Miracle-dz/UniFAR-FTUs huggingface dataset:
Condom use in penile-vaginal intercourse among Canadian adults: Results from the sex in Canada survey

Purpose This paper examines condom use in penile-vaginal sexual intercourse among adults in Canada. Data and method The Sex in Canada survey is a national survey of Canadian adults, ages 18+ (N = 2,303). The online survey used quota-based population sample matching of 2016 census targets for gender, age, region, language, visible minority status, and education level. We report general patterns of self-reported condom use, as well as results from zero-inflated negative binomial regression models on the relationship between condom use and social location, relationship status, and sexual health. Results Condom use varies by gender, age, education, visible minority status, and relationship status. Use of condoms is related to the perception of risk of being diagnosed with a sexually transmitted infection in the next six months and to the experience of receiving lessons in condom use. No significant associations were found between condom use and region, rural/urban residence, income, or religion. Among men, but not women, condom use is associated with language preference, past diagnosis with a sexually transmitted infection, and self-reported sexual health. Conclusion Canadian adults report using a condom in approximately 30% of their sexual encounters involving penile-vaginal sex. Condom use is highest among young adults. Single people use condoms more often than people with marital or common-law partners. Condom use is higher among those with higher levels of education, among people belonging to visible minorities relative to white people, and for men relative to women. People who think they are likely to be diagnosed with a sexually transmitted infection in the next six months are more likely to use condoms than those who do not.
SMCHD1 promotes ATM‐dependent DNA damage signaling and repair of uncapped telomeres

Structural maintenance of chromosomes flexible hinge domain‐containing protein 1 (SMCHD1) has been implicated in X‐chromosome inactivation, imprinting, and DNA damage repair, and mutations in SMCHD1 can cause facioscapulohumeral muscular dystrophy. More recently, SMCHD1 has also been identified as a component of telomeric chromatin. Here, we report that SMCHD1 is required for DNA damage signaling and non‐homologous end joining (NHEJ) at unprotected telomeres. Co‐depletion of SMCHD1 and the shelterin subunit TRF2 reduced telomeric 3′‐overhang removal in time‐course experiments, as well as the number of chromosome end fusions. SMCHD1‐deficient cells displayed reduced ATM S1981 phosphorylation and diminished formation of γH2AX foci and of 53BP1‐containing telomere dysfunction‐induced foci (TIFs), indicating defects in DNA damage checkpoint signaling. Removal of TPP1 and subsequent activation of ATR signaling rescued telomere fusion events in TRF2‐depleted SMCHD1 knockout cells. Together, these data indicate that SMCHD1 depletion reduces telomere fusions in TRF2‐depleted cells due to defects in ATM‐dependent checkpoint signaling and that SMCHD1 mediates DNA damage response activation upstream of ATM phosphorylation at uncapped telomeres.
Combined Effect of HPV and Several Gene SNPs in Laryngeal Cancer

Background and objectives: Laryngeal squamous cell carcinoma (LSCC) is one of the most common head and neck tumors. The molecular mechanism of LSCC remains unclear. The aim of this study was to evaluate the prevalence of Human papillomavirus (HPV) and single nucleotide polymorphisms (SNPs) of TP53, MDM2, MDM4, MTHFR, CASP8, and CCR5 genes in LSCC, and to assess their correlations with patient survival. Materials and Methods: 49 LSCC patients were enrolled in this study. PCR and qRT-PCR were used to detect, identify, and quantify HPV. SNPs were genotyped using PCR and PCR-RFLP. Results: By analyzing the interactions of the SNPs of the genes with clinical parameters, the majority of patients with lymph node status (N1,2) were identified as carriers of MDM2 T/G, CASP8 ins/del, CCR5 wt/wt SNP. Cluster analysis showed that patients with MDM2 T/T SNP survive longer than patients identified as CASP8 ins/ins, MTHFR C/C, and MDM4 A/A variant carriers; meanwhile, LSCC patients with MDM2 T/T polymorphic variant had the best survival. Multivariate analysis showed that HPV-positive patients without metastasis in regional lymph nodes (N0) and harboring CASP8 ins/del variant had the best survival. Meanwhile, HPV-negative patients with identified metastasis in lymph nodes (N1 and N2) and CASP8 ins/del variant had poor survival. Conclusions: This finding suggests patients survival prognosis and tumor behavior are different according HPV status, SNP variants, and clinical characteristics of the LSCC.
Short and simple sequences favored the emergence of N-helix phospho-ligand binding sites in the first enzymes

Significance The first enzymes emerged ∼4 billion y ago and have subsequently become the most diverse and functionally important component of life. But what were the first enzymes doing and how did they look? We probed the properties of the first enzymes by analyzing phospho-ligand binding across all known protein evolutionary lineages. We find that phospho-ligand binding was the founding function of the most ancient enzymes. As opposed to younger evolutionary lineages, ancient enzymes preferentially use N termini of α-helices to bind phosphate moieties. The dominance of N-helix binding sites in the earliest enzymes reflects the ability of the α-helix to realize binding via short and simple sequences, including serines and threonines that interact via both the backbone and side chain. The ubiquity of phospho-ligands suggests that phosphate binding emerged at the earliest stage of protein evolution. To evaluate this hypothesis and unravel its details, we identified all phosphate-binding protein lineages in the Evolutionary Classification of Protein Domains database. We found at least 250 independent evolutionary lineages that bind small molecule cofactors and metabolites with phosphate moieties. For many lineages, phosphate binding emerged later as a niche functionality, but for the oldest protein lineages, phosphate binding was the founding function. Across some 4 billion y of protein evolution, side-chain binding, in which the phosphate moiety does not interact with the backbone at all, emerged most frequently. However, in the oldest lineages, and most characteristically in αβα sandwich enzyme domains, N-helix binding sites dominate, where the phosphate moiety sits atop the N terminus of an α-helix. This discrepancy is explained by the observation that N-helix binding is uniquely realized by short, contiguous sequences with reduced amino acid diversity, foremost Gly, Ser, and Thr. The latter two amino acids preferentially interact with both the backbone amide and the side-chain hydroxyl (bidentate interaction) to promote binding by short sequences. We conclude that the first αβα sandwich domains emerged from shorter and simpler polypeptides that bound phospho-ligands via N-helix sites.
TOWARDS CREDIBLE PATIENT-CENTERED META-ANALYSIS.

Meta-analysis is widely used to combine the findings of multiple disparate studies of health risks or treatment response. Meta-analysis often uses a random-effects model to express heterogeneity across studies. The model interprets a weighted average of study-specific estimates as an estimate of a mean parameter across a hypothetical population of studies. The relevance of this methodology to patient care is not evident. Clinicians need to assess risks and choose treatments for populations of patients, not for populations of studies. This paper draws on econometric research on partial identification to propose principles for patient-centered meta-analysis. One specifies a patient prediction of concern and determines what each available study reveals. Given common imperfections in internal and external validity, studies typically yield credible set-valued rather than point predictions. Thus, a study may enable one to conclude that a probability of disease, or mean treatment response, lies within a range of possibilities. Patient-centered meta-analysis would combine the findings of multiple studies by computing the intersection of the set-valued predictions that they yield.
Ancient Origins of Allosteric Activation in a Ser/Thr Kinase

Evolution of a kinase allosteric site Enzyme activity is often regulated by conformational changes coupled to binding of an effector at an allosteric site, a feature especially important for enzymes involved in signaling cascades. Hadzipasic et al. studied the origins of allosteric regulation of Aurora A, a kinase involved in progression of the eukaryotic cell cycle. Aurora A is allosterically regulated through the binding of an effector protein named TPX2, which also targets the kinase to spindle microtubules. By reconstructing ancestor kinase sequences, they found that TPX2 bound to an early Aurora A but had very weak activation that was gradually strengthened by evolution of an allosteric network within the kinase. An evolutionary advantage from localizing the active protein at the mitotic spindle may have driven the development of this regulatory mechanism. Science, this issue p. 912 Ancestor reconstruction reveals a path in the evolution of an allosteric regulatory mechanism in Aurora kinase. A myriad of cellular events are regulated by allostery; therefore, evolution of this process is of fundamental interest. Here, we use ancestral sequence reconstruction to resurrect ancestors of two colocalizing proteins, Aurora A kinase and its allosteric activator TPX2 (targeting protein for Xklp2), to experimentally characterize the evolutionary path of allosteric activation. Autophosphorylation of the activation loop is the most ancient activation mechanism; it is fully developed in the oldest kinase ancestor and has remained stable over 1 billion years of evolution. As the microtubule-associated protein TPX2 appeared, efficient kinase binding to TPX2 evolved, likely owing to increased fitness by virtue of colocalization. Subsequently, TPX2-mediated allosteric kinase regulation gradually evolved. Surprisingly, evolution of this regulation is encoded in the kinase and did not arise by a dominating mechanism of coevolution.
A Feasible Method for Quantifying Living Pancreatic Human Islets in Murine Livers Posttransplantation by Confocal Laser Scanning Microscopy

Background. Current histological methods cannot accurately determine the survival rate of human pancreatic islets following portal vein infusion. This is due, in part, to the low number of infused islets relative to the whole liver. In this study, we assessed the ability of confocal laser scanning microscopy (CLSM) to track human islets posttransplantation. Methods. Immunodeficient mice were transplanted with human islets. Following engraftment, animals were euthanized, livers procured, and human islet β cells immunofluorescently labeled with an insulin-specific antibody and evaluated by CLSM. A calibration curve comparing the area of insulin + hepatic islet β cells to the number of human islets collected was developed. Levels of human C-peptide were measured in transplant recipients to determine islet function. Results. The short-term survival rate of islet transplants was defined as y = 0.0422x + 2.7008, in which x is human islet number and y is liver islet β cell area. Employing CLSM, human islets were detected in immunofluorescent labeled murine liver tissue sections posttransplantation. The β cell-relative area of human islets in 500 islet equivalent (IEQ) specimens was 20.21 ± 1.16 mm2 and in 1000 IEQ specimens 39.4 ± 2.23 mm2 posttransplantation. Human islet posttransplant survival rates were 82.9 ± 5.50% (500 IEQ group) and 86.9 ± 5.28% (1000 IEQ group). Conclusions. These data indicate that CLSM can be employed to quantify and characterize pancreatic human islets after transplantation to murine livers.
Relationships between Foot Morphology and Foot Muscle Strength in Healthy Adults

The purpose of this study was to investigate if measurements of foot morphology in sitting and standing positions can predict foot muscle strength. Twenty-six healthy male adults were recruited, and their foot morphology and foot muscle strength were measured. Foot morphological variables, toe flexor strength, and metatarsophalangeal joint flexor strength were measured by using a digital caliper, Ailitech-AFG500 dynameter and metatarsophalangeal joint flexor strength tester, respectively. Partial correlation and multivariate stepwise regression were used to explore the relationships between foot morphology and toe/metatarsophalangeal joint strength. Results adjusted by age and body mass index were as follows: (1) truncated foot length in sitting and standing positions and foot width in standing position were positively correlated with the flexor strength of the first toe; (2) foot length, foot width, and truncated foot length in both positions were positively related to the flexor strength of the other toes; (3) arch height index in sitting position and differences in navicular height were negatively associated with the flexor strength of the other toes; (4) differences in foot width were negatively associated with metatarsophalangeal joint flexor strength; and (5) the multivariate stepwise regression model showed that truncated foot length in sitting position, navicular height in standing position, differences in navicular height, foot width in sitting position, and differences in foot width were significantly correlated with toe/metatarsophalangeal joint flexor strength. Simple measurements of foot morphological characteristics can effectively predict foot muscle strength. Preliminary findings provided practical implications for the improvement of the foot ability by making specific foot muscle training sessions in professional sports and by compensating the predicted muscle strength defects to prevent foot injury.
Electrochemical Impedance Characterization of Blood Cell Suspensions. Part 1: Basic Theory and Application to Two-Phase Systems

Electrochemical impedance spectra of composite materials contain information on the topological arrangement, volume fraction, and shape of particles, as well as the dielectric properties of the matrix and particles. The objective of this study is to investigate how these parameters affect the dielectric spectrum and what reliable information can be extracted from experimental data. The main attention was focused on systems with dielectric behavior similar to that of human blood. Mostly plasma and erythrocytes determine the dielectric properties of whole blood. Erythrocytes suspended in plasma can be considered as three-phase systems with single-shelled particles. A theoretical approach based on the effective medium theory is developed for calculating the effective permittivity and conductivity of three-phase composites at a wide frequency range (from 0 to 1 GHz). A finite-difference method is applied to model three-dimensional periodic structures. A special case of two-phase materials is used to demonstrate the influence of the shape and arrangement of particles on dielectric properties. Theoretical and numerical approaches are applied to two-phase composites with spherical, spheroidal and biconcave particles and are compared with each other and with published data. It is shown that two-phase composites exhibit only β-dispersion. In contrast to the quasi-static limit, the wide-bandwidth impedance spectroscopy makes it possible to distinguish between disordered and regular arrangements of spheroidal and biconcave particles. The results can be used to analyze the dielectric properties of blood, which is very promising for various medical applications. This study of two-phase composites can be further extended to three-phase composites.
Editorial: Systematic reviews reveal a need for more, better data to inform antimicrobial stewardship practices in animal agriculture

Abstract This editorial summarizes the key observations from a special issue of Animal Health Research Reviews comprising 14 articles related to the efficacy of antimicrobial and non-antimicrobial approaches to reduce disease in beef, dairy cattle, swine, and broiler chickens. The articles used evidence-based methods, including scoping reviews, systematic reviews, meta-analyses, and network meta-analyses. Despite finding evidence of efficacy for some of the interventions examined, across the body of research, there was a lack of replication and inconsistency in outcomes among the included trials, and concerns related to completeness of reporting and trial design and execution. There is an urgent need for more and better data to inform antimicrobial stewardship practices in animal agriculture.
Platelet Concentrates in Musculoskeletal Medicine

Platelet concentrates (PCs), mostly represented by platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) are autologous biological blood-derived products that may combine plasma/platelet-derived bioactive components, together with fibrin-forming protein able to create a natural three-dimensional scaffold. These types of products are safely used in clinical applications due to the autologous-derived source and the minimally invasive application procedure. In this narrative review, we focus on three main topics concerning the use of platelet concentrate for treating musculoskeletal conditions: (a) the different procedures to prepare PCs, (b) the composition of PCs that is related to the type of methodological procedure adopted and (c) the clinical application in musculoskeletal medicine, efficacy and main limits of the different studies.
A Low-Cost Lower-Limb Brain-Machine Interface Triggered by Pedaling Motor Imagery for Post-Stroke Patients Rehabilitation

A low-cost Brain-Machine Interface (BMI) based on electroencephalography for lower-limb motor recovery of post-stroke patients is proposed here, which provides passive pedaling as feedback, when patients trigger a Mini-Motorized Exercise Bike (MMEB) by executing pedaling motor imagery (MI). This system was validated in an On-line phase by eight healthy subjects and two post-stroke patients, which felt a closed-loop commanding the MMEB due to the fast response of our BMI. It was developed using methods of low-computational cost, such as Riemannian geometry for feature extraction, Pair-Wise Feature Proximity (PWFP) for feature selection, and Linear Discriminant Analysis (LDA) for pedaling imagery recognition. The On-line phase was composed of two sessions, where each participant completed a total of 12 trials per session executing pedaling MI for triggering the MMEB. As a result, the MMEB was successfully triggered by healthy subjects for almost all trials (ACC up to 100%), while the two post-stroke patients, PS1 and PS2, achieved their best performance (ACC of 41.67% and 91.67%, respectively) in Session #2. These patients improved their latency (2.03 ± 0.42 s and 1.99 ± 0.35 s, respectively) when triggering the MMEB, and their performance suggests the hypothesis that our system may be used with chronic stroke patients for lower-limb recovery, providing neural relearning and enhancing neuroplasticity.
Main Chain–Type Block Copolymers through Atom Transfer Radical Polymerization from Double-Decker–Shaped Polyhedral Oligomeric Silsesquioxane Hybrids

In this study, we synthesized two main chain–type block copolymers featuring hydrogen bond donor and acceptor segments through atom transfer radical polymerization (ATRP) using a bifunctionalized polyhedral oligomeric silsesquioxane (POSS) nanoparticle as the initiator. Hydrosilylation of vinylbenzyl chloride at the two corners of a double-decker silsesquioxane (DDSQ) provided the bifunctionalized benzyl chloride initiator VBC-DDSQ-VBC, which we applied as a platform to prepare a main chain–type polystyrene homopolymer (PS-DDSQ-PS), the diblock copolymer poly(styrene–b–4-vinylpyridine) (P4VP-b-PS-DDSQ-PS-b-P4VP), and the diblock copolymer poly(styrene–b–tert-butoxystyrene) (PtBuOS-b-PS-DDSQ-PS-b-PtBuOS) through sequential ATRP. Selective hydrolysis of the tert-butoxyl units of PtBuOS-b-PS-DDSQ-PS-b-PtBuOS yielded the strongly hydrogen bonding diblock copolymer poly (styrene-b-vinylphenol) (PVPh-b-PS-DDSQ-PS-b-PVPh). We used Fourier transfer infrared spectroscopy, nuclear magnetic resonance spectroscopy, size exclusion chromatography, differential scanning calorimetry, mass-analyzed laser desorption ionization mass spectrometry, and transmission electron microscopy to investigate the chemical structures, thermal behavior, and self-assembled nanostructures formed by these main chain–type block copolymers based on DDSQ.
EP3R-Expressing Glutamatergic Preoptic Neurons Mediate Inflammatory Fever

Fever is a common phenomenon during infection or inflammatory conditions. This stereotypic rise in body temperature (Tb) in response to inflammatory stimuli is a result of autonomic responses triggered by prostaglandin E2 action on EP3 receptors expressed by neurons in the median preoptic nucleus (MnPOEP3R neurons). To investigate the identity of MnPOEP3R neurons, we first used in situ hybridization to show coexpression of EP3R and the VGluT2 transporter in MnPO neurons. Retrograde tracing showed extensive direct projections from MnPOVGluT2 but few from MnPOVgat neurons to a key site for fever production, the raphe pallidus. Ablation of MnPOVGluT2 but not MnPOVgat neurons abolished fever responses but not changes in Tb induced by behavioral stress or thermal challenges. Finally, we crossed EP3R conditional knock-out mice with either VGluT2-IRES-cre or Vgat-IRES-cre mice and used both male and female mice to confirm that the neurons that express EP3R and mediate fever are glutamatergic, not GABAergic. This finding will require rethinking current concepts concerning the central thermoregulatory pathways based on the MnPOEP3R neurons being GABAergic. SIGNIFICANCE STATEMENT Body temperature is regulated by the CNS. The rise of the body temperature, or fever, is an important brain-orchestrated mechanism for fighting against infectious or inflammatory disease, and is tightly regulated by the neurons located in the median preoptic nucleus (MnPO). Here we demonstrate that excitatory MnPO neurons mediate fever and examine a potential central circuit underlying the development of fever responses.
Transcriptomic Analysis Reveals Cu/Zn SODs Acting as Hub Genes of SODs in Hylocereus undatus Induced by Trypsin during Storage

It has been revealed by us that superoxide scavenging is a new activity of trypsin. In this study, the synergistic mechanisms of trypsin and superoxide dismutases (SODs) were evaluated in Hylocereus undatus (pitaya). Trypsin significantly improved the storage quality of H. undatus, including weight loss impediment and decrease of cellular injury. The regulatory mechanisms of 16 SOD genes by trypsin were revealed using transcriptomic analysis on H. undatus. Results revealed that important physiological metabolisms, such as antioxidant activities or metal ion transport were induced, and defense responses were inhibited by trypsin. Furthermore, the results of protein–protein interaction (PPI) networks showed that besides the entire ROS network, the tiny SODs sub-network was also a scale-free network. Cu/Zn SODs acted as the hub that SODs synergized with trypsin during the storage of H. undatus.