Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative effect of administration and discontinuation of sildenafil and/or clomipramine on the hepatic, cardiac and testicular tissues of male rats

In this study, we examined the adverse consequences of prolonged treatment with sildenafil and/or clomipramine (CLO) on the hepatic, cardiac and testicular tissues of rats. Additionally, we investigated the potential effects of treatment discontinuation. To this end, 60 adult male rats were randomly assigned into six groups and were orally treated with 4.5 mg sildenafil /kg BW (SLD) and 9 mg/ kg BW (SHD), 2.25 mg CLO/kg BW (CLO), 4.5 mg sildenafil/kg BW + 2.25 mg CLO/kg BW (SLD‐CLO) and 9 mg sildenafil/kg BW + 2.25 mg CLO/kg BW (SHD‐CLO) while the control rats received 0.5 ml distilled water for 8 weeks. Then, five rats from each group were sacrificed and the other five rats were left untreated for another four weeks to recover from the drug treatment. Long‐term administration of sildenafil and/or CLO led to oxidative stress, inflammation and structural changes in the liver, heart and testis, reduction in sperm count and motility, an increase in abnormalities, and a reduction in serum testosterone, FSH and LH levels. All tested parameters returned to the normal state following the four‐week discontinuation of sildenafil. Additionally, all the alterations caused by long‐term administration of CLO, SLD‐CLO and SHD‐CLO were significantly improved during the recovery period.
Post-stroke cognitive impairment on the Mini-Mental State Examination primarily relates to left middle cerebral artery infarcts

Background Post-stroke cognitive impairment can occur after damage to various brain regions, and cognitive deficits depend on infarct location. The Mini-Mental State Examination (MMSE) is still widely used to assess post-stroke cognition, but it has been criticized for capturing only certain cognitive deficits. Along these lines, it might be hypothesized that cognitive deficits as measured with the MMSE primarily involve certain infarct locations. Aims This comprehensive lesion-symptom mapping study aimed to determine which acute infarct locations are associated with post-stroke cognitive impairment on the MMSE. Methods We examined associations between impairment on the MMSE (<5th percentile; normative data) and infarct location in 1198 patients (age 67 ± 12 years, 43% female) with acute ischemic stroke using voxel-based lesion-symptom mapping. As a frame of reference, infarct patterns associated with impairments in individual cognitive domains were determined, based on a more detailed neuropsychological assessment. Results Impairment on the MMSE was present in 420 patients (35%). Large voxel clusters in the left middle cerebral artery territory and thalamus were significantly (p < 0.01) associated with cognitive impairment on the MMSE, with highest odds ratios (>15) in the thalamus and superior temporal gyrus. In comparison, domain-specific impairments were related to various infarct patterns across both hemispheres including the left medial temporal lobe (verbal memory) and right parietal lobe (visuospatial functioning). Conclusions Our findings indicate that post-stroke cognitive impairment on the MMSE primarily relates to infarct locations in the left middle cerebral artery territory. The MMSE is apparently less sensitive to cognitive deficits that specifically relate to other locations.
Surface modification of quantum dots and magnetic nanoparticles with PEG-conjugated chitosan derivatives for biological applications

In this paper, amphiphilic chitosan derivatives (N-octyl-N-mPEG-chitosan, mPEG = poly(ethylene glycol) monomethyl ether; OPEGC) were successfully synthesised via the Schiff base reduction reaction of chitosan and mPEG-aldehyde, or octanal, with chitosan acting as the backbone of the grafted copolymers, and mPEG-aldehyde providing the hydrophilic chain or octanal providing the hydrophobic alkyl chain. The synthesis was confirmed by characterisation employing Fourier transform infrared spectroscopy (FTIR) and 1H NMR. In the subsequent procedure, water-soluble quantum dots (QDs) and iron(II,III) oxide (IO) nanoparticles, widely used as nanoprobes in medical applications, were produced by the incorporation of QDs or IO inside the polymeric micelle core. Finally, the optical properties of QDs incorporated into OPEGC (OPEGC@QDs) were characterised by UV-VIS spectroscopy, fluorescence spectroscopy, cell viability was obtained through MTT, and the morphology of their assembly formed in water were observed by atomic force microscope (AFM) and transmission electron microscope (TEM) and the QDs content of OPEGC@QDs was calculated following thermo gravimetric analysis (TGA). In addition, the properties of IO incorporated into OPEGC (OPEGC@IO) were characterised by vibrating sample magnetometry (VSM), FT-IR, MTT, TGA, AFM, and TEM. The results indicated that the OPEGC composite nanoparticles with size narrowly distributed, good water solubility, and low cytotoxicity were prepared here, which represented a high quantum yield or good super-paramagnetism.
Obesity and Energy Balance Considerations in Triple-Negative Breast Cancer

Abstract Obesity is an increasingly prevalent state of energy imbalance that contributes to breast cancer risk and outcomes. The effects of obesity differ by breast cancer subtype and menopause. While most studies have focused on postmenopausal hormone receptor–positive disease, less is known about the relationship between obesity and triple-negative breast cancer (TNBC). Here we will review the observations linking obesity to TNBC, the socioeconomic disparities that contribute to obesity-related TNBC, and putative biologic mechanisms. Finally, we will consider the impact of obesity on surgical and medical treatment of TNBC and novel strategies to improve energy balance after cancer diagnosis.
Reconstruction strategies for intraoperative CSF leak in endoscopic endonasal skull base surgery: systematic review and meta-analysis

Abstract Background Endoscopic endonasal surgery (EES) is one of the preferred options for skull base pathologies. Cerebrospinal fluid (CSF) leak is a significant complication of EES and neurosurgeons have proposed various reconstructive strategies to decrease this morbidity. We describe and compare the efficacy of these strategies. Methods We searched PubMed, Cochrane Library, and Web of Science for publications between 1990 and November 2019. We defined a reconstruction hierarchy of seven levels from inside to outside: fat graft, intracranial intradural layer (inlay), intracranial extradural layer (onlay), buttress, mucosal flap, nasal packing and lumbar drainage. A single-arm analysis was performed for the primary outcome of CSF leak rate. Results Of 3641 records identified, 48 studies met the inclusion criteria. Pituitary tumors had lower postoperative CSF leak rate than other diseases (1.8% vs. 6.5%, RD = −4.7% [−7.1%, −2.1%]). In high CSF flow group, the post-operative leak rate was reduced by application of mucosal flap (4.3% vs. without mucosal flap at 12.8%, RD = −8.5% [−15.1%, −1.9%]). The use of inlay showed potential of decreasing the post-operative leak rate (5.0% vs. 7.2%, RD = −2.2% [−7.7%, 3.3%]). In low CSF flow group, tampon was better than balloon for nasal packing (1.0% vs. 10.5%, RD = −9.5% [−16.5%, −2.4%]). Conclusions Mucosal flap and inlay for high-flow intraoperative CSF leak and tampon (compared with balloon) for low-flow intraoperative CSF leak, improved the postoperative CSF leak rate. Further studies are required to establish more robust evidence.
Screening for PIK3CA mutations among Saudi women with ovarian cancer

Abstract The study aimed to screen for PIK3CA gene mutations among Saudi women with Ovarian Cancer. The study included 298 Saudi women with epithelial ovarian cancers (EOC). DNA sequence analysis was employed to screen for the mutations. DNA sequence analysis of a coding region of exon 9 and 20 of PIK3CA gene revealed mutations in 37/298 (12.4%) EOC patients. About 21/37(56.8%) somatic mutations were identified in exons 9, and 16/37(43.2%) in exon 20. All analysed mutations were missense mutations, the frequencies of which varied from 2.7% to 43.2%. PIK3CA mutation was found to be significantly associated with age (p = .023), grade (p = .001) and histological types (p = .032). Only 6.6% of serous carcinomas and 3.8% of endometrioid had PIK3CA mutation. The Mutated PIK3CA gene was significantly involved in the pathogenesis of EOC among Saudi women. PIK3CA gene mutation and overexpression represent important clinical implications for diagnosis, and prognosis, which can be utilised for better EOC management. Impact statement What is already known on this subject? The detailed molecular and genetic phenomenon underlying the progression of these tumours is still unclear. Recently, the pathogenesis of ovarian cancer has been attributed to mutations of PIK3CA. What do the results of this study add? Mutation in the PIK3CA gene leads to altered PI3K/AKT signalling pathways responsible for the progression of the epithelial ovarian cancer. What are the implications of these findings for clinical practice and/or further research? The Mutated PIK3CA gene was significantly involved in the pathogenesis of EOC among Saudi women. PIK3CA gene mutation and overexpression represent important clinical implications for diagnosis, and prognosis, which can be utilised for better EOC management.
Identifying DNA‐binding proteins based on multi‐features and LASSO feature selection

DNA‐binding proteins perform an indispensable function in the maintenance and processing of genetic information and are inefficiently identified by traditional experimental methods due to their huge quantities. On the contrary, machine learning methods as an emerging technique demonstrate satisfactory speed and accuracy when used to study these molecules. This work focuses on extracting four different features from primary and secondary sequence features: Reduced sequence and index‐vectors (RS), Pseudo‐amino acid components (PseAACS), Position‐specific scoring matrix‐Auto Cross Covariance Transform (PSSM‐ACCT), and Position‐specific scoring matrix‐Discrete Wavelet Transform (PSSM‐DWT). Using the LASSO dimension reduction method, we experiment on the combination of feature submodels to obtain the optimized number of top rank features. These features are respectively input into the training Ensemble subspace discriminant, Ensemble bagged tree and KNN to predict the DNA‐binding proteins. Three different datasets, PDB594, PDB1075, and PDB186, are adopted to evaluate the performance of the as‐proposed approach in this work. The PDB1075 and PDB594 datasets are adopted for the five‐fold cross‐validation, and the PDB186 is used for the independent experiment. In the five‐fold cross‐validation, both the PDB1075 and PDB594 show extremely high accuracy, reaching 86.98% and 88.9% by Ensemble subspace discriminant, respectively. The accuracy of independent experiment by multi‐classifiers voting is 83.33%, which suggests that the methodology proposed in this work is capable of predicting DNA‐binding proteins effectively.
Perceived exertion and performance modulation: effects of caffeine ingestion and subject expectation.

BACKGROUND It is well established that caffeine has ergogenic effects on endurance performance. This evidence often comes from studies in which subjects receive either caffeine or placebo in double-blind, randomized and counterbalanced order. Here, we propose a new methodology which aims to estimate the effects of participant expectancy of ergogenic or anti-ergogenic effects on performance. METHODS Sixteen (16) physically active participants (nonathletes engaged in systematic physical training >3 months, at least three times a week) performed three (3) 30-minute running tests after being told they would be provided with either a harmful treatment (lactic acid), a beneficial treatment (caffeine) or a placebo. In each blinded case, subjects were given caffeine. The velocity and Rating of Perceived Exertion (RPE) during the time trial were examined in light of the participant's expectancy before and after the endurance event using Bayesian multilevel models. RESULTS For pre-exercise expectancy, there is a 92% probability that caffeine expectation decreases RPE (posterior median±SD -0.65±0.36) and a 79% probability that lactic acid expectation increases RPE (posterior median±SD 0.58±0.47) with expectations for placebo and 'not sure' falling in between (posterior median±SD: -0.37±0.32 and -0.22±0.37, respectively). In general, our interventions suggest an 81% probability that caffeine lowers RPE. However, there was no effect of caffeine supplementation on running velocity (median±SD 0.04±0.08 km.h-1). CONCLUSIONS When a participant believed they are under a potentially positive treatment, their RPE decreased but if they believed themselves to be under a harmful treatment, their RPE increased, regardless of the actual positive intervention; neither caffeine nor the expectancy of a particular intervention improved actual performance as measured by running velocity in a 30-minute period.
Midwakh: Assessment of levels of Carcinogenic Polycyclic Aromatic Hydrocarbons (PAHs) and Nicotine in Dokha Tobacco Smoke.

Midwakh, originated in the Middle East, has started to spread globally with different brands commercialized online and in local stores across Europe and USA. Dokha is the tobacco used in Midwakh. To this day risk of Midwakh smoking is poorly understood. Three different types of dokha were evaluated in this study classified as cold, medium and hot using gas chromatography/mass spectrometry (GC/MS). The concentrations of nicotine and polycyclic aromatic hydrocarbons (PAHs) in raw and smoke dokha samples were measured and the results were compared to data in the literature on different types of tobacco products. PAH concentrations were used to estimate the Toxic equivalency quotient, daily exposures, incremental lifetime cancer risk, and hazard quotient. The level of nicotine in raw dokha exceeded by far the levels reported in cigarettes, cigar, waterpipe, and chewing tobacco. Although only a portion of the nicotine is released into the smoke, the amount of nicotine in dokha smoke exceeded those reported for cigarettes. Two PAHs were found in raw dokha at trace amounts and 12 PAHs were detected in dokha smoke in amounts that exceeded those reported for cigarette smoke. The PAHs distribution showed a specific pattern in the smoke and a higher risk factor than that obtained for cigarettes and other tobacco products. Dokha products present a potential higher risk and immediate action should be taken to avoid its global consumption.
Application of Robot Positioning for Cannulated Screw Internal Fixation in the Treatment of Femoral Neck Fracture: Retrospective Study

Background Femoral neck fracture is a common type of hip fracture. Conventional surgical treatment aims at fixing the fracture site with screws and then gradually promoting bone healing. A robot-assisted orthopedic surgery system is computer technology applied to surgical treatment. Objective This study aimed to explore the therapeutic effect and prognostic value of percutaneous cannulated screw internal fixation using robot-assisted positioning in patients with femoral neck fractures. Methods From July 2018 to September 2019, 42 cases of femoral neck fracture admitted to the Second Affiliated Hospital of Luohe Medical College were randomly and averagely divided into control and study groups. The patients in the control group were treated with conventional percutaneous cannulated screw internal fixation, while the patients in the study group were treated with robot-assisted percutaneous cannulated screw fixation during surgical treatment. We compared the treatment conditions and results of the operation between the 2 groups. The Harris score was used to evaluate the treatment efficacy. The state of fracture healing was followed up and compared between the 2 groups. Results The duration of the operation was shorter, there was less fluoroscopy use, and there were fewer drilled holes in the study group than in the control group (all, P<.001). There was no statistical difference in the amount of intraoperative bleeding between the 2 groups (P=.33). The Harris score (P=.045) and number of excellent and good ratings (P=.01) were significantly higher in the study group than in the control group. The difference in the fracture healing rate between the 2 groups was not statistically significant (P=.23). The fracture healing duration of the study group was shorter than that of the control group (P=.001). Conclusions The use of robotic positioning aids in the treatment of femoral neck fractures with percutaneous cannulated screw fixation can effectively improve the efficiency of surgery, shorten the duration of surgery, and reduce the radiation damage to patients. Meanwhile, it improves postoperative treatment and recovery rates of the patients and shortens the fracture healing time.
Physical Activity, Mental Health, and Technology Preferences to Support Cancer Survivors During the COVID-19 Pandemic: Cross-sectional Study

Background COVID-19 has had significant health-related and behavioral impacts worldwide. Cancer survivors (hereafter referred to as “survivors”) are particularly prone to behavioral changes and are encouraged to be more vigilant and observe stricter social distancing measures. Objective We explored (1) changes in physical activity and sedentary behaviors since the onset of COVID-19, along with changes in mental health status, and (2) alternative strategies to support survivors’ physical activity and social health during and after COVID-19, along with the role of digital health in such strategies. Methods A questionnaire was distributed among survivors participating (currently or previously) in the community-based physical activity program LIVESTRONG at the Young Men’s Christian Association (YMCA), from 3 sites outside an urban area in Massachusetts. Questions addressed pre–COVID-19 vs current changes in physical activity and sedentary behavior. Anxiety and depression were assessed using the 2-item Generalized Anxiety Disorder scale (GAD-2) and 2-item Patient Health Questionnaire (PHQ-2), and scores ≥3 indicated a clinical diagnosis of anxiety or depression, respectively. Digital health preferences were assessed through closed-ended questions. Open-ended responses addressing other preferences for physical activity programs and social support were analyzed, coded, and categorized into themes. Results Among 61 participants (mean age 62 [SD 10.4] years; females: 51/61 [83.6%]), 67.2% (n=41) reported decreased physical activity and 67.2% (n=41) reported prolonged sitting times since the onset of COVID-19. Further, 24.6% (n=15) and 26.2% (n=16) met the GAD-2 and PHQ-2 criteria for clinical anxiety and depression, respectively. All participants owned a cellphone; 90% (n=54) owned a smartphone. Preferences for physical activity programs (n=28) included three themes: (1) use of digital or remote platforms (Zoom, other online platforms, and video platforms), (2) specific activities and locations (eg, outdoor activities, walking, gardening, biking, and physical activities at the YMCA and at senior centers), and (3) importance of social support regardless of activity type (eg, time spent with family, friends, peers, or coaches). The survey revealed a mean score of 71.8 (SD 21.4; scale 0-100) for the importance of social support during physical activity programs. Social support preferences (n=15) revealed three themes: (1) support through remote platforms (eg, texting, Zoom, phone calls, emails, and Facebook), (2) tangible in-person support (YMCA and senior centers), and (3) social support with no specific platform (eg, small gatherings and family or friend visits). Conclusions Physical activity and mental health are critical factors for the quality of life of survivors, and interventions tailored to their activity preferences are necessary. Digital or remote physical activity programs with added social support may help address the ongoing needs of survivors during and after the pandemic.
Blocking LOXL2 and TGFβ1 signalling induces collagen I turnover in precision-cut lung slices derived from patients with idiopathic pulmonary fibrosis

We recently identified epigallocatechin gallate (EGCG), a trihydroxyphenolic compound, as a dual inhibitor of lysyl oxidase-like2 and transforming growth factor-β1 (TGFβ1) receptor kinase that when given orally to patients with idiopathic pulmonary fibrosis (IPF) reversed profibrotic biomarkers in their diagnostic biopsies. Here, we extend these findings to advanced pulmonary fibrosis using cultured precision-cut lung slices from explants of patients with IPF undergoing transplantation. During these experiments, we were surprised to discover that not only did EGCG attenuate TGFβ1 signalling and new collagen accumulation but also activated matrix metalloproteinase-dependent collagen I turnover, raising the possibility of slow fibrosis resolution with continued treatment.
What is the ideal route of administration of tranexamic acid in total knee arthroplasty? A meta-analysis based on randomized controlled trials.

BACKGROUND Tranexamic acid (TXA) was conducive in total knee arthroplasty (TKA) to reduce blood loss and transfusion demand. The purpose of this meta-analysis was to assess the efficacy and safety of different administration of TXA in primary TKA. METHODS Database PubMed, Medline, Web of Science and Embase were searched. The relative risks (RRs) with 95% confidence intervals (CIs) were calculated to analysis dichotomous outcomes. The mean differences (MD) with 95% CIs were calculated to analysis dichotomous outcomes. Data was analyzed using RevMan 5.3. RESULTS Twenty-eight randomized controlled trials (RCTs) studies were included in this meta-analysis involving a total of 4,200 participants. There were no obvious differences between oral, intravenous or topical TXA group in total blood loss (intravenous vs. topical: MD =11.55, 95% CI, -10.23 to 33.34, oral vs. intravenous or topical: MD =-52.25, 95% CI, -121.28 to 16.78), transfusion rate (intravenous vs. topical: RR =1.04, 95%CI, 0.64 to 1.69, oral vs. intravenous or topical: RR =0.75, 95% CI, 0.36 to 1.54), incidence of venous thrombotic events (VTE) (intravenous vs. topical: RR =1.43, 95% CI, 0.81 to 2.54). The topical TXA administration had significantly increased postoperative hemoglobin (HB) level compared with the intravenous TXA administration (MD =-0.37, 95% CIs, -0.47 to -0.26). In the combined group, the total blood loss (MD =-119.58, 95% CI, -181.68 to -57.49) and postoperative HB level (MD =0.54, 95% CI, 0.45 to 0.64) were more acceptable than the single-route group. CONCLUSIONS Combined administration of TXA can reduce total blood loss, postoperative HB drop compared with intravenous, topical or oral TXA alone. Oral administration of TXA is similar to intravenous or topical TXA use alone.