Miracle-dz/UniFAR-FTUs huggingface dataset:
Deleterious Outcomes in Long-Hauler COVID-19: The Effects of SARS-CoV-2 on the CNS in Chronic COVID Syndrome

Amid our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the mechanisms involved in the causation of acute-phase coronavirus disease (COVID-19), we have come across clinical cases that have been shown to run a protracted course of COVID-19 with complex clinical findings related to organ systems in general and the CNS in particular that deserve to be addressed in the COVID long-haulers, for which the more clinically-related term chronic COVID syndrome (CCS) has been coined recently. An in-depth understanding of the mechanism that forms the basis of CCS and neurological deficits in CCS is needed as this can help in determining the management of cases of neuro-COVID, which is emerging as a less lethal but more disabling disease state. This Viewpoint highlights this syndrome, the possible pathogenetic pathways involved, and the treatment approaches that can be taken to help manage COVID long-haulers in CCS.
Human myoelectric spatial patterns differ among lower limb muscles and locomotion speeds

The spatial distribution of myoelectric activity within lower limb muscles is often nonuniform and can change during different stationary tasks. Recent studies using high‐density electromyography (EMG) have suggested that spatial muscle activity may also differ among muscles during locomotion, but contrasting electrode array sizes and experimental designs have limited cross‐study comparisons. Here, we sought to determine if spatial EMG patterns differ among lower limb muscles and locomotion speeds. We recorded high‐density EMG from the vastus medialis, tibialis anterior, biceps femoris, medial gastrocnemius, and lateral gastrocnemius muscles of 11 healthy subjects while they walked (1.2 and 1.6 m/s) and ran (2.0, 3.0, 4.0, and 5.0 m/s) on a treadmill. To overcome the detrimental effects of cable, electrode, and soft tissue movements on high‐density EMG signal quality during locomotion, we applied multivariate signal cleaning methods. From these data, we computed the spatial entropy and center of gravity from the total myoelectric activity within each recording array during the stance or swing phases of the gait cycle. We found heterogeneous spatial EMG patterns evidenced by contrasting spatial entropy among lower limb muscles. As locomotion speed increased, mean entropy values decreased in four of the five recorded muscles, indicating that EMG signal amplitudes were more spatially heterogeneous, or localized, at faster speeds. The EMG center of gravity location also shifted in multiple muscles as locomotion speed increased. Contrasting myoelectric spatial distributions among muscles likely reflect differences in muscle architecture, but increasingly localized activity and spatial shifts in the center of gravity location at faster locomotion speeds could be influenced by preferential recruitment of faster motor units under greater loads.
Budget impact analysis of subcutaneous trastuzumab compared to intravenous trastuzumab in Saudi HER2-positive breast cancer patients

ABSTRACT Background: This study was aimed to assess the budget impact of SC trastuzumab compared to IV trastuzumab in patients with HER2-positive breast cancer (BC) from the perspective of the governmental health sector in Saudi Arabia, over a 3-year time horizon. Methods: A model was developed to calculate the direct medical and indirect costs for 394 incidents HER2-positive BC patients per year who would receive SC trastuzumab compared to IV formulation. We calculated drug acquisition costs for fixed, loading, and subsequent doses of trastuzumab. One-way sensitivity analysis was conducted. Results: Two scenarios were modeled: the first scenario evaluated the impact of gradual replacement of IV formulation by SC, the second scenario, evaluated impact of totally replacing IV formulation. The total annual costs in the first scenario were estimated to be SAR 177 million (USD 98 million) for IV trastuzumab compared to SAR 143 million (USD 79 million) for SC formulation, leading to a total budget saving of SAR 34,527,346 (USD 19,181,858). In the second scenario, the total annual costs were estimated to be SAR 108 million (USD 60 million) for SC trastuzumab compared to SAR 177 million (USD 98 million) for IV formulation, leading to budget savings of SAR 69,054,692 (USD 36,363,717). Conclusion: Benefits of the SC formulation over IV infusions are being converted to realistic monetary benefits for all providers and payers.
Intestinal Strongyle Genera in Different Typology of Donkey Farms in Tuscany, Central Italy

Intestinal strongyles are common helminths of donkeys, in which they may be responsible for disease and poor performance. This study aimed to identify intestinal strongyle genera in 55 naturally infected donkeys from three different farm typologies in Tuscany, central Italy, using morphological and metrical analysis of third stage larvae (L3) obtained from faecal cultures. Larvae were identified using two previous reported morphological identification keys. Moreover, eggs per gram (EPG) data were also evaluated to assess differences, if any, according to the farm typology, sex, and age of the examined donkeys. The results showed that small strongyles were prevalent in all donkey farms. In all examined farms, most (92–100%) of L3 were identified as cyathostomin species of the genera Cylicocyclus spp. and Cylicostephanus spp. Large strongyles of the genera Strongylus spp. and Triodontophorus spp. , were identified at low percentage (8%), only in the single organic farm included in the study. A high agreement was observed between the two different morphometric keys used. No significant differences were found for EPG according to farm typology, and sex and age from the examined donkeys. This is the first report about genera identification of intestinal strongyles infecting donkeys in Tuscany, Italy.
Primary treatment of atlantoaxial rotatory fixation in children: a multicenter, retrospective series of 125 cases.

OBJECTIVE The primary treatment for atlantoaxial rotatory fixation (AARF) remains controversial. The aim of this study was to investigate the primary treatment for AARF and create an algorithm for primary treatment. METHODS The authors analyzed the data of 125 pediatric patients at four medical institutions from April 1989 to December 2018. The patients were reported to have neck pain, torticollis, and restricted neck range of motion and were diagnosed according to the Fielding classification as type I or II. As a primary treatment, 88 patients received neck collar fixation, and 28 of these patients did not show symptom relief and required Glisson traction. Thirty-seven patients were primarily treated with Glisson traction. In total, 65 patients, including neck collar treatment failure patients, underwent Glisson traction in hospitals. RESULTS The success rate of treatment was significantly higher in the Glisson traction group (97.3%) than in the neck collar fixation group (68.2%) (p = 0.0001, Wilcoxon test). In the neck collar effective group, Fielding type I was more predominant (p = 0.0002, Wilcoxon test) and the duration from onset to the first visit was shorter (p = 0.02, Wilcoxon test) than that in the neck collar ineffective group. Using multivariate logistic regression analysis with the above items, the authors generalized from the estimated formula: logit [p(success group by neck collar fixation group)|duration from onset to the first visit (x1), Fielding type (x2)] = 0.4(intercept) - 0.15x1 + 1.06x2, where x1 is the number of days and x2 = 1 (for Fielding type I) or -1 (for Fielding type II). In cases for which the score is a positive value, the neck collar should be chosen. Conversely, in cases for which the score is a negative value, Glisson traction should be the first choice. CONCLUSIONS According to this formula, in patients with Fielding type I AARF, neck collar fixation should be allowed only if the duration from onset is ≤ 10 days. In patients with Fielding type II, because the score would be a negative value, Glisson traction should be performed as the primary treatment.
ATG5-Dependent Autophagy Uncouples T-cell Proliferative and Effector Functions and Separates Graft-versus-Host Disease from Graft-versus-Leukemia

These findings demonstrate that induction of autophagy in donor T-cell promotes GVHD, while inhibition of T-cell autophagy mitigates GVHD without substantial loss of GVL responses. Autophagy is a vital cellular process whose role in T immune cells is poorly understood, specifically, in its regulation of allo-immunity. Stimulation of wild-type T cells in vitro and in vivo with allo-antigens enhances autophagy. To assess the relevance of autophagy to T-cell allo-immunity, we generated T-cell–specific Atg5 knock-out mice. Deficiency of ATG5-dependent autophagy reduced T-cell proliferation and increased apoptosis following in vitro and in vivo allo-stimulation. The absence of ATG5 in allo-stimulated T cells enhanced their ability to release effector cytokines and cytotoxic functions, uncoupling their proliferation and effector functions. Absence of autophagy reduced intracellular degradation of cytotoxic enzymes such as granzyme B, thus enhancing the cytotoxicity of T cells. In several in vivo models of allo-HSCT, ATG5-dependent dissociation of T-cell functions contributed to significant reduction in graft-versus-host disease (GVHD) but retained sufficient graft versus tumor (GVT) response. Our findings demonstrate that ATG5-dependent autophagy uncouples T-cell proliferation from its effector functions and offers a potential new strategy to enhance outcomes after allo-HSCT. Significance: These findings demonstrate that induction of autophagy in donor T-cell promotes GVHD, while inhibition of T-cell autophagy mitigates GVHD without substantial loss of GVL responses.
Parkinson Disease Propagation Using MRI Biomarkers and Partial Least Squares Path Modeling

Objectives The classic Braak neuropathologic staging model in Parkinson disease (PD) suggests that brain lesions progress from the medulla oblongata to the cortex. An alternative model in which neurodegeneration first occurs in the cortex has also been proposed. These 2 models may correspond to different patient phenotypes. To test these 2 models and to investigate whether they were influenced by the presence of REM sleep behavior disorder (RBD), we used multimodal MRI and partial least squares path modeling (PLS-PM) assuming that patients with RBD followed distinct neurodegeneration pattern. Methods Fifty-four patients with PD (34 with RBD) and 25 healthy volunteers were scanned with T1-weighted, diffusion tensor, and neuromelanin-sensitive imaging. Volume, signal, and mean, axial, and radial diffusivities were calculated in brainstem, basal forebrain, and cortical regions. PLS-PM, estimating a network of causal relationships between blocks of variables, was used to build and test an analytical model based on Braak staging. The overall quality of the model was assessed with goodness of fit coefficient (Gof). Results PLS-PM was run on patients with PD with RBD and without RBD separately. In PD with RBD, a brainstem-to-cortex model had significant Gof (0.71, p = 0.01), whereas a cortex-to-brainstem model did not. In contrast, in patients with PD without RBD, the brainstem-to-cortex model was not significant (Gof = 0.64, p = 0.27), and the cortex-to-brainstem model was highly significant (Gof = 0.72, p = 0.008). Conclusions With the PLS-PM imaging–based model, the neurodegeneration pattern of patients with PD with RBD was consistent with the Braak brainstem-to-cortex model, whereas that of patients without RBD followed the cortex-to-brainstem model.
Effects of aspirin on pancreatic cancer cells PANC-1 and its potential molecular mechanism.

PURPOSE To explore the effects of aspirin on the proliferation and apoptosis of human pancreatic cancer cells and its potential molecular mechanism. METHODS This study included patients with pancreatic cancer who were divided into experimental group and control group. The cell proliferation ability was detected via cell counting kit-8 (CCK-8) assay and colony forming ability via colony formation assay. In addition, changes in proteins in the phosphatidyl inositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway were assessed using Western blotting, and rescue experiment was conducted to investigate whether aspirin can affect cell proliferation by inhibiting the PI3K/Akt/mTOR signaling pathway. RESULTS The results of CCK-8 assay showed that the proliferation rate of PANC-1 cells was decreased in a time- and dose-dependent manner after they were treated with aspirin at different concentrations. Colony formation assay confirmed that cell colony forming ability was significantly reduced with the increase in aspirin treatment concentration (p<0.05). Besides, the apoptosis rate and the number of cells in the experimental group were higher and larger than those in the control group (p<0.05). According to Western blotting results, the protein expressions of PI3K, phosphorylated (p)-Akt and p-mTOR were decreased after aspirin treatment. Rescue experimental results manifested that insulin-like growth factor 1 (IGF-1) supplementation remarkably elevated the expressions of PI3K, p-Akt and p-mTOR compared with phosphate-buffered saline (PBS) supplementation. It was found in CCK-8 assay that IGF-1 supplementation markedly reversed the inhibition of aspirin on the proliferation of PANC-1 cells in comparison with PBS supplementation. CONCLUSIONS Aspirin inhibits the proliferation and promotes the apoptosis of pancreatic cancer cells by inactivating the PI3K/Akt/mTOR signaling pathway.
The Wide Spectrum of Pathophysiologic Mechanisms of Paraproteinemic Neuropathy

Monoclonal gammopathy is encountered quite frequently in the general population. This type of hematologic abnormality may be mild, referred to as monoclonal gammopathy of undetermined significance or related to different types of hematologic malignancies. The association of a peripheral neuropathy with monoclonal gammopathy is also fairly common, and hemopathy may be discovered in an investigation of peripheral neuropathy. In such a situation, it is essential to determine the exact nature of the hematologic process in order not to miss a malignant disease and thus initiate the appropriate treatment (in conjunction with hematologists and oncologists). In this respect, nerve biopsy (discussed on a case-by-case basis) is of great value in the management of such patients. We therefore propose to present the objectives and main interests of nerve biopsy in this situation.
Solid-State EDLC Device Based on Magnesium Ion-Conducting Biopolymer Composite Membrane Electrolytes: Impedance, Circuit Modeling, Dielectric Properties and Electrochemical Characteristics

The polymer electrolyte based on Dx:Cs:Mg(CH3COO)2:Ni with three different glycerol concentrations have been prepared. The impedance study has verified that the electrolyte with 42 wt. % of glycerol (A3) has the highest ionic conductivity of 7.71 × 10−6 S cm−1 at room temperature. The ionic conductivity is found to be influenced by the transport parameters. From the dielectric analysis, it was shown that the electrolytes in this system obeyed the non-Debye behavior. The A3 electrolyte exhibited a dominancy of ions (tion > te) with a breakdown voltage of 2.08 V. The fabricated electrochemical double layer capacitor (EDLC) achieved the specific capacitance values of 24.46 F/g and 39.68 F/g via the cyclic voltammetry (CV) curve and the charge–discharge profile, respectively. The other significant parameters to evaluate the performance of EDLC have been determined, such as internal resistance (186.80 to 202.27 Ω) energy density (4.46 Wh/kg), power density (500.58 to 558.57 W/kg) and efficiency (92.88%).
The Complete Chloroplast Genome of the Vulnerable Oreocharis esquirolii (Gesneriaceae): Structural Features, Comparative and Phylogenetic Analysis

Oreocharis esquirolii, a member of Gesneriaceae, is known as Thamnocharis esquirolii, which has been regarded a synonym of the former. The species is endemic to Guizhou, southwestern China, and is evaluated as vulnerable (VU) under the International Union for Conservation of Nature (IUCN) criteria. Until now, the sequence and genome information of O. esquirolii remains unknown. In this study, we assembled and characterized the complete chloroplast (cp) genome of O. esquirolii using Illumina sequencing data for the first time. The total length of the cp genome was 154,069 bp with a typical quadripartite structure consisting of a pair of inverted repeats (IRs) of 25,392 bp separated by a large single copy region (LSC) of 85,156 bp and a small single copy region (SSC) of18,129 bp. The genome comprised 114 unique genes with 80 protein-coding genes, 30 tRNA genes, and four rRNA genes. Thirty-one repeat sequences and 74 simple sequence repeats (SSRs) were identified. Genome alignment across five plastid genomes of Gesneriaceae indicated a high sequence similarity. Four highly variable sites (rps16-trnQ, trnS-trnG, ndhF-rpl32, and ycf 1) were identified. Phylogenetic analysis indicated that O. esquirolii grouped together with O. mileensis, supporting resurrection of the name Oreocharis esquirolii from Thamnocharis esquirolii. The complete cp genome sequence will contribute to further studies in molecular identification, genetic diversity, and phylogeny.
Machine Learning Supports Automated Digital Image Scoring of Stool Consistency in Diapers

Supplemental Digital Content is available in the text ABSTRACT Background/Aims: Accurate stool consistency classification of non–toilet-trained children remains challenging. This study evaluated the feasibility of automated classification of stool consistencies from diaper photos using machine learning (ML). Methods: In total, 2687 usable smartphone photos of diapers with stool from 96 children younger than 24 months were obtained after independent ethical study approval. Stool consistency was assessed from each photo according to the original 7 types of the Brussels Infant and Toddler Stool Scale independently by study participants and 2 researchers. A health care professional assigned a final score in case of scoring disagreement between the researchers. A proof-of-concept ML model was built upon this collected photo database, using transfer learning to re-train the classification layer of a pretrained deep convolutional neural network model. The model was built on random training (n = 2478) and test (n = 209) subsets. Results: Agreements between study participants and both researchers were 58.0% and 48.5%, respectively, and between researchers 77.5% (assessable n = 2366). The model classified 60.3% of the test photos in exact agreement with the final score. With respect to the 4-class grouping of the 7 Brussels Infant and Toddler Stool Scale types, the agreement between model-based and researcher classification was 77.0%. Conclusion: The automated and objective scoring of stool consistency from diaper photos by the ML model shows robust agreement with human raters and overcomes limitations of other methods relying on caregiver reporting. Integrated with a smartphone application, this new framework for photo database construction and ML classification has numerous potential applications in clinical studies and home assessment.
Evidence Based Use of LT4/LT3 Combinations in Treating Hypothyroidism: A Consensus Document.

Background Fourteen clinical trials have not shown a consistent benefit of combination therapy with levothyroxine (LT4) and liothyronine (LT3). Despite the publication of these trials, combination therapy is widely used and patients reporting benefit continue to generate patient and physician interest in this area. Recent scientific developments may provide insight into this inconsistency and guide future studies. Methods The ATA, BTA and ETA held a joint conference on November 3rd 2019 (live-streamed between Chicago and London) to review new basic science and clinical evidence regarding combination therapy with presentations and input from twelve content experts. Following the presentations, the material was synthesized and used to develop Summary Statements of the current state of knowledge. After review and revision of the material and Summary Statements, there was agreement that there was equipoise for a new clinical trial of combination therapy. Consensus Statements encapsulating the implications of the material discussed with respect to the design of future clinical trials of LT4/LT3 combination therapy were generated. Authors voted upon the Consensus Statements. Iterative changes were made in several rounds of voting and following comments from ATA/BTA/ETA members. Results Of 34 Consensus Statements available for voting 28 received at least 75% agreement, with 13 receiving 100% agreement. Those with 100% agreement included studies being powered to study the effect of deiodinase and thyroid hormone transporter polymorphisms on study outcomes, inclusion of patients dissatisfied with their current therapy and requiring at least 1.2 mcg/kg of levothyroxine daily, use of twice daily liothyronine or preferably a slow-release preparation if available, use of patient-reported outcomes as a primary outcome (measured by a tool with both relevant content validity and responsiveness) and patient preference as a secondary outcome, and utilization of a randomized, placebo-controlled, adequately powered double-blinded parallel design. The remaining statements are presented as potential additional considerations. Discussion This manuscript summarizes the areas discussed and presents Consensus Statements to guide development of future clinical trials of LT4/LT3 combination therapy. The results of such redesigned trials are expected to be of benefit to patients and of value to inform future thyroid hormone replacement clinical practice guidelines treatment recommendations.
Role of Gut Microbiota on Onset and Progression of Microvascular Complications of Type 2 Diabetes (T2DM)

Type 2 diabetes mellitus (T2DM) remains one of the most problematic and economic consumer disorders worldwide, with growing prevalence and incidence. Over the last years, substantial research has highlighted the intricate relationship among gut microbiota, dysbiosis and metabolic syndromes development. Changes in the gut microbiome composition lead to an imbalanced gastrointestinal habitat which promotes abnormal production of metabolites, inflammatory status, glucose metabolism alteration and even insulin resistance (IR). Short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), lipopolysaccharide, aromatic amino acids and their affiliated metabolites, contribute to T2DM via different metabolic and immunologic pathways. In this narrative review, we discuss the immunopathogenic mechanism behind gut dysbiosis, T2DM development and the major known diabetic microvascular complications (retinopathy, neuropathy and nephropathy), the beneficial use of pre- and pro-biotics and fecal microbiota transplantation in T2DM management and new findings and future perspectives in this field.