Miracle-dz/UniFAR-FTUs huggingface dataset:
More than the Sum of its Parts: Exploring the Development of Ratio Magnitude vs. Simple Magnitude Perception.

Humans perceptually extract quantity information from our environments, be it from simple stimuli in isolation, or from relational magnitudes formed by taking ratios of pairs of simple stimuli. Some have proposed that these two types of magnitude are processed by a common system, whereas others have proposed separate systems. To test these competing possibilities, the present study examined the developmental trajectories of simple and relational magnitude discrimination and relations among these abilities for preschoolers (n = 42), 2nd -graders (n = 31), 5th -graders (n = 29), and adults (n = 32). Participants completed simple magnitude and ratio discrimination tasks in four different nonsymbolic formats, using dots, lines, circles, and irregular blobs. All age cohorts accurately discriminated both simple and ratio magnitudes. Discriminability differed by format such that performance was highest with line and lowest with dot stimuli. Moreover, developmental trajectories calculated for each format were similar across simple and ratio discriminations. Although some characteristics were similar for both types of discrimination, ratio acuity in a given format was more closely related with ratio acuities in alternate formats than to within-format simple magnitude acuity. Results demonstrate ratio magnitude processing several similarities to simple magnitude processing, but is also substantially different.
NEDD4-like ubiquitin ligase 2 Protein (NEDL2) in porcine spermatozoa, oocytes, and preimplantation embryos and its role in oocyte fertilization†.

The ubiquitin-proteasome system (UPS) plays diverse regulatory and homeostatic roles in mammalian reproduction. Ubiquitin ligases are the substrate-specific mediators of ubiquitin-binding to its substrate proteins. The NEDD4-like ubiquitin ligase 2 (aliases NEDL2, HECW2) is a HECT-type ubiquitin ligase that contains one N-terminal HECW ubiquitin ligase domain, one C-terminal HECT ubiquitin ligase domain, one C2 domain,, and two WW protein-protein interaction modules. Beyond its predicted ubiquitin-ligase activity, its cellular functions are largely unknown. Current studies were designed to investigate the content and distribution of NEDL2 in porcine spermatozoa, oocytes, zygotes, and early preimplantation embryos, and in cumulus cells before and after in vitro maturation with oocytes, and fibroblast cells as positive control by Western blot and immunocytochemistry, and to examine its roles during oocyte fertilization. Multiple isoforms of NEDL2 were identified by WB. One at approximately 52 kDa was detected only in the germinal vesicle stage and metaphase II oocytes, and in early preimplantation embryos. Other isoforms were high mass bands at 91, 136, and 155 kDa, which were only detected in somatic cells. Interestingly, ejaculated spermatozoa prominently displayed the same 52 kDa band as oocytes; they also had two minor bands of 74 and 129 kDa, which were not detected in somatic cells or oocytes. By immunofluorescence, NEDL2 showed a diffused cytoplasmic localization in all cell types and accumulated in distinct foci in the germinal vesicles of immature oocytes, in maternal and paternal pronuclei of zygotes and nuclei of embryo blastomeres and somatic cells. In blastocysts, the labeling intensity of NEDL2 was stronger in the inner cell mass than in trophoblast, indicating higher NEDL2 content in the ICM cells than in trophectoderm. NEDL2 abundance was ten times higher in post maturation oocyte-surrounding cumulus cells than that of cumulus cells before in vitro maturation with hormones, indicating that NEDL2 may have a unique role in cumulus cells after ovulation. Microinjection of anti-NEDL2 antibody into oocyte before IVF did not affect the percentage of oocytes fertilized, percentage of oocytes cleaved, or blastocyst formation. However, the anti-NEDL2 antibody decreased the number of pronuclei, accelerated the formation of nuclear precursor bodies at 6 h post-fertilization, inhibited sperm DNA decondensation, and resulted in more fertilized oocytes without male pronuclear formation. In summary, NEDL2 may play a key role during fertilization, especially during sperm DNA decondensation.
Role of the Scavenger Receptor CD36 in Accelerated Diabetic Atherosclerosis

Diabetes mellitus entails increased atherosclerotic burden and medial arterial calcification, but the precise mechanisms are not fully elucidated. We aimed to investigate the implication of CD36 in inflammation and calcification processes orchestrated by vascular smooth muscle cells (VSMCs) under hyperglycemic and atherogenic conditions. We examined the expression of CD36, pro-inflammatory cytokines, endoplasmic reticulum (ER) stress markers, and mineralization-regulating enzymes by RT-PCR in human VSMCs, cultured in a medium containing normal (5 mM) or high glucose (22 mM) for 72 h with or without oxidized low-density lipoprotein (oxLDL) (24 h). The uptake of 1,1′-dioctadecyl-3,3,3′,3-tetramethylindocarbocyanine perchlorate-fluorescently (DiI) labeled oxLDL was quantified by flow cytometry and fluorimetry and calcification assays were performed in VSMC cultured in osteogenic medium and stained by alizarin red. We observed induction in the expression of CD36, cytokines, calcification markers, and ER stress markers under high glucose that was exacerbated by oxLDL. These results were confirmed in carotid plaques from subjects with diabetes versus non-diabetic subjects. Accordingly, the uptake of DiI-labeled oxLDL was increased after exposure to high glucose. The silencing of CD36 reduced the induction of CD36 and the expression of calcification enzymes and mineralization of VSMC. Our results indicate that CD36 signaling is partially involved in hyperglycemia and oxLDL-induced vascular calcification in diabetes.
Spinal radiculomedullary vein and bridging vein

“The antireflux mechanism – angiographic anatomy and clinical implications” authored by Dr. Philippe Gailloud is very interesting because not only of beautiful illustration by Dr. Lydia Gregg and precise spinal angiograms, but of the way to prove the anti-reflux mechanism (ARM) by clinical images of the spinal cord veins in the normal and pathological conditions. He showed the ARM at the dural exit of radioculomedullary vein (RMV) coursing from perimedullary to epidural venous systems radio-anatomically. I would like to comment on this article, especially focusing on anatomical nomenclature of RMV and its roles in the normal and pathological circumstances.
Nuclear lamin phosphorylation: an emerging role in gene regulation and pathogenesis of laminopathies

ABSTRACT Decades of studies have established that nuclear lamin polymers form the nuclear lamina, a protein meshwork that supports the nuclear envelope structure and tethers heterochromatin to the nuclear periphery. Much less is known about unpolymerized nuclear lamins in the nuclear interior, some of which are now known to undergo specific phosphorylation. A recent finding that phosphorylated lamins bind gene enhancer regions offers a new hypothesis that lamin phosphorylation may influence transcriptional regulation in the nuclear interior. In this review, we discuss the regulation, localization, and functions of phosphorylated lamins. We summarize kinases that phosphorylate lamins in a variety of biological contexts. Our discussion extends to laminopathies, a spectrum of degenerative disorders caused by lamin gene mutations, such as cardiomyopathies and progeria. We compare the prevailing hypothesis for laminopathy pathogenesis based on lamins’ function at the nuclear lamina with an emerging hypothesis based on phosphorylated lamins’ function in the nuclear interior.
Identifying the health care initiated and self-initiated interventions used by women for the management of rectal emptying difficulty secondary to obstructive defecation: a scoping review protocol.

OBJECTIVE This scoping review aims to identify interventions used by women for the management of rectal emptying difficulty secondary to obstructive defecation. INTRODUCTION Rectal emptying difficulty is typically a symptom of obstructive defecation syndrome. Even though a range of interventions are already available for this condition, this review is necessary to increase understanding of what interventions women find useful and are acceptable for them. This depth of understanding will facilitate the development of a specific care pathway to support women living with rectal emptying difficulty secondary to obstructive defecation syndrome. INCLUSION CRITERIA This review will consider studies that include adult women (over 18 years of age) living in the community who have experienced difficulty with rectal emptying secondary to obstructive defecation and who have not had surgical intervention. Exclusion criteria include prolapse surgery and surgical techniques, oral laxatives, vaginal pessaries, cognitive impairment, pregnancy, and those residing in care homes. METHODS The databases to be searched include MEDLINE, EMBASE, CINAHL, PsycINFO, Emcare, AMED, Web of Science, Scopus, PROSPERO, Open Grey, ClinicalTrials.gov, International Clinical Trials Registry Platform Search Portal, UK Clinical Trials Gateway, International Standard Randomised Controlled Trial Number Registry, JBI Evidence Synthesis, Epistemonikos, Cochrane Library and gray literature. Studies conduct in English from any time period will be considered for inclusion. The titles and abstracts will then be screened by two independent reviewers for assessment against the inclusion criteria for the review.
Association of Study Methods and Industry Sponsorship With Inconsistent Performance of Molecular Assays for Indeterminate Thyroid Nodules.

Association of Study Methods and Industry Sponsorship With Inconsistent Performance of Molecular Assays for Indeterminate Thyroid Nodules A subset (15%-25%) of thyroid nodules undergoing biopsy cannot be classified as benign or malignant. Under the Bethesda System for Reporting Thyroid Cytopathology, these cytologically indeterminate thyroid nodules (ITNs) are categories III and IV.1 Molecular assays using genetic and/or gene expression data may help risk stratify ITNs, potentially guiding decisions to operate or observe. These assays include the Afirma Gene Expression Classifier and Genomic Sequencing Classifier (Veracyte), and ThyroSeq v2 and v3 (CBLPath). Afirma panels are marketed to rule out malignancy with high negative predictive value, and ThyroSeq panels are marketed as rule out/ rule in tests with high negative predictive values (NPV) and positive predictive values (PPV). Recently, some studies have observed that the real-world performance of these assays often falls short of that reported by initial industry-sponsored studies.2-4 Causes for this divergence between efficacy (performance under ideal circumstances) and effectiveness (performance in real-world conditions) are not well understood. In this article, we examined whether methodologic differences in study design were associated with observed performance of molecular assays for ITNs.
Action observation training and brain-computer interface controlled functional electrical stimulation enhance upper extremity performance and cortical activation in patients with stroke: a randomized controlled trial

ABSTRACT Purpose Brain-computer interface (BCI)-functional electronic stimulation (FES) systems are increasingly being explored as potential neuro-rehabilitation tools. Here, we investigate the effect of action observation training (AOT) plus electroencephalogram (EEG)-based BCI-controlled FES system on motor recovery of upper extremity and cortical activation in patients with stroke. Method There were a total of 26 patients: an AOT plus BCI-FES group (n = 13) and a control group (n = 13). The control group performed FES treatment and the conventional physical therapy, while the AOT plus BCI-FES group performed AOT plus BCI-FES and the conventional physical therapy. Upper extremity performance was measured using the Fugl-Meyer Assessment of the Upper Extremity (FMA-UE), Wolf Motor Function Test (WMFT), Motor Activity Log (MAL) and Modified Barthel Index (MBI). Cortical activation was measured using electro-encephalographic recordings from alpha and beta power, concentration, and activation. Results After intervention, there were significant differences between two groups in FMA-UE, WMFT, MAL and MBI and the results of EEG including alpha power, beta power, concentration and activation. Conclusions This study demonstrated that AOT plus BCI-FES can enhance motor function of upper extremity and cortical activation in patients with stroke. This training method may be feasible and suitable for individuals with stroke.
Cryo-EM and MD infer water-mediated proton transport and autoinhibition mechanisms of Vo complex

A 2.7-Å cryo-EM structure and MD simulations explain water-mediated H+ transport and autoinhibition of yeast Vo proton channel. Rotary vacuolar adenosine triphosphatases (V-ATPases) drive transmembrane proton transport through a Vo proton channel subcomplex. Despite recent high-resolution structures of several rotary ATPases, the dynamic mechanism of proton pumping remains elusive. Here, we determined a 2.7-Å cryo–electron microscopy (cryo-EM) structure of yeast Vo proton channel in nanodisc that reveals the location of ordered water molecules along the proton path, details of specific protein-lipid interactions, and the architecture of the membrane scaffold protein. Moreover, we uncover a state of Vo that shows the c-ring rotated by ~14°. Molecular dynamics simulations demonstrate that the two rotary states are in thermal equilibrium and depict how the protonation state of essential glutamic acid residues couples water-mediated proton transfer with c-ring rotation. Our cryo-EM models and simulations also rationalize a mechanism for inhibition of passive proton transport as observed for free Vo that is generated as a result of V-ATPase regulation by reversible disassembly in vivo.
The impact of learning Unified Medical Language System knowledge embeddings in relation extraction from biomedical texts

OBJECTIVE We explored how knowledge embeddings (KEs) learned from the Unified Medical Language System (UMLS) Metathesaurus impact the quality of relation extraction on 2 diverse sets of biomedical texts. MATERIALS AND METHODS Two forms of KEs were learned for concepts and relation types from the UMLS Metathesaurus, namely lexicalized knowledge embeddings (LKEs) and unlexicalized KEs. A knowledge embedding encoder (KEE) enabled learning either LKEs or unlexicalized KEs as well as neural models capable of producing LKEs for mentions of biomedical concepts in texts and relation types that are not encoded in the UMLS Metathesaurus. This allowed us to design the relation extraction with knowledge embeddings (REKE) system, which incorporates either LKEs or unlexicalized KEs produced for relation types of interest and their arguments. RESULTS The incorporation of either LKEs or unlexicalized KE in REKE advances the state of the art in relation extraction on 2 relation extraction datasets: the 2010 i2b2/VA dataset and the 2013 Drug-Drug Interaction Extraction Challenge corpus. Moreover, the impact of LKEs is superior, achieving F1 scores of 78.2 and 82.0, respectively. DISCUSSION REKE not only highlights the importance of incorporating knowledge encoded in the UMLS Metathesaurus in a novel way, through 2 possible forms of KEs, but it also showcases the subtleties of incorporating KEs in relation extraction systems. CONCLUSIONS Incorporating LKEs informed by the UMLS Metathesaurus in a relation extraction system operating on biomedical texts shows significant promise. We present the REKE system, which establishes new state-of-the-art results for relation extraction on 2 datasets when using LKEs.
Predicting 30-day mortality of patients with pneumonia in an emergency department setting using machine-learning models

Objective This study aimed to confirm the accuracy of a machine-learning-based model in predicting the 30-day mortality of patients with pneumonia and evaluating whether they were required to be admitted to the intensive care unit (ICU). Methods The study conducted a retrospective analysis of pneumonia patients at an emergency department (ED) in Seoul, Korea, from January 1, 2016 to December 31, 2017. Patients aged 18 years or older with a pneumonia registry designation on their electronic medical record were enrolled. We collected their demographic information, mental status, and laboratory findings. Three models were used: the pre-existing CURB-65 model, and the CURB-RF and Extensive CURB-RF models, which were machine-learning models that used a random forest algorithm. The primary outcomes were ICU admission from the ED or 30-day mortality. Receiver operating characteristic curves were constructed for the models, and the areas under these curves were compared. Results Out of the 1,974 pneumonia patients, 1,732 patients were eligible to be included in the study; from these, 473 patients died within 30 days or were initially admitted to the ICU from the ED. The area under receiver operating characteristic curves of CURB-65, CURB-RF, and extensive-CURB-RF were 0.615 (0.614–0.616), 0.701 (0.700–0.702), and 0.844 (0.843–0.845), respectively. Conclusion The proposed machine-learning models could predict the mortality of patients with pneumonia more accurately than the pre-existing CURB-65 model and can help decide whether the patient should be admitted to the ICU.
A comparison and review of three sets of classification criteria for systemic lupus erythematosus for distinguishing systemic lupus erythematosus from pure mucocutaneous manifestations in the lupus disease spectrum

Although the original purpose of the systemic lupus erythematosus (SLE) classification criteria was to distinguish SLE from other mimic diseases, and to facilitate sample selection in scientific research, they have become widely used as diagnostic criteria in clinical situations. It is not known yet if regarding classification criteria as diagnostic criteria, what problems might be encountered? This is the first study comparing the three sets of classification criteria for SLE, the 1997 American College of Rheumatology (ACR’97), 2012 Systemic Lupus International Collaborating Clinics (SLICC’12) and 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR’19), for their ability to distinguish patients with SLE from patients with pure mucocutaneous manifestations (isolated cutaneous lupus erythematosus without internal disease, i-CLE) in the lupus disease spectrum. 1,865 patients with SLE and 232 patients with i-CLE were recruited from a multicenter study. We found that, due to low specificity, none of the three criteria are adept at distinguishing patients with SLE from patients with i-CLE. SLICC’12 performed best among the original three criteria, but if a positive ANA was removed as an entry criterion, EULAR/ACR’19 would performed better. A review of previous studies that compared the three sets of criteria was presented in this work.
An NIR‐II‐Emissive Photosensitizer for Hypoxia‐Tolerant Photodynamic Theranostics

As a common feature in a majority of malignant tumors, hypoxia has become the Achilles’ heel of photodynamic therapy (PDT). The development of type‐I photosensitizers that show hypoxia‐tolerant PDT efficiency provides a straightforward way to address this issue. However, type‐I PDT materials have rarely been discovered. Herein, a π‐conjugated molecule with A–D–A configuration, COi6‐4Cl, is reported. The H2O‐dispersible nanoparticle of COi6‐4Cl can be activated by an 880 nm laser, and displays hypoxia‐tolerant type I/II combined PDT capability, and more notably, a high NIR‐II fluorescence with a quantum yield over 5%. Moreover, COi6‐4Cl shows a negligible photothermal conversion effect. The non‐radiative decay of COi6‐4Cl is suppressed in the dispersed and aggregated state due to the restricted molecular vibrations and distinct intermolecular steric hindrance induced by its four bulky side chains. These features make COi6‐4Cl a distinguished single‐NIR‐wavelength‐activated phototheranostic material, which performs well in NIR‐II fluorescence‐guided PDT treatment and shows an enhanced in vivo anti‐tumor efficiency over the clinically approved Chlorin e6, by the equal stresses on hypoxia‐tolerant anti‐tumor therapy and deep‐penetration imaging. Therefore, the great potential of COi6‐4Cl in precise PDT cancer therapy against hypoxia challenges is demonstrated.
Who Did the Arthroplasty? Hip Fracture Surgery Reoperation Rates are Not Affected by Type of Training-An Analysis of the HEALTH Database.

OBJECTIVES This study compares outcomes for patients with displaced femoral neck fractures undergoing hemiarthroplasty (HA) or total hip arthroplasty (THA) by surgeons of different fellowship training. DESIGN Retrospective review of HEALTH trial data. SETTING Eighty clinical sites across 10 countries. PATIENTS/PARTICIPANTS One thousand four hundred forty-one patients ≥50 years with low-energy hip fractures requiring surgical intervention. INTERVENTION Patients were randomized to either HA or THA groups in the initial data set. Surgeons' fellowship training was ascertained retrospectively, and outcomes were compared. MAIN OUTCOME MEASUREMENTS The main outcome was an unplanned secondary procedure at 24 months. Secondary outcomes included death, serious adverse events, prosthetic joint infection (PJI), dislocation, discharge disposition, and use of ambulatory devices postoperatively. RESULTS There was a significantly higher risk of PJI in patients treated by surgeons without fellowship training in arthroplasty (P = 0.01), surgeons with unknown fellowship training (P = 0.03), and surgeons with no fellowship training (P = 0.02) than those treated by an arthroplasty-trained surgeon. There were significantly higher odds of being discharged to a facility rather than home in patients who underwent surgery by a surgeon with no fellowship training compared with arthroplasty-fellowship-trained surgeons (P = 0.03). CONCLUSIONS Arthroplasty for hip fracture can be performed by all orthopaedic surgeons with equivalent reoperation rates. Infection prevention strategies and use of "care pathways" by arthroplasty-fellowship-trained surgeons may account for the lower risk of PJI and higher rate of discharge to home. The authors advocate for the use of evidence-based infection prevention initiatives and standardized care pathways in this patient population. LEVEL OF EVIDENCE Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.