Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of the trometamol-balanced solution with two other crystalloid solutions for fluid resuscitation of a rat hemorrhagic model

Currently, the optimal resuscitation fluid remains debatable. Therefore, in the present study, we designed a trometamol-balanced solution (TBS) for use as a resuscitation fluid for hemorrhagic shock. Hemorrhagic shock was induced in 18 male Wistar-Kyoto rats, which were assigned to normal saline (NS), Ringer's solution (RS), and TBS groups. During the hemorrhagic state, their hemodynamic parameters were recorded using an Abbott i-STAT analyzer with the CG4+ cartridge (for pH, pressure of carbon dioxide, pressure of oxygen, total carbon dioxide, bicarbonate, base excess, oxygen saturation, and lactate), the CG6+ cartridge (for sodium, potassium, chloride, blood glucose, blood urea nitrogen, hematocrit, and hemoglobin), and enzyme-linked immunosorbent assay kits (calcium, magnesium, creatinine, aspartate aminotransferase, alanine aminotransferase, bilirubin, and albumin). Similar trends were found for the parameters of biochemistries, electrolytes, and blood gas, and they revealed no significant changes after blood withdrawal-induced hemorrhagic shock. However, the TBS group showed more effective ability to correct metabolic acidosis than the NS and RS groups. TBS was a feasible and safe resuscitation solution in this study and may be an alternative to NS and RS for resuscitation in hemorrhagic shock patients without liver damage.
The novel proautophagy anticancer drug ABTL0812 potentiates chemotherapy in adenocarcinoma and squamous nonsmall cell lung cancer

Around 40% of newly diagnosed lung cancer patients are Stage IV, where the improvement of survival and reduction of disease‐related adverse events is the main goal for oncologists. In this scenario, we present preclinical evidence supporting the use of ABTL0812 in combination with chemotherapy for treating advanced and metastatic Nonsmall cell lung adenocarcinomas (NSCLC) and squamous carcinomas. ABTL0812 is a new chemical entity, currently in Phase 1b/2a clinical trial for advanced squamous NSCLC in combination with paclitaxel and carboplatin (P/C), after successfully completing the first‐in‐human trial where it showed an excellent safety profile and signs of efficacy. We show here that ABTL0812 inhibits Akt/mTOR axis by inducing the overexpression of TRIB3 and activating autophagy in lung squamous carcinoma cell lines. Furthermore, treatment with ABTL0812 also induces AMPK activation and ROS accumulation. Moreover, combination of ABTL0812 with chemotherapy markedly increases the therapeutic effect of chemotherapy without increasing toxicity. We further show that combination of ABTL0812 and chemotherapy induces nonapoptotic cell death mediated by TRIB3 activation and autophagy induction. We also present preliminary clinical data indicating that TRIB3 could serve as a potential novel pharmacodynamic biomarker to monitor ABTL0812 activity administered alone or in combination with chemotherapy in squamous NSCLC patients. The safety profile of ABTL0812 and its good synergy with chemotherapy potentiate the therapeutic potential of current lines of treatment based on chemotherapy regimens, arising as a promising option for improving these patients therapeutic expectancy.
Relation Between Perceived Vulnerability to HIV and Precautionary Sexual Behavior

A review of the research literature on the relationship between sexual behavior and perceptions of vulnerability to human immunodeficiency virus (HIV) provided limited support for the hypothesis that risk and preventive measures influence estimates of vulnerability but no support for the theory that perceptions of vulnerability to HIV motivate subsequent precautionary sexual behavior. The 32 primarily cross-sectional studies published on this topic from 1986-94 encompassed 15440 participants. Condom use was significantly less likely to be related to risk estimates than measures that combined two or more risk and preventive behaviors. Groups at low risk of HIV (e.g. older people women and college students) were more likely than their high-risk counterparts to base their risk estimates on their behavior. Age gender experience with risk behaviors and risk status all seemed to affect whether risk perceptions were a reflection of current behavior and the motivational power of these perceptions. Four factors specific to the HIV epidemic are assumed to explain the lesser applicability of health protective behavior models to this condition compared to non-fatal threats: emotions associated with decisions about sex the social nature of precautionary sexual behavior the lengthy incubation period for HIV and the uncertainty and ambiguity surrounding the process of infection. Recommended to expand theoretical and practical knowledge of this issue are longitudinal studies measures of the affective as well as cognitive dimensions of vulnerability perceptions and experimental studies.
Challenges in the field of obstetric fistula

Thirteen years after the last supplement on obstetric fistula, the authors challenge the progress achieved. Citing the ongoing need for a standardized classification system, uniform surgical training and certification, evaluation, follow‐up, and research, we emphasize the need for improved communication and coordination between government and nongovernment entities invested in ending obstetric fistula. Struck by the call by the United Nations to end obstetric fistula by 2030, we stress the need for increased and targeted funding of programs that are of the highest quality and impact.
Time Spent at Work and Its Impact on the Academic Performance of Pharmacy Students

The objective of this study was to determine the impact of time spent at work (workload) on the academic performance of pharmacy students. A cross-sectional 12-item survey was administered to pharmacy students at the end of the spring 2011 semester to primarily assess the type of employment and their weekly workload during the 2010–2011 academic year. Academic performance was determined by semester and cumulative grade point average (GPA). Descriptive statistics were performed. Stratified multiple linear regression models were obtained to assess the association between students’ workload and GPA. Analysis of covariance was used to compare academic performance by workload after accounting for work type and potential covariates. Statistical significance was defined a priori as p < 0.05. For both fall and spring semesters, nonpharmacy-related work was significant and positively associated with GPA. Both semester GPAs were fairly similar among three student classifications (P1–P3). However, GPAs across both semesters varied by classification. The negative association of workload on GPA was significant in the fall but not in the spring semester. Although workload matters, future studies using a mixed-method approach might help explain the role of workload on the academic performance of pharmacy during the first three years of their professional training.
Role of glucocorticoid signaling in exercise-associated changes in high-fat diet preference in rats

The simultaneous introduction of wheel running (WR) and diet choice (high-carbohydrate chow vs. high-fat diet) results in sex-specific diet choice patterns in rats. WR induces a high-fat (HF) diet avoidance, and such avoidance persists in the majority of males, but not females, throughout a 2-wk period. Exercise is a physiological stressor that activates the hypothalamic-pituitary-adrenal (HPA) axis and stimulates glucocorticoid (GC) release, which can alter dietary preferences. Here, we examined the role of the HPA axis and GC signaling in mediating exercise-induced changes in diet preference and the associated neurobiological adaptations that may underlie sex differences in diet choice patterns. Experiment 1 revealed that adrenalectomy did not significantly alter the initiation and persistence of running-induced HF diet avoidance in male rats. Experiment 2 showed that acute WR resulted in greater neural activation than chronic WR in the medial prefrontal (mPFC) and insular cortices (IC) in male rats. Experiment 3 revealed sex differences in the molecular adaptation to exercise and diet preference. First, exercise increased gene expression of fkbp5 in the mPFC, IC, and hippocampus of WR females but had limited influence in males. Second, male and female WR rats that reversed or maintained HF diet avoidance showed distinct sex- and HF diet preference-dependent expression profiles of genes involved in cortical GC signaling (e.g., nr3c1, nr3c2, and src1). Taken together, our results suggest sex differences in region-specific neural adaptations may underlie sex differences in diet preference and the health benefits from exercise.
Informal Caregiving, Chronic Physical Conditions, and Physical Multimorbidity in 48 Low- and Middle-Income Countries

Abstract Background The health of the caregivers is crucial to sustain informal care provision, while multimorbidity is an important health risk concept. However, studies on the association between informal caregiving and physical multimorbidity are currently lacking. Therefore, we investigated this association in adults from 48 low- and middle-income countries (LMICs). Method Cross-sectional data from 242,952 adults (mean age 38.4 years) participating in the World Health Survey 2002–2004 were analyzed. Informal caregivers were considered those who provided help in the past year to a relative or friend (adult or child) who has a long-term physical or mental illness or disability, or is getting old and weak. Nine physical conditions were assessed. Multivariable logistic regression analyses were conducted to assess associations between informal caregiving and physical multimorbidity, while the between-country heterogeneity in this relationship was studied with country-wise analyses. Results The overall prevalence of informal caregiving and physical multimorbidity (ie, two or more physical conditions) was 19.2% and 13.2%, respectively. Overall, caregivers had 1.40 (95% confidence interval = 1.29–1.52) times higher odds for physical multimorbidity. This association was particularly pronounced in younger caregivers (eg, 18–44 years: odds ratio = 1.54; 95% confidence interval = 1.37–1.72), whereas this association was not statistically significant among those aged ≥65 and older (odds ratio = 1.19; 95% confidence interval = 0.98–1.44). Country-wise analyses corroborated these findings, and there was a negligible level of between-country heterogeneity (I2 = 24.0%). Conclusions In LMICs, informal caregivers (especially young caregivers) were more likely to have physical multimorbidity. This should be taken into account in policies that address the health and well-being of informal caregivers.
Embodied aspects of learning to be a surgeon

Abstract Embodied learning is an educational concept that has been applied to various aspects of education, but only touched on in medical education, largely in relation to the teaching and learning of anatomy. Thus far, the medical literature has not addressed embodied learning as it specifically relates to learning to operate and be a surgeon. This paper will discuss relevant principles of embodied learning/cognition, ways it is important both for learning to function as a surgeon and for learning to perform technical aspects of surgery, and finally will discuss implications for surgical education. In particular, it will address ways in which embodied learning can and should be incorporated into educational activities specific to surgery.
Identification of Metabonomics Changes in Longissimus Dorsi Muscle of Finishing Pigs Following Heat Stress through LC-MS/MS-Based Metabonomics Method

Simple Summary Limited research exists on muscle metabolomics of finishing pigs under heat stress. In this study, nine different metabolites in the longissimus dorsi (LD) muscle of finishing pigs under heat stress were screened and identified. Through quantitative verification, it was concluded that the content of L-carnitine in the LD muscles of the finishing pigs could be significantly decreased due to heat stress, which might be a biomarker for monitoring the animal health status and muscle quality under heat stress. Abstract Heat stress (HS) negatively affects meat quality by affecting material and energy metabolism, and exploring the mechanism underlying the muscle response to chronic HS in finishing pigs is important for the global pork industry. This study investigated changes in the metabolic profiles of the longissimus dorsi (LD) muscle of finishing pigs under high temperature using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS) and multivariate data analysis (MDA). Castrated male DLY pigs (Duroc × Landrance × Yorkshire pigs, n = 24) from 8 litters were divided into three treatment groups: constant optimal ambient temperature at 22 °C and ad libitum feeding (CR, n = 8); constant high ambient temperature at 30 °C and ad libitum feeding (HS, n = 8); and constant optimal ambient temperature 22 °C and pair-feeding to the control pigs (PF, n = 8). The metabolic profile data from LD muscle samples were analyzed by MDA and external search engines. Nine differential metabolites (L-carnosine, acetylcholine, inosinic acid, L-carnitine, L-anserine, L-α-glycerylphosphorylcholine, acetylcarnitine, thiamine triphosphate, and adenosine thiamine diphosphate) were involved in antioxidant function, lipid metabolism, and cell signal transduction, which may decrease post mortem meat quality and play important roles in anti-HS. Four metabolites (L-carnosine, acetylcholine, inosinic acid, and L-carnitine) were verified, and it was indicated that the muscle L-carnitine content was significantly lower in HS than in CR (p < 0.01). The results show that constant HS affects the metabolites in the LD muscle and leads to coordinated changes in the endogenous antioxidant defense and meat quality of finishing pigs. These metabonomics results provide a basis for researching nutritional strategies to reduce the negative effects of heat stress on livestock and present new insights for further research.
The Erythrocytic Hypothesis of Brain Energy Crisis in Sporadic Alzheimer Disease: Possible Consequences and Supporting Evidence

Alzheimer’s disease (AD) is a fatal form of dementia of unknown etiology. Although amyloid plaque accumulation in the brain has been the subject of intensive research in disease pathogenesis and anti-amyloid drug development; the continued failures of the clinical trials suggest that amyloids are not a key cause of AD and new approaches to AD investigation and treatment are needed. We propose a new hypothesis of AD development based on metabolic abnormalities in circulating red blood cells (RBCs) that slow down oxygen release from RBCs into brain tissue which in turn leads to hypoxia-induced brain energy crisis; loss of neurons; and progressive atrophy preceding cognitive dysfunction. This review summarizes current evidence for the erythrocytic hypothesis of AD development and provides new insights into the causes of neurodegeneration offering an innovative way to diagnose and treat this systemic disease.
Left Ventricular Ejection Fraction Recovery in Patients with Heart Failure and Reduced Ejection Fraction Treated with Sacubitril/Valsartan

Background: A significant number of heart failure (HF) patients with reduced left ventricular ejection fraction (LVEF) experience ventricular function recovery during follow-up. We studied the variables associated with LVEF recovery in patients treated with sacubitril/valsartan (SV) in clinical practice. Methods: We analyzed data from a prospective and multicenter registry including 249 HF outpatients with reduced LVEF who started SV between October 2016 and March 2017. The patients were classified into 2 groups according to LVEF at the end of follow-up (>35%: group R, or ≤35%: group NR). Results: After a mean follow-up of 7 ± 0.1 months, 62 patients (24.8%) had LVEF >35%. They were older (71.3 ± 10.8 vs. 67.5 ± 12.1 years, p = 0.025), and suffered more often from hypertension (83.9 vs. 73.8%, p = 0.096) and higher blood pressure before and after SV (both, p < 0.01). They took more often high doses of beta-blockers (30.6 vs. 27.8%, p = 0.002), with a smaller proportion undergoing cardiac resynchronization therapy (14.8 vs. 29.0%, p = 0.028) and fewer implanted cardioverter defibrillators (ICD; 32.8 vs. 67.9%, p < 0.001), this being the only predictive variable of NR in the multivariate analysis (OR 0.26, 95% CI 0.13–0.47, p < 0.0001). At the end of follow-up, the mean LVEF in group R was 41.9 ± 8.1% (vs. 26.3 ± 4.7% in group NR, p < 0.001), with an improvement compared with the initial LVEF of 14.6 ± 10.8% (vs. 0.8 ± 4.5% in group NR, p < 0.0001). Functional class improved in both groups, mainly in group R (p = 0.035), with fewer visits to the emergency department (11.5 vs. 21.6%, p = 0.07). Conclusions: In patients with LVEF ≤35% treated with SV, not carrying an ICD was independently associated with LVEF recovery, which was related to greater improvement in functional class.
Effect of DPP-4 inhibitor saxagliptin on endothelium-dependent vasodilation in patients with type 2 diabetes

Objective To investigate the effect of DPP-4 inhibitor saxagliptin on endothelium-dependent flow mediated vasodilatation( FMD) in patients with type 2 diabetes. Methods A total of 80 newly diagnosed patients with type 2 diabetes were randomly divided into two groups( n = 40 in each group). The patients were treated with exercise- diet therapy and saxagliptin 5 mg / d in treatment group,and exercise- diet therapy and placebo in control group. Fasting blood-glucose( FPG),2 h postprandial plasma glucose( 2 hPG),glycosylated hemoglobin A1C( HbA1C) levels and FMD were evaluated before treatment and after 12-week treatment. Results Compared with control group,the levels of FPG,2 hPG,HbA1C were obviously decreased in treatment group( P 0. 05) and FMD were obviously increased( P 0. 05). Conclusion Saxagliptin could improve the FMD in patients with type 2 diabetes.
Metabolic Profiling Reveals a Dependency of Human Metastatic Breast Cancer on Mitochondrial Serine and One-Carbon Unit Metabolism

Breast cancer is the most common cancer among American women and a major cause of mortality. To identify metabolic pathways as potential targets to treat metastatic breast cancer, we performed metabolomics profiling on the breast cancer cell line MDA-MB-231 and its tissue-tropic metastatic subclones. Here, we report that these subclones with increased metastatic potential display an altered metabolic profile compared with the parental population. In particular, the mitochondrial serine and one-carbon (1C) unit pathway is upregulated in metastatic subclones. Mechanistically, the mitochondrial serine and 1C unit pathway drives the faster proliferation of subclones through enhanced de novo purine biosynthesis. Inhibition of the first rate-limiting enzyme of the mitochondrial serine and 1C unit pathway, serine hydroxymethyltransferase (SHMT2), potently suppresses proliferation of metastatic subclones in culture and impairs growth of lung metastatic subclones at both primary and metastatic sites in mice. Some human breast cancers exhibit a significant association between the expression of genes in the mitochondrial serine and 1C unit pathway with disease outcome and higher expression of SHMT2 in metastatic tumor tissue compared with primary tumors. In addition to breast cancer, a few other cancer types, such as adrenocortical carcinoma and kidney chromophobe cell carcinoma, also display increased SHMT2 expression during disease progression. Together, these results suggest that mitochondrial serine and 1C unit metabolism plays an important role in promoting cancer progression, particularly in late-stage cancer. Implications: This study identifies mitochondrial serine and 1C unit metabolism as an important pathway during the progression of a subset of human breast cancers.
Prediction of Protein–Protein Interaction Sites Using Convolutional Neural Network and Improved Data Sets

Protein–protein interaction (PPI) sites play a key role in the formation of protein complexes, which is the basis of a variety of biological processes. Experimental methods to solve PPI sites are expensive and time-consuming, which has led to the development of different kinds of prediction algorithms. We propose a convolutional neural network for PPI site prediction and use residue binding propensity to improve the positive samples. Our method obtains a remarkable result of the area under the curve (AUC) = 0.912 on the improved data set. In addition, it yields much better results on samples with high binding propensity than on randomly selected samples. This suggests that there are considerable false-positive PPI sites in the positive samples defined by the distance between residue atoms.
Fighting and aggressive sound determines larger male to win male‐male competition in a bark beetle

Intrasexual selection occurs in male‐male competition over access to females and usually results in the larger male winning. While much research has documented that size matters, little is known about how the larger male wins. Dendroctonus valens is an aggregating monogamous bark beetle in which males have large variation in body size and display intense competition over females. Behavioral observation showed two males fight each other within the gallery by pushing/shoving and stridulated more when two males encountered each other. Experiments using two different‐sized males synchronously competing showed that larger males won 95% of contests. Reciprocal displacement experiments using muted and intact males of different or equal size were used to simulate male‐male competition. Larger males displaced the smaller resident male in 90% of contests, while smaller males prevailed over larger residents in 6.7% of contests. With both males silenced, larger males displaced smaller males in 80% of contests, while smaller males prevailed in 8% of contests. Further experiments using equal‐sized males showed aggressive sound‐emitting males displaced muted males in 67% of contests, yet intact males displaced other intact males in only 37.5% of contests. Sound analysis showed sound pressure level is an honest signal of body size and males chose soft sounds over loud aggressive sounds in assays. Therefore, D. valens males have evolved dual behaviors, fighting and aggressive sounds associated with body size, to assess rivals to compete for a partner, gaining insights in male‐male competition for this species and for other animals.
Alexithymic traits predict the speed of classifying non-literal statements using nonverbal cues

ABSTRACT There is increasing interest in exploring the impact of alexithymia on interpersonal interactions. This study explored relationships between alexithymia and the complex mentalising skills needed to infer how a speaker intended a non-literal statement to be understood. A sample of university students (N = 70) viewed videotaped exchanges and attempted to classify remarks as literal, sarcastic, jocular, or white lies. Alexithymia was not associated with less consistent labelling of statement types. However, after accounting for variance due to verbal intelligence and sex, we found that those who reported more difficulties identifying their own feelings needed more time to distinguish between different statement types on the basis of the speaker's nonverbal cues. These findings highlight the value of examining response times, and of accounting for individual differences in specific alexithymic traits, when assessing social perception and cognition.