Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy of Tenapanor in Treating Patients With Irritable Bowel Syndrome With Constipation: A 26-Week, Placebo-Controlled Phase 3 Trial (T3MPO-2)

INTRODUCTION: Tenapanor is a first-in-class, minimally absorbed, small-molecule inhibitor of the gastrointestinal sodium/hydrogen exchanger isoform 3. This phase 3 trial assessed the long-term efficacy and safety of tenapanor 50 mg b.i. d. for the treatment of patients with irritable bowel syndrome with constipation (IBS-C). METHODS: In this randomized double-blind study (ClinicalTrials.gov identifier: NCT02686138), patients with IBS-C received tenapanor 50 mg b.i. d. or placebo b.i. d. for 26 weeks. The primary endpoint was the proportion of patients who had a reduction of ≥30.0% in average weekly worst abdominal pain and an increase of ≥1 weekly complete spontaneous bowel movement from baseline, both in the same week, for ≥6 of the first 12 treatment weeks (6/12-week combined responder). RESULTS: Of the 620 randomized patients with IBS-C, 593 (95.6%) were included in the intention-to-treat analysis set (tenapanor: n = 293; placebo: n = 300) and 481 patients (77.6%) completed the 26-week treatment period. In the intention-to-treat analysis set (mean age: 45.4 years; 82.1% women), a significantly greater proportion of patients treated with tenapanor were 6/12-week combined responders than those treated with placebo (36.5% vs 23.7%; P < 0.001). Abdominal symptoms and global symptoms of IBS were significantly improved with tenapanor compared with placebo. Diarrhea, the most common adverse event, was typically transient and mild to moderate in severity. Diarrhea led to study drug discontinuation for 19 (6.5%) and 2 patients (0.7%) receiving tenapanor and placebo, respectively. DISCUSSION: Tenapanor 50 mg b.i. d. improved IBS-C symptoms over 26 weeks and was generally well tolerated, offering a potential new long-term treatment option for patients with IBS-C (see Visual abstract, Supplementary Digital Content 1, http://links.lww.com/AJG/B797).
Conjugates Containing Two and Three Trithiolato-Bridged Dinuclear Ruthenium(II)-Arene Units as In Vitro Antiparasitic and Anticancer Agents

The synthesis, characterization, and in vitro antiparasitic and anticancer activity evaluation of new conjugates containing two and three dinuclear trithiolato-bridged ruthenium(II)-arene units are presented. Antiparasitic activity was evaluated using transgenic Toxoplasma gondii tachyzoites constitutively expressing β-galactosidase grown in human foreskin fibroblasts (HFF). The compounds inhibited T. gondii proliferation with IC50 values ranging from 90 to 539 nM, and seven derivatives displayed IC50 values lower than the reference compound pyrimethamine, which is currently used for treatment of toxoplasmosis. Overall, compound flexibility and size impacted on the anti-Toxoplasma activity. The anticancer activity of 14 compounds was assessed against cancer cell lines A2780, A2780cisR (human ovarian cisplatin sensitive and resistant), A24, (D-)A24cisPt8.0 (human lung adenocarcinoma cells wild type and cisPt resistant subline). The compounds displayed IC50 values ranging from 23 to 650 nM. In A2780cisR, A24 and (D-)A24cisPt8.0 cells, all compounds were considerably more cytotoxic than cisplatin, with IC50 values lower by two orders of magnitude. Irrespective of the nature of the connectors (alkyl/aryl) or the numbers of the di-ruthenium units (two/three), ester conjugates 6–10 and 20 exhibited similar antiproliferative profiles, and were more cytotoxic than amide analogues 11–14, 23, and 24. Polynuclear conjugates with multiple trithiolato-bridged di-ruthenium(II)-arene moieties deserve further investigation.
Docking Prediction, Antifungal Activity, Anti-Biofilm Effects on Candida spp., and Toxicity against Human Cells of Cinnamaldehyde

Objective: This study evaluated the antifungal activity of cinnamaldehyde on Candida spp. In vitro and in situ assays were carried out to test cinnamaldehyde for its anti-Candida effects, antibiofilm activity, effects on fungal micromorphology, antioxidant activity, and toxicity on keratinocytes and human erythrocytes. Statistical analysis was performed considering α = 5%. Results: The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of cinnamaldehyde ranged from 18.91 μM to 37.83 μM. MIC values did not change in the presence of 0.8 M sorbitol, whereas an 8-fold increase was observed in the presence of ergosterol, suggesting that cinnamaldehyde may act on the cell membrane, which was subsequently confirmed by docking analysis. The action of cinnamaldehyde likely includes binding to enzymes involved in the formation of the cytoplasmic membrane in yeast cells. Cinnamaldehyde-treated microcultures showed impaired cellular development, with an expression of rare pseudo-hyphae and absence of chlamydoconidia. Cinnamaldehyde reduced biofilm adherence by 64.52% to 33.75% (p < 0.0001) at low concentrations (378.3–151.3 µM). Cinnamaldehyde did not show antioxidant properties. Conclusions: Cinnamaldehyde showed fungicidal activity through a mechanism of action likely related to ergosterol complexation; it was non-cytotoxic to keratinocytes and human erythrocytes and showed no antioxidant activity.
The Application of Trichoderma Strains or Metabolites Alters the Olive Leaf Metabolome and the Expression of Defense-Related Genes

Biocontrol fungal strains of the genus Trichoderma can antagonize numerous plant pathogens and promote plant growth using different mechanisms of action, including the production of secondary metabolites (SMs). In this work we analyzed the effects of repeated applications of selected Trichoderma strains or SMs on young olive trees on the stimulation of plant growth and on the development of olive leaf spot disease caused by Fusicladium oleagineum. In addition, metabolomic analyses and gene expression profiles of olive leaves were carried out by LC–MS Q-TOF and real-time RT-PCR, respectively. A total of 104 phenolic compounds were detected from olive leave extracts and 20 were putatively identified. Targeted and untargeted approaches revealed significant differences in both the number and type of phenolic compounds accumulated in olive leaves after Trichoderma applications, as compared to water-treated plants. Different secoiridoids were less abundant in treated plants than in controls, while the accumulation of flavonoids (including luteolin and apigenin derivatives) increased following the application of specific Trichoderma strain. The induction of defense-related genes, and of genes involved in the synthesis of the secoiridoid oleuropein, was also analyzed and revealed a significant variation of gene expression according to the strain or metabolite applied.
Low-Cycle Fatigue Behavior of the Novel Steel and 30SiMn2MoV Steel at 700 °C

As a newly developed gun barrel steel, the novel steel has shown excellent high-temperature strength, high resistance to wear and erosion, contributing to the superior ballistic life of gun barrels. As ballistic life increases, the fatigue life becomes essential for the safety and reliability of gun barrels. This paper presents a comparison of the low cycle fatigue (LCF) behaviors between a novel steel and 30SiMn2MoV steel at 700 °C. A strain-controlled fatigue test was carried out on the novel steel and 30SiMn2MoV steel in the strain range from 0.2 to 0.6%. The cyclic stress response behaviors of the novel steel and 30SiMn2MoV steel show cyclic softening behavior. In addition, the shape of the hysteresis rings of the novel steel and 30SiMn2MoV steel exhibit no-Masing model behavior. Energy–life relationships results show that the novel steel has higher fatigue resistance than the 30SiMn2MoV steel at 700 °C. The results of fatigue fracture analysis show that the failure mode of the 30SiMn2MoV steel is a mixed mode of intergranular fracture and transgranular fracture, while the failure mode of the novel steel is intergranular fracture. The cyclic softening of the two materials can be attributed to the lath structure with a high density of dislocations gradually transforms into low energy subcrystalline and cellular structures at 700 °C. The novel steel has a better fatigue life than the 30SiMn2MoV steel at 700 °C and different strain amplitudes, which is mainly related to the carbides and lath martensite in the materials.
Differences in the Prevalence of Fruit and Vegetable Consumption in Spanish Workers

The present study aims to examine the differences in daily fruit and vegetable consumption in the working population in Spain. A cross-sectional study was conducted, using data from the 2017 National Health Survey (n = 10,700 workers aged between 18 and 65 years). The daily consumption of fruit and vegetables was evaluated using two items included in a food frequency questionnaire. Occupations were classified into the 17 main groups of the National Classification of Occupations of 2011 (CNO-11). The prevalence (P) of daily fruit and vegetable consumption was calculated in relation to sociodemographic characteristics, health behaviors, work-related characteristics and occupations. Logistic regression analysis was performed to examine the association, with simple and adjusted Odds Ratio (aOR). The P of daily consumption of fruit and vegetables in workers was 60% for fruit and 40% for vegetables. After adjusting for sociodemographic characteristics and health behaviors, workers working night or rotating shifts had a lower consumption of fruits (aOR:0.9; p < 0.05), and those working on temporary contracts had a lower consumption of vegetables (aOR:0.8; p < 0.05). Engineers, scientists, health care workers and teachers had the highest fruit consumption (74.5%) and the highest vegetable consumption (55.1%). The lowest consumption of fruits was presented by the military (42.3%) and unskilled workers in the service sector (45.8%), and the lowest consumption of vegetables was presented by skilled construction workers (25.5%). These findings could aid in workplace health promotion and could be used in future studies to evaluate the impact of the activities adopted.
Genetic Parameters of Bovine Milk Fatty Acid Profile, Yield, Composition, Total and Differential Somatic Cell Count

Simple Summary In the last years, consumers have shown a remarkable interest in the qualitative and healthy aspects of milk, leading to an increase of the demand for dairy products with high nutritional value. By applying a genetic approach, it is possible to improve the quality of the fat contained in milk and its derivatives. In the present study we explored the genetic aspects of bovine milk fatty acids, in order to evaluate the feasibility of including them in breeding programs to alter their proportions in milk and improve the nutritional and healthy quality of fat. Our results indicate that genetic selection on fatty acid profile is feasible, as fatty acids present sufficient genetic variability and are moderately heritable. However, in the light of estimated correlations with other milk traits, a clear breeding objective should first be established. Abstract The growing interest of consumers for milk and dairy products of high nutritional value has pushed researchers to evaluate the feasibility of including fatty acids (FA) in selection programs to modify milk fat profile and improve its nutritional quality. Therefore, the aim of this study was to estimate genetic parameters of FA profile predicted by mid-infrared spectroscopy, milk yield, composition, and total and differential somatic cell count. Edited data included 35,331 test-day records of 25,407 Italian Holstein cows from 652 herds. Variance components and heritability were estimated using single-trait repeatability animal models, whereas bivariate repeatability animal models were used to estimate genetic and phenotypic correlations between traits, including the fixed effects of stage of lactation, parity, and herd-test-date, and the random effects of additive genetic animal, cow permanent environment and the residual. Heritabilities and genetic correlations obtained in the present study reflected both the origins of FA (extracted from the blood or synthesized de novo by the mammary gland) and their grouping according to saturation or chain length. In addition, correlations among FA groups were in line with correlation among individual FA. Moderate negative genetic correlations between FA and milk yield and moderate to strong positive correlations with fat, protein, and casein percentages suggest that actual selection programs are currently affecting all FA groups, not only the desired ones (e.g., polyunsaturated FA). The absence of association with differential somatic cell count and the weak association with somatic cell score indicate that selection on FA profile would not affect selection on resistance to mastitis and vice versa. In conclusion, our findings suggest that genetic selection on FA content is feasible, as FA are variable and moderately heritable. Nevertheless, in the light of correlations with other milk traits estimated in this study, a clear breeding goal should first be established.
Adaptation of babies in three types of placement: An ethological approach.

The present pilot study focuses on the adaptive processes of babies who are placed during their first months of life. It used an ethological approach to explore the behavioural adjustment of 19 infants from their arrival in placement through their first 6 weeks in Residential Care (RC; France), a Foster Family (FF; Québec) or an Infant-Mother Centre (IMC; Québec). Direct observations were conducted once a week during feeding sessions. Observed behaviours were as follows: sleep-wake state, self-soothing, burp, visual exploration, motor activity, facial and vocal expressions. Then, a Kruskal-Wallis test was conducted to examine differences in babies' adaption as a function of placement setting. Results showed that, in RC, the duration of the post-feeding phase is the shortest. Moreover, these institutionalized babies showed the most modes of self-protection and the fewest vocalizations. By contrast, babies placed in the IMC spent the least time in withdrawal, expressed motor activity more regularly and were never placed back in their recliner before burping. Larger differences appear comparing placement in RC and that in the IMC, the placement in FF showing intermediate results.
Histomorphological and immunophenotypical spectrum of cutaneous myoepitheliomas: A series of 35 cases

Myoepithelial tumors comprise a group of mesenchymal lesions that show heterogeneous histomorphological features, including dual epithelial, neural, and myoid differentiation. Cutaneous myoepithelioma is a rare neoplasm that is composed primarily of myoepithelial cells and represents one end of a histopathological spectrum of cutaneous myoepithelial neoplasms including chondroid syringoma and myoepithelial carcinoma. These tumors display a wide histopathological spectrum and immunophenotypical profile often showing epithelial and myoepithelial differentiation. In this series, we studied 35 cases of cutaneous myoepitheliomas. Our cases highlighted the broad histopathological range where most cases showed a non‐infiltrative and non‐encapsulated tumor exclusively located in the dermis and with no subcutaneous involvement. The majority of our cases had a solid growth pattern (syncytial pattern) and the remainder of cases had a multinodular growth pattern. The tumor cells were epithelioid in 23 cases, spindled in eight cases and there was a mixture of epithelioid and spindled cells in four cases. Mitotic figures ranged from 0 to 5 per 10 HPF. By immunohistochemistry epithelial membrane antigen (EMA) was expressed in 59% of cases S100 was positive in 88% of cases, CAM 5.2 was positive in 16% of cases, AE1/AE3 was positive in 44% of cases, p63 was positive in 17% of cases, smooth muscle actin was positive in 38% of cases, desmin was positive in 6% of cases, calponin was positive in 22% of cases, and glial fibrillary acidic protein was positive in 36% of cases. In addition, there were five cases without EMA, keratin, or p63 expression that only showed S100 expression. We describe a large series of cutaneous myoepitheliomas delineating their histomorphological spectrum and immunophenotypical profile. Awareness of some of the unusual histopathological features and the heterogeneous immunohistochemical may pose difficulties for the diagnosis.
Examining the relationship between physical and sexual violence and psychosocial health in young people living with HIV in rural South Africa

Experiences of violence during youth contravene young people’s rights and increase the risk of depression and poor human immunodeficiency virus (HIV) care outcomes among youth living with HIV (YLWH). Intervention targets for mitigating the negative psychosocial effects of violence are needed, particularly in areas like rural South Africa where violence remains pervasive and mental healthcare is limited. This study aims to quantify the associations between physical and sexual violence and depressive symptoms in YLWH in rural South Africa and explore the modification of these associations by key measures of psychosocial well‐being.
Birnessite-type MnO2 Nanowalls and Their Magnetic Properties

Birnessite-type MnO2 nanowalls have been fabricated on Si(111) substrate by a facile solution method. The XRD pattern indicates that the sample has the typical feature of turbostratic disorder and prefers to grow in the ab plane. The nanowalls are composed of thin flakes distributing uniformly over the surface of the Si(111) substrate. A magnetic transition temperature of 9.2 K is determined. Prominent magnetic anisotropy with the easy magnetization direction in the ab plane is observed at 5 K.
Detection of White Matter Ultrastructural Changes for Amyotrophic Lateral Sclerosis Characterization: A Diagnostic Study from Dti-Derived Data

In amyotrophic lateral sclerosis (ALS), magnetic resonance imaging (MRI) allows investigation at the microstructural level, employing techniques able to reveal white matter changes. In the current study, a diffusion tensor imaging (DTI) analysis, with a collection of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) indexes, was performed in ALS patients to correlate geno- and phenotype features with MRI data, to investigate an in-vivo correlation of different neuropathological patterns. All patients who underwent the MR-DTI analysis were retrospectively recruited. MRI scan was collected within three months from diagnosis. FA and ADC values were collected in corpus callosum (CC), corona radiata (CR), cerebral peduncle (CR), cerebellar peduncle (CbP) and corticospinal tract at posterior limb of internal capsule (CST). DTI analysis performed in the whole ALS cohort revealed significant FA reduction and ADC increase in all selected regions, as widespread changes. Moreover, we observed a higher value of FA in rCR in bulbar patients. A positive correlation between ALS Functional Rating Scale-Revised and FA in rCP was evident. In consideration of the non-invasiveness, the reliability and the easy reproducibility of the method, we believe that brain MRI with DTI analyses may represent a valid tool usable as a diagnostic marker in ALS.
Building the evidence-base to reduce electronic health record-related clinician burden

Clinicians face competing pressures of being clinically productive while using imperfect electronic health record (EHR) systems and maximizing face-to-face time with patients. EHR use is increasingly associated with clinician burnout and underscores the need for interventions to improve clinicians' experiences. With an aim of addressing this need, we share evidence-based informatics approaches, pragmatic next steps, and future research directions to improve 3 of the highest contributors to EHR burden: (1) documentation, (2) chart review, and (3) inbox tasks. These approaches leverage speech recognition technologies, natural language processing, artificial intelligence, and redesign of EHR workflow and user interfaces. We also offer a perspective on how EHR vendors, healthcare system leaders, and policymakers all play an integral role while sharing responsibility in helping make evidence-based sociotechnical solutions available and easy to use.
Nano-Biomimetic Drug Delivery Vehicles: Potential Approaches for COVID-19 Treatment

The current COVID-19 pandemic has tested the resolve of the global community with more than 35 million infections worldwide and numbers increasing with no cure or vaccine available to date. Nanomedicines have an advantage of providing enhanced permeability and retention and have been extensively studied as targeted drug delivery strategies for the treatment of different disease. The role of monocytes, erythrocytes, thrombocytes, and macrophages in diseases, including infectious and inflammatory diseases, cancer, and atherosclerosis, are better understood and have resulted in improved strategies for targeting and in some instances mimicking these cell types to improve therapeutic outcomes. Consequently, these primary cell types can be exploited for the purposes of serving as a “Trojan horse” for targeted delivery to identified organs and sites of inflammation. State of the art and potential utilization of nanocarriers such as nanospheres/nanocapsules, nanocrystals, liposomes, solid lipid nanoparticles/nano-structured lipid carriers, dendrimers, and nanosponges for biomimicry and/or targeted delivery of bioactives to cells are reported herein and their potential use in the treatment of COVID-19 infections discussed. Physicochemical properties, viz., hydrophilicity, particle shape, surface charge, composition, concentration, the use of different target-specific ligands on the surface of carriers, and the impact on carrier efficacy and specificity are also discussed.
Step vs. Two-Phase Gradual Volume Reduction Tapering Protocols in Strength Training: Effects on Neuromuscular Performance and Serum Hormone Concentrations

Abstract Seppänen, S and Häkkinen, K. Step vs. two-phase gradual volume reduction tapering protocols in strength training: Effects on neuromuscular performance and serum hormone concentrations. J Strength Cond Res 36(10): 2771–2779, 2022—This study assessed effects of 2 reduced volume tapering protocols on neuromuscular performance and serum hormone concentrations in 14 recreationally strength-trained men (21–30 years). After an 8-week strength training period subjects were divided to the step (54% volume reduction immediately) and 2-phase gradual (38% reduction for the first week and 70% for the second week) tapering groups for 2 weeks. One repetition maximum (1RM) squat, maximal isometric bilateral leg press force (leg press MVIC), electromyography (EMG) of vastus lateralis (VL) and vastus medialis, cross-sectional area of VL, serum testosterone, cortisol, and sex hormone-binding globuline (SHBG) concentrations were measured before and repeatedly during training and tapering periods. Both tapering protocols led to significant increases (p < 0.01) in squat 1RM. However, the increase in the step group (3.4 ± 2.1%) was higher (p < 0.05) than in the gradual group (1.7 ± 0.9%). The maximal integrated EMG of VL increased (p < 0.05) during tapering in the step group. Serum testosterone concentration increased (p < 0.05) and T/SHBG ratio reached the highest level after 1-week tapering in the step group. In the gradual group, T/SHBG ratio was (p < 0.05) higher after the taper than after the training period. Individual changes in T/SHBG ratio in the total group correlated positively (p < 0.05) with individual changes in leg press MVIC during the taper. These results suggest that reducing training volume can be an effective way to peak maximal strength. However, a higher volume reduction rate at the beginning of taper seems to lead to more favorable changes in maximal strength accompanied by positive changes in the neuromuscular system and serum hormone concentrations when taper follows an overreaching period.