Miracle-dz/UniFAR-FTUs huggingface dataset:
Butorphanol attenuates inflammation via targeting NF-κB in septic rats with brain injury.

OBJECTIVE To observe the therapeutic effect of butorphanol on brain tissue injury in rats with sepsis through the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. MATERIALS AND METHODS Sprague-Dawley rats were divided into control group (n=20), sepsis model group [cecal ligation and perforation (CLP) group, n=20], and butorphanol treatment group (n=20). After successful modeling, the blood and brain tissues were collected from rats at 24 h. The content of serum brain injury indexes was detected. Hematoxylin-eosin (HE) staining assay and enzyme-linked immunosorbent assay (ELISA) were separately carried out to observe the pathological changes and measure the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and myeloperoxidase (MPO) activity. The neurological function was scored in rats. Glial fibrillary acidic protein (GFAP), S100, and NF-κB signaling pathway genes and proteins in brain tissues were detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and Western blotting. RESULTS CLP group showed remarkably increased levels of serum glucosuria (GLU), creatinine (CR), and Na+ but an evidently reduced level of K+ in comparison with the control group (p<0.05), while the treatment group displayed contrary trends. Histopathological observations showed that the rats in the CLP group suffered a brain injury, while those in the treatment group had mild pathological changes. The MPO in the CLP group was significantly increased compared with that in the control group (p<0.05). The levels of TNF-α and IL-6 were overtly higher in the CLP group than those in the control group, and these indexes in the treatment group were close to those in the control group. The messenger ribonucleic acid (mRNA) expression levels of S100, GFAP, Toll-like receptor 2 (TLR2), and NF-κB in CLP group were evidently higher than those in the control group and treatment group (p<0.05). The results of Western blotting revealed that the protein expression of NF-κB was significantly higher in CLP group than that in the control group, and it declined in the treatment group, which was close to that in the control group. CONCLUSIONS Butorphanol can reduce the content of inflammatory factors TNF-α, IL-1, and IL-6 through the NF-κB signaling pathway, thereby relieving the brain injury caused by sepsis.
Synthesis and Structure-Activity Relationship Study of Antimicrobial Auranofin Against ESKAPE Pathogens.

Auranofin, an FDA-approved arthritis drug, has recently been repurposed as a potential antimicrobial agent where it performed well against many Gram-positive bacteria, including multidrug resistant strains. It is however inactive towards Gram-negative bacteria, which are in dire need for new therapies. In this work, 40 auranofin and analogs were synthesized by varying the structures of the thiol and phosphine ligands, and their activities were tested against ESKAPE pathogens. The study identified compounds that exhibited up to over 2 logs higher bacterial inhibition (MIC) and killing (MBC) activities than auranofin, making them effective against Gram-negative pathogens. Both thiol and the phosphine structures influence the activities of the analogs. The trimethylphosphine and triethylphosphine ligand gave the highest activities against Gram-negative and Gram-positive bacteria, respectively. Our SAR study revealed that the thiol ligand is also very important, the structure of which can modulate the activities of the AuI complexes for both Gram-negative and Gram-positive bacteria. Moreover, these analogs had either similar or lower mammalian cell toxicity compared to auranofin.
“Bad things come in small packages”: predicting venom-induced coagulopathy in Bothrops atrox bites using snake ontogenetic parameters

Abstract Introduction: Snake venom composition shows significant inter- and intra-species variation. In the case of the viperid species Bothrops atrox, responsible for the majority of snakebites in the Amazon region, geographical and ontogenetic variables affect venom composition, with ecological and medical implications. Previous studies had shown that venom from neonate and juvenile Bothrops specimens have a higher in vitro coagulant activity. The aim of this investigation was to assess the association of clinical outcomes, such as venom-induced coagulopathy and local complications, with B. atrox ontogenetic variables. Methods: This study explored the relationship between some clinical parameters in patients suffering envenomations by B. atrox in the Amazon and several morphometric parameters of the snake specimens causing the bites. Results: There were 248 specimens confirmed as agents of envenomation, mostly female snakes (70.5%) and classified as juveniles (62.7%). Patients bitten by neonates compared to adult snakes [OR = 2.70 (95%CI 1.15-6.37); p = . 021] and by snakes with white tail tip [OR = 1.98 (95%CI 1.15–3.41); p = . 013] were more likely to develop coagulopathy. Time from patient admission to the unclottable blood reversion was not affected by the snake gender (p = .214) or age (p = .254). Patients bitten by neonate (p = .024) or juvenile snakes (p < .0001) presented a lower frequency of moderate to severe edema, as compared to those bitten by adult snakes. In agreement with experimental observations, patients bitten by neonates and by snakes with a white tail tip were more likely to develop coagulopathy than those bitten by adult snakes. In contrast, envenomations by adult snakes were associated with a higher incidence of severe local edema. Conclusion: Despite these variations, no difference was observed in the time needed to recover blood clotting in these patients after Bothrops antivenom administration.
An Extension of two Phase Locking to Support Parallel Updates of Data Warehouses

Even though Two Phase Locking (2PL) has shown a good performance in various applications for on-line transaction processing, it failed to provide analytical transactions with fresh data in data warehousing systems. One of the main reasons for such poor freshness is due to the lack of parallel updates of data warehouses. If several update transactions in 2PL are allowed to execute concurrently without an adequate concurrency control, data inconsistency between data warehouses and operational databases inevitably arises due to incorrect propagation of the updates on the operational databases into the data warehouses. To prevent such an incorrect propagation of update transactions, we extended 2PL so as to process update transactions in an order of their creation if they conflict with each other. In addition, to speed up analytical transactions, locking rules of 2PL are slightly modified in a way of minimizing conflicts among transactions. To investigate the applicable areas of our algorithm, its performance is evaluated by means of simulation approach. Our experimental results show that the extended 2PL enables OLAP transactions to read fresher data than the conventional 2PL.
Managing demand for social care among adults with intellectual disabilities: A systematic scoping review.

BACKGROUND Demand for formal social services support for adults with intellectual disabilities is increasing internationally. Initiatives which empower individuals with intellectual disabilities to improve their health, develop living skills or manage chronic illnesses may promote independence and reduce unnecessary dependency on social services. METHODS A "preventative framework" to managing demand comprising several domains was developed from existing literature to guide the search strategy. RESULTS Fourteen papers related to three domains in the predetermined preventative framework were selected for inclusion in the review, including twelve economic studies. Outcomes included measurement of care needs, and cost-comparison between social care models or cost-effectiveness of interventions. Due to the heterogeneity, the present authors were not able to quantitatively synthesize findings. CONCLUSIONS The present authors conclude that evidence linking initiatives across sectors to demand for adult social care is lacking. The present authors identify several gaps in the literature and make recommendations for future research and data recording in practice.
Correlations between ocular biometrics and refractive error: A systematic review and meta‐analysis

The understanding of correlations between different biometric parameters is essential for personalized eye care in the field of cataract and refractive surgery. This systematic review offers a clear overview of the previous literature assessing these correlations including a meta‐analysis. The review is focused on the following five correlations: (1) axial length and refractive error; (2) anterior chamber depth and refractive error; (3) axial length and anterior chamber depth; (4) corneal power and refractive error; (5) corneal power and axial length. An expected strong correlation between axial length and refractive error was found. Correlations including corneal power were weak and might be clinically insignificant.
Factors explaining physical activity level in Parkinson´s disease: A gender focus

ABSTRACT Objective: To analyze the multivariate associations between self-rated level of physical activity and demographic characteristics, self-efficacy for physical activity, fall-related self-efficacy, fear of falling, enjoyment from participation in physical activity, social support, fatigue, and health-related quality of life in persons with PD with a focus on gender. Method: Participants were persons with PD (n = 285, mean age 69.1 ± 7 years). Self-reported scales measuring level of physical activity (Physical Activity Disability Survey–Revised), enjoyment of physical activity (study- specific questions), self-efficacy for physical activity (Exercise Self-Efficacy Scale), fall-related self-efficacy (Falls Efficacy Scale), social support (Social Influences on Physical Activity), fatigue (Fatigue Severity Scale) and health-related quality of life (Parkinson’s Disease Questionnaire-39) were used. The response rate was 58.2%. Results: Multiple regression analyses showed that 54.5% of the level of physical activity was explained by low-degree limitations in mobility and activities of daily life (ADL), being younger, higher self-efficacy for physical activity, communication limitations, bodily discomfort, social support and shorter time since diagnosis. Enjoyment of physical activity explained the level of physical activity for women, whereas self-efficacy for physical activity explained the level of physical activity for men. Conclusion: Implementing strategies to increase functional mobility, self-efficacy for physical activity, social support, and enjoyment of physical activity might facilitate persons with PD beginning and/or maintain different physical activities.
How does medical education affect empathy and compassion in medical students? A meta-ethnography: BEME Guide No. 57

Abstract Background: Empathy and compassion are important in healthcare delivery, and are necessary qualities in medical students. Aims: To explore medical students', patients' and educators' perceptions of what affects empathy and the expression of compassion; and to address gaps in knowledge, attitudes and skills on how education affects empathy and the expression of compassion in medical students. Methods: The seven steps by Noblit and Hare were used for this meta-ethnography. Databases were searched for studies in English, published from 2007 to 2017 with outcomes of empathy and compassion. Key themes and concepts were identified, and accounts from the studies were used to build interpretations. Findings: Thirty-three qualitative studies were included and four main themes were derived: seeing the patient as a person; appreciating the elements of empathy and compassion; navigating in the training environment; and being guided by ideals. Interactions between the patient, the medical student and training environment which affect the development of empathy and compassion are illustrated in a conceptual model. Conclusions: This meta-ethnography extends our understanding of how medical education affects the expression of empathy and compassion in medical students. The results provide important considerations for medical educators and faculty developers in further developing and improving medical curricula.
Stability and plasticity of positional memory during limb regeneration in Ambystoma mexicanum

Urodele amphibians are capable of regenerating their organs after severe damage. During such regeneration, participating cells are given differentiation instructions by the surrounding cells. Limb regeneration has been investigated as a representative phenomenon of organ regeneration. Cells known as blastema cells are induced after limb amputation. In this process, dermal fibroblasts are dedifferentiated and become undifferentiated similar to limb bud cells. Just like limb bud cells, the induced blastema cells are positioned along the three limb developmental axes: the dorsoventral, the anteroposterior, and the proximodistal. The accurate developmental axes are essential for reforming the structures correctly. Despite the importance of the developmental axes, the relationship between the newly establishing developmental axes and existing limb axes was not well described with molecular markers.
Correlation between l‐lactate and glucose concentrations and body condition score in healthy horses and ponies

Abstract Background Blood l‐lactate and glucose concentrations were higher in ponies with gastrointestinal disease than in horses, possibly because of differences in body condition (BC). Objectives To investigate whether l‐lactate and glucose concentrations correlate with BC and differ between healthy horses and ponies. Animals Systemically healthy client‐owned ponies (n = 101) and horses (n = 51). Methods Prospective observational study. Breed, weight, height, and subjective and objective measures of BC were recorded and l‐lactate and glucose concentrations were measured. Correlations between l‐lactate and glucose concentrations and BC were established. The association between l‐lactate concentrations, equid type (pony or horse), BC, age, and glucose concentrations was investigated using a multivariable model. Results Weak but significant (P = .001) negative correlations were detected between l‐lactate concentration and average BC score (r = −0.29), heart girth:height ratio (r = −0.27), and age (r = −0.27). Glucose concentrations were significantly (P < .001) positively correlated with neck length:heart girth ratio (r = 0.37) and heart girth:height ratio (r = 0.31). l‐lactate and glucose concentrations were weakly correlated (r = 0.15; P = .04). In the final multivariable model, age (−0.02 ± 0.006; P = .001) and heart girth:height ratio (−1.74 ± 0.53; P = .001) were significantly associated with the natural logarithm of l‐lactate concentration (Lnl‐Lactate). This represents a 2% decrease in l‐lactate concentration per year increase in age and 10% decrease in l‐lactate concentration per 0.06 unit increase in heart girth:height ratio. Conclusions and Clinical Importance In healthy horses and ponies, age and BC significantly influence l‐lactate concentrations.
Emerging lysosomal pathways for quality control at the endoplasmic reticulum

Protein misfolding occurring in the endoplasmic reticulum (ER) might eventually lead to aggregation and cellular distress, and is a primary pathogenic mechanism in multiple human disorders. Mammals have developed evolutionary‐conserved quality control mechanisms at the level of the ER. The best characterized is the ER‐associated degradation (ERAD) pathway, through which misfolded proteins translocate from the ER to the cytosol and are subsequently proteasomally degraded. However, increasing evidence indicates that additional quality control mechanisms apply for misfolded ER clients that are not eligible for ERAD. This review focuses on the alternative, ERAD‐independent, mechanisms of clearance of misfolded polypeptides from the ER. These processes, collectively referred to as ER‐to‐lysosome–associated degradation, involve ER‐phagy, microautophagy or vesicular transport. The identification of the underlying molecular mechanisms is particularly important for developing new therapeutic approaches for human diseases associated with protein aggregate formation.
A win ratio approach to the re-analysis of Multiple Risk Factor Intervention Trial

Background: Composite outcomes, which combine multiple types of clinical events into a single outcome, are common in clinical trials. The usual analysis considers the time to first occurrence of any event in the composite. The major criticisms of such an approach are (1) this implicitly treats the outcomes as if they were of equal importance, but they often vary in terms of clinical relevance and severity, (2) study participants often experience more than one type of event, and (3) often less severe events occur before more severe ones, but the usual analysis disregards any information beyond that first event. Methods: A novel approach, referred to as the win ratio, which addresses the aforementioned criticisms of composite outcomes, is illustrated with a re-analysis of data on fatal and non-fatal cardiovascular disease time-to-event outcomes reported for the Multiple Risk Factor Intervention Trial. In this trial, 12,866 participants were randomized to a special intervention group (n = 6428) or a usual care (n = 6438) group. Non-fatal outcomes were ranked by risk of cardiovascular disease death up to 20 years after trial. In one approach, participants in the special intervention and usual care groups were first matched on coronary heart disease risk at baseline and time of enrollment. Each matched pair was categorized as a winner or loser depending on which one experienced a cardiovascular disease death first. If neither died of cardiovascular disease causes, they were evaluated on the most severe non-fatal outcome. This process continued for all the non-fatal outcomes. A second win ratio statistic, obtained from Cox partial likelihood, was also estimated. This statistic provides a valid estimate of the win ratio using multiple events if the marginal and conditional survivor functions of each outcome satisfy proportional hazards. Loss ratio statistics (inverse of win ratios) are compared to hazard ratios from the usual first event analysis. A larger 11-event composite was also considered. Results: For the 7-event cardiovascular disease composite, the previously reported first event analysis based on 581 events in the special intervention group and 652 events in the usual care group yielded a hazard ratio (95% confidence interval) of 0.89 (0.79–0.99), compared to 0.86 (0.77–0.97) and 0.91 (0.81–1.02) for the severity ranked estimates. Results for the 11-event composite also confirmed the findings of the first event analysis. Conclusion: The win ratio analysis was able to leverage information collected past the first experienced event and rank events by severity. The results were similar to and confirmed previously reported traditional first event analysis. The win ratio statistic is a useful adjunct to the traditional first event analysis for trials with composite outcomes.
Reports of recovered memories of childhood abuse in therapy in France

ABSTRACT Recovered memories of abuse in therapy are especially controversial if the clients were not aware they were abused before therapy. In the past, such memory recovery has led to legal action, as well as a debate about whether such memories might be repressed, forgotten, or false memories. More than two decades after the height of the controversy, it is unclear to what degree such memories are still recovered today, and to what extent it occurs in France. In our French survey of 1312 participants (Mage = 33; 53% female), 551 reported having done therapy at some point. Of that 551, 33 (6%) indicated they had recovered memories of abuse in therapy that they did not know about before therapy. Sexual abuse was the most commonly reported type that was recovered in therapy (79%). As in past research, discussing the possibility of repressed memories with therapists was associated with reports of recovered memories of abuse. Surprisingly, memory recovery occurred just as much in behavioural and cognitive therapies as it did in therapies focused on trauma. We found recovered memories in a proportion of clients who began therapy recently. Recovered memories in therapy appears to be an ongoing concern in France.
Drought sensitivity of an N2 -fixing tree may slow temperate deciduous forest recovery from disturbance.

Increased drought intensity and frequency due to climate change may reduce the abundance and activity of nitrogen (N2 ) fixing plants, which supply new N to terrestrial ecosystems. As a result, drought may indirectly reduce ecosystem productivity through its effect on the N cycle. Here, we manipulated growing season net rainfall across a series of plots in an early successional mesic deciduous forest to understand how drought affects the aboveground productivity of the N2 -fixing tree Robinia pseudoacacia and three co-occurring non-fixing tree species. We found that lower soil moisture was associated with reduced productivity of R. pseudoacacia but not of non-fixing trees. As a result, the relative biomass and density of R. pseudoacacia declined in drier soils over time. Greater aboveground biomass of R. pseudoacacia was also associated with greater total soil N, extractable inorganic N, N mineralization rates, and productivity of non-fixing trees. These soil N effects may reflect current N2 fixation by R. pseudoacacia saplings, or the legacy effect of former trees in the same location. Our results suggest that R. pseudoacacia promotes the growth of non-fixing trees in early succession through its effect on the N cycle. However, the sensitivity of R. pseudoacacia to dry soils may reduce N2 fixation under scenarios of increasing drought intensity and frequency, demonstrating a mechanism by which drought may indirectly diminish potential forest productivity and recovery rate from disturbance. This article is protected by copyright. All rights reserved.
Current Strategies to Enhance Adipose Stem Cell Function: An Update

Mesenchymal stem cells (MSCs) emerged as a promising therapeutic tool targeting a variety of inflammatory disorders due to their multiple remarkable properties, such as superior immunomodulatory function and tissue-regenerative capacity. Although bone marrow (BM) is a dominant source for adult MSCs, increasing evidence suggests that adipose tissue-derived stem cells (ASCs), which can be easily obtained at a relatively high yield, have potent therapeutic advantages comparable with BM-MSCs. Despite its outstanding benefits in pre-clinical settings, the practical efficacy of ASCs remains controversial since clinical trials with ASC application often resulted in unsatisfactory outcomes. To overcome this challenge, scientists established several strategies to generate highly functional ASCs beyond the naïve cells, including (1) pre-conditioning of ASCs with various stimulants such as inflammatory agents, (2) genetic manipulation of ASCs and (3) modification of culture conditions with three-dimensional (3D) aggregate formation and hypoxic culture. Also, exosomes and other extracellular vesicles secreted from ASCs can be applied directly to recapitulate the beneficial performance of ASCs. This review summarizes the current strategies to improve the therapeutic features of ASCs for successful clinical implementation.