Miracle-dz/UniFAR-FTUs huggingface dataset:
Ionizing Radiation Curtails Immunosuppressive Effects From Cancer-Associated Fibroblasts on Dendritic Cells

Cancer-associated fibroblasts (CAFs) participate actively in tumor development and affect treatment responses, by among other mechanisms, promoting an immunosuppressive tumor microenvironment. In contrast to normal fibroblasts, reactive CAFs secrete a myriad of immunomodulatory soluble factors at high levels, i.e. growth factors, cytokines, and chemokines, which directly influence tumor immunity and inflammation. CAFs have been identified as important players in tumor radioresistance. However, knowledge on the immunomodulatory functions of CAFs during/after radiotherapy is still lacking. In this study, we investigated the effects of ionizing radiation on CAF-mediated regulation of dendritic cells (DCs). CAFs were obtained from freshly operated lung cancer tissues, while DCs were procured from peripheral blood of healthy donors. Experimental settings comprised both co-cultures and incubations with conditioned medium from control and irradiated CAFs. Functional assays to study DC differentiation/activation consisted on cytokine release, expression of cell-surface markers, antigen uptake, migration rates, T cell priming, and DC-signaling analysis. We demonstrate that CAFs induce a tolerogenic phenotype in DCs by promoting down-regulation of: i) signature DC markers (CD14, CD1a, CD209); ii) activation markers (CD80, CD86, CD40, and HLA-DR) and iii) functional properties (migration, antigen uptake, and CD4+ T cell priming). Notably, some of these effects were lost in conditioned medium from CAFs irradiated at fractionated medium-dose regimens (3x6 Gy). However, the expression of relevant CAF-derived regulatory agents like thymic stromal lymphopoietin (TSLP) or tryptophan 2,3-dioxygenase (TDO2) was unchanged upon irradiation. This study demonstrates that CAFs interfere with DC immune functions and unveil that certain radiation regimens may reverse CAF-mediated immunosuppressive effects.
Effects of Psychopathy on Neurocognitive Domains of Impulsivity in Abstinent Opiate and Stimulant Users

Background: Psychopathy and substance use disorders (SUDs) are both characterized by neurocognitive impairments reflecting higher levels of impulsivity such as reward-driven decision-making and deficient inhibitory control. Previous studies suggest that psychopathy may exacerbate decision-making deficits, but it may be unrelated to other neurocognitive impairments among substance dependent individuals (SDIs). The aim of the present study was to examine the role of psychopathy and its interpersonal-affective and impulsive-antisocial dimensions in moderating the relationships between dependence on different classes of drugs and neurocognitive domains of impulsivity. Method: We tested 693 participants (112 heroin mono-dependent individuals, 71 heroin polysubstance dependent individuals, 115 amphetamine mono-dependent individuals, 76 amphetamine polysubstance dependent individuals, and 319 non-substance dependent control individuals). Participants were administered the Psychopathy Checklist: Screening Version (PCL:SV) and seven neurocognitive tasks measuring impulsive choice/decision-making (Iowa Gambling Task; Cambridge Gambling Task; Kirby Delay Discounting Task; Balloon Analog Risk Task), and impulsive action/response inhibition (Go/No-Go Task, Immediate Memory Task, and Stop Signal Task). Results: A series of hierarchical multiple regressions revealed that the interpersonal-affective dimension of psychopathy moderated the association between decision-making, response inhibition and both amphetamine and heroin dependence, albeit differently. For amphetamine users, low levels of interpersonal-affective traits predicted poor decision-making on the Iowa Gambling Task and better response inhibition on the Stop Signal task. In contrast, in heroin users high interpersonal-affective psychopathy traits predicted lower risk taking on the Cambridge Gambling Task and better response inhibition on the Go/No-Go task. The impulsive-antisocial dimension of psychopathy predicted poor response inhibition in both amphetamine and heroin users. Conclusions: Our findings reveal that psychopathy and its dimensions had both common and unique effects on neurocognitive function in heroin and amphetamine dependent individuals. Our results suggest that the specific interactions between psychopathy dimensions and dependence on different classes of drugs may lead to either deficient or superior decision-making and response inhibition performance in SDIs, suggesting that psychopathy may paradoxically play a protective role for some neurocognitive functions in specific subtypes of substance users.
Metabolic Aspects of Migraine: Association With Obesity and Diabetes Mellitus

Migraine is a disabling neurovascular disorder, characterized by moderate to severe unilateral headaches, nausea, photophobia, and/or phonophobia, with a higher prevalence in women than in men, which can drastically affect the quality of life of migraine patients. In addition, this chronic disorder is related with metabolic comorbidities associated with the patient's lifestyle, including obesity and diabetes mellitus (DM). Beyond the personal and socioeconomic impact caused by migraine, obesity and DM, it has been suggested that these metabolic disorders seem to be related to migraine since: (i) they are a risk factor for developing cardiovascular disorders or chronic diseases; (ii) they can be influenced by genetic and environmental risk factors; and (iii) while clinical and epidemiological studies suggest that obesity is a risk factor for migraine, DM (i.e., type 1 and type 2 DM) have been reported to be either a protective or a risk factor in migraine. On this basis, and given the high worldwide prevalence of migraine, obesity, and DM, this article provides a narrative review of the current literature related to the association between the etiology and pathophysiology of migraine and these metabolic disorders, considering lifestyle aspects, as well as the possible involvement of neurotransmitters, neuropeptides, and/or sex hormones. While a link between migraine and metabolic disorders has been suggested, many studies are contradictory and the mechanisms involved in this association are not yet sufficiently established. Therefore, further research should be focused on understanding the possible mechanisms involved.
What’s in the Pipeline? Evidence on the Transmission of SARS-CoV-2 via Building Wastewater Plumbing Systems

There is emerging evidence of the transmission of SARS-CoV-2 via the sanitary plumbing wastewater system, a known transmission pathway of SARS-CoV-1. These events can no longer be dismissed as isolated cases, yet a lack of awareness and of basic research makes it impossible to say just how widespread this mode of transmission might be. Virus is transmitted within wastewater systems by the aerosolisation of wastewater and subsequent transport of bioaerosols on naturally occurring airflows within the piped network. Central to the debate around risk to building occupants from SARS-CoV-2 spread via wastewater plumbing systems is the question of infectivity of faeces, urine and associated aerosols. This paper presents an examination of the processes which underlie this mode of transmission, and the existing epidemiological evidence, as well as existing mitigation strategies; significant gaps in the state of the knowledge are also identified. It is hoped that this review will cultivate a wider awareness and understanding of this most overlooked of threats, and to facilitate the selection and adoption of appropriate mitigation strategies. Key gaps in the knowledge span the rate of generation of bioaerosols within the building drainage system, their composition and transport properties, and the viability and infectivity of virions and other pathogens which they carry. While much of this work will be conducted in the laboratory, we also identify a dearth of field observations, without which it is impossible to truly grasp the scale of this problem, its character, or its solution.
Activity-Induced Fluidization and Arrested Coalescence in Fusion of Cellular Aggregates

At long time scales, tissue spheroids may flow or appear solid depending on their capacity to reorganize their internal structure. Understanding the relationship between intrinsic mechanical properties at the single cell level, and the tissue spheroids dynamics at the long-time scale is key for artificial tissue constructs, which are assembled from multiple tissue spheroids that over time fuse to form coherent structures. The dynamics of this fusion process are frequently analyzed in the framework of liquid theory, wherein the time scale of coalescence of two droplets is governed by its radius, viscosity and surface tension. In this work, we extend this framework to glassy or jammed cell behavior which can be observed in spheroid fusion. Using simulations of an individual-cell based model, we demonstrate how the spheroid fusion process can be steered from liquid to arrested by varying active cell motility and repulsive energy as established by cortical tension. The divergence of visco-elastic relaxation times indicates glassy relaxation near the transition toward arrested coalescence. Finally, we investigate the role of cell growth in spheroid fusion dynamics. We show that the presence of cell division introduces plasticity in the material and thereby increases coalescence during fusion.
Association Between BoLA-DRB3.2 Polymorphism and Bovine Papillomavirus Infection for Bladder Tumor Risk in Podolica Cattle

Blood samples from 260 unrelated cattle (132 animals affected by papillomavirus-associated bladder tumors and 128 healthy) were genotyped using the classic polymerase chain reaction/restriction fragment length polymorphism method to screen MHC class II bovine leukocyte antigen-DRB3. 2 polymorphism. The DRB3*22 allele was significantly (p ≤ 0.01) detected in healthy cattle, thus appearing to have a negative association (protective effect) with virus infection of the urinary bladder known to represent a bladder tumor risk for cattle living free at pasture. Considering the two sequence alleles identified in animals carrying DRB3*22, DRB3*011:01 allele from samples of animals harboring the unexpressed bovine papillomaviruses (BPV)-2 E5 gene was characterized by amino acid residues believed to have a protective effect against BPV infection such as arginine at position 71 (R71) in pocket 4, histidine at position 11 (H11) in pocket 6, and both glutamine at position 9 (Q9) and serine at position 57 (S57) in pocket 9 of the antigen-binding groove. The DRB3*011:02v allele from affected animals was characterized by amino acids believed to be susceptibility residues such as lysine (K71), tyrosine (Y11), glutamic acid (E9), and aspartic acid (D57) in these pockets. These results suggest that animals harboring the DRB3*011:01 allele may have a lower risk of BPV infection and, consequently, a reduced risk of bladder tumors.
Proficiency From Immersion: A Human-Centered Design in Cross-Cultural Surgical Training

Ensuring surgeons are well-trained in various skills is of paramount importance to patient safety. Surgical simulators were introduced to laparoscopy training during the last 2 decades for basic skills training. The main drawback of current simulation-based laparoscopy training is their lack of true representation of the intro-operative experience. To create a complete surgical surrounding, the required amount of resources is demanding. Moreover, organizing immersive training with surgical teams burdens daily clinical routines. High-end virtual reality (VR) headsets bring an opportunity to generate an immersive virtual OR with accessible and affordable expenses. Pilot studies reveal that personalization and localization are key needs of the virtual operating room (VOR). They are therefore key in this study. The focus of this study was to explore the effect of different human factors, such as domain knowledge, culture, and familiarity of VR technologies, on the perception of VOR experience. A human-centered design approach was applied to investigate the presence and usability of a VOR. Sixty-four surgical practitioners joined the study in the Netherlands and India. The surgeons were referred to as “experts” and surgical trainees as “novices. ” The VOR system we used is composed of a laparoscopic simulator, a graphic virtual OR surrounding, and an Oculus Rift VR headset. Participants conducted the “complete Lapchol” task with the VOR. Afterward, four questionnaires were used to collect subjective ratings on presence and usability. Participant’s qualitative feedback was collected using a semi-structural interview as the final stage. Results showed the surgical knowledge only affected perceived mental demand when using a VOR. The cultural difference would alter the rating on the majority of items in these questionnaires. VR experience mainly affected the judgment on presence including “quality of interface” and “reversible actions. ” The interaction effects between surgical knowledge either with culture difference or with VR experience were obvious. This study demonstrated the influences of cultural differences on the perception of immersion and usability. Integrating immersive technologies such as virtual reality and augmented reality to human-centered design opens a brand new horizon for health care and similar professional training.
Behind the Reasons: The Relationship Between Adolescent and Young Adult Mental Health Risk Factors and Exposure to Season One of Netflix’s 13 Reasons Why

With increasing media choice, particularly through the rise of streaming services, it has become more important for empirical research to examine how youth decide which programs to view, particularly when the content focuses on difficult health topics such as suicide. The present study investigated why adolescents and young adults chose to view or not view season 1 of 13 Reasons Why and how individual-level variables related to adolescents’ and young adults’ viewing. Using survey data gathered from a sample of 1,100 adolescents and young adult viewers and non-viewers of the series in the United States, we examined how participants’ resilience, loneliness, and social anxiety related to whether participants viewed the first season or not. Our descriptive results indicate that adolescents who watched the show reported that it accurately depicted the social realities of their age group, they watched it because friends recommended it, and they found the subject matter to be interesting. Non-viewers reported that they chose not to view the show because the nature of the content was upsetting to them. In addition, results demonstrated that participants’ social anxiety and resilience related to participants’ viewing decisions, such that those with higher social anxiety and higher resilience were more likely to report watching season 1. Together, these data suggest that youth make intentional decisions about mental health-related media use in an attempt to choose content that is a good fit for based on individual characteristics.
A Hyperthermophilic Argonaute From Ferroglobus placidus With Specificity on Guide Binding Pattern

Argonaute proteins (Agos) from thermophilic archaea are involved in several important processes, such as host defense and DNA replication. The catalytic mechanism of Ago from different microbes with great diversity and genome editing potential is attracting increasing attention. Here, we describe an Argonaute from hyperthermophilic Ferroglobus placidus (FpAgo), with a typical DNA-guided DNA endonuclease activity but adopted with only a short guide 15–20 nt length rather than a broad guide selectivity for reported Agos. FpAgo performed the precise cleavage of phosphodiester bonds between 10 and 11 nt on the target strand (counting from the guide strand) guided strictly by 5′-phosphorylated DNA at temperatures ranging from 75 to 99°C. The cleavage activity was regulated by the divalent cations Mn2+, Mg2+, Co2+, and Ni2+. In addition, FpAgo possesses guide/target mismatch tolerance in the seed region but is sensitive to mismatches in the 3′-guide region. Notably, the EMSA assay revealed that the FpAgo-guide-target ternary complex exhibited a stronger binding affinity for short 15 and 16 nt guide DNAs than longer guides. Moreover, we performed structural modeling analyses that implied the unique PAZ domain of FpAgo for 3′-guide recognition and binding to affect guide length specificity. This study broadens our understanding of thermophilic Agos and paves the way for their use in DNA manipulation.
Reproducibility and Characterization of Head Kinematics During a Large Animal Acceleration Model of Traumatic Brain Injury

Acceleration parameters have been utilized for the last six decades to investigate pathology in both human and animal models of traumatic brain injury (TBI), design safety equipment, and develop injury thresholds. Previous large animal models have quantified acceleration from impulsive loading forces (i.e., machine/object kinematics) rather than directly measuring head kinematics. No study has evaluated the reproducibility of head kinematics in large animal models. Nine (five males) sexually mature Yucatan swine were exposed to head rotation at a targeted peak angular velocity of 250 rad/s in the coronal plane. The results indicated that the measured peak angular velocity of the skull was 51% of the impulsive load, was experienced over 91% longer duration, and was multi- rather than uni-planar. These findings were replicated in a second experiment with a smaller cohort (N = 4). The reproducibility of skull kinematics data was mostly within acceptable ranges based on published industry standards, although the coefficients of variation (8.9% for peak angular velocity or 12.3% for duration) were higher than the impulsive loading parameters produced by the machine (1.1 vs. 2.5%, respectively). Immunohistochemical markers of diffuse axonal injury and blood–brain barrier breach were not associated with variation in either skull or machine kinematics, suggesting that the observed levels of variance in skull kinematics may not be biologically meaningful with the current sample sizes. The findings highlight the reproducibility of a large animal acceleration model of TBI and the importance of direct measurements of skull kinematics to determine the magnitude of angular velocity, refine injury criteria, and determine critical thresholds.
Case Report: Sellar Ependymomas: A Clinic-Pathological Study and Literature Review

Ependymomas are primary glial tumors arising from cells related to the ependymal lining of the ventricular system. They are classified into at least nine different molecular subtypes according to molecular phenotype, histological morphology, and tumor location. Primary sellar ependymoma is an extremely rare malignancy of the central nervous system, with only 12 known cases reported in humans. We herein report a case of ependymoma located at the pituitary region in a 44-year-old female patient and discuss the molecular subtype, natural history, clinical presentation, radiological findings, histological features, immunohistochemical characteristics, ultrastructural examinations, treatment, and prognosis of sellar ependymoma. This case report may serve as a helpful reference for clinicians and radiologists in clinical practice.
Obesity Challenge Drives Distinct Maternal Immune Response Changes in Normal Pregnant and Abortion-Prone Mouse Models

Obesity is prevalent among women of reproductive age and is associated with increased risk of developing multiple pregnancy disorders. Pregnancy must induce immune tolerance to avoid fetal rejection, while obesity can cause chronic inflammation through activating the immune system. Impaired maternal immuno-tolerance leads to pregnancy failure, such as recurrent spontaneous abortion (RSA), one of the most common complications during early pregnancy. How does maternal immune response change under obesity stress in normal pregnancy and RSA? In turn, is obesity affected by different gestational statuses? Limited information is presently available now. Our study investigated pregnancy outcomes and maternal immune responses in two murine models (normal pregnancy and spontaneous abortion models) after obesity challenge with a high-fat diet (HFD). Abortion-prone mice fed HFD had significantly higher weight gains during pregnancy than normal pregnant mice with HFD feeding. Nonetheless, the embryo implantation and resorption rates were comparable between HFD and normal chow diet (NCD)-fed mice in each model. Evaluation of immune cell subsets showed HFD-induced obesity drove the upregulation of activated NK cell-activating receptor (NKp46)+ NK cells and pro-inflammatory macrophages (MHCIIhigh Mφ) as well as CD4+ and CD8+ T cells in the normal pregnancy group. However, in the abortion-prone group, relative more immature NK cells with decreased activity phenotypes were found in obese mice. Moreover, there were increased DCreg (CD11bhigh DC) cells and decreased CD4+ and CD8+ T cells detected in the HFD abortion-prone mice relative to those fed the NCD diet. Our findings reveal how pregnancy obesity and maternal immune regulation are mutually influenced. It is worth noting that the abortion-prone model where active maternal immune status was intensified by obesity, in turn stimulated an overcompensation response, leading to an over-tolerized immune status, and predisposing to potential risks of perinatal complications.
Factors Determining Consumer Acceptance of Biofortified Food: Case of Zinc-Fortified Wheat in Pakistan's Punjab Province

Zinc (Zn) is a fundamental micronutrient required by all living organisms. Zn deficiency among children under 5 years, pregnant, and child-bearing women has been identified in developing countries such as Pakistan. Biofortified crops can increase micronutrient levels and decrease deficiencies. Meanwhile, consumer acceptance is essential, given that genetic alterations can occur during biofortification, resulting in changes in sensory traits and the quality of grains. Therefore, the present study focuses on the determining factors for consumer acceptance of Zn-biofortified wheat. , an experimental survey was conducted to achieve the study's objectives. Qualitative and quantitative data were collected and analyzed from 203 respondents in the Punjab province. The results regarding sensory perceptions revealed that people attached great importance to the appearance of the chapati prepared with Zn-biofortified wheat. Therefore, they were willing to purchase Zn-biofortified wheat when asked to choose between the conventional wheat and the Zn-biofortified wheat. Moreover, the probit model illustrates that the level of education in the family and having young children aged under 5 years in the household positively impacted the acceptance of Zn-biofortified wheat among the participants. The findings suggest that there is significant scope for promoting Zn-biofortified wheat in the country. It is also imperative to ensure its availability across various regions so that households with weak purchasing power can buy and address their Zn deficiency. Furthermore, policymakers could introduce reforms targeting business communities for food management, keeping Zn-biofortified wheat in the priority stream.