Miracle-dz/UniFAR-FTUs huggingface dataset:
CAPILLARY LEAK AND EDEMA AFTER RESUSCITATION: THE POTENTIAL CONTRIBUTION OF REDUCED ENDOTHELIAL SHEAR STRESS CAUSED BY HEMODILUTION

Large volume resuscitation in hemorrhagic shock, although essential, causes hemodilution leading to reduction in apparent blood viscosity and persistent reduction in endothelial shear stress. This perpetuates microcirculatory dysfunction and causes endothelial leak and edema formation. ABSTRACT Normal shear stress is essential for the normal structure and functions of the microcirculation. Hemorrhagic shock leads to reduced shear stress due to reduced tissue perfusion. Although essential for the urgent restoration of cardiac output and systemic blood pressure, large volume resuscitation with currently available solutions causes hemodilution, further reducing endothelial shear stress. In this narrative review, we consider how the use of currently available resuscitation solutions results in persistent reduction in endothelial shear stress, despite successfully increasing cardiac output and systemic blood pressure. We consider how this reduced shear stress causes (1) a failure to restore normal vasomotor function and normal tissue perfusion thus leading to persistent tissue hypoxia and (2) increased microvascular endothelial permeability resulting in edema formation and impaired organ function. We discuss the need for clinical research into resuscitation strategies and solutions that aim to quickly restore endothelial shear stress in the microcirculation to normal.
Types of Nursing Intervention on Improving Quality of Life among Patients with Diabetes Mellitus: A Systematic Review

Background: Long-term treatment of patients with diabetes mellitus (DM) is considered a major factor causing disease complications. DM complications mostly impact the patient’s quality of life (QoL). Only a few studies have been conducted summarizing the types of nursing interventions for improving the QoL of DM patients. Objective: The objective of this study is to explore the types of nursing interventions that can improve the QoL of DM patients. Methods: The online databases, including ScienceDirect, Medline, Google Search, and Pro-Quest, were used to search for the relevant articles. Articles that met the inclusion criteria were analyzed, and their level of evidence was determined and synthesized. Results: A total of 30 articles defining the types of nursing intervention on improving the QoL of DM patients were discovered, comprising the five types of nursing interventions, such as health education (15 articles), exercise (8 articles), WhatsApp/short message service (WA/SMS) gateway (3 articles), blood glucose control (3 articles), and black garlic herbal therapy (1 article). Conclusion: Sequentially, the most common types of nursing interventions to improve the QoL of DM patients was health education, followed by exercise, WA/SMS gateway, and glucose control. A personal approach to health education is a significant point in improving the QoL of DM patients in the future. The findings of this study might not be strongly generalized, so further randomized controlled trial (RCT) studies with larger samples are needed.
Predictors of Stigma toward Alcohol Misuse in Mexico

Abstract Objective: This study explored factors associated with public stigma toward individuals misusing alcohol in Mexico. Methods: A randomized experimental vignette methodology was used to assess multiple domains of substance use-related stigma and their relationship to the gender of the vignette subject and the sociodemographic characteristics of respondents. Results: Although levels of stigma toward women who were misusing alcohol did not differ significantly from stigma toward men misusing alcohol, stigma levels and type of stigma reported varied with the sociodemographic characteristics of respondents. Education level, gender, self-stigma and openness to seeking mental health services were differentially associated with the three stigma domains. Conclusions: Accordingly, targeted community based stigma reduction efforts are needed to decrease stigma toward those misusing alcohol, and to support treatment initiation, ongoing treatment engagement and long term recovery efforts. Suggestions for future research on the relationship between substance use and stigma are offered.
Effects of gait modifications on tissue‐level knee mechanics in individuals with medial tibiofemoral osteoarthritis: A proof‐of‐concept study towards personalized interventions

Gait modification is a common nonsurgical approach to alter the mediolateral distribution of knee contact forces, intending to decelerate or postpone the progression of mechanically induced knee osteoarthritis (KOA). Nevertheless, the success rate of these approaches is controversial, with no studies conducted to assess alterations in tissue‐level knee mechanics governing cartilage degradation response in KOA patients undertaking gait modifications. Thus, here we investigated the effect of different conventional gait conditions and modifications on tissue‐level knee mechanics previously suggested as indicators of collagen network damage, cell death, and loss of proteoglycans in knee cartilage. Five participants with medial KOA were recruited and musculoskeletal finite element analyses were conducted to estimate subject‐specific tissue mechanics of knee cartilages during two gait conditions (i.e., barefoot and shod) and six gait modifications (i.e., 0°, 5°, and 10° lateral wedge insoles, toe‐in, toe‐out, and wide stance). Based on our results, the optimal gait modification varied across the participants. Overall, toe‐in, toe‐out, and wide stance showed the greatest reduction in tissue mechanics within medial tibial and femoral cartilages. Gait modifications could effectually alter maximum principal stress (~20 ± 7%) and shear strain (~9 ± 4%) within the medial tibial cartilage. Nevertheless, lateral wedge insoles did not reduce joint‐ and tissue‐level mechanics considerably. Significance: This proof‐of‐concept study emphasizes the importance of the personalized design of gait modifications to account for biomechanical risk factors associated with cartilage degradation.
A comparative analysis of energy usage and emissions of transport systems

This study compares transport systems with respect to their energy consumption and airborne emissions. Both of these characteristics have been quantified with respect to the distance travelled by users at current occupancy rates. The study concludes that the petrol fuelled car equipped with a threeway catalytic converter currently offers the least overall impact upon the urban environment when compared with the diesel car, train and possibly bus. However, should these vehicles adopt the use of certain emissions reduction technologies this situation is likely to change. Electric forms of transport offer improved characteristics in the urban area and incur lower quantities of 'greenhouse' gases. Nevertheless, the problem of high sulphur dioxide emissions will remain for the foreseeable future. The Personal Rapid Transit option offers the possibility of mitigating many of the problems created by personal mobility.
The effectiveness of hippotherapy simulation exercises for muscle strength, disease activity and quality of life in sedentary adults with ankylosing spondylitis

Abstract Introduction/Objective Newly created systems called hippotherapy simulators (HS) mimic the primitive movements of a live horse. As they are new systems, research examining their usefulness has been well received. The aim of this study is to research the effects of HS on disease activity, quality of life and muscle strength in patients with ankylosing spondylitis (AS). Methods In a prospective, assessor-blinded, block-randomized trial, 48 AS patients were randomly assigned in a 1:1 ratio to receive either HS or conventional home (CH) exercise therapy. All Participants received 48 sessions, that is 4 sessions a week for 12 consecutive weeks. The primary outcome measures included the quadriceps muscle strength, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI) and Ankylosing Spondylitis Quality of Life Scale (ASQoL). Results Both groups demonstrated significant improvement in BASDAI, BASFI, BASMI, ASQoL and muscle strength scores compared to the baseline (p < 0.05). BASDAI, BASFI and BASMI scores decreased significantly in the HS group compared to the CH group at week 12 (p=.005, p=.003, p=.045, respectively), but there was no significant difference between the groups in terms of ASQoL and muscle strength scores at week 12 (p=.245, p=.212, respectively). Conclusions The results of this clinical trial of HS exercises for AS patients indicate a positive effect on disease activity, quality of life and muscle strength. Therefore, horse-riding simulator exercises can be used as an alternative method for the management of individuals with AS.
Awareness, Knowledge and Attitude Regarding Cervical Cancer among Women Living with HIV in the Souss-Massa Region, Southern Morocco: A Cross-Sectional Study

Background: Human immunodeficiency virus- positive women have an increased risk of precancerous lesions and invasive cervical cancer. This study aims to identify the level of awareness/knowledge and attitudes toward cervical cancer among women living with Human immunodeficiency virus in the region of Souss-Massa in southern Morocco. Methods: This is a multicenter cross-sectional study conducted in the Souss-Massa region (southern Morocco) among women attending Human immunodeficiency virus treatment and care centers between March 2022 and September 2022. A questionnaire was used for data collection. The Chi-square test and logistic regression were deployed to identify factors associated with cervical cancer awareness among the target population. Results: A total of 494 respondents to the questionnaire, 440 (89.1%) are aware of cervical cancer. Nevertheless, 405 (82.0%) and 369 (74.7%) were unaware of cervical cancer risk factors and symptoms, respectively. Only 125 (25.3%) knew the exact frequency of cervical cancer screening among Human immunodeficiency virus positive women, whereas 221 (44.7%) had ever been tested for cervical cancer. Factors associated with women’s awareness of cervical cancer are as follows: level of education (adjusted Odds Ratio = 3.78 with 95% CI, 1.23-11.65), time since diagnosis of Human immunodeficiency virus (adjusted Odds Ratio = 4.31 with 95% CI, 1.12- 16.52), knowledge of women with cervical cancer (adjusted Odds Ratio = 6.30 with 95% CI, 1.87-21.18) and heard the pap- smear/visual inspection with acetic acid (adjusted Odds Ratio = 4.92 with 95% CI, 2.35-10.33). Conclusion: The general knowledge of seropositive women regarding cervical cancer remains very low, which justifies the integration of cervical cancer prevention services with Human immunodeficiency virus care, and pinpoints the crucial role of patient education.
Knockout of Matrix Metalloproteinase 2 Opposes Hypertension- and Diabetes-induced Nephropathy

Supplemental Digital Content is Available in the Text. Abstract: The progression of chronic kidney disease results from the accumulation of extracellular matrix leading to end-stage renal disease. We previously demonstrated that a broad-spectrum matrix metalloproteinase (MMP) inhibitor reduced renal injury in rat models of hypertension and diabetes. However, the isoforms and mechanisms involved are unclear. This study examined the role of MMP2 during the development of proteinuria and renal injury after induction of hypertension or diabetes in Dahl salt-sensitive (SS) and MMP2 knockout (KO) rats. Mean arterial pressure rose from 115 ± 2 to 145 ± 2 mm Hg and 116 ± 1 to 152 ± 3 mm Hg in MMP2 KO and SS rats fed a high-salt (8% NaCl) diet for 3 weeks. The degree of proteinuria, glomerular injury, renal fibrosis, and podocyte loss was lower in MMP2 KO rats than in SS rats. Blood glucose and HbA1c levels, and mean arterial pressure rose to the same extent in streptozotocin-treated SS and MMP2 KO rats. However, the degree of proteinuria, glomerulosclerosis, renal fibrosis, renal hypertrophy, glomerular permeability to albumin, and the renal expression of MMP2 and TGFβ1 were significantly reduced in MMP2 KO rats. Glomerular filtration rate fell by 33% after 12 weeks of diabetes in streptozotocin-treated SS rats compared with time-control rats, but glomerular filtration rate only fell by 12% in MMP2 KO rats. These results indicate that activation of MMP2 plays an essential role in the pathogenesis of hypertensive and diabetic nephropathy and suggests that an MMP2 inhibitor might slow the progression of chronic kidney disease.
Pharmacotherapy for obstructive sleep apnea: targeting specific pathophysiological traits

ABSTRACT Introduction The pathophysiology of obstructive sleep apnea (OSA) is multi-factorial and complex. Varying OSA’s pathophysiological traits have been identified, including pharyngeal collapsibility, upper airway muscle reactivity, arousal threshold, and regulation of the ventilatory drive. Being CPAP of difficult tolerance and other interventions reserved to specific subpopulations new pharmacological treatments for OSA might be resolutive. Areas covered Several existing and newly developed pharmacological drugs can impact one or more endotypes and could therefore be proposed as treatment options for sleep disordered breathing. With this review we will explore different pathophysiological traits as new targets for OSA therapy. This review will summarize the most promising pharmacological treatment for OSA accordingly with their mechanisms of action on upper airway collapsibility, muscle responsiveness, arousal threshold, and loop gain. Expert opinion Only understanding the pathophysiological traits causing OSA in each patient and placing the disease in the framework of patient comorbidities, we will be able to evolve interventions toward OSA. The development of new drug’s combinations will permit different approaches and different choices beside conventional treatments. In the next future, we hope that sleep specialists will select the treatment for a specific patient on the base of its pathophysiology, defining a precision medicine for OSA.
Grp78 is required for intestinal Kras-dependent glycolysis proliferation and adenomagenesis

Heterozygous deletion of Grp78 reduces Apc–Kras-driven colorectal adenomagenesis. Apc–Kras-mutated cells rely on GLUT1 transporter for glycolysis, which is inhibited by Grp78 heterozygosity. In development of colorectal cancer, mutations in APC are often followed by mutations in oncogene KRAS. The latter changes cellular metabolism and is associated with the Warburg phenomenon. Glucose-regulated protein 78 (Grp78) is an important regulator of the protein-folding machinery, involved in processing and localization of transmembrane proteins. We hypothesize that targeting Grp78 in Apc and Kras (AK)-mutant intestines interferes with the metabolic phenotype imposed by Kras mutations. In mice with intestinal epithelial mutations in Apc, KrasG12D and heterozygosity for Grp78 (AK-Grp78HET) adenoma number and size is decreased compared with AK-Grp78WT mice. Organoids from AK-Grp78WT mice exhibited a glycolysis metabolism which was completely rescued by Grp78 heterozygosity. Expression and correct localization of glucose transporter GLUT1 was diminished in AK-Grp78HET cells. GLUT1 inhibition restrained the increased growth observed in AK-mutant organoids, whereas AK-Grp78HET organoids were unaffected. We identify Grp78 as a critical factor in Kras-mutated adenomagenesis. This can be attributed to a critical role for Grp78 in GLUT1 expression and localization, targeting glycolysis and the Warburg effect.
Verbal and Visuospatial Short-Term and Working Memory in Children:

This study explored the structure of verbal and visuospatial short-term and working memory in children between ages 4 and 11 years. Multiple tasks measuring 4 different memory components were used to capture the cognitive processes underlying working memory. Confirmatory factor analyses indicated that the processing component of working memory tasks was supported by a common resource pool, while storage aspects depend on domain-specific verbal and visuospatial resources. This model is largely stable across this developmental period, although some evidence exists that the links between the domain-specific visuospatial construct and the domain-general processing construct were higher in the 4- to- 6-year age group. The data also suggest that all working memory components are in place by 4 years of age. The term working memory refers to the capacity to store and manipulate information over brief periods of time (Baddeley & Hitch, 1974; Just & Carpenter, 1992). Extensive research over the past three decades has established that working memory is not a single store, but a memory system comprised of separable interacting components. Functioning in concert, these components provide a kind of flexible mental workspace that can be used to maintain and transform information in the course of demanding cognitive activities, and that acts as a temporary bridge between externally and internally generated mental representations. There are a range of alternative theoretical accounts of working memory capacity. Some researchers suggest that working memory consists of a domain-general aspect that coordinates information in two independent domain-specific storage components for verbal and visuospatial codes (Baddeley, 1986; see Engle, Kane, & Tuholski, 1999a, for a review). Others argue instead that working memory resources are separated into verbal and visuospatial constructs (Shah & Miyake, 1996). These studies have largely been restricted to adult
Optimizing treatment allocation in randomized clinical trials by leveraging baseline covariates

We consider the problem of optimizing treatment allocation for statistical efficiency in randomized clinical trials. Optimal allocation has been studied previously for simple treatment effect estimators such as the sample mean difference, which are not fully efficient in the presence of baseline covariates. More efficient estimators can be obtained by incorporating covariate information, and modern machine learning methods make it increasingly feasible to approach full efficiency. Accordingly, we derive the optimal allocation ratio by maximizing the design efficiency of a randomized trial, assuming that an efficient estimator will be used for analysis. We then expand the scope of optimization by considering covariate‐dependent randomization (CDR), which has some flavor of an observational study but provides the same level of scientific rigor as a standard randomized trial. We describe treatment effect estimators that are consistent, asymptotically normal, and (nearly) efficient under CDR, and derive the optimal propensity score by maximizing the design efficiency of a CDR trial (under the assumption that an efficient estimator will be used for analysis). Our optimality results translate into optimal designs that improve upon standard practice. Real‐world examples and simulation results demonstrate that the proposed designs can produce substantial efficiency improvements in realistic settings.
Effects of branched-chain amino acids supplementation on patients undergoing hepatic intervention: a meta-analysis of randomised controlled trials

Abstract The benefits of branched-chain amino acid (BCAA) administration after hepatic intervention in patients with liver diseases remain unclear. We conducted a systematic review and meta-analysis to evaluate the effects of BCAA on patients undergoing hepatectomy, trans-arterial embolisation and radiofrequency ablation. Relevant randomised controlled trials (RCT) were obtained from PubMed, EMBASE and Cochrane Library databases. A meta-analysis was performed to calculate the pooled effect size by using random-effects models. The primary outcomes were survival and tumour recurrence. The secondary outcomes were hospital stay, nutrition status, biochemistry profile, complication rate of liver treatment and adverse effect of BCAA supplementation. In total, eleven RCT involving 750 patients were included. Our meta-analysis showed no significant difference in the rates of tumour recurrence and overall survival between the BCAA and control groups. However, the pooled estimate showed that BCAA supplementation in patients undergoing hepatic intervention significantly increased serum albumin (mean difference (MD): 0·11 g/dl, 95 % CI: 0·02, 0·20; 5 RCT) at 6 months and cholinesterase level (MD: 50·00 U/L, 95 % CI: 21·08, 78·92; 1 RCT) at 12 months and reduced ascites incidence (risk ratio: 0·39, 95 % CI: 0·21, 0·71; 4 RCT) at 12 months compared with the control group. Additionally, BCAA administration significantly increased body weight at 6 months and 12 months and increased arm circumference at 12 months. In conclusion, BCAA supplementation significantly improved the liver function, reduced the incidence of ascites and increased body weight and arm circumference. Thus, BCAA supplementation may beneficial for selected patients undergoing liver intervention.
Spontaneous mutational patterns and novel mutations for bedaquiline and clofazimine resistance in Mycobacterium tuberculosis

ABSTRACT The 2022 World Health Organization guidelines recommend use of two core anti-tuberculosis (TB) drugs, bedaquiline (BDQ) and clofazimine (CFZ), for treatment of drug-resistant (DR)-TB. However, several mutated Mycobacterium tuberculosis (MTB) genes, conferring BDQ and CFZ resistance, have been reported that predominantly arose from sporadic mutations that have not been comprehensively characterized. Herein, MTB clinical isolates collected from drug-susceptible (DS)-, multidrug-resistant (MDR)-, and extensively drug-resistant (XDR)-TB patients were cultured in vitro with BDQ or CFZ to generate progeny strains with resistance to these drugs. Progeny strains exposed to CFZ exhibited increased CFZ minimum inhibitory concentrations (MICs) that exceeded MIC increases of BDQ-exposed progeny strains. Notably, mmpR and pepQ mutations accounted for 83% and 17% of BDQ-induced spontaneous gene mutations, respectively, and 86% and 14% of CFZ-induced spontaneous gene mutations, respectively. Analyses of predicted mutation-induced changes in amino acid sequences and structures of MmpR and PepQ mutants revealed several point mutations affected sequence conversation and functionality as an underlying mechanism for observed acquired BDQ/CFZ resistance. Moreover, our results revealed differences in patterns of BDQ- and CFZ-induced acquired spontaneous mutations that may enhance our understanding of MTB BDQ/CFZ-resistance mechanisms. IMPORTANCE This study of MTB drug resistance mechanisms revealed patterns of spontaneous MTB mutations associated with acquired BDQ and CFZ resistance that arose after clinical MTB isolates were cultured in vitro with BDQ or CFZ. Results of protein sequence and structural analyses provided insights into potential mechanisms underlying associations between MTB gene mutations and DR phenotypes. Taken together, these results revealed differences in acquired BDQ and CFZ resistance mechanisms as a new perspective that may enhance our understanding of BDQ/CFZ resistance mechanisms and facilitate the development of new methods for detecting MTB drug resistance genes. This study of MTB drug resistance mechanisms revealed patterns of spontaneous MTB mutations associated with acquired BDQ and CFZ resistance that arose after clinical MTB isolates were cultured in vitro with BDQ or CFZ. Results of protein sequence and structural analyses provided insights into potential mechanisms underlying associations between MTB gene mutations and DR phenotypes. Taken together, these results revealed differences in acquired BDQ and CFZ resistance mechanisms as a new perspective that may enhance our understanding of BDQ/CFZ resistance mechanisms and facilitate the development of new methods for detecting MTB drug resistance genes.