Miracle-dz/UniFAR-FTUs huggingface dataset:
Platelet Transcriptome Heterogeneity: A Role for RNA Uptake in Vascular Health and Disease

As our understanding of the platelet’s systemic role continues to expand beyond hemostasis and thrombosis, interrogation of the platelet’s ability to affect diverse biological processes is required. Studies of the platelet’s non-traditional roles have focused on developing our understanding of the platelet’s relation to specific disease phenotypes as well as elucidation of platelet characteristics, content, and function. The generic content, traditional function and heterogeneity of platelets have long been accepted; more ambiguous and controversial has been how these factors are interrelated. Investigation of platelet content revealed the presence of biologically functional RNA in anucleated platelets, the correlation of platelet RNA to distinct phenotypes, and the ability of platelets to transfer RNA to other vascular cells; however how these processes occur is unclear. To further interrogate platelet RNA processes, we utilized sorting and RNA sequencing to develop platelet subpopulation transcriptome profiles. We found that platelet heterogeneity extends to the platelet transcriptome: distinct RNA profiles exist dependent on platelet size. We hypothesized that this RNA heterogeneity is the result of RNA transfer between platelets and vascular cells. Using in vitro and in vivo modeling, we were able to show the novel ability of platelets to take up RNA from vascular cells, correlating to the unique functional profile associated with small platelet transcriptomes. These findings reveal a role for platelet RNA transfer in platelet RNA heterogeneity, with potential correlation to platelet functional diversity
Corneal endothelium tissue engineering: An evolution of signaling molecules, cells, and scaffolds toward 3D bioprinting and cell sheets

Cornea is an avascular and transparent tissue that focuses light on retina. Cornea is supported by the corneal‐endothelial layer through regulation of hydration homeostasis. Restoring vision in patients afflicted with corneal endothelium dysfunction‐mediated blindness most often requires corneal transplantation (CT), which faces considerable constrictions due to donor limitations. An emerging alternative to CT is corneal endothelium tissue engineering (CETE), which involves utilizing scaffold‐based methods and scaffold‐free strategies. The innovative scaffold‐free method is cell sheet engineering, which typically generates cell layers surrounded by an intact extracellular matrix, exhibiting tunable release from the stimuli‐responsive surface. In some studies, scaffold‐based or scaffold‐free technologies have been reported to achieve promising outcomes. However, yet some issues exist in translating CETE from bench to clinical practice. In this review, we compare different corneal endothelium regeneration methods and elaborate on the application of multiple cell types (stem cells, corneal endothelial cells, and endothelial precursors), signaling molecules (growth factors, cytokines, chemical compounds, and small RNAs), and natural and synthetic scaffolds for CETE. Furthermore, we discuss the importance of three‐dimensional bioprinting strategies and simulation of Descemet's membrane by biomimetic topography. Finally, we dissected the recent advances, applications, and prospects of cell sheet engineering for CETE.
Structural analysis of full-length SARS-CoV-2 spike protein from an advanced vaccine candidate

Structure of a vaccine candidate Much effort is being targeted at developing vaccines that will provide protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A trimeric spike protein that decorates the virus is a primary target of the host immune system and the focus of vaccine development. Bangaru et al. present the structure of a leading vaccine candidate: a full-length spike protein with some modifications aimed at enhancing stability that is formulated in polysorbate 80 detergent. The study confirms that the full-length immunogen is in a stable prefusion conformation and provides a basis for understanding immune responses to the vaccine. Science, this issue p. 1089 Cryo-EM and glycan analysis of a leading SARS-CoV-2 subunit vaccine candidate reveals a stable prefusion conformation of the spike immunogen. Vaccine efforts to combat the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for the current coronavirus disease 2019 (COVID-19) pandemic, are focused on SARS-CoV-2 spike glycoprotein, the primary target for neutralizing antibodies. We performed cryo–election microscopy and site-specific glycan analysis of one of the leading subunit vaccine candidates from Novavax, which is based on a full-length spike protein formulated in polysorbate 80 detergent. Our studies reveal a stable prefusion conformation of the spike immunogen with slight differences in the S1 subunit compared with published spike ectodomain structures. We also observed interactions between the spike trimers, allowing formation of higher-order spike complexes. This study confirms the structural integrity of the full-length spike protein immunogen and provides a basis for interpreting immune responses to this multivalent nanoparticle immunogen.
Automatic Telerehabilitation System in a Home Environment Using Computer Vision

In this paper, we follow up on research dealing with body tracking and motor rehabilitation. We describe the current situation in telerehabilitation in the home environment. Existing solutions do not allow wide adoption due to hardware requirements and complicated setup. We come with the possibility of telerehabilitation using only laptop or mobile web camera. Together with physiotherapists, we have compiled a set of complex motor exercises to show that the system can be practically used.
The antinociceptive properties of an isoform-selective inhibitor of Nav1.7 derived from saxitoxin in mouse models of pain.

The voltage gated sodium channel Nav1.7 is highly expressed in nociceptive afferents and is critically involved in pain signal transmission. Nav1.7 is a genetically validated pain target in humans, as loss-of-function mutations cause congenital insensitivity to pain, and gain-of-function mutations cause severe pain syndromes. Consequently pharmacological inhibition has been investigated as an analgesic therapeutic strategy. We describe a small molecule Nav1.7 inhibitor, ST-2530, that is an analog of the naturally occurring sodium channel blocker saxitoxin. When evaluated against human Nav1.7 by patch clamp electrophysiology using a protocol that favors the resting state, the Kd of ST-2530 was 25 ± 7 nM. ST-2530 exhibited greater than 500-fold selectivity over human voltage gated sodium channel isoforms Nav1.1-Nav1.6 and Nav1.8. While ST-2530 had lower affinity against mouse Nav1.7 (Kd = 250 ± 40 nM), potency was sufficient to assess analgesic efficacy in mouse pain models. A 3 mg/kg dose administered subcutaneously was broadly analgesic in acute pain models employing noxious thermal, mechanical, and chemical stimuli. ST-2530 also reversed thermal hypersensitivity following a surgical incision on the plantar surface of the hind paw. In the spared nerve injury model of neuropathic pain, ST-2530 transiently reversed mechanical allodynia. These analgesic effects were demonstrated at doses that did not affect locomotion, motor coordination or olfaction. Collectively, results from the present study indicate that pharmacological inhibition of Nav1.7 by a small molecule agent with affinity for the resting state of the channel is sufficient to produce analgesia in a range of preclinical pain models.
HIV Protease Inhibitors Block HPV16-Induced Murine Cervical Carcinoma and Promote Vessel Normalization in Association with MMP-9 Inhibition and TIMP-3 Induction

Antiretrovirals belonging to the human immunodeficiency virus (HIV) protease inhibitor (HIV-PI) class exert inhibitory effects across several cancer types by targeting tumor cells and its microenvironment. Cervical carcinoma represents a leading cause of morbidity and mortality, particularly in women doubly infected with high-risk human papillomaviruses (HR-HPV) and HIV; of note, combined antiretroviral therapy has reduced cervical carcinoma onset and progression in HIV-infected women. We evaluated the effectiveness and mechanism(s) of action of HIV-PI against cervical carcinoma using a transgenic model of HR-HPV–induced estrogen-promoted cervical carcinoma (HPV16/E2) and found that treatment of mice with ritonavir-boosted HIV-PI, including indinavir, saquinavir, and lopinavir, blocked the growth and promoted the regression of murine cervical carcinoma. This was associated with inhibition of tumor angiogenesis, coupled to downregulation of matrix metalloproteinase (MMP)-9, reduction of VEGF/VEGFR2 complex, and concomitant upregulation of tissue inhibitor of metalloproteinase-3 (TIMP-3). HIV-PI also promoted deposition of collagen IV at the epithelial and vascular basement membrane and normalization of both vessel architecture and functionality. In agreement with this, HIV-PI reduced tumor hypoxia and enhanced the delivery and antitumor activity of conventional chemotherapy. Remarkably, TIMP-3 expression gradually decreased during progression of human dysplastic lesions into cervical carcinoma. This study identified the MMP-9/VEGF proangiogenic axis and its modulation by TIMP-3 as novel HIV-PI targets for the blockade of cervical intraepithelial neoplasia/cervical carcinoma development and invasiveness and the normalization of tumor vessel functions. These findings may lead to new therapeutic indications of HIV-PI to treat cervical carcinoma and other tumors in either HIV-infected or uninfected patients.
Genetic Architecture Underpinning Yield Components and Seed Mineral–Nutrients in Sesame

Genetic dissection of yield components and seed mineral-nutrient is crucial for understanding plant physiological and biochemical processes and alleviate nutrient malnutrition. Sesame (Sesamum indicum L.) is an orphan crop that harbors rich allelic repertoire for seed mineral–nutrients. Here, we harness this wide diversity to study the genetic architecture of yield components and seed mineral–nutrients using a core-collection of worldwide genotypes and segregating mapping population. We also tested the association between these traits and the effect of seed nutrients concentration on their bio-accessibility. Wide genetic diversity for yield components and seed mineral–nutrients was found among the core-collection. A high-density linkage map consisting of 19,309 markers was constructed and used for genetic mapping of 84 QTL associated with yield components and 50 QTL for seed minerals. To the best of our knowledge, this is the first report on mineral–nutrients QTL in sesame. Genomic regions with a cluster of overlapping QTL for several morphological and nutritional traits were identified and considered as genomic hotspots. Candidate gene analysis revealed potential functional associations between QTL and corresponding genes, which offers unique opportunities for synchronous improvement of mineral–nutrients. Our findings shed-light on the genetic architecture of yield components, seed mineral–nutrients and their inter- and intra- relationships, which may facilitate future breeding efforts to develop bio-fortified sesame cultivars.
Secondary Crystalline Phases Influence on Optical Properties in Off-Stoichiometric Cu2S–ZnS–SnS2 Thin Films

Cu2ZnSnS4 (CZTS) is an economically and environmentally friendly alternative to other toxic and expensive materials used for photovoltaics, however, the variation in the composition during synthesis is often followed by the occurrence of the secondary binary and ternary crystalline phases. These phases produce changes in the optical absorption edge important in cell efficiency. We explore here the secondary phases that emerge in a combinatorial Cu2S–ZnS–SnS2 thin films library. Thin films with a composition gradient were prepared by simultaneous magnetron sputtering from three binary chalcogenide targets (Cu2S, SnS2 and ZnS). Then, the samples were crystallized by sulfurization annealing at 450 °C under argon flow. Their composition was measured by energy dispersive X-ray spectroscopy (EDX), whereas the structural and optical properties were investigated by grazing incidence X-ray diffraction (GIXRD), Raman spectroscopy and optical transmission measurements. As already known, we found that annealing in a sulfur environment is beneficial, increasing the crystallinity of the samples. Raman spectroscopy revealed the presence of CZTS in all the samples from the library. Secondary crystalline phases such as SnS2, ZnS and Cu–S are also formed in the samples depending on their proximity to the binary chalcogenide targets. The formation of ZnS or Cu–S strongly correlates with the Zn/Sn and Cu/Zn ratio of the total sample composition. The presence of these phases produces a variation in the bandgap between 1.41 eV and 1.68 eV. This study reveals that as we go further away from CZTS in the composition space, in the quasi-ternary Cu2S–ZnS–SnS2 diagram, secondary crystalline phases arise and increase in number, whereas the bandgap takes values outside the optimum range for photovoltaic applications.
Evaluation of Changes in the Levels of Firmicutes and Bacteroidetes Phyla of Sheep Feces Depending on the Breed

Simple Summary The microbiome plays an important role in the digestive system of ruminants. It affects the health status of animals and their development and production rates. However, its composition may be influenced by factors such as diet, age, gender, and health condition. The study was conducted on three breeds of sheep that were kept in one environment and fed with the same feed. The microbiological analysis showed that the animal microbiome is also influenced by breed. Abstract Studies carried out so far have indicated the effect of the microbiome on the composition of ruminant products. Recent studies have shown that not only diet, but also genetic factors can affect the microbiological composition of the digestive system. The aim of the study was to determine the differences in the levels of selected bacterial phyla in terms of breed differences. Three sheep breeds, i.e., Olkuska, Romanov, and old-type Polish Merino, differing in their use (meat–wool, meat, prolificacy) and country of breed origin were included in the study. Sheep at the same age and of the same sex were kept for a period of 3 months in the same environmental conditions and fed the same feed in the same proportions. The study included real-time PCR (polymerase chain reaction) analysis of feces collected before the slaughter and measurements of body weight and chilled carcasses. The obtained results showed significant differences between the breeds in the levels of bacterial populations tested. There were also differences in body weight between the breeds during the first weight measurements, however, the final results did not show any differences—after three months of maintenance all of them reached similar body weights, despite differences in fecal microbiological composition. The study suggests that in addition to diet and environmental conditions, the microbiology can also be influenced by breed.
Outcomes and adverse effects of ablative vs nonablative lasers for skin resurfacing: A systematic review of 1093 patients

It is generally believed that ablative laser therapies result in prolonged healing and greater adverse events when compared with nonablative lasers for skin resurfacing. To evaluate the efficacy of ablative laser use for skin resurfacing and adverse events as a consequence of treatment in comparison to other modalities, a PRISMA‐compliant systematic review (Systematic Review Registration Number: 204016) of twelve electronic databases was conducted for the terms “ablative laser” and “skin resurfacing” from March 2002 until July 2020. Studies included meta‐analyses, randomized control trials, cohort studies, and case reports to facilitate evaluation of the data. All articles were evaluated for bias. The search strategy produced 34 studies. Of 1093 patients included in the studies of interest, adverse events were reported in a total of 106 patients (9.7%). Higher rates of adverse events were described in nonablative therapies (12.2% ± 2.19%, 31 events) when compared with ablative therapy (8.28% ± 2.46%, 81 events). 147 patients (13.4%) reported no side effects, 68 (6.22%) reported expected, transient self‐resolving events, and five (0.046%) presented with hypertrophic scarring. Excluding transient events, ablative lasers had fewer complications overall when compared with nonablative lasers (2.56% ± 2.19% vs 7.48% ± 3.29%). This systematic review suggests ablative laser use for skin resurfacing is a safe and effective modality to treat a range of pathologies from photodamage and acne scars to hidradenitis suppurativa and posttraumatic scarring from basal cell carcinoma excision. Further studies are needed, but these results suggest that ablative lasers are a superior, safe, and effective modality to treat damaged skin.
Bidirectional pathways between psychosocial risk factors and paranoid ideation in a general nonclinical population

Abstract We investigated (a) whether psychosocial factors (experienced stress, anticipatory worry, social detachment, sleeping disturbances, alcohol use) predict the course of paranoid ideation between the ages of 24 to 50 years and (b) whether the predictive relationships are more likely to proceed from the psychosocial factors to paranoid ideation, or vice versa. The participants (N = 1534–1553) came from the population-based Young Finns study. Paranoid ideation and psychosocial factors were assessed by reliable self-report questionnaires in 2001, 2007, and 2011/2012. The data were analyzed using growth curve and structural equation models. High experienced stress, anticipatory worry, social detachment, frequent sleeping disturbances, and frequent alcohol use predicted more paranoid ideation. More risk factors predicted increasing paranoid ideation. There were bidirectional predictive relationships of paranoid ideation with experienced stress, anticipatory worry, social detachment, and sleeping disturbances. The link between alcohol use and paranoid ideation was only correlative. In conclusion, paranoid ideation increases by reciprocal interactions with stress, worry, social detachment, and sleeping disturbances. The findings support the threat–anticipation model of paranoid ideation, providing important implications for treatment of paranoia.
Detection of subjects with ischemic heart disease by using machine learning technique based on heart rate total variability parameters

Objective: Ischemic heart disease (IHD), in its chronic stable form, is a subtle pathology due to its silent behavior before developing in unstable angina, myocardial infarction or sudden cardiac death. The clinical assessment is based on typical symptoms and finally confirmed, invasively, by coronary angiography. Recently, heart rate variability (HRV) analysis as well as some machine learning algorithms like artificial neural networks (ANNs) were used to identify cardiovascular arrhythmias and, only in few cases, to classify IHD segments in a limited number of subjects. The goal of this study was the identification of the ANN structure and the HRV parameters producing the best performance to identify IHD patients in a non-invasive way, validating the results on a large sample of subjects. Moreover, we examined the influence of a clinical non-invasive parameter, the left ventricular ejection fraction (LVEF), on the classification performance. Approach: To this aim, we extracted several linear and non-linear parameters from 24 h RR signal, considering both normal and ectopic beats (heart rate total variability), of 251 normal and 245 IHD subjects, matched by age and gender. ANNs using several different combinations of these parameters together with age and gender were tested. For each ANN, we varied the number of hidden neurons from 2 to 7 and simulated 100 times, changing randomly the training and test dataset. Main results: The HRTV parameters showed significant greater variability in IHD than in normal subjects. The ANN applied to mean RR, LF, LF/HF, beta exponent, SD2 together with age and gender reached a maximum accuracy of 71.8% and, by adding as input LVEF, an accuracy of 79.8%. Significance: The study provides a deep insight into how a combination of some HRTV parameters and LVEF could be exploited to reliably detect the presence of subjects affected by IHD.
Paternal rejection, psychological maladjustment, and child emotional eating: Path analysis in 8- to 11-year-old boys and girls

We examined the impact of paternal rejection (based on father’s and children’s reports) on the children’s emotional eating behavior and if child psychological maladjustment mediated this relationship. Three hundred sixty-nine dyads of fathers and children were screened using self-report measures of demographic data, parental rejection, child psychological maladjustment, and disordered eating behavior. Children’s subjective perceptions of relationship with father have more impact on their psychological outcomes and unhealthy dietary patterns than father reported parenting quality. Children’s unhealthy psychological adjustment may be an essential underlying mechanism linking perceived paternal rejection of children’s emotional eating behaviors.
Guidance for Restarting Inflammatory Bowel Disease Therapy in Patients Who Withheld Immunosuppressant Medications During COVID-19

Abstract Patients with inflammatory bowel diseases [IBD] are frequently treated with immunosuppressant medications. During the coronavirus disease 2019 [COVID-19] pandemic, recommendations for IBD management have included that patients should stay on their immunosuppressant medications if they are not infected with the severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], but to temporarily hold these medications if symptomatic with COVID-19 or asymptomatic but have tested positive for SARS-CoV-2. As more IBD patients are infected globally, it is important to also understand how to manage IBD medications during convalescence while an individual with IBD is recovering from COVID-19. In this review, we address the differences between a test-based versus a symptoms-based strategy as related to COVID-19, and offer recommendations on when it is appropriate to consider restarting IBD therapy in patients testing positive for SARS-CoV-2 or with clinical symptoms consistent with COVID-19. In general, we recommend a symptoms-based approach, due to the current lack of confidence in the accuracy of available testing and the clinical significance of prolonged detection of virus via molecular testing.
A Qualitative Community Assessment of Racial/Ethnic Sexual Gender Minority Young Adults: Principles for Strategies to Motivate Action(s) for Realistic Tasks (SMART Thinking) Addressing HIV/AIDS, Viral Hepatitis, Mental Health, and Substance Abuse

HIV/STI, substance use, and mental health issues disproportionately affect racial/ethnic sexual minority young adults. These health vulnerabilities intensify across the life course, most notably when young adults are independent college students. To identify the perspectives of racial/ethnic sexual gender minorities living on or near an urban university, we implemented an intersectionality-informed SWOT (strengths, weakness, opportunities, and threats) analysis, as a qualitative community assessment situated within in a campus-community setting. The community needs assessment was the first step in the strategic prevention framework (SPF) to co-locate substance abuse, mental health, viral hepatitis, and HIV prevention care services for Latinx and Black/African American sexual gender minority young adults at a minority-serving institution. The SWOT analysis identified principles for selecting, adapting, and implementing an evidence-based intervention. The significance of these principles demonstrates the value of intersectionality in evidence-based interventions to influence health education and behavior among racial/ethnic sexual gender minorities.