Miracle-dz/UniFAR-FTUs huggingface dataset:
Topic: A Comparative Study between Conventional and Endoscopic Dacryocystorhinostomy

Introduction: Dacryocystorhinostomy (DCR) has been the standard procedure for acquired nasolacrimal duct obstruction. Lacrimal sac can be approached (1) Conventional External (Ex-DCR) or (2) Endoscopic (EN-DCR) Objective : To compare success rate , complication rate between the procedures Materials and Methods: Study design, prospective, interventional , clinical study was conducted in department of otorhinolaryngology in conjuction with ophthalmology,AMCH ,Duration of study : One year , from july 2011 to june 2012 , No. of cases : 60 cases(30 Endo-DCR,30 Ex-DCR) . Data were analysed by graphpad prism version 6.01 for Microsoft, Independent-sample t test &, chi square test with Yates correction was applied for comparison between groups , P value of <0.05 was considered stastically significant . Results and Observations : Total 60( 47 females,13 males) cases randomised into 30( 27females, 3males) endoscopic dcr, 30( 20females,10 males) external dcr, Mean age (32.367 )with range 18-55 yrs. in endoscopic dcr, Mean age (37.534 )with range 16-66 yrs. in external dcr. Present study shows success rate of 86.67% for En-DCR & 90% for Ex-DCR with P-value 0.557 CONCLUSION : The present study clearly shows that EnDCR is having results comparable EX-DCR ,
Associations of Thigh and Abdominal Adipose Tissue Radiodensity with Glucose and Insulin in Nondiabetic African‐Ancestry Men

Decreased radiodensity of adipose tissue (AT) located in the visceral AT (VAT), subcutaneous AT (SAT), and intermuscular AT (IMAT) abdominal depots is associated with hyperglycemia, hyperinsulinemia, and insulin resistance independent of AT volumes. These associations were sought in African‐ancestry men, who have higher risk for type 2 diabetes and have been underrepresented in previous studies.
Pervasive Strong Selection at the Level of Codon Usage Bias in Drosophila melanogaster

Codon usage bias (CUB), where certain codons are used more frequently than expected by chance, is a ubiquitous phenomenon and occurs across the tree of life. The dominant paradigm is that the proportion of preferred codons is set by weak selection. While experimental changes in codon usage have at times shown large phenotypic effects in contrast to this paradigm, genome-wide population genetic estimates have supported the weak selection model. Here we use deep genomic population sequencing of two Drosophila melanogaster populations to measure selection on synonymous sites in a way that allowed us to estimate the prevalence of both weak and strong purifying selection. We find that selection in favor of preferred codons ranges from weak (|Nes| ∼ 1) to strong (|Nes| > 10), with strong selection acting on 10–20% of synonymous sites in preferred codons. While previous studies indicated that selection at synonymous sites could be strong, this is the first study to detect and quantify strong selection specifically at the level of CUB. Further, we find that CUB-associated polymorphism accounts for the majority of strong selection on synonymous sites, with secondary contributions of splicing (selection on alternatively spliced genes, splice junctions, and spliceosome-bound sites) and transcription factor binding. Our findings support a new model of CUB and indicate that the functional importance of CUB, as well as synonymous sites in general, have been underestimated.
The impact of a service-learning foot soak experience on nursing students' attitudes towards the homeless.

BACKGROUND Opportunities for meaningful engagement with the homeless can alter negative attitudes. The purpose of this study was to assess changes in attitudes towards the homeless among undergraduate nursing students participating in a service-learning foot soak experience. METHODS This was a prospective, pretest, and posttest interventional study. Student attitudes were measured through: (a) the attitudes toward homelessness inventory and (b) thematic analysis of a guided reflection on the experience. RESULTS Mean posttest total scores (mean = 50.06; standard deviation = 7.004) were significantly (P = .001) higher from mean pretest scores (mean = 47.06; standard deviation = 5.455), indicating more positive attitudes towards the homeless (n = 47) after the clinic. Three categories of themes reflected student experiences are as follows: (a) benefits, (b) context, and, (c) potential consequences. CONCLUSIONS A foot soak clinic can increase students' understanding of experiences faced by homeless persons through genuine human interaction, and has benefits to community members and learners.
Multiple neuronal circuits for variable object–action choices based on short- and long-term memories

At each time in our life, we choose one or few behaviors, while suppressing many other behaviors. This is the basic mechanism in the basal ganglia, which is done by tonic inhibition and selective disinhibition. Dysfunctions of the basal ganglia then cause 2 types of disorders (difficulty in initiating necessary actions and difficulty in suppressing unnecessary actions) that occur in Parkinson’s disease. The basal ganglia generate such opposite outcomes through parallel circuits: The direct pathway for initiation and indirect pathway for suppression. Importantly, the direct pathway processes good information and the indirect pathway processes bad information, which enables the choice of good behavior and the rejection of bad behavior. This is mainly enabled by dopaminergic inputs to these circuits. However, the value judgment is complex because the world is complex. Sometimes, the value must be based on recent events, thus is based on short-term memories. Or, the value must be based on historical events, thus is based on long-term memories. Such memory-based value judgment is generated by another parallel circuit originating from the caudate head and caudate tail. These circuit-information mechanisms allow other brain areas (e.g., prefrontal cortex) to contribute to decisions by sending information to these basal ganglia circuits. Moreover, the basal ganglia mechanisms (i.e., what to choose) are associated with cerebellum mechanisms (i.e., when to choose). Overall, multiple levels of parallel circuits in and around the basal ganglia are essential for coordinated behaviors. Understanding these circuits is useful for creating clinical treatments of disorders resulting from the failure of these circuits.
Optogenetic stimulation of kisspeptin neurones within the posterodorsal medial amygdala increases luteinising hormone pulse frequency in female mice

Kisspeptin within the arcuate nucleus of the hypothalamus is a critical neuropeptide in the regulation of reproduction. Together with neurokinin B and dynorphin A, arcuate kisspeptin provides the oscillatory activity that drives the pulsatile secretion of gonadotrophin‐releasing hormone (GnRH), and therefore luteinising hormone (LH) pulses, and is considered to be a central component of the GnRH pulse generator. It is well established that the amygdala also exerts an influence over gonadotrophic hormone secretion and reproductive physiology. The discovery of kisspeptin and its receptor within the posterodorsal medial amygdala (MePD) and our recent finding showing that intra‐MePD administration of kisspeptin or a kisspeptin receptor antagonist results in increased LH secretion and decreased LH pulse frequency, respectively, suggests an important role for amygdala kisspeptin signalling in the regulation of the GnRH pulse generator. To further investigate the function of amygdala kisspeptin, the present study used an optogenetic approach to selectively stimulate MePD kisspeptin neurones and examine the effect on pulsatile LH secretion. MePD kisspeptin neurones in conscious Kiss1‐Cre mice were virally infected to express the channelrhodopsin 2 protein and selectively stimulated by light via a chronically implanted fibre optic cannula. Continuous stimulation using 5 Hz resulted in an increased LH pulse frequency, which was not observed at the lower stimulation frequencies of 0.5 and 2 Hz. In wild‐type animals, continuous stimulation at 5 Hz did not affect LH pulse frequency. These results demonstrate that selective activation of MePD Kiss1 neurones can modulate hypothalamic GnRH pulse generator frequency.
VNRX-5133 (Taniborbactam), a Broad-Spectrum Inhibitor of Serine- and Metallo-β-Lactamases, Restores Activity of Cefepime in Enterobacterales and Pseudomonas aeruginosa

As shifts in the epidemiology of β-lactamase-mediated resistance continue, carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) are the most urgent threats. ABSTRACT As shifts in the epidemiology of β-lactamase-mediated resistance continue, carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) are the most urgent threats. Although approved β-lactam (BL)–β-lactamase inhibitor (BLI) combinations address widespread serine β-lactamases (SBLs), such as CTX-M-15, none provide broad coverage against either clinically important serine-β-lactamases (KPC, OXA-48) or clinically important metallo-β-lactamases (MBLs; e.g., NDM-1). VNRX-5133 (taniborbactam) is a new cyclic boronate BLI that is in clinical development combined with cefepime for the treatment of infections caused by β-lactamase-producing CRE and CRPA. Taniborbactam is the first BLI with direct inhibitory activity against Ambler class A, B, C, and D enzymes. From biochemical and structural analyses, taniborbactam exploits substrate mimicry while employing distinct mechanisms to inhibit both SBLs and MBLs. It is a reversible covalent inhibitor of SBLs with slow dissociation and a prolonged active-site residence time (half-life, 30 to 105 min), while in MBLs, it behaves as a competitive inhibitor, with inhibitor constant (Ki) values ranging from 0.019 to 0.081 μM. Inhibition is achieved by mimicking the transition state structure and exploiting interactions with highly conserved active-site residues. In microbiological testing, taniborbactam restored cefepime activity in 33/34 engineered Escherichia coli strains overproducing individual enzymes covering Ambler classes A, B, C, and D, providing up to a 1,024-fold shift in the MIC. Addition of taniborbactam restored the antibacterial activity of cefepime against all 102 Enterobacterales clinical isolates tested and 38/41 P. aeruginosa clinical isolates tested with MIC90s of 1 and 4 μg/ml, respectively, representing ≥256- and ≥32-fold improvements, respectively, in antibacterial activity over that of cefepime alone. The data demonstrate the potent, broad-spectrum rescue of cefepime activity by taniborbactam against clinical isolates of CRE and CRPA.
Long-Term Exposure to Ambient Fine Particulate Matter (PM2.5) and Lung Function in Children, Adolescents, and Young Adults: A Longitudinal Cohort Study

Background: The association between long-term exposure to ambient fine particulate matter with aerodynamic diameter ≤2. 5μm (PM2.5) and lung function in young people remains uncertain, particularly in Asia, where air pollution is generally a serious problem. Objectives: This study investigated the association between long-term exposure to ambient PM2.5 and lung function in Taiwanese children, adolescents, and young adults. Methods: This study comprised 24,544 participants 6–24 years of age, with 33,506 medical observations made between 2000 and 2014. We used a spatiotemporal model to estimate PM2.5 concentrations at participants’ addresses. Spirometry parameters, i.e., forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and maximum midexpiratory flow (MMEF), were determined. A generalized linear mixed model was used to examine the associations between long-term exposure to ambient PM2.5 and lung function. The odds ratios (ORs) of poor lung function were also calculated after adjusting for a range of covariates. Results: Every 10-μg/m3 increase in the 2-y average PM2.5 concentration was associated with decreases of 2.22% [95% confidence interval (CI): −2.60, −1.85], 2.94 (95% CI: −3.36, −2.51), and 2.79% (95% CI: −3.15, −2.41) in the FVC, FEV1, and MMEF, respectively. Furthermore, it was associated with a 20% increase in the prevalence of poor lung function (OR: 1.20; 95% CI: 1.12, 1.29). Conclusions: Two-year ambient PM2.5 concentrations were inversely associated with lung function and positively associated with the prevalence of poor lung function in children, adolescents, and young adults in Taiwan. https://doi.org/10.1289/EHP5220
Pressure Ulcer Monitoring Platform-A Prospective, Human Subject Clinical Study to Validate Patient Repositioning Monitoring Device to Prevent Pressure Ulcers.

Objective: The objective of this prospective clinical study was to validate two prototype pressure ulcer monitoring platform (PUMP) devices, (PUMP1 and PUMP2), to promote optimal bed repositioning of hospitalized patients to prevent pressure ulcers (PUs). Approach: PUMP1 was a wearable electronic device attached to the patient gown with no skin contact. PUMP2 was a set of four identical electronic devices placed under the patient's bed wheels. A video camera recorded events in the patient room while measurements from the PUMP devices were correlated with true patient repositioning activity. The performance of these PUMP devices developed by our research team were evaluated and compared by both clinicians and engineers. Results: Ten mobility-restricted patients were enrolled into the study. Repositioning movement was recorded by both PUMP devices for 10 ± 2 h and corroborated with video capture. One hundred thirty-seven movements in total were detected by both PUMP1 and PUMP2 over 105 h of capture. Two false positives were detected by the sensors and 11 movements were missed by the sensors. PUMP1 and PUMP2 never conflicted in data collection. Innovation: The presented study evaluated two different sensors' abilities to capture accurate patient repositioning to eventually prevent PU formation. Importantly, detection of patient motion was completed without contact to patient skin. Conclusion: The clinical study demonstrated successful capture of patient repositioning movement by both PUMP1 and PUMP2 devices with 85% reliability, 2 false positives, and 11 missed movements. In future studies, the PUMP devices will be combined with a SMS-based mobile phone alert system to improve caregiver repositioning behavior.
Ultrasmall silica nanoparticles directly ligate the T cell receptor complex

Significance Ultrasmall nanoparticles, which have diameters <10 nm, are mobile, often cell active, and have marked therapeutic potential. Amorphous silica in this size range, at relatively low doses, was recently demonstrated to activate T cells in vitro prior to its dissolution into benign orthosilicic acid [Si(OH)4]. For both safety and therapeutic applications, a mechanism of action greatly facilitates translation. This work shows that ultrasmall amorphous silica nanoparticles directly ligate the T cell receptor (TCR) complex, notably the extracellular domains of CD3, and initiate signaling downstream. This surprising receptor selectivity, the well-known safety of the rapidly formed degradation product and the low cost of silica, bode well for use of these particles as affordable and accessible therapeutic TCR:CD3 agonists. The impact of ultrasmall nanoparticles (<10-nm diameter) on the immune system is poorly understood. Recently, ultrasmall silica nanoparticles (USSN), which have gained increasing attention for therapeutic applications, were shown to stimulate T lymphocytes directly and at relatively low-exposure doses. Delineating underlying mechanisms and associated cell signaling will hasten therapeutic translation and is reported herein. Using competitive binding assays and molecular modeling, we established that the T cell receptor (TCR):CD3 complex is required for USSN-induced T cell activation, and that direct receptor complex–particle interactions are permitted both sterically and electrostatically. Activation is not limited to αβ TCR-bearing T cells since those with γδ TCR showed similar responses, implying that USSN mediate their effect by binding to extracellular domains of the flanking CD3 regions of the TCR complex. We confirmed that USSN initiated the signaling pathway immediately downstream of the TCR with rapid phosphorylation of both ζ-chain–associated protein 70 and linker for activation of T cells protein. However, T cell proliferation or IL-2 secretion were only triggered by USSN when costimulatory anti-CD28 or phorbate esters were present, demonstrating that the specific impact of USSN is in initiation of the primary, nuclear factor of activated T cells-pathway signaling from the TCR complex. Hence, we have established that USSN are partial agonists for the TCR complex because of induction of the primary T cell activation signal. Their ability to bind the TCR complex rapidly, and then to dissolve into benign orthosilicic acid, makes them an appealing option for therapies targeted at transient TCR:CD3 receptor binding.
Cryptosporidium parvum elongation factor 1α (CpEF1α) participates in the formation of base structure at the infection site during invasion.

Cryptosporidium is a genus of apicomplexan parasites, the causative agents of cryptosporidiosis in humans and/or animals. While most apicomplexans parasitize within the host cell cytosols, Cryptosporidium resides on top of host cells, but embraced by a double-layer parasitophorous vacuole membrane (PVM) derived host cells. There is an electron-dense band to separate the parasite from host cell cytoplasm, making it as an intracellular, but extracytoplasmic parasite. In the present study, we discovered that a C. parvum translation elongation factor 1α (CpEF1α) was discharged from the invading sporozoites onto host cells, forming a crescent-shaped patch that fully resembles the electron-dense band. At the same time, host cell F-actin aggregated to form a globular shaped plug beneath the CpEF1α patch. The CpEF1α patch remained for most of the time, but became weakened and dissolved upon the completion of the invasion process. Additionally, recombinant CpEF1α protein could effectively interfere the invasion of sporozoites into host cells. These observations indicate that CpEF1α plays a role in the parasite invasion by participating in the formation of electron-dense band at the base of the parasite infection site.
Clinicopathological Characterization of Renal Cell Carcinoma in Young Adults: a contemporary update and review of literature.

BACKGROUND Renal cell carcinomas are relatively rare in children and young adults. While well characterized in adults, the morphologic and molecular characterization of these tumors in young patients is relatively lacking. OBJECTIVE To explore the spectrum of renal cell carcinoma (RCC) subtypes in children and young adults and to determine their clinical-pathological, immunohistochemical and molecular characteristics, by evaluating a large retrospective cohort of renal cell carcinoma patients 30 years of age or younger. RESULTS Sixty-eight cases with confirmed diagnosis of renal cell carcinoma at 30 years of age or younger were identified at our institution. Clear cell carcinoma accounted for the most common subtype seen in this age group. Translocation renal cell carcinoma and rare familial syndrome subtypes such as succinate dehydrogenase deficient renal cell carcinoma and Tuberous Sclerosis Complex- associated renal cell carcinoma were found relatively more frequently in this cohort. Despite applying the 2016 WHO classification criteria, a high proportion of the tumors in our series remained unclassified. CONCLUSIONS Our results suggest that renal cell carcinoma in children and young adults is a relatively rare disease that shares many histologic similarities to renal cell carcinoma occurring in adults and yet demonstrate some unique clinical-pathological differences. MiT family translocation RCC and rare familial syndrome subtypes are relatively more frequent in the pediatric and adolescent age groups than in adults. Clear cell RCC still accounted for the most common subtype seen in this age group. MiT family translocation RCC patients presented with advanced stage disease and had poor clinical outcomes. The large and heterogeneous subgroup of unclassified renal cell carcinoma contains phenotypically distinct tumors with further potential for future subcategories in the renal cell carcinoma classification.
Unstructured regions in IRE1α specify BiP-mediated destabilisation of the luminal domain dimer and repression of the UPR

Coupling of endoplasmic reticulum (ER) stress to dimerisation-dependent activation of the UPR transducer IRE1 is incompletely understood. Whilst the luminal co-chaperone ERdj4 promotes a complex between the Hsp70 BiP and IRE1’s stress-sensing luminal domain (IRE1LD) that favours the latter’s monomeric inactive state and loss of ERdj4 de-represses IRE1, evidence linking these cellular and in vitro observations is presently lacking. We report that enforced loading of endogenous BiP onto endogenous IRE1α repressed UPR signalling in CHO cells and deletions in the IRE1α locus that de-repressed the UPR in cells, encode flexible regions of IRE1LD that mediated BiP-induced monomerisation in vitro. Changes in the hydrogen exchange mass spectrometry profile of IRE1LD induced by ERdj4 and BiP confirmed monomerisation and were consistent with active destabilisation of the IRE1LD dimer. Together, these observations support a competition model whereby waning ER stress passively partitions ERdj4 and BiP to IRE1LD to initiate active repression of UPR signalling.
Association of ABCC2 with levels and toxicity of methotrexate in Malaysian Childhood Acute Lymphoblastic Leukemia (ALL)

Abstract Studies had shown that genetic polymorphism plays a significant role in the pharmacokinetics and pharmacodynamics variation of high dose methotrexate (MTX), 5000 mg/m2 regimen. The objective of this study was to investigate the genetic variations associated with the serum level and toxicity of MTX in Malaysian children with acute lymphoblastic leukemia (ALL). Thirty-eight patients were genotyped for rs717620 (ABCC2), rs4948496 (ARID5B), rs1801133 (MTHFR) and rs4149056 (SLCO1B1). Serum levels of MTX at 48 h post 24 h of intravenous infusion were analyzed by high-performance liquid chromatography-mass spectrometry. The ABCC2 genotype was significantly associated with the serum levels of MTX at 48 h after treatment (p = 0.017). Patients with CT and TT of rs717620 (ABCC2) and TC and CC of rs4948496 (ARID5B) were significantly associated with leukopenia grade I–IV (Fisher Exact Test; p = 0.03 and 0.02, respectively). The three most common MTX related toxicities were leukopenia (60.5%), increased alanine aminotransferase enzyme (47.4%), and thrombocytopenia (47.4%). Our results demonstrate that by prescreening of patients for ABCC2 and ARID5B associated with the serum levels and adverse effects of MTX would identify patients at risk and therefore help a pediatric oncologist to personalize chemotherapy drugs for precision health.