Miracle-dz/UniFAR-FTUs huggingface dataset:
Multiple steps characterise ventricular layer attrition to form the ependymal cell lining of the adult mouse spinal cord central canal

The ventricular layer of the spinal cord is remodelled during embryonic development and ultimately forms the ependymal cell lining of the adult central canal, which retains neural stem cell potential. This anatomical transformation involves the process of dorsal collapse; however, accompanying changes in tissue organisation and cell behaviour as well as the precise origin of cells contributing to the central canal are not well understood. Here, we describe sequential localised cell rearrangements which accompany the gradual attrition of the spinal cord ventricular layer during development. This includes local breakdown of the pseudostratified organisation of the dorsal ventricular layer prefiguring dorsal collapse and evidence for a new phenomenon, ventral dissociation, during which the ventral‐most floor plate cells separate from a subset that are retained around the central canal. Using cell proliferation markers and cell‐cycle reporter mice, we further show that following dorsal collapse, ventricular layer attrition involves an overall reduction in cell proliferation, characterised by an intriguing increase in the percentage of cells in G1/S. In contrast, programmed cell death does not contribute to ventricular layer remodelling. By analysing transcript and protein expression patterns associated with key signalling pathways, we provide evidence for a gradual decline in ventral sonic hedgehog activity and an accompanying ventral expansion of initial dorsal bone morphogenetic protein signalling, which comes to dominate the forming the central canal lining. This study identifies multiple steps that may contribute to spinal cord ventricular layer attrition and adds to increasing evidence for the heterogeneous origin of the spinal cord ependymal cell population, which includes cells from the floor plate and the roof plate as well as ventral progenitor domains.
Development and Validation of a Nomogram for Early Detection of Malignant Gallbladder Lesions

OBJECTIVES: Preoperative decision-making for differentiating malignant from benign lesions in the gallbladder remains challenging. We aimed to create a diagnostic nomogram to identify gallbladder cancer (GBC), especially for incidental GBC (IGBC), before surgical resection. METHODS: A total of 587 consecutive patients with pathologically confirmed gallbladder lesions from a hospital were randomly assigned to a training cohort (70%) and an internal validation cohort (30%), with 287 patients from other centers as an external validation cohort. Radiological features were developed by the least absolute shrinkage and selection operator logistic regression model. Significant radiological features and independent clinical factors, identified by multivariate analyses, were used to construct a nomogram. RESULTS: A diagnostic nomogram was established by age, CA19.9, and 6 radiological features. The values of area under the curve in the internal and external validation cohorts were up to 0.91 and 0.89, respectively. The calibration curves for probability of GBC showed optimal agreement between nomogram prediction and actual observation. Compared with previous methods, it demonstrated superior sensitivity (91.5%) and accuracy (85.1%) in the diagnosis of GBC. The accuracy using the nomogram was significantly higher in GBC groups compared with that by radiologists in the training cohort (P < 0.001) and similarly in each cohort. Notably, most of the IGBC, which were misdiagnosed as benign lesions, were successfully identified using this nomogram. DISCUSSION: A novel nomogram provides a powerful tool for detecting the presence of cancer in gallbladder masses, with an increase in accuracy and sensitivity. It demonstrates an unprecedented potential for IGBC identification.
Electrochemical characteristics of ultramicro-dimensioned SIROF electrodes for neural stimulation and recording

Objective. With ever increasing applications of neural recording and stimulation, the necessity for developing neural interfaces with higher selectivity and lower invasiveness is inevitable. Reducing the electrode size is one approach to achieving such goals. In this study, we investigated the effect of electrode geometric surface area (GSA), from 20 μm2 to 1960 μm2, on the electrochemical impedance and charge-injection properties of sputtered iridium oxide (SIROF) coated electrodes in response to current-pulsing typical of neural stimulation. These data were used to assess the electrochemical properties of ultra-small SIROF electrodes (GSA < 200 μm2) for stimulation and recording applications. Approach. SIROF charge storage capacities (CSC), impedance, and charge-injection characteristics during current-pulsing of planar, circular electrodes were evaluated in an inorganic model of interstitial fluid (model-ISF). Main results. SIROF electrodes as small as 20 μm2 could provide 1.3 nC/phase (200 μs pulse width, 0.6 V versus Ag|AgCl interpulse bias) of charge during current pulsing. The 1 kHz impedance of all electrodes used in this study were below 1 MΩ, which is suitable for neural recording. Significance. Ultra-small SIROF electrodes are capable of charge injection in buffered saline at levels above some reported thresholds for neural stimulation with microelectrodes.
The Impact of Complications and Pain on Patient Satisfaction

Objective: To measure the association between patient-reported satisfaction and regret and clinical outcomes. Summary of Background Data: Patient-reported outcomes are becoming an increasingly important marker of the quality of patient care. It is unclear however, how well patient-reported outcomes adequately reflect care quality and clinical outcomes in surgical patients. Methods: Retrospective, population-based analysis of adults ages 18 and older undergoing surgery across 38 hospitals in Michigan between January 1, 2017 and May 31, 2018. Results: In this study, 9953 patients (mean age 56 years; 5634 women (57%)) underwent 1 of 16 procedures. 9550 (96%) patients experienced no complication, whereas 240 (2%) and 163 (2%) patients experienced Grade 1 and Grade 2–3 complications, respectively. Postoperative pain scores were: none (908 (9%) patients), mild (3863 (40%) patients), moderate (3893 (40%) patients), and severe (1075 (11%) patients). Overall, 7881 (79%) patients were highly satisfied and 8911 (91%) had absolutely no regret after surgery. Patients were less likely to be highly satisfied if they experienced a Grade 1 complication [odds ratio (OR) 0.50, 95% confidence interval (CI) 0.37–0.66], Grade 2–3 complication (OR 0.44, 95% CI 0.31–0.62), minimal pain (OR 0.80, 95% CI 0.64–0.99, moderate pain (OR 0.39, 95% CI 0.32–0.49), or severe pain (OR 0.23, 95% CI 0.18–0.29). Patients were less likely to have no regret if they experienced a Grade 1 complication (OR 0.48, 95% CI 0.33–0.70), Grade 2–3 complication (OR 0.39, 95% CI 0.25–0.60), moderate pain (OR 0.55, 95% CI 0.40–0.76), or severe pain (OR 0.22, 95% CI 0.16–0.31). The predicted probability of being highly satisfied was 79% for patients who had no complications and 88% for patients who had no pain. Conclusions: Patients who experienced postoperative complications and pain were less likely to be highly satisfied or have no regret. Notably, postoperative pain had a more significant effect on satisfaction and regret after surgery, suggesting focused postsurgical pain management is an opportunity to substantially improve patient experiences. More research and patient education are needed for managing expectations of postoperative pain, and use of adjuncts and regional anesthesia.
Multiple sclerosis has a distinct lipid signature in plasma and cerebrospinal fluid.

OBJECTIVE The diagnosis of multiple sclerosis (MS) has changed over the last decade, but remains a composite of clinical assessment and magnetic resonance imaging to prove dissemination of lesions in time and space. The intrathecal synthesis of immunoglobulin may be a nonspecific marker and there are no plasma biomarkers that are useful in the diagnosis of MS, presenting additional challenges to their early detection. METHODS We performed a preliminary untargeted qualitative lipidomics mass spectrometry analysis, comparing cerebrospinal fluid (CSF) and plasma samples from patients with MS, other inflammatory neurological diseases and idiopathic intracranial hypertension. RESULTS Lipid identification revealed that fatty acids and sphingolipids were the most abundant classes of lipids in the CSF and that glycerolipids and fatty acids were the main class of lipids in the plasma of patients with MS. The area under the curve was 0.995 (0.912-1) and 0.78 (0.583-0.917), respectively. The permutation test indicated that this ion combination was useful for distinguishing MS from other inflammatory diseases (p < 0.001 and 0.055, respectively). CONCLUSION This study concluded that the CSF and plasma from patients with MS bear a unique lipid signature that can be useful as a diagnostic biomarker.
Analysis of anti-tuberculosis drug resistance and sociodemographic and clinical aspects of patients admitted in a referral hospital

ABSTRACT Objective To determine the occurrence of anti-tuberculosis drug resistance and its association with sociodemographic and clinical characteristics of patients in a referral hospital. Methods This was a cross-sectional study based on data from patients who had mycobacterial culture identified and defined antimicrobials sensitivity profile (June 2014 to February 2016). The descriptive statistical analysis and Fisher’s exact test were used to compare proportions. Results The study included 104 patients who had positive results for Mycobacterium tuberculosis . Bacilloscopy had high positivity (93.3%). A total of 15 patients (14.4%) had resistant strains and six (5.6%) multidrug-resistant. The sociodemographic and clinical characteristics were not related with resistance. Conclusion This study contributed to further the understandings about the tuberculosis patients’ profile, the study also served as a tool for development of specific public policies. Patients diagnosed with resistant tuberculosis must be under greater supervision.
Higher social cue utilisation improves communication, reduces perceived workload, and improves performance amongst ad hoc dyads in simulated rail control

Abstract The objective was to examine whether ad hoc dyads with different collective social cue utilisation would record differences in performance and perceptions of workload during a simulated rail control task that incorporated distinct levels of demand. The frequency of two types of communicative statements was also examined as mediating factors: closing the loop and informative responding. A quasi-experimental design was employed using 40 dyadic teams. The results indicated that ad hoc teams whose members comprised higher social cue utilisation recorded relatively faster response times and perceived lower levels of workload, and engaged in a greater frequency of communicative statements that involved ‘closing the loop’ and ‘informative responses’. Social cue utilisation also exerted an indirect effect on perceived workload through informative responding. The outcomes have theoretical implications for models of ad hoc team performance, and practical implications for the selection and training of teams that operate on an ad hoc basis. Practitioner summary: This study indicates that, in the context of simulation tasks requiring teamwork, higher social cue utilisation amongst ad hoc team members is associated with communication, workload perception, and overall performance.
Trends in the surgical treatment of meniscal tears in patients with and without concurrent anterior cruciate ligament tears

ABSTRACT Objectives Meniscal and anterior cruciate ligament (ACL) tears are common injuries. The purpose of this study was to determine trends in meniscal repair and meniscectomy both in the presence and absence of ACL reconstruction (ACLR). Methods The PearlDiver database (www.pearldiverinc.com, Fort Wayne, IN) was queried for surgical management of patients who underwent arthroscopic meniscectomy (Current Procedural Terminology [CPT] codes 29880, 29881), meniscus repair (29882, 29883), and ACLR (29888) from 2010 to 2015. Patient groups included meniscectomy alone, meniscus repair alone, meniscus repair followed by meniscectomy, ACLR with meniscus repair, and ACLR with meniscus repair followed by meniscectomy. Linear regression was performed to determine the significance of yearly trend across each procedure. Statistical analysis was performed with RStudio, Version 1.1. 442 (RStudio Inc. Boston, MA) for α value of . 05. Results The incidence of isolated meniscectomies decreased from 32.5/10,000 to 28.3/10,000 across the study period (p = 0.0230), whereas the incidence of isolated meniscus repairs and all meniscus repairs remained unchanged (p = 0.3000, p = 0.1260). For patients undergoing concomitant meniscal repair and ACLR, the highest proportion of patients was in the age range 15–24 years old with 45.7% of patients being 15–19. Of the ACLR, 18.6% involved a concomitant meniscus repair, and 54.0% involved a concomitant meniscectomy. The risk of subsequent meniscectomy was less in patients undergoing meniscal repair with ACLR than in patients undergoing isolated meniscal repair (10.8% versus 12.4%; aOR = 0.71, 95% CI 0.53–0.95, p = 0.0226). Conclusions The highest rates of concurrent meniscal repair with ACLR are in the 15–24-year-old population. From 2010 to 2015, the rate of meniscectomy declined while that of isolated meniscal repairs, as well as meniscal repair with ACLR, remained stable. Patients undergoing meniscal repair with ACLR had lower rates of subsequent meniscectomy compared to patients undergoing isolated meniscal repair in the absence of ACL tear. Level of evidence Level III.
β-Lactam pharmacodynamics in Gram-negative bloodstream infections in the critically ill.

OBJECTIVES To determine the β-lactam exposure associated with positive clinical outcomes for Gram-negative blood stream infection (BSI) in critically ill patients. PATIENTS AND METHODS Pooled data of critically ill patients with mono-microbial Gram-negative BSI treated with β-lactams were collected from two databases. Free minimum concentrations (fCmin) of aztreonam, cefepime, ceftazidime, ceftriaxone, piperacillin (co-administered with tazobactam) and meropenem were interpreted in relation to the measured MIC for targeted bacteria (fCmin/MIC). A positive clinical outcome was defined as completion of the treatment course or de-escalation, without other change of antibiotic therapy, and with no additional antibiotics commenced within 48 h of cessation. Drug exposure breakpoints associated with positive clinical outcome were determined by classification and regression tree (CART) analysis. RESULTS Data from 98 patients were included. Meropenem (46.9%) and piperacillin/tazobactam (36.7%) were the most commonly prescribed antibiotics. The most common pathogens were Escherichia coli (28.6%), Pseudomonas aeruginosa (19.4%) and Klebsiella pneumoniae (13.3%). In all patients, 87.8% and 71.4% achieved fCmin/MIC ≥1 and fCmin/MIC >5, respectively. Seventy-eight patients (79.6%) achieved positive clinical outcome. Two drug exposure breakpoints were identified: fCmin/MIC >1.3 for all β-lactams (predicted difference in positive outcome 84.5% versus 15.5%, P < 0.05) and fCmin/MIC >4.95 for meropenem, aztreonam or ceftriaxone (predicted difference in positive outcome 97.7% versus 2.3%, P < 0.05). CONCLUSIONS A β-lactam fCmin/MIC >1.3 was a significant predictor of a positive clinical outcome in critically ill patients with Gram-negative BSI and could be considered an antibiotic dosing target.
Dento-Skeletal Characteristics of 8-13 Year-old Boys and Girls with Class II Division 1 Malocclusion in Fars Province; a Cephalometric Study

Statement of Problem: The dentoskeletal characteristics of the Class II Division 1 patients dictate their treatment plan and mechanotherapy. Purpose : This study was undertaken to describe the dentofacial characteristics of this type of malocclusion in 8-13 year-old children in Fars Province. Materials and Method: The materials examined included 693 lateral head radiographs comprising two series of 213 films of normal occlusion children and 480 films of Class II Division 1 patients reffered to Orthodontic Department of Shiraz Dental School, taken during the years 2002 to 2004. The controls and the Class II Division 1 subjects were each divided into three groups according to age including 10-11, 12-13 and 14-15 and then divided into two subgroups according to gender. The radiographs were converted into computer-readable X and Y coordinate data and 36 linear and 15 angular measurements in the cranial base, maxilla, mandible and dentition, were provided (based on 35 points) and compared. Results: The statistical analysis showed that the anterior cranial base was larger and more protrusive, with an increase in cranial base angle compared with controls. The mandible was smaller and its form and position was different from controls whereas, the maxilla (at the level of palate and alveolus) and the dentition were protrusive. The palate was inclined superiorly at its anterior half. The vertical maxillary exess and the increase of mid-facial convexity were visible. Conclusion: Various factors ranging from mandibular deficiency to maxillary protrusion with different dental configurations were responsible for the presence of Class II Division 1 malocclusion in our patients. Key words: Class II Division 1, Malocclusion, Dentofacial, Children, Fars Province
Single Cell Sequencing of Mouse Heart Immune Infiltrate in Pressure Overload-Driven Heart Failure Reveals Extent of Immune Activation.

Background: Inflammation is a key component of cardiac disease, with macrophages and T lymphocytes mediating essential roles in the progression to heart failure (HF). Nonetheless, little insight exists on other immune subsets involved in the cardiotoxic response. Methods: Here we used single-cell RNA sequencing to map the cardiac immune composition in the standard murine non-ischemic, pressure-overload HF model. By focusing our analysis on CD45+ cells, we obtained a higher resolution identification of the immune cell subsets in the heart, at early and late stages of disease and in controls. We then integrated our findings using multi-parameter flow cytometry, immunohistochemistry and tissue clarification immunofluorescence, in mouse and human. Results: We found that most major immune cell subpopulations, including macrophages, B cells, T cells and regulatory T cells (Treg), dendritic cells, NK cells, neutrophils and mast cells are present in both healthy and diseased hearts. Most cell subsets are found within the myocardium, whilst mast cells are found also in the epicardium. Upon induction of pressure overload, immune activation occurs across the entire range of immune cell types. Activation led to upregulation of key subset-specific molecules, such as Osm in pro-inflammatory macrophages and PD-1 in Treg, that may help explain clinical findings such as the refractivity of HF patients to anti-TNF therapy and cardiac toxicity during anti-PD-1 cancer immunotherapy, respectively. Conclusions: Despite the absence of infectious agents or an autoimmune trigger, induction of disease leads to immune activation that involves far more cell types than previously thought, including neutrophils, B cells, NK cells and mast cells. This opens up the field of cardio-immunology to further investigation using toolkits that have already been developed to study the immune subsets above. The subset-specific molecules that mediate their activation may thus become useful targets for diagnostics or therapy of HF.
Anti-Tumor Activity and Safety of Multikinase Inhibitors in Advanced and/or Metastatic Thyroid Cancer: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

Abstract Many trials have demonstrated prime antitumor activity of novel, small molecule multikinase inhibitors (MKIs) in advanced and/or metastatic thyroid cancer (TC). In this work, the PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, SCOPUS, and clinicaltrials.gov databases were searched. Quality/risk of bias were assessed using GRADE criteria. Randomized clinical trials (RCTs) comparing two or more systemic therapies in patients with advanced and/or metastatic thyroid cancer were assessed. A total of 1347 articles and 548 clinical trials in clinicaltrials.gov were screened. We included seven relevant RCTs comprising 1934 unique patients assigned to different MKIs. Two separate network meta-analyses included four RCTs in radioiodine refractory well-differentiated thyroid cancer (RR-WDTC) and three RCTs in medullary thyroid cancer (MTC), respectively; all with a low risk of bias. We identified three therapies for RR-WDTC: sorafenib [disease control rate (DCR) odds ratio (OR): 0.11 (95% CI: 0.03–0.40); progression-free survival (PFS) hazard ratio (HR): 1.99 (95% CI: 1.62–2.46)], vandetanib [DCR_OR:0.26 (95% CI: 0.06–1.24); PFS_HR: 0.99 (95% CI: 0.82–1.20)] and lenvatinib [DCR_OR: 0.26 (95% CI: 0.05–1.33); PFS_HR: 0.99 (95% CI: 0.81–1.22)]; and the following therapies for MTC: vandetanib 300 mg [objective response rate (ORR)_OR: 3.31 (95% CI: 0.68–16.22); vandetanib 150 mg ORR_OR: 0.60 (95% CI: 0.16–2.33)]; and cabozantinib [ORR_OR: 85.32 (95% CI: 5.22–1395.15)]. Serious side effect (SE) analysis per organ/system demonstrated a varying MKI SE profile across both RR-WDTC and MTC diagnoses, more commonly involving metabolic/nutritional disorders [OR: 2.07 [95% CI: 0.82–5.18)] and gastrointestinal SE [OR: 1.63 (95% CI: 1.0–2.66)]. This network meta-analysis on advanced and/or metastatic TC points towards a higher efficacy of lenvatinib in RR-WDTC. The included MKIs exhibit a varying SE profile across different organs/systems favoring a patient-tailored approach with the anticipated toxicities guiding clinicians’ decisions.
Enhanced Reactant Distribution in Redox Flow Cells

Redox flow batteries (RFBs), provide a safe and cost-effective means of storing energy at grid-scale, and will play an important role in the decarbonization of global electricity networks. Several approaches have been explored to improve their efficiency and power density, and recently, cell geometry modification has shown promise in efforts to address mass transport limitations which affect electrochemical and overall system performance. Flow-by electrode configurations have demonstrated significant power density improvements in laboratory testing, however, flow-through designs with conductive felt remain the standard at commercial scale. Concentration gradients exist within these cells, limiting their performance. A new concept of redistributing reactants within the flow frame is introduced in this paper. This research shows a 60% improvement in minimum V3+ concentration within simulated vanadium redox flow battery (VRB/VRFB) cells through the application of static mixers. The enhanced reactant distribution showed a cell voltage improvement by reducing concentration overpotential, suggesting a pathway forward to increase limiting current density and cycle efficiencies in RFBs.