Miracle-dz/UniFAR-FTUs huggingface dataset:
Biomarkers for demographic research: sperm counts and other male infertility biomarkers

ABSTRACT Some male infertility biomarkers are etiologically linked to idiopathic infertility in men, the direct cause of which often cannot be determined with conventional sperm count parameters. Open questions remain regarding the universal and generic infertility definitions that cover and combine the clinical, epidemiological, and demographic perspectives. The main effort in the application of these infertility biomarkers are accounted by more or less strict discrimination criteria. For male infertility, beyond classical sperm count assessments, the DNA fragmentation index (DFI) is an adequate biomarker. DFI strongly correlates with pregnancy rates and even strict discrimination criteria for infertility outcomes. Other common biomarkers are reactive oxygen species (ROS) and antisperm antibodies (ASAs), which can explain some biomedical infertility disorders within major constraints. More frequently applied in demographic research, telomere length component analysis is based on identifying the genetic impact of cellular longevity. Sperm telomere length is becoming established as a potential biomarker in infertility research. The aim of this review is to provide an overview of the current status and limitations to the application of novel biomarkers, including TEX101, for infertility research. The review also discusses potential options for the use of biomarkers in population-based studies. Abbreviations: ASAs: antisperm antibodies; DFI: DNA fragmentation index; DNA: deoxyribonucleic acid; ECM1: extracellular matrix protein 1; FSH: follicle stimulating hormone; HS: hypospermatogenesis: IVF: in vitro fertilization; LDHC: L-lactata dehydrogenase C chain; MA: maturation arrest; microTESE: microdissection testicular sperm extraction; NOA: nonobstructive azoospermia; NP: nonprogressive; OA: obstructive azoospermia; pH: potential Hyrogenii (pH-value); PR: progressive; PTGDS: prostaglandin D synthese; ROS: reactive oxygen species; SA: semen analysis; SCO: sertoli cell only; SCSA: sperm chromatin structure assay (SCSA); TL: telomere length; TESE: testicular sperm extraction; TEX101: a glycoprotein that belongs to Ly6/urokinase type plasminogen activator receptor-like protein (uPAR)(LU) superfamily, to be a germ-cell-specific molecular sperm extraction; TUNEL: terminal deoxnucleotidyl dispersion tranferase dUTP nick-end labeling; WHO: World Health Organization
Systematic genetics and single‐cell imaging reveal widespread morphological pleiotropy and cell‐to‐cell variability

Our ability to understand the genotype‐to‐phenotype relationship is hindered by the lack of detailed understanding of phenotypes at a single‐cell level. To systematically assess cell‐to‐cell phenotypic variability, we combined automated yeast genetics, high‐content screening and neural network‐based image analysis of single cells, focussing on genes that influence the architecture of four subcellular compartments of the endocytic pathway as a model system. Our unbiased assessment of the morphology of these compartments—endocytic patch, actin patch, late endosome and vacuole—identified 17 distinct mutant phenotypes associated with ~1,600 genes (~30% of all yeast genes). Approximately half of these mutants exhibited multiple phenotypes, highlighting the extent of morphological pleiotropy. Quantitative analysis also revealed that incomplete penetrance was prevalent, with the majority of mutants exhibiting substantial variability in phenotype at the single‐cell level. Our single‐cell analysis enabled exploration of factors that contribute to incomplete penetrance and cellular heterogeneity, including replicative age, organelle inheritance and response to stress.
A novel rice fragile culm 24 mutant encodes a UDP-glucose epimerase that affects cell wall properties and photosynthesis

Abstract UDP-glucose epimerases (UGEs) are essential enzymes for catalysing the conversion of UDP-glucose (UDP-Glc) into UDP-galactose (UDP-Gal). Although UDP-Gal has been well studied as the substrate for the biosynthesis of carbohydrates, glycolipids, and glycoproteins, much remains unknown about the biological function of UGEs in plants. In this study, we selected a novel rice fragile culm 24 (Osfc24) mutant and identified it as a nonsense mutation of the FC24/OsUGE2 gene. The Osfc24 mutant shows a brittleness phenotype with significantly altered cell wall composition and disrupted orientation of the cellulose microfibrils. We found significantly reduced accumulation of arabinogalactan proteins in the cell walls of the mutant, which may consequently affect plant growth and cell wall deposition, and be responsible for the altered cellulose microfibril orientation. The mutant exhibits dwarfism and paler leaves with significantly decreased contents of galactolipids and chlorophyll, resulting in defects in plant photosynthesis. Based on our results, we propose a model for how OsUGE2 participates in two distinct metabolic pathways to co-modulate cellulose biosynthesis and cell wall assembly by dynamically providing UDP-Gal and UDP-Glc substrates.
Neurophysiological Features of Peripheral Nervous System Involvement and Immunological Profile of Patients with Primary Sjögren Syndrome

Objective The aim of this study was to evaluate the prevalence, type of neuropathy, and the relationship between the presence of autoantibodies and neuropathy development in patients with primary Sjögren syndrome (pSS). Methods Sixty-one patients with pSS underwent a complete neurological and electrophysiological examination as well as immunological tests including rheumatoid factor (RF) and autoantibodies such as antinuclear antibodies (ANA), anti-Ro/SSa, and anti-La/SSB antibodies. Results The axonal loss or demyelination were found in 39 patients (63.9%). Twenty-nine (47.5%) subjects fulfilled both clinical and electrophysiological criteria of peripheral neuropathy of predominantly axonal type. Seropositivity to both anti-Ro and anti-La antibodies was more frequently found in patients with normal nerve conduction study. Seropositivity to anti-Ro alone was present in the majority of patients with axonal neuropathy (P < 0.05). The presence of RF was associated with several electrodiagnostic signs of demyelination (P < 0.01). The ANA titer showed no independent association with neuropathy. Conclusion Peripheral neuropathy is a frequent complication in patients with pSS. Seropositivity limited to anti-Ro is associated with increased risk of axonal neuropathy in comparison to seropositivity to both anti-Ro and anti-La antibodies. Seropositivity to RF may contribute to demyelination.
Intra-guild predation (IGP) can increase or decrease prey density depending on the strength of IGP.

In consumer communities, intra-guild predation (IGP) is a commonly observed interaction that is widely believed to increase resource density. However, some recent theoretical work predicts that resource density should first decrease, and then increase as the strength of IGP increases. This occurs because weak to intermediate IGP increases the IG predator density more than it reduces the IG prey density, so that weak to intermediate IGP leads to the lowest resource density compared to weak or strong IGP. We test this prediction that basal resource density would first decrease and then increase as the strength of IGP increase. We used a well-studied system with two protozoa species engaged in IGP and three bacteria species as the basal resources. We experimentally manipulated the percentage of the IG prey population that was available to an IG predator as a proxy for IGP strength. We found that bacterial density first decreased (by ca. 25%) and then increased (by ca. 30%) as the strength of IGP increased. Using a modified version of a published IGP model, we were able to explain ∼70% of the variation in protozoa and bacterial density. Agreement of the empirical results with model predictions suggests that IGP first increased the IG predator density by consuming a small proportion of the IG prey population, which in turn increased the summed consumer density and decreased the bacterial resource density. As IGP strength increased further, the IG predator became satiated by the IG prey, which then freed the bacterial resource from predation and thus increased bacterial density. Consequently, our work shows that IGP can indeed decrease or increase basal resource density depending on its strength. Consequently, the impacts of IGP on resource density is potentially more complex than previously thought.
Endoscopic Full Thickness Resection for Gastrointestinal Tumors - Challenges and Solutions

Standard polypectomy, endoscopic mucosal resection, and endoscopic submucosal dissection (ESD) are established techniques for the treatment of gastrointestinal tumors. However, resection of submucosal tumors via ESD often results in low rates of microscopically margin-negative (R0) resection and high rates of perforation. Endoscopic full thickness resection (EFTR) overcomes this adverse event and aids in the therapeutic management of complex tumors. Multiple techniques for EFTR have been developed, each with its own advantages and disadvantages. Submucosal tunneling and non-exposed techniques are generally preferable, because the layer of overlying intact mucosa reduces the incidence of intraperitoneal contamination by the gastric fluid and dissemination of the tumor cells. However, adoption of EFTR by endoscopists in clinical practice remains low. The major challenge seems to be the technical difficulty in performing laparoscopic and/or endoscopic suturing using the currently available instruments. We developed a novel robotic endoscopic platform with suturing capabilities to overcome the technical challenges of suturing. This platform allows easy maneuvering and triangulation of the instruments, thus facilitating endoscopic suturing using robotic arms. Our studies have demonstrated that this robotic endoscopic platform with suturing capabilities is an effective and safe method for performing EFTR with endoscopic suturing.
The WIT and the WES: Tools for Categorizing and Evaluating Physician Well-Being Programs.

T here is growing awareness of a high prevalence of work-related stress and burnout in physicians, the toll it takes on physicians, its cost to institutions, and its consequences for patient care. Recognizing the need to make wellbeing a principal component of its activities, the Accreditation Council for Graduate Medical Education (ACGME) established new standards, and education and outreach activities to promote wellbeing in accredited programs and institutions. The multiple dimensions of the well-being standards and diverse needs of specialties make it important for programs and institutions to make reasoned choices about well-being interventions, well-being programs (sets of interventions targeted to groups such as residents or faculty), and methods for program evaluation. To assist in these decisions, we introduce (1) a WellBeing Interventions Typology (WIT) of various approaches, and (2) a Well-Being Evaluation Schema (WES) to facilitate robust evaluation of well-being programs.
Radiogenomic Models Using Machine Learning Techniques to Predict EGFR Mutations in Non-Small Cell Lung Cancer

Background: The purpose of this study was to build radiogenomics models from texture signatures derived from computed tomography (CT) and 18F-FDG PET-CT (FDG PET-CT) images of non-small cell lung cancer (NSCLC) with and without epidermal growth factor receptor (EGFR) mutations. Methods: Fifty patients diagnosed with NSCLC between 2011 and 2015 and with known EGFR mutation status were retrospectively identified. Texture features extracted from pretreatment CT and FDG PET-CT images by manual contouring of the primary tumor were used to develop multivariate logistic regression (LR) models to predict EGFR mutations in exon 19 and exon 20. Results: An LR model evaluating FDG PET-texture features was able to differentiate EGFR mutant from wild type with an area under the curve (AUC), sensitivity, specificity, and accuracy of 0.87, 0.76, 0.66, and 0.71, respectively. The model derived from CT texture features had an AUC, sensitivity, specificity, and accuracy of 0.83, 0.84, 0.73, and 0.78, respectively. FDG PET-texture features that could discriminate between mutations in EGFR exon 19 and 21 demonstrated AUC, sensitivity, specificity, and accuracy of 0.86, 0.84, 0.73, and 0.78, respectively. Based on CT texture features, the AUC, sensitivity, specificity, and accuracy were 0.75, 0.81, 0.69, and 0.75, respectively. Conclusion: Non-small cell lung cancer texture analysis using FGD-PET and CT images can identify tumors with mutations in EGFR. Imaging signatures could be valuable for pretreatment assessment and prognosis in precision therapy.
Visual priming influences olfactomotor response and perceptual experience of smells.

Whereas contextual influences in the visual and auditory domains have been largely documented, little is known about how chemical senses might be affected by our multi-sensory environment. In the present study, we aimed to better understand how a visual context can affect the perception of a rather pleasant (floral) and a rather unpleasant (damp) odor. To this end, 19 healthy participants performed a series of tasks including odor detection followed by perceptual evaluations of odor intensity, pleasantness, flowery and damp characters of both odors presented at two different concentrations. A visual context (either congruent or incongruent with the odor; or a neutral control context) preceded odor stimulations. Olfactomotor responses as well as response times were recorded during the detection task. Results showed an influence of the visual context on semantic and motor responses to the target odors. First, congruency between context and odor increased the saliency of the olfactory feature of the memory trace, for the pleasant floral odor only (higher perceived flowery note). Clinical applications of this finding for olfactory remediation in dysosmic patients are proposed. Second, the unpleasant odor remained unaffected by visual primes, whatever the condition. In addition, incongruency between context and odor (regardless of odor type) had a disruptive effect on odor sampling behavior, which was interpreted as a protective behavior in response to expectancy violation. Altogether, this second series of effects may serve an adaptive function, especially the avoidance of, or simply vigilance towards, aversive and unpredictable stimuli.
Development of an effective microsatellite marker system to determine the genetic structure of Meriones meridianus populations

Understanding the genetic quality of the gerbil, Meriones meridianus, plays an important role in the study of medical biology. However, no effective system has been established for evaluating a population’s genetic diversity to date. In the present study, we established a set of reasonable evaluative systems based on microsatellite markers of the Mongolian gerbil by using the method of cross-amplification of species. Following electrophoresis analysis, short tandem repeat (STR) scanning, and sequencing, 11 microsatellite loci were identified by matching the criteria characteristics and were used to evaluate the genetic diversity of two stocks of Meriones meridianus: Meriones meridianus jei Wang, 1964 (M. m. jei) and Meriones meridianus cryptorhinus Blanford, 1875 (M. m. cryptorhinus) from Xinjiang, China. The microsatellite loci screened were highly polymorphic and were suitable for genetic quality control of Meriones meridianus. In addition, the quality of the non-bred M. m. jei and M. m. cryptorhinus strains in our study is sufficient for them to be promising stocks in the future for the farmed animal industry.
Advantages and detection of phase coding in the absence of rhythmicity

The encoding of information in spike phase relative to local field potential (LFP) oscillations offers several theoretical advantages over equivalent firing rate codes. One notable example is provided by place and grid cells in the rodent hippocampal formation, which exhibit phase precession—firing at progressively earlier phases of the 6–12 Hz movement‐related theta rhythm as their spatial firing fields are traversed. It is often assumed that such phase coding relies on a high amplitude baseline oscillation with relatively constant frequency. However, sustained oscillations with fixed frequency are generally absent in LFP and spike train recordings from the human brain. Hence, we examine phase coding relative to LFP signals with broadband low‐frequency (2–20 Hz) power but without regular rhythmicity. We simulate a population of grid cells that exhibit phase precession against a baseline oscillation recorded from depth electrodes in human hippocampus. We show that this allows grid cell firing patterns to multiplex information about location, running speed and movement direction, alongside an arbitrary fourth variable encoded in LFP frequency. This is of particular importance given recent demonstrations that movement direction, which is essential for path integration, cannot be recovered from head direction cell firing rates. In addition, we investigate how firing phase might reduce errors in decoded location, including those arising from differences in firing rate across grid fields. Finally, we describe analytical methods that can identify phase coding in the absence of high amplitude LFP oscillations with approximately constant frequency, as in single unit recordings from the human brain and consistent with recent data from the flying bat. We note that these methods could also be used to detect phase coding outside of the spatial domain, and that multi‐unit activity can substitute for the LFP signal. In summary, we demonstrate that the computational advantages offered by phase coding are not contingent on, and can be detected without, regular rhythmicity in neural activity.
The STRIVE Initiative: A Resident-Led Mentorship Framework for Underrepresented Minority Medical Students.

Background Underrepresented minority (URM) trainees face unique challenges in academic medicine. Near-peer mentorship is an under-described method to support URM trainees. Objective We created and evaluated the Student to Resident Institutional Vehicle for Excellence (STRIVE) program in a large urban medical school and associated residency programs. Methods All URM residents were invited to participate in the STRIVE mentorship program consisting of 3 pillars of programming: medical school curriculum review sessions, panel discussions, and social events for medical students. The program was evaluated through participation rates and a 7-item survey delivered in May 2019 after 3 years of implementation. Results The STRIVE initiative conducted 25 events. Thirty-five of 151 eligible (23%) URM residents participated as mentors for an average of 50 of 110 eligible (45%) URM medical students annually. Resident mentors participated for an average of 3 to 4 hours each year. Twenty of 32 eligible resident mentors (63%) completed the survey. Ninety-five percent (19 of 20) of survey respondents agreed that STRIVE made them a better mentor; 90% (18 of 20) reported that they would have appreciated an equivalent program during their medical school training; and 75% (15 of 20) agreed that the program helped them address the challenges of underrepresentation in medicine. Conclusions Over a 3-year period, STRIVE required a modest amount of resident time and was valued by the URM residents and medical students who participated in the program.
Too Much on Your “Plate”? Spectrum of Pathologies Involving the Tectal Plate

The tectal plate comprises the posterior portion of the midbrain, borders the quadrigeminal cistern, and includes the superior and inferior colliculi. Benign and malignant pathologies occurring in this location may lead to aqueductal stenosis, obstructive hydrocephalus, and Parinaud syndrome. Both computed tomography and magnetic resonance imaging can be used to further characterize lesions involving the tectal plate. In this pictorial essay, we review various tectal plate lesions and their imaging features.
Acquired hemophilia A

Abstract Acquired inhibitors of coagulation are a group of rare but potentially life-threatening blood disorders characterized by the presence of autoantibodies directed against clotting factor. Autoantibody against factor VIII is the most common form of clotting factor inhibitor, a condition also known as acquired hemophilia A. We present a clinical series of nine patients diagnosed and treated for acquired hemophilia A at our institution. Among these nine patients, there were five men and four women with a median age of 64 years. All patients presented with bleeding diathesis. Factor eight inhibitor bypassing agent and/or recombinant factor VIIa were predominantly used for control of active bleeding. For elimination of autoantibodies, either steroids alone or the combination of steroids with rituximab or oral cyclophosphamide was used. Despite aggressive measures, two of the patients had a poor outcome; seven of the nine patients (77%) had a good clinical outcome. Acquired hemophilia A should be strongly suspected in any patient presenting with bleeding and a prolonged activated partial thromboplastin time. Early initiation of factor bypassing agents such as activated prothrombin complex concentrates or recombinant factor VIIa, along with the use of immunosuppressive agents, can be lifesaving.
Transcranial contrast-enhanced ultrasound in the rat brain reveals substantial hyperperfusion acutely post-stroke

Direct and real-time assessment of cerebral hemodynamics is key to improving our understanding of cerebral blood flow regulation in health and disease states such as stroke. While a number of sophisticated imaging platforms enable assessment of cerebral perfusion, most are limited either spatially or temporally. Here, we applied transcranial contrast-enhanced ultrasound (CEU) to measure cerebral perfusion in real-time through the intact rat skull before, during and after ischemic stroke, induced by intraluminal filament middle cerebral artery occlusion (MCAO). We demonstrate expected decreases in cortical and striatal blood volume, flow velocity and perfusion during MCAO. After filament retraction, blood volume and perfusion increased two-fold above baseline, indicative of acute hyperperfusion. Adjacent brain regions to the ischemic area and the contralateral hemisphere had increased blood volume during MCAO. We assessed our data using wavelet analysis to demonstrate striking vasomotion changes in the ischemic and contralateral cortices during MCAO and reperfusion. In conclusion, we demonstrate the application of CEU for real-time assessment of cerebral hemodynamics and show that the ischemic regions exhibit striking hyperemia post-MCAO. Whether this post-stoke hyperperfusion is sustained long-term and contributes to stroke severity is not known.