Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluating and Improving Current Risk Prediction Tools in Emergency Laparotomy.

PURPOSE Emergency Laparotomy (EL) encompasses a high-risk group of operations, which are increasingly performed on a heterogenous population of patients, making pre-operative risk assessment potentially difficult. The UK National Emergency Laparotomy Audit (NELA) recently produced a risk predictive tool for EL that has not yet been externally validated. We aimed to externally validate and potentially improve the NELA tool for mortality prediction after EL. METHODOLOGY We reviewed computer and paper records of EL patients from May 2012 to June 2017 at Middlemore Hospital (New Zealand). The inclusion criteria mirrored the UK NELA. We examined the NELA, P-POSSUM, APACHE-II and ACS-NSQIP risk predictive tools for 30-day mortality. The Hosmer-Lemeshow test was used to assess calibration and the c-statistic to evaluate discrimination (accuracy) of the tools. We added the modified frailty index (mFI) and nutrition to improve the accuracy of risk predictive tools. RESULTS 758 patients met the inclusion criteria, with an observed 30-day mortality of 7.9%. The NELA was the only well calibrated tool, with predicted 30-day mortality of 7.4%(p=0.22). When combined with mFI and nutritional status, the c-statistic for NELA improved from 0.83 to 0.88. ACS-NSQIP, APACHE-II and P-POSSUM had lower c-statistics, albeit also showing an improvement (0.84, 0.81 and 0.74 respectively). CONCLUSION We have demonstrated the NELA tool to be most predictive of mortality after EL. The NELA tool would therefore facilitate pre-operative risk assessment and operative decision making most precisely in EL. Future research should consider adding mFI and nutritional status to the NELA tool. LEVEL OF EVIDENCE Level IV.
Cross-cultural adaptation of the 4-Habits Coding Scheme into French to assess physician communication skills

Background The Four Habits Coding Scheme (4-HCS) is a standardized instrument designed to assess physicians’ communication skills from an external rater’s perspective, based on video-recorded consultations. Objective To perform the cross-cultural adaptation of the 4-HCS into French and to assess its psychometric properties. Methods The 4-HCS was cross-culturally adapted by conducting forward and backward translations with independent translators, following international guidelines. Four raters rated 200 video-recorded medical student consultations with standardized patients, using the French version of the 4-HCS. We examined the internal consistency, factor structure, construct validity, and reliability of the 4-HCS. Results The mean overall 4-HCS score was 76.44 (standard deviation, 12.34), with no floor or ceiling effects across subscales. The median rating duration of rating was 8 min (range, 4–19). Cronbach’s alpha was 0.94 for the overall 4-HCS, ranging from 0.72 to 0.88 across subscales. In confirmatory factor analysis, goodness-of-fit statistics did not corroborate the hypothesized 4-habit structure. Exploratory factor analysis resulted in two dimensions, with the merging of three conceptually related habits into a single dimension and substantial cross-loading for 15 out of 23 items. Median average absolute-agreement intra-class correlation coefficient estimates were 0.74 (range, 0.68–0.84) and 0.85 (range, 0.76–0.91) for inter- and intra-rater reliability of habit subscales, respectively. Conclusion The French version of the 4-HCS demonstrates satisfactory internal consistency but requires the use of two independent raters to achieve acceptable reliability. The underlying factor structure of the original US version and cross-cultural adaptations of the 4-HCS deserve further investigation.
Restricted mobility and unheard voices: perceptions of accessibility and inclusion expressed on Romanian disability-specific blogs and forums

Abstract Purpose Concerning psychosocial aproaches to disability, Romania is characterized by significant discrepancies between the Disability Rights legislation and reality, while the input of people with disabilities regarding the matter is largely overlooked. This study aims to explore perceptions regarding Romania's built and sociocultural environment, as they are expressed by bloggers with disabilities and users of disability-specific forums. Materials and methods Data were collected from four personal blogs and three discussion forums on the topic of physical disabilities. Thematic analysis was performed. Results Four major themes emerged from the analysis: the disabling built environment; the isolating sociocultural environment; blaming others and the past; self-empowerment and the movement towards independent living. Conclusions The resistance of disabled people to negative perceptions of disability and their calls to action in this regard may foster positive changes in social attitudes towards disability. Implications for Rehabilitation Romanians with physical disabilities perceive that the adaptation and implementation of inclusion and accessibility regulations are superficial. They promote a proactive defence of their rights, independence, and dignity, to resist against discrimination and stigma resulting from the medicalization of disability. Education regarding disability, its evaluation, and the development of inclusion policies should stop focusing on “incapacity” as an individual attribute and focus more on the disabling roles of environmental factors. Responsible authorities should understand and enforce the implementation of inclusion and accessibility regulations accordingly.
Naturally occurring modified ribonucleosides

The chemical identity of RNA molecules beyond the four standard ribonucleosides has fascinated scientists since pseudouridine was characterized as the “fifth” ribonucleotide in 1951. Since then, the ever‐increasing number and complexity of modified ribonucleosides have been found in viruses and throughout all three domains of life. Such modifications can be as simple as methylations, hydroxylations, or thiolations, complex as ring closures, glycosylations, acylations, or aminoacylations, or unusual as the incorporation of selenium. While initially found in transfer and ribosomal RNAs, modifications also exist in messenger RNAs and noncoding RNAs. Modifications have profound cellular outcomes at various levels, such as altering RNA structure or being essential for cell survival or organism viability. The aberrant presence or absence of RNA modifications can lead to human disease, ranging from cancer to various metabolic and developmental illnesses such as Hoyeraal–Hreidarsson syndrome, Bowen–Conradi syndrome, or Williams–Beuren syndrome. In this review article, we summarize the characterization of all 143 currently known modified ribonucleosides by describing their taxonomic distributions, the enzymes that generate the modifications, and any implications in cellular processes, RNA structure, and disease. We also highlight areas of active research, such as specific RNAs that contain a particular type of modification as well as methodologies used to identify novel RNA modifications.
Entamoeba histolytica and Entamoeba dispar: Morphological and Behavioral Differences Induced by Fibronectin through GTPases Activation and Actin‐Binding Proteins

Early steps of tissue invasion by Entamoeba histolytica are mediated by adhesion and migration through matrix components such as fibronectin with the participation of the actin cytoskeleton. Striking differences in their produced structures, movement, and migration were found. These observations suggest differential changes in their ability to organize the actin cytoskeleton and, therefore, to modify its morphology after adhesion to fibronectin. To understand these observations, we explore deeper the cytoskeleton pathway of E. histolytica compared to Entamoeba dispar, analyzing the activation and involvement of actin cytoskeleton regulatory proteins such as small GTPases (Rho, Rac1 and Cdc42), myosin IB, paxillin, alpha‐actinin, and ARP2/3 during interaction with fibronectin. Results showed a higher activation of Rac1 in E. histolytica compared to E. dispar, while Cdc42 and RhoA were equally activated in both amebae; besides, variations in the amount of myosin IB, paxillin, and ARP2/3 were detected among these species, coinciding and reflected in formation of lamellipodia in E. histolytica and filopodia in E. dispar. These could partially explain the higher invasive capacity of E. histolytica compared to E. dispar, due to its pleomorphic ability, high motility, migration, activation, and abundance of proteins involved in the cytoskeleton arrangement.
COPD Patients Have a Restricted Breathing Pattern That Persists with Increased Metabolic Demands

Abstract A healthy respiratory system has variability from breath-to-breath and patients with COPD (PwCOPD) have abnormal variability in breath cycles. The aim of this study was to determine if interbreath-interval and tidal-volume variability, and airflow regularity change as metabolic demands increase (seated, standing, and walking) in PwCOPD as compared to controls. Sixteen PwCOPD (64.3 ± 7.9 yr, 61.3 ± 44.1% FEV1%predicted) and 21 controls (60.2 ± 6.8 yr, 97.5 ± 16.8% FEV1%predicted) sat, stood, and walked at their preferred-pace for five-minutes each while breathing patterns were recorded. The mean, standard deviation, and coefficient of variation of interbreath-intervals and tidal-volume, and the regularity (sample entropy) of airflow were quantified. Results were subjected to ANOVA analysis. Interbreath-interval means were shorter in PwCOPD compared to controls (p = 0.04) and as metabolic demand increased (p < 0.0001), standard deviation was decreased in PwCOPD compared to controls during each condition (p’s < 0.002). Mean tidal-volume did decrease as metabolic demand increased across groups (p < 0.0001). Coefficient of variation findings (p = 0.002) indicated PwCOPD decline in tidal-volume variability from sitting to standing to walking; whereas, controls do not. There was an interaction for airflow (p = 0.02) indicating that although, PwCOPD had a more regular airflow across all conditions, control’s airflow became more irregular as metabolic demand increased. PwCOPD’s airflow was always more regular compared to controls (p = 0.006); although, airflow became more irregular as metabolic demand increased (p < 0.0001). Healthy respiratory systems have variability and irregularity from breath-to-breath decreases with adaptation to demand. PwCOPD have more regular and restricted breathing pattern that may affect their ability to adjust in demanding situations.
Efficacy and cardiorespiratory effects of lumbosacral intrathecal 2% procaine and 2% xylazine with or without sedation in calves undergoing umbilical surgery

ABSTRACT Aims: To compare the effects of intrathecal anaesthesia using procaine and xylazine, with and without sedation with I/V xylazine and butorphanol, on sedation and cardiorespiratory measures in calves undergoing umbilical surgery. Methods: Male dairy calves, aged <3 months, were recruited that had enlargement of the umbilical stalk which was abnormal when palpated. They were assigned to receive either intrathecal injection between the sixth lumbar and first sacral vertebrae of 4 mg/kg of 2% procaine and 0.2 mg/kg 2% xylazine, with I/V injection of 0.02 mg/kg xylazine and 0.1 mg/kg of butorphanol (IT + SED group; n = 6), or the same intrathecal injection and I/V injection of 0.9% saline (IT group; n = 7). Surgery to correct abnormalities was carried out with calves positioned in dorsal recumbency. Rescue analgesia with injections of 2% procaine around the surgical wound was administered when movements triggered by surgery were observed. Post-operative analgesia was provided using I/V 0.5 mg/kg meloxicam. Duration of surgery was recorded, as well as degree of sedation, heart rate, systolic (SAP), diastolic (DAP) and mean (MAP) arterial blood pressure during surgery. Results: All anaesthetic and surgical procedures were successfully performed. Mean total duration of surgery was similar for the IT + SED and the IT groups (30.33 (SD 10.09) and 31.00 (SD 10.21) minutes, respectively) (p = 0.92). All calves were at least mildly sedated from 5 minutes after injections to the end of the surgery. One calf in the IT + SED group and three calves in the IT group required rescue analgesia when the umbilicus was manipulated. Between 0 and 10–15 minutes after injection, decreases in mean heart rate, SAP, MAP and DAP were observed in both groups. Mean SAP was lower in the IT + SED than the IT group. Hypotension (MAP<60 mm Hg) was present in four calves from the IT + SED group and in one from the IT group. Conclusions and clinical relevance: Intrathecal administration of 2% procaine and 2% xylazine allowed the successful completion of umbilical surgery, but 30% of calves needed rescue analgesia during surgery. Clinically, the addition of I/V sedation seemed to provide better analgesia than intrathecal block alone but resulted in greater hypotension.
Antimicrobial activity of selected plants against fungal species isolated from South African AIDS patients and their antigonococcal activity

Abstract Background Sexually transmitted infections continue to be a major health concern in sub-Saharan Africa where antimicrobial drugs are becoming ineffective due to increasing resistance. Many healthcare seekers in lower socio-economic settings depend on invasive alien plants administered by traditional health practitioners to treat sexually transmitted infections. Methods Roots of selected plants were analysed for phytoconstituents using standard methods. Both the disc diffusion model and microdilution technique were used to determine the inhibition zone and minimum inhibitory concentration (MIC) of plant extracts against six clinical fungal strains and standard strain of Neisseria gonorrhoea. One-way ANOVA was used to find significant differences. Results Different phytoconstituents such as alkaloids, steroids, cardiac glycosides, terpenes, flavonoids, tannins and saponins were qualitatively detected, depending on plant species. Acetone extracted the highest number of phytoconstituents in Senna didymobotrya, while methanol revealed most from Ricinus communis. Senna didymobotrya showed significant inhibition against Candida glabrata, C. krusei, C. parapsilosis and C. tropicalis. Dichloromethane extract of Catharanthus roseus and methanol extract of S. didymobotrya demonstrated excellent MIC values of 0.03 and 0.08 mg/mL, respectively, against C. glabrata. Catharanthus roseus, Opuntia ficus-indica and Ricinus communis demonstrated moderate to good antigonococcal activity, with all exhibiting more than 63% inhibition. Catharanthus roseus had the best antigonococcal activity with a moderate MIC value of 0.63 mg/mL. Conclusion Some of the plant extracts demonstrated potency towards clinically isolated fungal strains and against N. gonorrhoea, which validate the notion that some of the species need further pharmacological studies for isolation and characterisation of active compounds.
Reactive oxygen species signaling in primordial germ cell development in Drosophila embryos

REDOX mechanisms that induce biosynthesis of the reactive oxygen species (ROS) have attracted considerable attention due to both the deleterious and beneficial responses elicited by the reactive radical. In several organisms including Drosophila melanogaster, modulation of ROS activity is thought to be crucial for the maintenance of cell fates in developmental contexts. Interestingly, REDOX mechanisms have been shown to be involved in maintaining progenitor fate of stem cells as well as their proliferation and differentiation. Here, we have explored the possible functions of ROS during proper specification and developmental progression of embryonic primordial germ cells (PGCs). Indicating its potential involvement in these processes, ROS can be detected in the embryonic PGCs and the surrounding somatic cells from very early stages of embryogenesis. Using both “loss” and “gain” of function mutations in two different components of the REDOX pathway, we show that ROS levels are likely to be critical in maintaining germ cell behavior, including their directed migration. Altering the activity of a putative regulator of ROS also adversely influences the ability of PGCs to adhere to one another in cellular blastoderm embryos, suggesting potential involvement of this pathway in orchestrating different phases of germ cell migration.
TEG improves anticoagulation management during cardiopulmonary bypass complicated by antiphospholipid syndrome

Cardiopulmonary bypass (CPB) in antiphospholipid syndrome (APS) patients carries a high risk of thrombosis and hemorrhage. However, optimal anticoagulation surveillance methods have not been established and heparin optimization has not yet been totally validated as reflective of anticoagulation status.
Use of IMMPACT domains in clinical trials of acupuncture for chronic pain: A methodological survey

Acupuncture is one of the therapeutic resources used for the management of chronic pain. Variability in outcome measurements in randomized clinical trials of non-oncologic chronic pain (RCT-NOCP) generates inconsistencies in determining effects of treatments. The objective of this survey was to assess the adherence to the recommendations made by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) in the measurement of RCT-NOCP of acupuncture. This methodological research made a systematic search for eligible studies from different sources of information. Eligible studies included those with number of patients ≥100, who randomized and allocated patients with chronic non-oncologic pain to be treated with acupuncture or with “sham” acupuncture, or non-acupuncture. This research included the recommendations for IMMPACT in the measurement of RCT-NOCP: presence of outcomes pain, physical function, emotional state and improvement perception of patient, the source of the outcome information pain and the tools used to measure such domains. From a total of 1,386 studies, 24 were included in this survey. Eleven studies presented low risk of bias. Pain outcome was measured in 23 studies, physical function in 22 studies, emotional state in 14 studies and improvement perception of patient in one study. As for the pain outcome, the patient was the information source in 50% of the studies. The measurement tools recommended for IMMPACT were included in eight studies (35%) that evaluated pain, one study that evaluated the emotional state (7%), and one study that evaluated the improvement perception and satisfaction of patient. It was observed that studies which did not adhere to the recommendations had more favorable results for acupuncture in the outcome pain. This study concludes that randomized clinical trials that used acupuncture to manage chronic pain failed to adhere to IMMPACT recommendations. Clinical societies and IMMPACT do not share the same recommendations. This fact reflects in the diversity of outcomes and instruments adopted in the studies, making it difficult to compare the results.
Resolvin E1 is a pro-repair molecule that promotes intestinal epithelial wound healing

Significance Resolvin E1 (RvE1) promotes resolution of inflammation by damping proinflammatory responses and activating restorative pathways. While mechanisms by which RvE1 signaling in immune cells contribute to resolution of inflammation are extensively studied, its role in epithelial signaling and wound repair remains undefined. Intestinal epithelial barrier compromise during an inflammatory event can result in pathogen access to tissue compartments. Thus, efficient repair of denuded intestinal mucosal surfaces is vital in restoring homeostasis. Here we demonstrate that RvE1 promotes intestinal epithelial cell migration and proliferation leading to wound repair. These findings suggest that RvE1 has the potential to serve as a targeted immunoresolvent therapeutic agent that not only dampens inflammation but activates prorepair pathways to enhance colonic mucosal wound repair. Resolution of intestinal inflammation and wound repair are active processes that mediate epithelial healing at mucosal surfaces. Lipid molecules referred to as specialized proresolving mediators (SPMs) play an important role in the restorative response. Resolvin E1 (RvE1), a SPM derived from omega-3 fatty acids, has been reported to dampen intestinal inflammation by promoting anti-inflammatory responses including increased neutrophil spherocytosis and macrophage production of IL-10. Despite these observations, a role for RvE1 in regulating intestinal epithelial cell migration and proliferation during mucosal wound repair has not been explored. Using an endoscopic biopsy-based wound healing model, we report that RvE1 is locally produced in response to intestinal mucosal injury. Exposure of intestinal epithelial cells to RvE1 promoted wound repair by increasing cellular proliferation and migration through activation of signaling pathways including CREB, mTOR, and Src-FAK. Additionally, RvE1-triggered activation of the small GTPase Rac1 led to increased intracellular reactive oxygen species (ROS) production, cell–matrix adhesion, and cellular protrusions at the leading edge of migrating cells. Furthermore, in situ administration of RvE1-encapsulated synthetic targeted polymeric nanoparticles into intestinal wounds promoted mucosal repair. Together, these findings demonstrate that RvE1 functions as a prorepair lipid mediator by increasing intestinal epithelial cell migration and proliferation, and highlight potential therapeutic applications for this SPM to promote mucosal healing in the intestine.
Corneal Stroma Cell Density Evolution in Keratoconus Corneas Following the Implantation of Adipose Mesenchymal Stem Cells and Corneal Laminas: An In Vivo Confocal Microscopy Study

Purpose To report the corneal stroma cell density evolution identified by in vivo corneal confocal microscopy in humans using injected autologous adipose-derived adult stem cells (ADASCs) and corneal decellularized laminas in corneas with advanced keratoconus. Methods Interventional prospective, consecutive, randomized, comparative series of cases. A total of 14 keratoconic patients were randomly distributed into three groups for three types of surgical interventions: group 1 (G-1), autologous ADASC implantation (n = 5); group 2 (G-2), decellularized human corneal stroma (n = 5); and group 3 (G-3), autologous ADASCs + decellularized human corneal stroma (n = 4). Results A gradual and significant increase (P < 0.001) was observed in the cellularity in the anterior and posterior stroma of patients in G-1, G-2, and G-3 a year after the surgery in comparison with the preoperative density level. The same result was observed at the mid-corneal stroma in G-1 and at the anterior and posterior surfaces and within the laminas in G-2 and G-3. The cell density of patients receiving ADASC recellularized laminas (G-3) was statistically significantly higher (P = 0.011) at the anterior surface and within the lamina (P = 0.029) and at the posterior surface than in those implanted only with decellularized laminas (G-2). Conclusions A significant increase in cell density occurred up to 1 postoperative year at the corneal stroma following the implantation of ADASCs alone, as well as in those cases implanted with decellularized and recellularized laminas at the different levels of the analysis. However, this increase was significantly higher in the ADASC recellularized laminas.