Miracle-dz/UniFAR-FTUs huggingface dataset:
Fatigue induces altered spatial myoelectric activation patterns in the medial gastrocnemius during locomotion.

Sustained voluntary muscle contractions can lead to fatigue, which diminishes the muscle's ability to absorb energy and produce force at a desired level. Prolonged fatigue can lead to a decline in human performance and increase the muscle's susceptibility to injury. In this study, we investigated how localized muscle fatigue affected spatial EMG patterns during locomotion. We recorded high-density electromyography (EMG) from the medial gastrocnemius of 11 healthy subjects while they walked (1.2 m/s) and ran (3.0 m/s) on a treadmill before and after performing a task that locally fatigued their ankle plantarflexor muscles. We applied multivariate signal cleaning methods to remove motion artifacts from the recorded signals. From these data, we computed the peak EMG amplitude, spatial entropy, peak EMG barycenter, and mean power frequency content during walking and running before and after subjects fatigued. We also calculated sagittal plane lower limb joint kinematics and kinetics in each condition. We found that peak EMG activity significantly decreased during walking and running after the fatigue task, and the location of the peak EMG barycenter had shifted proximally compared to its pre-fatigue location. We also observed an increase in the EMG mean power frequency during locomotion post-fatigue. Despite the changes in spatial EMG activation, lower limb biomechanics were similar before and after fatigue. These results suggest that motor unit recruitment was altered to sustain force production and forward propulsion. This may be a protective mechanism to more broadly distribute muscle loads and avoid myotendinous injury.
Electrospun orally disintegrating film formulation of telmisartan

Abstract Telmisartan (TEL) is an antihypertensive BCS class II drug with low solubility at physiological pH. However, the solubility of TEL increases with the presence of an alkalizer. Electrospinning is one of the most recent techniques for the solubility enhancement studies. In this study, an electrospun orally disintegrating film (ODF) formulation of TEL was developed with L-arginine and polyvinylpyrrolidone K90 (PVP), and its characterization studies were performed. Preformulation studies were performed to investigate possible incompatibilities in the components of formulation with differential scanning calorimetry (DSC) and Fourier transform infrared spectrometer (FT-IR) analyses. ODFs were characterized in terms of drug content and uniformity, mechanical properties, fiber shape and diameter and in vitro dissolution profile. Smooth nanofibers without any beads were obtained. The dissolution rate of the TEL significantly increased. The chosen formulation had acceptable mechanical properties with much faster dissolution compared to the commercially available product. Developed ODF and marketed product were compared with a dissolution study in phosphate-buffered solution (pH 7.4). ODF and marketed product both reached 100% release in the 45th minute, and ODF results showed that ODF had much faster release than marketed product. In this study, TEL ODF formulation was successfully produced and characterized.
Prognostic tools or clinical predictions: Which are better in palliative care?

Purpose The Palliative Prognostic (PaP) score; Palliative Prognostic Index (PPI); Feliu Prognostic Nomogram (FPN) and Palliative Performance Scale (PPS) have all been proposed as prognostic tools for palliative cancer care. However, clinical judgement remains the principal way by which palliative care professionals determine prognoses and it is important that the performance of prognostic tools is compared against clinical predictions of survival (CPS). Methods This was a multi-centre, cohort validation study of prognostic tools. Study participants were adults with advanced cancer receiving palliative care, with or without capacity to consent. Key prognostic data were collected at baseline, shortly after referral to palliative care services. CPS were obtained independently from a doctor and a nurse. Results Prognostic data were collected on 1833 participants. All prognostic tools showed acceptable discrimination and calibration, but none showed superiority to CPS. Both PaP and CPS were equally able to accurately categorise patients according to their risk of dying within 30 days. There was no difference in performance between CPS and FPN at stratifying patients according to their risk of dying at 15, 30 or 60 days. PPI was significantly (p<0.001) worse than CPS at predicting which patients would survive for 3 or 6 weeks. PPS and CPS were both able to discriminate palliative care patients into multiple iso-prognostic groups. Conclusions Although four commonly used prognostic algorithms for palliative care generally showed good discrimination and calibration, none of them demonstrated superiority to CPS. Prognostic tools which are less accurate than CPS are of no clinical use. However, prognostic tools which perform similarly to CPS may have other advantages to recommend them for use in clinical practice (e.g. being more objective, more reproducible, acting as a second opinion or as an educational tool). Future studies should therefore assess the impact of prognostic tools on clinical practice and decision-making.
The anti-Rac1-GTP antibody and the detection of active Rac1: a tool with a fundamental flaw

ABSTRACT Rac1 is a member of the Rho GTPase family and is involved in many cellular processes, particularly the formation of actin-rich membrane protrusions, such as lamellipodia and ruffles. With such a widely studied protein, it is essential that the research community has reliable tools for detecting Rac1 activation both in cellular models and tissues. Using a series of cancer cellular models, we recently demonstrated that a widely used antibody for visualizing active Rac1 (Rac1-GTP) does not recognize Rac1 but instead recognizes vimentin filaments (Baker MJ, J. Biol. Chem. 295:13698–13710, 2020). We believe that this tool has misled the field and impose on the GTPase research community the need to validate published results using this antibody as well as to continue the development of new resources to visualize endogenous active Rac1.
Southern Ocean anthropogenic carbon sink constrained by sea surface salinity

Observed sea surface salinity constrains past and future anthropogenic carbon uptake in the Southern Ocean. The ocean attenuates global warming by taking up about one quarter of global anthropogenic carbon emissions. Around 40% of this carbon sink is located in the Southern Ocean. However, Earth system models struggle to reproduce the Southern Ocean circulation and carbon fluxes. We identify a tight relationship across two multimodel ensembles between present-day sea surface salinity in the subtropical-polar frontal zone and the anthropogenic carbon sink in the Southern Ocean. Observations and model results constrain the cumulative Southern Ocean sink over 1850-2100 to 158 ± 6 petagrams of carbon under the low-emissions scenario Shared Socioeconomic Pathway 1-2.6 (SSP1-2.6) and to 279 ± 14 petagrams of carbon under the high-emissions scenario SSP5-8.5. The constrained anthropogenic carbon sink is 14 to 18% larger and 46 to 54% less uncertain than estimated by the unconstrained estimates. The identified constraint demonstrates the importance of the freshwater cycle for the Southern Ocean circulation and carbon cycle.
Influence of thermal growth of Au nanoparticles in the coupling efficiency of Au/SiO2 nanocomposite grating coupler

The Au/SiO2 nanocomposite grating coupler with a period of 600 nm was fabricated by implantation of 140 keV Au ions at a fluence of 6 × 1016 ions·cm−2 in combination with subsequent electron-beam lithography and ion beam etching. The thermal evolution of Au nanoparticles and its influence on the vertical coupling efficiency of the prepared grating coupler has been investigated in detail. The results clearly show that the coupling efficiency of the nanocomposite grating coupler could be affected by the thermal evolution of Au nanoparticles, which increases in the annealing temperature range up to 800 °C, and then decreases at 900 °C and above. Theoretical calculation demonstrates that the change of the coupling efficiency should be closely related to the synergistic effect of the scattering effect and the variation in the volume fraction of Au nanoparticles due to the thermal growth.
Circumpapillary optical coherence tomography angiography differences in perimetrically affected and unaffected hemispheres in primary open-angle glaucoma and the preperimetric fellow eye

Purpose: Evaluation of circumpapillary vessel density (VD) and perfusion density (PD) on optical coherence tomography angiography (OCTa) in mild-moderate glaucoma patients having unilateral visual field defects, with their fellow eyes and controls. Methods: Both eyes of 24 patients having a definitive nasal step or arcuate scotoma in one hemisphere of one eye only, and 24 controls, underwent OCTa. Results: In eyes with a superior field defect, the superior/inferior quadrant ratios, (SQ/IQ) of 3 mm scan of VD and PD were significantly higher in eyes with a superior arcuate scotoma than fellow eyes (P = 0.03,0.02) as also controls, (P = 0.004,0.001). The mean percentage loss of inferior quadrant VD between control to fellow eyes, and superior nasal step eyes were similar, 20.19%/19.57% respectively, P = 0.85, while a loss in arcuate scotoma eyes was 38.81% (P = 0.001). The percentage decrease in inferior quadrant PD in fellow eyes was 14.70%, superior nasal step 23.39%, and an arcuate scotoma 34.74% (P = 0.02). Eyes with a superior nasal step had significantly lower VD and PD absolute values in the inferior quadrant OCTa in 3 mm and 6 mm circle scan only as compared to control eyes, VD, P = 0.03,0.04/PD, P = 0.008,0.02. Fellow eyes of superior field defects had significantly lower VD and PD absolute values in the inferior quadrant in 3 mm and 6 mm circle scan as compared to control eyes, VD, P = 0.006,0.04/PD, P = 0.01,0.03. Eyes with an isolated inferior field defect in only one eye, showed a significant decrease in both VD and PD in all quadrants as compared to fellow eyes and control eyes. A significant positive correlation was found between VD and RNFL thickness in peripapillary superior unaffected quadrants in eyes with superior field defects and inferior unaffected quadrants in inferior defects (P = 0.001 and 0.01). Conclusion: There was a statistically significant increasing SQ/IQ ratio and percentage loss of vascular parameters from control to fellow eyes, those with a superior nasal step, and those with a superior arcuate scotoma. Inferior VFDs appeared to be associated with a more generalized circulatory loss. The asymmetry between hemispheres and between eyes could be used as a biomarker for early glaucomatous neuropathy.
Dynamic changes of genome sizes and gradual gain of cell‐specific distribution of C4 enzymes during C4 evolution in genus Flaveria

C4 plants are believed to have evolved from C3 plants through various C3–C4 intermediate stages in which a photorespiration‐dependent CO2 concentration system known as C2 photosynthesis operates. Genes involved in the C4 cycle were thought to be recruited from orthologs present in C3 species and developed cell‐specific expression during C4 evolution. To understand the process of establishing C4 photosynthesis, we performed whole‐genome sequencing and investigated expression and mesophyll‐ or bundle‐sheath‐cell‐specific localization of phosphoenolpyruvate carboxylase (PEPC), NADP‐malic enzyme (NADP‐ME), pyruvate, orthophosphate dikinase (PPDK) in C3, C3–C4 intermediate, C4–like, and C4 Flaveria species. While genome sizes vary greatly, the number of predicted protein‐coding genes was similar among C3, C3–C4 intermediate, C4–like, and C4 Flaveria species. Cell‐specific localization of the PEPC, NADP‐ME, and PPDK transcripts was insignificant or weak in C3–C4 intermediate species, whereas these transcripts were expressed cell‐type specific in C4–like species. These results showed that elevation of gene expression and cell‐specific control of pre‐existing C4 cycle genes in C3 species was involved in C4 evolution. Gene expression was gradually enhanced during C4 evolution, whereas cell‐specific control was gained independently of quantitative transcriptional activation during evolution from C3–C4 intermediate to C4 photosynthesis in genus Flaveria.
Whole genome sequencing of a clinical drug resistant Candida albicans isolate reveals known and novel mutations in genes involved in resistance acquisition mechanisms

Candida albicans is an opportunistic pathogen accounting for the majority of cases of Candida infections. Currently, C. albicans are developing resistance towards different classes of antifungal drugs and this has become a global health burden that does not spare Lebanon. This study aims at determining point mutations in genes known to be involved in resistance acquisition and correlating resistance to virulence and ergosterol content in the azole resistant C. albicans isolate CA77 from Lebanon. This pilot study is the first of its kind to be implemented in Lebanon. We carried out whole genome sequencing of the azole resistant C. albicans isolate CA77 and examined 18 genes involved in antifungal resistance. To correlate genotype to phenotype, we evaluated the virulence potential of this isolate by injecting it into BALB/c mice and we quantified membrane ergosterol. Whole genome sequencing revealed that eight out of 18 genes involved in antifungal resistance were mutated in previously reported and novel residues. These genotypic changes were associated with an increase in ergosterol content but no discrepancy in virulence potential was observed between our isolate and the susceptible C. albicans control strain SC5314. This suggests that antifungal resistance and virulence potential in this antifungal resistant isolate are not correlated and that resistance is a result of an increase in membrane ergosterol content and the occurrence of point mutations in genes involved in the ergosterol biosynthesis pathway.
Brentuximab Vedotin Combined With Chemotherapy in Patients With Newly Diagnosed Early-Stage, Unfavorable-Risk Hodgkin Lymphoma

PURPOSE To improve curability and limit long-term adverse effects for newly diagnosed early-stage (ES), unfavorable-risk Hodgkin lymphoma. METHODS In this multicenter study with four sequential cohorts, patients received four cycles of brentuximab vedotin (BV) and doxorubicin, vinblastine, and dacarbazine (AVD). If positron emission tomography (PET)-4–negative, patients received 30-Gy involved-site radiotherapy in cohort 1, 20-Gy involved-site radiotherapy in cohort 2, 30-Gy consolidation-volume radiotherapy in cohort 3, and no radiotherapy in cohort 4. Eligible patients had ES, unfavorable-risk disease. Bulk disease defined by Memorial Sloan Kettering criteria (> 7 cm in maximal transverse or coronal diameter on computed tomography) was not required for cohorts 1 and 2 but was for cohorts 3 and 4. The primary end point was to evaluate safety for cohort 1 and to evaluate complete response rate by PET for cohorts 2-4. RESULTS Of the 117 patients enrolled, 116 completed chemotherapy, with the median age of 32 years: 50% men, 98% stage II, 86% Memorial Sloan Kettering–defined disease bulk, 27% traditional bulk (> 10 cm), 52% elevated erythrocyte sedimentation rate, 21% extranodal involvement, and 56% > 2 involved lymph node sites. The complete response rate in cohorts 1-4 was 93%, 100%, 93%, and 97%, respectively. With median follow-up of 3.8 years (5.9, 4.5, 2.5, and 2.2 years for cohorts 1-4), the overall 2-year progression-free and overall survival were 94% and 99%, respectively. In cohorts 1-4, the 2-year progression-free survival was 93%, 97%, 90%, and 97%, respectively. Adverse events included neutropenia (44%), febrile neutropenia (8%), and peripheral neuropathy (54%), which was largely reversible. CONCLUSION BV + AVD × four cycles is a highly active and well-tolerated treatment program for ES, unfavorable-risk Hodgkin lymphoma, including bulky disease. The efficacy of BV + AVD supports the safe reduction or elimination of consolidative radiation among PET-4–negative patients.
The effects of tocotrienols intake on obesity, blood pressure, inflammation, liver and glucose biomarkers: a meta-analysis of randomized controlled trials

Abstract The objective of this study is to accomplish a systematic review and meta-analysis of all randomized controlled trials that dissected the influence of tocotrienol supplementation on various anthropometric and cardiometabolic indices in all individuals, irrespective of health condition. This research was carried out in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines. 17 eligible articles were included in the final quantitative analysis. Current study revealed that tocotrienol consumption was not associated with CRP, WC, MDA, BMI, IL-6, HbA1C, ALT, AST, creatinine TNF-α, FPG, BW, DBP, and SBP. We did observe an overall increase in BW (SMD: 0.063 kg, 95% CI: −0.200, 0.327, p = 0.637) and DBP (SMD: 0.249 mmHg, 95% CI: 0.053, 0.446, p = 0.013). In addition, a significant reduction in SBP was observed (SMD: −0.616 mmHg, 95% CI: −1.123, −0.110, p = 0.017). In summary, our meta-analysis revealed that tocotrienol consumption was associated with increase in BW and DBP and decrease in SBP. Significant associations were not observed for other outcomes.
Associations of spicy food flavour and intake frequency with blood lipid levels and risk of abnormal serum lipid levels in Chinese rural population: a cross-sectional study

Abstract Objective: The purpose of the current study was to investigate associations between spicy food intake and serum lipids levels in Chinese rural population. Design: Information on spicy food flavour and intake frequency was obtained using a two-item questionnaire survey. Dietary data were collected using a validated thirteen-item FFQ. Fasting blood samples were collected and measured for total cholesterol (TC), TAG, HDL-cholesterol and LDL-cholesterol. Multivariate linear and logistic regression models were employed to examine the relationship between spicy food and serum lipids levels according to the spicy food flavour and intake frequency, respectively. Setting: A cross-sectional study in Henan Province. Participants: 38 238 participants aged 18–79 years old. Results: Spicy flavour and intake frequency were consistently associated with decreased TC and non-HDL-cholesterol levels but mildly associated with elevated TAG levels. Each level increment in spicy flavour was inversely associated with high TC (OR: 0·91; 95 % CI 0·88, 0·93) and high non-HDL-cholesterol (OR: 0·88; 95 % CI 0·85, 0·91) but positively associated with high TAG (OR: 1·04; 95 % CI 1·01, 1·07). Similarly, 1-d increment in spicy food intake frequency was also inversely associated with high TC (OR: 0·92; 95 % CI 0·91, 0·94) and high non-HDL-cholesterol (OR: 0·91; 95 % CI 0·89, 0·93) but positively associated with high TAG (OR: 1·04; 95 % CI 1·02, 1·06). Conclusions: Spicy food intake was mildly associated with increased risk of abnormal TAG level, significantly associated with decreased risk of abnormal TC and non-HDL levels. Spicy food intake may be contribute to the management of lipid levels.
Tumour necrosis factor α-308 G/a and -238 G/a polymorphisms as predicator of diabetic retinopathy in Egyptians

Abstract Background Diabetic retinopathy (DR) is a duration dependent serious micro vascular insult of diabetes mellitus. Inflammation has a critical role in the development of early and late stage of DR. Tumour necrosis factor alpha (TNF-α) is an inflammatory cytokine that promoteup regulation of adhesion molecule expression, leukocyte recruitment and monocyte attraction. TNF-α levels are increased in retinas or vitreous of diabetic animals. A cross-sectional, observational study was performed in a sample of diabetic patients who attend diabetes polyclinic of RIO Hospital, Giza, Egypt, between October 2016 and December 2019. Three hundred diabetic patients were studied (150 males and 150 females). 100 diabetic patients without retinopathy, 100 diabetic patients with proliferative retinopathy (PDR), 100diabetic patients with non-proliferative retinopathy (NPDR), also 100 healthy subjects as a control group All patients and subjects were analysed for serum TNF-α levels by ELISA assay and -308 G/A and -238 G/A polymorphism by using Restriction fragment length polymorphisms. Aim Evaluating the role of tumour necrosis factor α and -308 G/A, -238 G/A polymorphisms in the pathogenesis of proliferative diabetic retinopathy among Egyptian patients. Results A statistically significant increase in TNF-α levels was detected in diabetic without retinopathy, NPDR and PDR groups compared to control group (p > .001). There were no significant different in Genotype and allele frequencies of the -308G/A, and -238 G/A, polymorphisms in both NPDR and PDR. However, the G/G genotype of the -308 G/A polymorphism occurred more frequently in PDR patients with than NPDR patients (0.74% vs 0.68%). Conclusion The present study clearly demonstrated increased levels of TNF-α, in diabetic patients with diabetic without retinopathy, NPDR and PDR. Furthermore, this study suggested that TNF-α assay could be used as diagnostic tools to predict the initiation and progression of diabetic retinopathy. They could serve as biomarkers not only for an early detection of the disease, but also to monitor the effects of therapy. Also, the G/G genotype of the -308 G/A polymorphism and the G allele of TNF-α gene were more frequent in PDR patients than with NPDR.
Long noncoding RNA‐dependent methylation of nonhistone proteins

In the last decade, an intriguing new paradigm of regulation has emerged in which some transcripts longer than 200 nucleotides and no coding potential, long noncoding RNA (lncRNAs), exhibit the capability to control posttranslational modifications of nonhistone proteins in both invertebrates and vertebrates. The extent of such a regulation is still largely unknown. We performed a systematic review to identify and evaluate the potential impact of lncRNA‐dependent methylation of nonhistone proteins. Collectively, these lncRNAs primarily act as scaffolds upon which methyltransferases (MTases) and targets are brought in proximity. In this manner, the N‐MTase activity of EZH2, protein arginine‐MTase 1/4/5, and SMYD2 is exploited to modulate the stability or the compartmentalization of several nonhistone proteins with roles in cell signaling, gene expression, and RNA processing. Moreover, these lncRNAs can indirectly affect the methylation of nonhistone proteins by transcriptional or posttranscriptional regulation of MTases. Strikingly, the lncRNAs/MTases/nonhistone proteins networking seem to be relevant to carcinogenesis and neurological disorders.