Miracle-dz/UniFAR-FTUs huggingface dataset:
Rett Syndrome–Associated Scoliosis

Study Design. Retrospective database cohort study. Objective. To evaluate U.S. treatment trends and inpatient outcomes for children undergoing posterior spinal fusion (PSF) for Rett syndrome (RTT)–associated scoliosis (RAS). Summary of Background Data. RTT is a rare, sporadic neurodevelopmental disorder presenting in childhood with developmental regression, ataxia, and seizures. RAS occurs in 50% to 80% of cases of RTT, but little is known about the case volume and perioperative experience for children undergoing PSF. Materials and Methods. Using the International Classification of Diseases Ninth and 10th revision codes in the national Kids’ Inpatient Database, we identified children with RTT who underwent PSF from 2000 to 2019. Annual case volumes were analyzed. Clinical characteristics and outcomes were compared with those of a cohort of patients with neuromuscular scoliosis (NMS). Results. Among 220 patients with RAS, 216 (98.2%) were females (mean age at surgery: 12.3±3.3 yr). Surgical case incidence steadily increased over 19 years, with more RAS admissions in the South (31.4%). Overall, patients with RAS demonstrated a higher mean Elixhauser Comorbidity Index score (2 vs. 1, P < 0.001) and had more perioperative complications (41.4% vs. 18%, P < 0.001) than patients with NMS. RTT diagnosis independently predicted higher odds of any complications (odds ratio: 1.98, P < 0.001) and increased length of stay (odds ratio: 1.18, P = 0.009) for admissions for PSF. Conclusions. Surgical treatment for RAS is rare but increased over a 19-year period. Cases appear to be clustering by region, with the highest proportion in the South. The higher Elixhauser Comorbidity Index in RAS patients predicted higher costs, longer hospital stays, more complications (particularly respiratory), and more nonroutine discharge disposition than in other patients with NMS. RTT was independently associated with higher odds of complications and longer length of stay. Because RAS cases appear to be increasing in number, future studies should emphasize methods to reduce morbidity and investigate deformity-specific metrics to help better understand this population.
Comprehensive Landscape of Active Deubiquitinating Enzymes Profiled by Advanced Chemoproteomics

Enzymes that bind and process ubiquitin, a small 76-amino-acid protein, have been recognized as pharmacological targets in oncology, immunological disorders, and neurodegeneration. Mass spectrometry technology has now reached the capacity to cover the proteome with enough depth to interrogate entire biochemical pathways including those that contain DUBs and E3 ligase substrates. We have recently characterized the breast cancer cell (MCF7) deep proteome by detecting and quantifying ~10,000 proteins, and within this data set, we can detect endogenous expression of 65 deubiquitylating enzymes (DUBs), whereas matching transcriptomics detected 78 DUB mRNAs. Since enzyme activity provides another meaningful layer of information in addition to the expression levels, we have combined advanced mass spectrometry technology, pre-fractionation, and more potent/selective ubiquitin active-site probes with propargylic-based electrophiles to profile 74 DUBs including distinguishable isoforms for 5 DUBs in MCF7 crude extract material. Competition experiments with cysteine alkylating agents and pan-DUB inhibitors combined with probe labeling revealed the proportion of active cellular DUBs directly engaged with probes by label-free quantitative (LFQ) mass spectrometry. This demonstrated that USP13, 39, and 40 are non-reactive to probe, indicating restricted enzymatic activity under these cellular conditions. Our extended chemoproteomics workflow increases depth of covering the active DUBome, including isoform-specific resolution, and provides the framework for more comprehensive cell-based small-molecule DUB selectivity profiling.
Danazol increases the oral bioavailability of midazolam by inactivation of hepatic and intestinal CYP3A in rats

Abstract Danazol (DNZ) is a synthetic androgen derivative used for the treatment of intractable hematological disorders. In this study, we investigated the effects of DNZ on CYP3A activity in hepatic and small intestinal microsomes and the pharmacokinetics of midazolam (MDZ), a typical substrate for CYP3A, in rats. MDZ 4-hydroxylation activities in hepatic and small intestinal microsomes significantly decreased 24 h after DNZ (100 mg/kg, i.p.) treatment. Time-dependent inactivation of MDZ 4-hydroxylation activities was noted when microsomes were pre-incubated with DNZ in the presence of a NADPH-generating system. The Western blot analysis indicated that the decrease observed in enzyme activity was not due to changes in the protein expression of CYP3A. In contrast to the intravenous administration, serum MDZ concentrations in DNZ-treated rats were markedly higher than those in control rats when administered orally. DNZ treatment increased MDZ oral bioavailability by approximately 2.5-folds. We herein demonstrated that DNZ increased the bioavailability of orally administered MDZ through irreversible inactivation of hepatic and intestinal CYP3A in rats.
Long COVID Symptoms in Non-Hospitalised Patients: A Retrospective Study.

INTRODUCTION The COVID-19 pandemic has presented numerous challenges to healthcare systems. As the number of affected individuals continues to rise, it is crucial to find preventive, diagnostic, and therapeutic approaches. This study aims to describe different COVID-19 sequelae within a Primary Health Care population. METHODS A retrospective cohort study was conducted in adults diagnosed with COVID-19 from March 2020 to April 2022, excluding pregnant women, minors, nursing home residents, hospitalizations, and deaths. Data was gathered from surveillance records on the Trace COVID-19® platform, a pre-set original questionnaire (which included the Portuguese version of the World Health Organization's Quality of Life Assessment Instrument), and, if needed, patient electronic health records. Information on sociodemographic and clinical characteristics of acute COVID-19 was collected along with long COVID symptoms. RESULTS This study included 284 patients, aged 19 to 99 years old. The five most prevalent acute COVID-19 symptoms were fever (50.0%), tiredness (48.2%), myalgias (44.7%), dry cough (37.7%) and odynophagia (36.3%). Symptoms related to the neurological system (23.2%) and tiredness (22.9%) were the most prevalent in long COVID symptoms. Acute tiredness and arthralgia were associated with all long COVID outcomes. The associations between acute COVID-19 symptoms with long COVID outcomes were stronger for anosmia [OR = 5.07, 95% confidence interval (CI) 2.49 - 10.36, p < 0.001] on a neurological chapter, acute tiredness for long lasting tiredness (OR = 4.07, 95% CI 2.07 - 8.02, p = 0.041), fatigue for muscles and/or bones chapter (OR = 7.55, 95% CI 3.06 - 18.66, p < 0.001), tiredness on an endocrine/hormonal chapter (OR = 6.54, 95% CI 2.37 - 18.04, p < 0.001), dyspnea for respiratory symptoms (OR = 5.67, 95% CI 1.92 - 16.74, p = 0.002) and fever for stomach or intestine symptoms (OR = 8.06, 95% CI 2.55 - 25.47, p < 0.001). Almost all quality of life dimensions were negatively associated with the number of long COVID symptoms. CONCLUSION A higher number of acute symptoms, as well as the presence of specific COVID-19 symptoms were associated with reported symptoms ≥ 12 weeks after infection. In the studied population, an increased number of symptoms in both acute and long COVID had a significant negative impact on the perception of overall quality of life. The identification of these relationships could provide a new perspective for post-COVID care.
Phosphorylation-state dependent intraneuronal sorting of Aβ differentially impairs autophagy and the endo-lysosomal system

ABSTRACT Progressive accumulation of amyloid-β (Aβ) aggregates in extracellular plaques is a characteristic hallmark of Alzheimer disease (AD). Aβ is also found in intraneuronal deposits and associated with alterations of the endo-lysosomal system and impairment of macroautophagy/autophagy. Here, we assessed the effect of Aβ phosphorylation on neuronal autophagy and the endo-lysosomal pathway. Analysis of APP-PSEN1dE9 transgenic mice revealed a phosphorylation-state dependent intraneuronal accumulation of Aβ species in endo-lysosomal and autophagy-related compartments. Cell biological studies further demonstrate a differential uptake and sorting of phosphorylated Aβ variants in cultured neurons, and phosphorylation-state specific effects of Aβ variants on neuronal autophagy and lysosomal function. While Aβ phosphorylated at serine residue 8 accumulated in autophagosomes, Aβ phosphorylated at serine residue 26 showed efficient transport to lysosomes. The selective sorting of phosphorylated Aβ species caused differential impairment of vesicular transport and lysosomal function associated with neurotoxicity. Thus, the relative occurrence of phosphorylated Aβ species and their intraneuronal accumulation could contribute to AD pathogenesis, and to the commonly observed aberrations of the vesicular transport system already at the early stages of the disease. Abbreviations AD: Alzheimer disease; APP: amyloid beta precursor protein; ATG: autophagy related; Aβ: amyloid-β; CTSD: cathepsin D; DAPI: 4’,6-diamidino-2-phenylindole; EEA1: early endosome antigen 1; FA: formic acid; GFP: green fluorescent protein; LAMP2: lysosomal-associated membrane protein 2; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MAP2: microtubule-associated protein 2; nmAβ: non-modified amyloid-β; npAβ: non-phosphorylated amyloid-β; pAβ: phosphorylated amyloid-β; p-Ser26Aβ: amyloid-β phosphorylated at serine residue 26; p-Ser8Aβ: amyloid-β phosphorylated at serine residue 8; RAB: RAB, member RAS oncogene family; RFP: red fluorescent protein; SQSTM1/p62: sequestome 1; YFP: yellow fluorescent protein.
Impact of exercise on continence in prostate cancer patients post robotic assisted radical prostatectomy: a systematic review.

INTRODUCTION Urinary incontinence is one of the most common long term side effects after robotic prostatectomy (RALP), and significantly impacts patient quality of life. Pelvic floor muscle training (PFMT) has been a standard part of the urologist's armamentarium for maximizing continence outcomes post-op. Recently, aerobic and resistance exercises have been described as improving functional outcomes post RALP. We performed a systematic review to determine the influence of exercise, in the form of PFMT, aerobic exercise, and resistance training, on incontinence post-RALP. MATERIALS AND METHODS This systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with database searches performed on January 14, 2022 and again on August 10, 2022 to account for any new publications. The search identified 1675 papers. Of the 1675 papers, 1007 were found to be duplicates, leaving 668 total studies for screening. Of the 668 papers, nine met all inclusion criteria. Of the nine, four studies presented data from patients who had undergone RALP and were included in the final descriptive systematic review. RESULTS Sayilan et al. and Milios et al. showed postoperative PFMT and physical activity resulted in significantly improved continence outcomes at 1 and 6 months and 2, 6, and 12 weeks postoperatively, respectively. Heydenreich et al. combined PFMT with an oscillating rod therapy, which was found to significantly improve both postoperative urinary continence and health related quality of life compared to PFMT and relaxation techniques alone. On the contrary, Goode et al. examined delivery of exercise information and demonstrated no difference in continence outcomes between focused telehealth PFMT program and generic prostate cancer education. CONCLUSION Pelvic floor muscle training, with or without adjunct therapies, results in improved continence outcomes post RALP. Supervised training programs may or may not accelerate this finding. There is no recent literature to support or refute the benefit of aerobic exercise or resistance training on reducing post-prostatectomy incontinence after RALP.
An Approach for EEG Denoising Based on Wasserstein Generative Adversarial Network

Electroencephalogram (EEG) recordings often contain artifacts that would lower signal quality. Many efforts have been made to eliminate or at least minimize the artifacts, and most of them rely on visual inspection and manual operations, which is time/labor-consuming, subjective, and incompatible to filter massive EEG data in real-time. In this paper, we proposed a deep learning framework named Artifact Removal Wasserstein Generative Adversarial Network (AR-WGAN), where the well-trained model can decompose input EEG, detect and delete artifacts, and then reconstruct denoised signals within a short time. The proposed approach was systematically compared with commonly used denoising methods including Denoised AutoEncoder, Wiener Filter, and Empirical Mode Decomposition, with both public and self-collected datasets. The experimental results proved the promising performance of AR-WGAN on automatic artifact removal for massive data across subjects, with correlation coefficient up to 0.726±0.033, and temporal and spatial relative root-mean-square error as low as 0.176±0.046 and 0.761±0.046, respectively. This work may demonstrate the proposed AR-WGAN as a high-performance end-to-end method for EEG denoising, with many on-line applications in clinical EEG monitoring and brain-computer interfaces.
Pathophysiology of sex difference in refractoriness in lateral epicondylitis: Biomechanical study of wrist torque

Eccentric contractions of the wrist extensors worsen lateral epicondylitis (LE), whose pathophysiology may involve sex differences in wrist torque. This study aimed to investigate sex differences in wrist torque in patients with LE. The wrist extension and flexion torques of 22 patients with LE (11 males and 11 females) were measured. Maximum muscle output over time was measured for 20 s, initial torque was defined as muscle strength, and the degree of eccentric contraction was quantified and defined as the eccentric contraction index (ECI). The affected/unaffected side ratio of the wrist extensor, extensor/flexor ratio of muscle strength, and affected/unaffected side difference of ECI between sexes were statistically analyzed. Furthermore, correlations between wrist extensor torque, ECI, and Visual Analog Scale of pain during the examination were evaluated. Females were found to display lower affected/unaffected side ratios of the wrist extensor and wrist extension/flexion ratios for the affected side, compared with males; however, no differences were found in the wrist extension/flexion ratios for the unaffected side in both sexes. Additionally, females presented with larger differences between the affected and unaffected sides in the ECI. Based on correlations between wrist torques, ECI, and pain, females tended to suppress muscle output to prevent pain from eccentric contraction of wrist extensors more than males, which would induce an imbalance in muscle strength of the wrist extensors and flexors. This imbalance may result in chronic eccentric contraction of the wrist extensors with gripping, exacerbating LE.
Computational identification of key residues regulating fluorescence emission in a red/green cyanobacteriochrome

Cyanobacteriochromes (CBCRs) are linear tetrapyrrole bilin‐binding photoreceptors of cyanobacteria that exhibit high spectral diversity, gaining attention in optogenetics and bioimaging applications. Several engineering studies on CBCRs were attempted, especially for designing near‐infrared (NIR) fluorescent proteins with longer fluorescence wavelengths. However, despite continuous efforts, a key component regulating fluorescence emission property in CBCRs is still poorly understood. As a model system, we focused on red/green CBCR Slr1393g3, from the unicellular cyanobacterium Synechocystis sp. PCC 6803 to engineer Pr to get far‐red light‐emitting property. Energy profiling and pairwise structural comparison of Slr1393g3 variants effectively reveal the mutations that are critical to the fluorescence changes. H497 seems to play a key role in stabilizing the chromophore environment, especially the α3 helix, while H495, T499, and Q502 are potential key residues determining fluorescence emission peak wavelength. We also found that mutations of α2 and α4 helical regions are closely related to the chromophore binding stability and likely affect fluorescence properties. Taken together, our computational analysis suggests that the fluorescence of Slr1393g3 is mainly controlled by the stabilization of the chromophore binding pocket. The predicted key residues potentially regulating the fluorescence emission property of a red/green CBCR will be advantageous for designing improved NIR fluorescent protein when combined with in vitro molecular evolution approaches.
Pediatric HIV Disclosure Intervention Improves Immunologic Outcome at 48 Weeks: The Sankofa Trial Experience

Supplemental Digital Content is Available in the Text. Background: The World Health Organization recommends disclosure of HIV status to children and adolescents living with HIV (CALWH). HIV disclosure improves adherence to antiretroviral therapy and immunologic and virologic outcomes. However, the prevalence of HIV disclosure is low in sub-Saharan Africa. We assessed the longitudinal effect of the Sankofa Pediatric HIV disclosure intervention on immunologic and virologic outcomes among CALWH in Ghana. Methods: We conducted a secondary analysis of a two-arm site-randomized clinical trial among CALWH aged 7–18 years. Data were collected at baseline, 24, and 48 weeks. Generalized linear mixed models were used to compare immunologic (CD4) and virologic (viral load) outcomes as both continuous and categorical variables by disclosure status and by intervention group. Results: Among participants who had their HIV status disclosed during this study, the proportion with CD4 percent >25% increased from 56.5% at baseline to 75.4% at week 48 (P = 0.03), with a slight increase in the undisclosed group (69.5% vs. 74.3%, P = 0.56). In the intervention arm, there was a steady increase in proportion with CD4 percent >25% from 47.1% at baseline to 67.8% at week 48 (P = 0.01) while it remained unchanged in the control arm (80.5% vs. 81.3% [P = 0.89]). Concurrently, declines in detectable viral load were observed in both disclosed (63.3% vs. 51.5%, P = 0.16) and undisclosed (69.9% vs. 62.0%, P = 0.17) groups while the intervention group experienced a meaningful drop from 72.9% to 57.6% at 24 weeks (P = 0.04), which was maintained at 48 weeks. Conclusions: A structured, culturally relevant disclosure intervention can improve clinical outcomes.
Non-polio enteroviruses in faeces of children diagnosed with acute flaccid 1 paralysis in Nigeria

TITLE: Non-polio enteroviruses in faeces of children diagnosed with acute flaccid 1 paralysis in Nigeria. 2 AUTHORS: 3 FALEYE, TOC, ADEWUMI, MO, JAPHET, MO, DAVID, OM, OLUYEGE, AO, 4 ADENIJI, JA, FAMUREWA, O. 5 Department of Microbiology, Faculty of Science, Ekiti State University, Ado-Ekiti, Ekiti 6 State, Nigeria, Department of Virology, College of Medicine, University of Ibadan, Ibadan, 7 Oyo State, Nigeria, Department of Microbiology, Faculty of Science, Obafemi Awolowo 8 University, Ile-Ife, Osun State, Nigeria, WHO, National Polio Laboratory, Department of 9 Virology, College of Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria. 10 Microbiology Unit, Department of Biological Sciences, Kings University, P.M. B. 555, 11 Odeomu, Osun State, Nigeria 12
Stony coral tissue loss disease intervention with amoxicillin leads to a reversal of disease‐modulated gene expression pathways

Stony coral tissue loss disease (SCTLD) remains an unprecedented disease outbreak due to its high mortality rate and rapid spread throughout Florida's Coral Reef and wider Caribbean. A collaborative effort is underway to evaluate strategies that mitigate the spread of SCTLD across coral colonies and reefs, including restoration of disease‐resistant genotypes, genetic rescue, and disease intervention with therapeutics. We conducted an in‐situ experiment in Southeast Florida to assess molecular responses among SCTLD‐affected Montastraea cavernosa pre‐ and post‐application of the most widely used intervention method, CoreRx Base 2B with amoxicillin. Through Tag‐Seq gene expression profiling of apparently healthy, diseased, and treated corals, we identified modulation of metabolomic and immune gene pathways following antibiotic treatment. In a complementary ex‐situ disease challenge experiment, we exposed nursery‐cultured M. cavernosa and Orbicella faveolata fragments to SCTLD‐affected donor corals to compare transcriptomic profiles among clonal individuals from unexposed controls, those exposed and displaying disease signs, and corals exposed and not displaying disease signs. Suppression of metabolic functional groups and activation of stress gene pathways as a result of SCTLD exposure were apparent in both species. Amoxicillin treatment led to a ‘reversal’ of the majority of gene pathways implicated in disease response, suggesting potential recovery of corals following antibiotic application. In addition to increasing our understanding of molecular responses to SCTLD, we provide resource managers with transcriptomic evidence that disease intervention with antibiotics appears to be successful and may help to modulate coral immune responses to SCTLD. These results contribute to feasibility assessments of intervention efforts following disease outbreaks and improved predictions of coral reef health across the wider Caribbean.
Accumulation and recovery of nitrogen in mixed farming systems using legumes and other fertility building crops

The economic and political pressure within the UK for efficiency in crop production has driven the re – examination of crop nutrition and provided a basis for this investigation. Green manures as organic nutrient sources offer the opportunity to alleviate the economic burden of inorganic nutrient sources and mediate a proportion of losse s from the system by maximising the capture of post harvest available N (Thorup – Kristensen et al., 2003). Their usage is mainly seen by the agricultural and research communities as being applicable to “organic” systems. However the ability to transcend to conventional systems and aid their challenges has not been so extensively studied. Cuttle et al., (2003) concluded that further research and clarity was required accurately to assess nitrogen availability from legumes in relation to the nutrition of subsequent crops. The emphasis for this research is to refine and util ise the knowledge and principles of “organic” agriculture green manuring and apply to a conventional agricultural system.