Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Fasting and Phoenix dactylifera on the Expression of Major Drug-Metabolizing Enzymes in the Mouse Livers.

AIMS This study aimed to investigate the effects of consuming Phoenix dactylifera and fasting on the mRNA expression of major hepatic drug-metabolizing enzymes in mice. METHODS Phoenix dactylifera ethanolic extract was analyzed using LC-MS/MS. We used forty-two male Balb/c mice which were treated with low (300 mg/kg) and high (2583 mg/kg) doses of Phoenix dactylifera and fasted for 24 hours, two weeks, and one month. Then, we analyzed the expression of cyp3a11, cyp2c29, cyp2d9, and ugt2b1 using real-time polymerase chain reaction assay. In addition, we assessed the relative liver weights of the mice and the hepatic phathohistological alterations. RESULTS We found that Phoenix dactylifera ethanolic extract contained 38 phytochemical compounds mainly kaempherol, campesterol, lutein, apigenin, genistein, and isoquercetin. Fasting significantly upregulated the mRNA expression of several drug-metabolizing enzymes in a time-dependent manner and we showed that consuming the low dose of Phoenix dactylifera significantly upregulated the expression of drug-metabolizing enzymes more than the high dose. The results of the histological examinations and relative liver weight showed that fasting and consuming of Phoenix dactylifera did not cause any toxicological alterations in the liver of the mice. CONCLUSION It is concluded from this study that fasting and consuming of Phoenix dactylifera upregulated the mRNA expression of major drug-metabolizing enzymes in mouse livers. These findings may explain, at least partly, the variation of drug response during fasting of the month of Ramadan and would direct future clinical studies in optimizing dosing of pharmacotherapeutic regimen.
Understanding Early Pandemic Severe Acute Respiratory Syndrome Coronavirus 2 Transmission in a Medical Center by Incorporating Public Sequencing Databases to Mitigate Bias

Abstract Background Throughout the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, healthcare workers (HCWs) have faced risk of infection from within the workplace via patients and staff as well as from the outside community, complicating our ability to resolve transmission chains in order to inform hospital infection control policy. Here we show how the incorporation of sequences from public genomic databases aided genomic surveillance early in the pandemic when circulating viral diversity was limited. Methods We sequenced a subset of discarded, diagnostic SARS-CoV-2 isolates between March and May 2020 from Boston Medical Center HCWs and combined this data set with publicly available sequences from the surrounding community deposited in GISAID with the goal of inferring specific transmission routes. Results Contextualizing our data with publicly available sequences reveals that 73% (95% confidence interval, 63%–84%) of coronavirus disease 2019 cases in HCWs are likely novel introductions rather than nosocomial spread. Conclusions We argue that introductions of SARS-CoV-2 into the hospital environment are frequent and that expanding public genomic surveillance can better aid infection control when determining routes of transmission.
Rate and oscillatory switching dynamics of a multilayer visual microcircuit model

The neocortex is organized around layered microcircuits consisting of a variety of excitatory and inhibitory neuronal types which perform rate- and oscillation-based computations. Using modeling, we show that both superficial and deep layers of the primary mouse visual cortex implement two ultrasensitive and bistable switches built on mutual inhibitory connectivity motives between somatostatin, parvalbumin, and vasoactive intestinal polypeptide cells. The switches toggle pyramidal neurons between high and low firing rate states that are synchronized across layers through translaminar connectivity. Moreover, inhibited and disinhibited states are characterized by low- and high-frequency oscillations, respectively, with layer-specific differences in frequency and power which show asymmetric changes during state transitions. These findings are consistent with a number of experimental observations and embed firing rate together with oscillatory changes within a switch interpretation of the microcircuit.
The Importance of Contact Zones for Distinguishing Interspecific from Intraspecific Geographic Variation.

With limited sampling, geographic variation within a single species can be difficult to distinguish from interspecific variation, confounding our ability to draw accurate species boundaries. We argue that thorough sampling and analysis of contact zones between putative taxa can determine if assortative mating or selection against hybrids exists (supporting the presence of two distinct species), or alternatively if mating is random among genotypes and admixture among adjacent populations is gradual and continuous (supporting geographic variation within a single species). Here, we test two alternative hypotheses for two pairs of named taxa at contact zones within the American milksnake (Lampropeltis triangulum) complex. A prior morphological analysis found areas of gradual intergradation among named taxa, and concluded that the taxa represented geographical races of a single polytypic species. In contrast, a subsequent analysis of gene sequence data, but with limited sampling near the contact zones, hypothesized distinct boundaries between species at the contact zones. At the contact zone between proposed species L. triangulum and L. gentilis, we examined a ∼700 km-wide transect across the states of Kansas and Missouri, with thorough sampling and reduced-representation genomic-level sequencing, to test the two opposing taxonomic hypotheses. Our transect analyses included examinations of population structure, fixed differences, cline-fitting, and an admixture index analysis. These analyses all supported a gradual and continuous geographic cline across a broad intergrade zone between two geographic forms of L. triangulum, thus providing strong support for a single species in this region (and no support for the recognition of L. gentilis as a distinct species). At a second contact zone between proposed species L. triangulum and L. elapsoides (but variously treated as species or subspecies by different researchers) in Kentucky and Tennessee, we re-evaluated morphological data. In this case, the contact zone analysis indicated sympatry and reproductive isolation of the two taxa, and thus strongly supported L. triangulum and L. elapsoides as distinct species. We conclude that detailed studies of contact zones, based on either genetic or morphological data, are essential for distinguishing intraspecific from interspecific variation in the case of widely and continuously distributed taxa.
Transfer learning enables prediction of myocardial injury from continuous single-lead electrocardiography

OBJECTIVE Chest pain is common, and current risk-stratification methods, requiring 12-lead electrocardiograms (ECGs) and serial biomarker assays, are static and restricted to highly resourced settings. Our objective was to predict myocardial injury using continuous single-lead ECG waveforms similar to those obtained from wearable devices and to evaluate the potential of transfer learning from labeled 12-lead ECGs to improve these predictions. METHODS We studied 10 874 Emergency Department (ED) patients who received continuous ECG monitoring and troponin testing from 2020 to 2021. We defined myocardial injury as newly elevated troponin in patients with chest pain or shortness of breath. We developed deep learning models of myocardial injury using continuous lead II ECG from bedside monitors as well as conventional 12-lead ECGs from triage. We pretrained single-lead models on a pre-existing corpus of labeled 12-lead ECGs. We compared model predictions to those of ED physicians. RESULTS A transfer learning strategy, whereby models for continuous single-lead ECGs were first pretrained on 12-lead ECGs from a separate cohort, predicted myocardial injury as accurately as models using patients' own 12-lead ECGs: area under the receiver operating characteristic curve 0.760 (95% confidence interval [CI], 0.721-0.799) and area under the precision-recall curve 0.321 (95% CI, 0.251-0.397). Models demonstrated a high negative predictive value for myocardial injury among patients with chest pain or shortness of breath, exceeding the predictive performance of ED physicians, while attending to known stigmata of myocardial injury. CONCLUSIONS Deep learning models pretrained on labeled 12-lead ECGs can predict myocardial injury from noisy, continuous monitor data early in a patient's presentation. The utility of continuous single-lead ECG in the risk stratification of chest pain has implications for wearable devices and preclinical settings, where external validation of the approach is needed.
Effects of aerobic and strength training on depression, anxiety, and health self-perception levels during the COVID-19 pandemic.

OBJECTIVE This study aimed at comparing the depression and anxiety levels, and health self-perception during the coronavirus disease 2019 pandemic among subjects who practice aerobic, strength, and mixed (aerobic and strength) exercises and nonsports participants. MATERIALS AND METHODS We included 304 Brazilians of both sexes in this cross-sectional study. All participants were recruited through online advertisement and completed a self-administered questionnaire regarding the personal information, level of restriction adopted, physical activity, and mood state screening (Patient Health Questionnaire-9 and General Anxiety Disorder-7). We divided the participants into four groups: strength sports group (CrossFit or strength training), aerobic/endurance sports groups (running, cycling, triathlon, or swimming), mixed sports groups (individuals who practice endurance and strength sports), and nonsports group. RESULTS The Kruskal-Wallis test showed a significant effect of the group on the depression and anxiety levels. Meanwhile, the post-hoc comparisons showed a significantly lower depression level in the mixed and aerobic sports groups than in the strength sports and nonsports groups, and a significantly lower anxiety level in the mixed and aerobic sports groups than in the nonsports group. Furthermore, participants in the mixed, strength, and aerobic sports groups presented a better level of health self-assessment than the nonsports group, and those in the mixed sports group had a better level of health self-assessment than the strength or aerobic sports groups. CONCLUSIONS Individuals practicing aerobic exercises present lower depression and anxiety levels than those practicing strength training and are inactive. However, individuals who practice strength exercises and aerobics have the best levels of health perception.
RAB21 controls autophagy and cellular energy homeostasis by regulating retromer-mediated recycling of SLC2A1/GLUT1

ABSTRACT The endosomal system maintains cellular homeostasis by coordinating multiple vesicular trafficking events, and the retromer complex plays a critical role in endosomal cargo recognition and sorting. Here, we demonstrate an essential role for the small GTPase RAB21 in regulating retromer-mediated recycling of the glucose transporter SLC2A1/GLUT1 and macroautophagy/autophagy. RAB21 depletion mis-sorts SLC2A1 to lysosomes and affects glucose uptake, thereby activating the AMPK-ULK1 pathway to increase autophagic flux. RAB21 depletion also increases lysosome function. Notably, RAB21 depletion does not overtly affect retrograde transport of IGF2R/CI-M6PR or WLS from endosomes to the trans-Golgi network. We speculate that RAB21 regulates fission of retromer-decorated endosomal tubules, as RAB21 depletion causes accumulation of the SNX27-containing retromer complex on enlarged endosomes at the perinuclear region. Functionally, RAB21 depletion sensitizes cancer cells to energy stress and inhibits tumor growth in vivo, suggesting an oncogenic role for RAB21. Overall, our study illuminates the role of RAB21 in regulating endosomal dynamics and maintaining cellular energy homeostasis and suggests RAB21 as a potential metabolic target for cancer therapy.
LBM–DEM modeling of fluid–solid interaction in porous media

Three porous media flow problems, in which the fluid mechanical interactions are critical, are studied in a mesoscopic–microscopic coupling system. In this system, fluid flow in the pore space is explicitly modeled at mesoscopic level by the lattice Boltzmann method, the geometrical representation and the mechanical behavior of the solid skeleton are modeled at microscopic level by the particulate distinct element method (DEM), and the interfacial interaction between the fluid and the solids is resolved by an immersed boundary scheme. In the first benchmark problem, the well‐known and frequently utilized Ergun equation is validated in periodic particle and periodic pore models. In the second problem, the upward seepage problem is simulated over three stages: The settlement of the column of sphere under gravity loading is measured to illustrate the accuracy of the DEM scheme; the system is solved to hydrostatic state with pore space filled with fluid, showing that the buoyancy effect is captured correctly in the mesoscopic–microscopic coupling system; then, the flow with constant rate is supplied at the bottom of the column; the swelling of the ground surface and pore pressure development from the numerical simulation are compared with the predictions of the macroscopic consolidation theory. In the third problem, the fluid‐flow‐induced collapse of a sand arch inside a perforation cavity is tested to illustrate a more practical application of the developed system. Through comparing simulation results with analytical solutions, empirical law and physical laboratory observations, it is demonstrated that the developed lattice Boltzmann–distinct element coupling system is a powerful fundamental research tool for investigating hydromechanical physics in porous media flow. Copyright © 2012 John Wiley & Sons, Ltd.
Patent landscape of inhibitors and PROTACs of the anti-apoptotic BCL-2 family proteins

ABSTRACT Introduction The anti-apoptotic BCL-2 family proteins, such as BCL-2, BCL-XL, and MCL-1, are excellent cancer therapeutic targets. The FDA approval of BCL-2 selective inhibitor venetoclax in 2016 validated the strategy of targeting these proteins with BH3 mimetic small molecule inhibitors. Areas covered This review provides an overview of the patent literature between 2016 and 2021 covering inhibitors and PROTACs of the anti-apoptotic BCL-2 proteins. Expert opinion Since the FDA approval of venetoclax, tremendous efforts have been made to develop its analogues with improved drug properties. These activities will likely result in new drugs in coming years. Significant progress on MCL-1 inhibitors has also been made, with multiple compounds entering clinical trials. However, MCL-1 inhibition could cause on-target toxicity to normal tissues especially the heart. Similar issue exists with BCL-XL inhibitors, which cause on-target platelet toxicity. To overcome this issue, several strategies have been applied, including prodrug, dendrimer-based drug delivery, antibody-drug conjugate (ADC), and proteolysis targeting chimera (PROTAC); and amazingly, each of these approaches has resulted in a drug candidate entering clinical trials. We envision technologies like ADC and PROTAC could also be utilized to increase the therapeutic index of MCL-1 inhibitors.
Symptomatic dry eye disease and associated factors among postgraduate students in Ethiopia

Background Symptomatic dry eye disease is a growing public health challenge especially among those who are visual display unit (VDU) users and other long-time near activity workers. Globally, computer user adults experience a surge in the prevalence of dry eye. Data is insufficient on the prevalence of dry eye disease among postgraduate students in Ethiopia. Therefore, the present was aimed to assess the prevalence of dry eye and its associated factors among postgraduate students at the University of Gondar, Northwest Ethiopia. Methods A cross-sectional study was conducted on a total of 423 postgraduate students who were selected based on a simple random sampling technique. Data was collected through online symptom-based ocular surface disease index questionnaire. Binary logistic regression was used to test the association and p-value of <0.05 was considered to determine the significance of the association. Results From the total postgraduate students, 404 completed the study with a response rate of 95.5%. The prevalence of symptomatic dry eye disease was 50.5% (95% CI, 45.1%-54.9%). Average continuous visual display unit use for 2-4hours per day[AOR = 2.57 (95% CI, 1.27–5.21)] and for> 4hours per day[AOR = 3.77 (95% CI 1.87–7.59)], duration of visual display unit use for 3–5 years [AOR = 2.24 (95% CI, 1.17–4.31)], 6–8 years [AOR = 2.46 (95% CI,1.31–4.62)] and > 8 years [AOR = 3.25 (95% CI, 1.63–6.48)], average sleeping hour < 7 hours/day within last week [AOR = 2.17 (95% CI, 1.35–3.49)] and current known allergic conjunctivitis [AOR = 5.42 (95% CI, 2.43–12.10)] were significantly associated with symptomatic dry eye disease. Conclusion and recommendation In this study, about half of postgraduate students faced symptomatic dry eye disease. Significant association was observed between symptomatic dry eye disease and average continuous hours of visual display unit use, duration of visual display unit use in years, shortage of sleep and current known allergic conjunctivitis. It is advisable for postgraduate students to limit screen exposure hour and establish regular breaking time along their exposure. It is also advisable to have optimum sleep as possible. It is also important to explore dry eye disease on a large sample incorporating clinical tests.
The aftermarket performance of initial public offerings: New evidence from an emerging market

This paper presents new updated evidence on the initial public offering (IPO) aftermarket performance for 144 public listed firms on the Colombo Stock Exchange from 1991 to 2017. We found that average aftermarket returns are always lower than 1%. On average, buy and hold abnormal returns are negative in a short period, and abnormal returns gradually become positive over a longer period (12.46% in 3 years). Further, aftermarket returns are positively related to investor sentiment and the annual volume of listings while being negatively related to initial returns, which is consistent with the divergence of opinion hypothesis. We suggest that investors should hold their subscriptions of IPO shares for a prolonged time, usually exceeding two years, as the dynamic of shares rewards the investors with positive abnormal returns in the long run.
Detection of invasive Escherichia coli in dogs with granulomatous colitis using immunohistochemistry

Granulomatous colitis in dogs can be associated with infection of the colonic mucosa by invasive strains of Escherichia coli. To date, fluorescence in situ hybridization (FISH) is the gold-standard method to assess intramucosal and intracellular bacterial invasion. However, FISH requires expensive fluorescence microscopy equipment and is therefore not widely available. We investigated the use of immunohistochemistry (IHC) as an alternative method to detect invasive E. coli in dogs with granulomatous colitis. Archived paraffin-embedded blocks were selected from 26 dogs with colitis, in which FISH had been performed by an outside laboratory. Using a polyclonal antibody, IHC for E. coli was performed on sections cut from the same blocks, and the presence of invasive E. coli was recorded. All 11 specimens in which FISH had detected E. coli were also positive on IHC, with strong immunolabeling in the cytoplasm of macrophages and extracellularly in the lamina propria; all 15 specimens that were negative for invasive bacteria on FISH were also negative on IHC. We found that IHC is a sensitive technique for the detection of invasive E. coli in dogs with granulomatous colitis.
New International Guidelines and Consensus on the Use of Lung Ultrasound

Following the innovations and new discoveries of the last 10 years in the field of lung ultrasound (LUS), a multidisciplinary panel of international LUS experts from six countries and from different fields (clinical and technical) reviewed and updated the original international consensus for point‐of‐care LUS, dated 2012. As a result, a total of 20 statements have been produced. Each statement is complemented by guidelines and future developments proposals. The statements are furthermore classified based on their nature as technical (5), clinical (11), educational (3), and safety (1) statements.
MRI‐Based Artificial Intelligence in Rectal Cancer

Rectal cancer (RC) accounts for approximately one‐third of colorectal cancer (CRC), with death rates increasing in patients younger than 50 years old. Magnetic resonance imaging (MRI) is routinely performed for tumor evaluation. However, the semantic features from images alone remain insufficient to guide treatment decisions. Functional MRIs are useful for revealing microstructural and functional abnormalities and nevertheless have low or modest repeatability and reproducibility. Therefore, during the preoperative evaluation and follow‐up treatment of patients with RC, novel noninvasive imaging markers are needed to describe tumor characteristics to guide treatment strategies and achieve individualized diagnosis and treatment. In recent years, the development of artificial intelligence (AI) has created new tools for RC evaluation based on MRI. In this review, we summarize the research progress of AI in the evaluation of staging, prediction of high‐risk factors, genotyping, response to therapy, recurrence, metastasis, prognosis, and segmentation with RC. We further discuss the challenges of clinical application, including improvement in imaging, model performance, and the biological meaning of features, which may also be major development directions in the future.
Transforaminal Versus Interlaminar Endoscopic Lumbar Discectomy for Lumbar Disc Herniation: A Systematic Review and Meta-Analysis

Study Design Meta-analysis and systematic review. Objective This study aims to investigate and compare patient-reported outcomes, perioperative data, and complications between 2 common endoscopic approaches for lumbar disc herniation: transforaminal and interlaminar endoscopic lumbar discectomy, by published high-quality evidence. Methods Electronic databases were searched for reported outcomes following TELD and IELD. Oswestry Disability Index (ODI), visual analog scale of back (VASB) and leg pain (VASL), and MacNab criteria were evaluated. Operative time, hospital stays, blood loss, radiation exposure, and complications were investigated. Odds ratio (OR) and mean differences (MD) with 95% confidence intervals (CI) were calculated using random and fixed-effect models. Results Total of 1948 patients from 18 studies were included, consisting of 1006 patients (51.6%) in TELD group and 942 (48.4%) patients in IELD group. TELD had better improvement of postoperative ODI (MD = 1.26; 95% CI: .07-2.16; P = .04), postoperative VASB (MD = −.23; 95% CI: −.40 to −.05; P = .01) and last follow-up VASB (MD = −.25; 95% CI: −.41 to −.09; P = .002), but with longer operative time (MD = 10.1 min; 95% CI: 1.925-18.77; P < .00001) and more fluoroscopic time (SMD = 4.12; 95% CI: 3.22-5.03; P < .00001), especially in L5-S1 operation. Bed rest time was significantly longer following IELD, with no difference in VASL, hospital stays, or complication. Conclusion We found comparable clinical outcomes in terms of ODI, VAS, patient satisfaction, hospital stays, and complication between both techniques. TELD required more radiation exposure and longer operative time at L5-S1 level than IELD. Our study provided results to help consider appropriate approaches for selected patients and informed consent of benefits from each approach.