by segment S1, M2, L1, L2 and S4.
Synthetic Zinc and Magnesium Chlorin Aggregates as Models for Supramolecular Antenna Complexes in Chlorosomes of Green Photosynthetic Bacteria

Abstract— A comparison of the spectra of in vitro (3‐hydroxymethyl‐131‐oxometallochlorin) and in vivo chlorosomal (bacterio‐chlorophyll‐c) aggregates suggests a similar supramolecular structure for the artificial oligomers and the bacte‐riochlorophyll‐c aggregates in the extramembranous antenna complexes (chlorosomes) of green photosynthetic bacteria. Synthetic zinc and magnesium chlorins have been found to aggregate in 1 % (vol/vol) tetrahydrofuran and hexane solutions and in thin films to form oligomers with the Qy absorption bands shifted to longer wavelengths by about 1900 (Zn chlorins) and 2100 cm−1 (Mg) relative to the corresponding monomer bands. Visible absorption and circular dichroism spectra of various zinc chlorins establish that a central metal, a 31‐hydroxy and a 131‐keto group are functional prerequisites for the aggregation. Vibrational bands measured by IR spectroscopy of solid films reveal two characteristic structural features of the oligomers: (1) a five‐coordinated metallochlorin macrocycle with an axial ligand (bands at 1500‐1630 cm−1), and (2) a hydrogen bond between the keto oxygen of one chlorin and the hydroxy group of a second chlorin, the oxygen of which is chelated to the metal atom of a third molecule, i.e. C=O…H‐O…M (=Zn or Mg).
OPEN VS LAPAROSCOPIC HERNIA REPAIR IN THE BRAZILIAN PUBLIC HEALTH SYSTEM. AN 11-YEAR NATIONWIDE POPULATION-BASED STUDY.

BACKGROUND Abdominal wall hernia is one of the most common surgical pathologies. The advent of minimally invasive surgery raised questions about the best technique to be applied, considering the possibility of reducing postoperative pain, a lower rate of complications, and early return to usual activities. OBJECTIVE To evaluate the frequency of open and laparoscopic hernioplasties in Brazil from 2008 to 2018, analyzing the rates of urgent and elective surgeries, mortality, costs, and the impact of laparoscopic surgical training on the public health system. METHODS Nationwide data from 2008 to 2018 were obtained from the public health registry database (DATASUS) for a descriptive analysis of the selected data and parameters. RESULTS 2,671,347 hernioplasties were performed in the period, an average of 242,850 surgeries per year (99.4% open, 0.6% laparoscopic). The economically active population (aged 20-59) constituted the dominant group (54.5%). There was a significant reduction (P<0.01) in open surgeries, without a compensatory increase in laparoscopic procedures. 22.3% of surgeries were urgent, with a significant increase in mortality when compared to elective surgeries (P<0.01). The distribution of laparoscopic surgery varied widely, directly associated with the number of digestive surgeons. CONCLUSION This study presents nationwide data on hernia repair surgeries in Brazil for the first time. Minimally invasive techniques represent a minor portion of hernioplasties. Urgent surgeries represent a high percentage when compared to other countries, with increased mortality. The data reinforce the need for improvement in the offer of services, specialized training, and equalization in the distribution of procedures in all regions.
Check the gap: Facemask performance and exhaled aerosol distributions around the wearer

Current facemask research focuses on material characterization and efficiency; however, facemasks are often not tested such that aerosol distributions are evaluated from the gaps in the sides, bottom, and nose areas. Poor evaluation methods could lead to misinformation on optimal facemasks use; a high-throughput, reproducible method which illuminates the issue of fit influencing aerosol transmission is needed. To this end, we have created an in vitro model to quantify particle transmission by mimicking exhalation aerosols in a 3D printed face-nose-mouth replica via a nebulizer and quantifying particle counts using a hand-held particle counter. A sewn, sewn with pipe cleaner nose piece, and sewn with a coffee filter facemask were used to evaluate current common homemade sewn facemask designs, benchmarked against industry standard surgical, N95 respirator tightly fit, and N95 respirator loosely fit facemasks. All facemasks have significantly reduced particle counts in front of the facemask, but the side and top of the facemask showed increases in particle counts over the no facemask condition at that same position, suggesting that some proportion of aerosols are being redirected to these gaps. An altered size distribution of aerosols that escape at the vulnerable positions was observed; escaped particles have larger count median diameters, with a decreased ratio of smaller to larger particles, possibly due to hygroscopic growth or aggregation. Of the homemade sewn facemasks, the facemask with a coffee filter insert performed the best at reducing escaped aerosols, with increased efficiency also observed for sewn masks with a pipe cleaner nose piece. Importantly, there were minimal differences between facemasks at increasing distances, which supports that social distance is a critical element in reducing aerosol transmission. This work brings to light the importance of quantifying particle count in positions other than directly in front of the facemask and identifies areas of research to be explored.