Miracle-dz/UniFAR-FTUs huggingface dataset:
Improved estimation in negative binomial regression

Negative binomial regression is commonly employed to analyze overdispersed count data. With small to moderate sample sizes, the maximum likelihood estimator of the dispersion parameter may be subject to a significant bias, that in turn affects inference on mean parameters. This article proposes inference for negative binomial regression based on adjustments of the score function aimed at mean or median bias reduction. The resulting estimating equations generalize those available for improved inference in generalized linear models and can be solved using a suitable extension of iterative weighted least squares. Simulation studies confirm the good properties of the new methods, which are also found to solve in many cases numerical problems of maximum likelihood estimation. The methods are illustrated and evaluated using two case studies: an Ames salmonella assay data set and data on epileptic seizures. Inference based on adjusted scores turns out to generally improve on maximum likelihood, and even on explicit bias correction, with median bias reduction being overall preferable.
Identification of gut microbiome and transcriptome changes in ulcerative colitis and pouchitis

Abstract Background Pouchitis is the common postoperative complication of ulcerative colitis (UC) and is also considered as inflammatory bowel disease. The aim was to investigate the microbiological and transcriptional differences between the two illnesses. Methods Eighty-five participants were enrolled (37 UC, 15 healthy UC pouches, 15 pouchitis and 18 healthy volunteers) and stool samples were collected. Microbial populations were analyzed by pyrosequencing of 16S ribosomal DNA. Furthermore, transcriptome data of 119 UC and 28 pouch patients were obtained from two data sets for bioinformatics analysis. Results The results of gut microbiota community analysis showed that with aggravation of UC, intestinal microorganisms were characterized by a gradual decreased in diversity and numbers of butyrate-producing bacteria and Bacteroides. Besides, in addition to the decrease of probiotics, the proliferation of Escherichia–Shigella and Ruminococcus gnavus was observed in pouchitis which is related to multiple infection pathways. The function enrichment of differential expression genes and hub genes, as well as the immunological condition was shown to be distinct using transcriptome bioinformatics analysis between UC and pouchitis. A stronger immune response occurs in UC and may be associated with high expression of tumor necrosis factor and interleukin, while multiple hub genes such as CDK1 in pouchitis are associated with cell cycle regulation. Conclusions The characteristics of gut microbiota disturbance and transcriptome alteration in UC and pouchitis are different. Our findings suggested that pouchitis may have a unique pathogenesis which was separated from UC.
Sorafenib-loaded nanostructured lipid carriers for topical ocular therapy of corneal neovascularization: development, in-vitro and in vivo study

Abstract Sorafenib (SRB), a multikinase inhibitor, is effective in reducing experimental corneal neovascularization (CNV) after oral administration; however, its therapeutic use in ocular surface disorders is restricted due to poor solubility and limited bioavailability. This study aimed to develop and optimize SRB-loaded nanostructured lipid carriers (SRB-NLCs) for topical ocular delivery by a central composite design response surface methodology (CCD-RSM). It was spherical and uniform in morphology with an average particle size of 111.87 ± 0.93 nm and a narrow size distribution. The in vitro drug release from the released SRB-NLC formulation was well fitted to Korsmeyer Peppas release kinetics. The cell counting kit-8 (CCK-8) cell viability assay demonstrated that SRB-NLC was not obviously cytotoxic to human corneal epithelial cells (HCECs). An in vivo ocular irritation test showed that SRB-NLC was well tolerated by rabbit eyes. Ocular pharmacokinetics revealed 6.79-fold and 1.24-fold increase in the area under concentration-time curves (AUC0-12h) over 12 h in rabbit cornea and conjunctiva, respectively, treated with one dose of SRB-NLC compared with those treated with SRB suspension. Moreover, SRB-NLC (0.05% SRB) and dexamethasone (0.025%) similarly suppressed corneal neovascularization in mice. In conclusion, the optimized SRB-NLC formulation demonstrated excellent physicochemical properties and good tolerance, sustained release, and enhanced ocular bioavailability. It is safe and potentially effective for the treatment of corneal neovascularization.
Invasion and diversity in Pseudomonas aeruginosa urinary tract infections

Introduction. P. aeruginosa is an opportunistic Gram-negative pathogen frequently isolated in urinary tract infections (UTI) affecting elderly and catheterized patients and associated with ineffective antibiotic treatment and poor clinical outcomes. Gap statement. Invasion has been shown to play an important role in UTI caused by E. coli but has only recently been studied with P. aeruginosa . The ability of P. aeruginosa to adapt and evolve in chronic lung infections is associated with resistance to antibiotics but has rarely been studied in P. aeruginosa UTI populations. Aim. We sought to determine whether phenotypic and genotypic heterogeneity exists in P. aeruginosa UTI isolates and whether, like urinary pathogenic Escherichia coli , these could invade human bladder epithelial cells – two factors that could complicate antibiotic treatment. Methodology. P. aeruginosa UTI samples were obtained from five elderly patients at the Royal Liverpool University Hospital as part of routine diagnostics. Fourty isolates from each patient sample were screened for a range of phenotypes. The most phenotypically diverse isolates were genome sequenced. Gentamicin protection assays and confocal microscopy were used to determine capacity to invade bladder epithelial cells. Results. Despite significant within-patient phenotypic differences, no UTI patient was colonized by distinct strains of P. aeruginosa . Limited genotypic differences were identified in the form of non-synonymous SNPs. Gentamicin protection assays and confocal microscopy provided evidence of P. aeruginosa ’s ability to invade bladder epithelial cells. Conclusions. Phenotypic variation and cell invasion could further complicate antibiotic treatment in some patients. More work is needed to better understand P. aeruginosa UTI pathogenesis and develop more effective treatment strategies.
Identification and analysis of offenders causing hit and run accidents using classification algorithms

Abstract Hit-and-run crashes are significant concern for many countries. Due to lack of information of offending vehicles it is difficult to understand dynamics of these crashes to have a prevention plan. The paper aims to identify the impacting vehicle in hit-and-run crashes. We studied fatal road crashes of New Delhi for eleven years (2006–2016) and found that approximately 40% fatal crashes are hit-and-run with unknown impacting vehicles. We proposed a framework using eleven different machine learning-based classification algorithms – Logistic-Regression, KNN, SVM-Linear and RBF-Kernel, Naïve-Bayes, Random-Forest, DecisionTree, AdaBoost, Multilayer-Perceptron, CART and Linear-Discriminant-Analysis. We found SVM-linear-kernel gave best results. Results reveal that cars, buses, and heavy vehicles are involved vehicles in hit-and-run crashes. Buses were primary cause leading to 39% of hit-and-run during 2006-2009 thereafter cars increased drastically. Our framework is robust and scalable to any city. The outcomes provide inputs to traffic engineers for better policy prescription and road user safety.
Lifestyle factors and hand eczema: A systematic review and meta‐analysis of observational studies

Evidence regarding the association between lifestyle factors and hand eczema is limited.To extensively investigate the association between lifestyle factors (smoking, alcohol consumption, stress, physical activity, body mass index, diet, and sleep) and the prevalence, incidence, subtype, severity, and prognosis of hand eczema, a systematic review and meta‐analysis were conducted in accordance with the Meta‐analysis Of Observational Studies in Epidemiology consensus statement. MEDLINE, Embase, and Web of Science were searched up to October 2021. The (modified) Newcastle‐Ottawa Scale was used to judge risk of bias. Quality of the evidence was rated using the Grades of Recommendation, Assessment, Development and Evaluation approach. Eligibility and quality were blindly assessed by two independent investigators; disagreements were resolved by a third investigator. Data were pooled using a random‐effects model, and when insufficient for a meta‐analysis, evidence was narratively summarized. Fifty‐five studies were included. The meta‐analysis (17 studies) found very low quality evidence that smoking is associated with a higher prevalence of hand eczema (odds ratio 1.18, 95% confidence interval 1.09‐1.26). No convincing evidence of associations for the other lifestyle factors with hand eczema were found, mostly due to heterogeneity, conflicting results, and/or the limited number of studies per outcome.
Turnbull‐Cutait pull‐through technique for delayed coloanal anastomosis after ultralow rectal resection: A step‐by‐step video vignette

R E FE R E N C E S 1. Strey CW, Wullstein C, Adamina M, Agha A, Aselmann H, Becker T, et al. Laparoscopic right hemicolectomy with CME: standardization using the ‘critical view’ concept. Surg Endosc. 2018;32(12):5021– 30. https://doi.org/10.1007/s0046 401862670 2. Le Voyer TE, Sigurdson ER, Hanlon AL, Mayer RJ, Macdonald JS, Catalano PJ, et al. Colon cancer survival is associated with increasing number of lymph nodes analyzed: a secondary survey of intergroup trial INT0089. J Clin Oncol. 2003;21(15):2912– 9. https:// doi.org/10.1200/JCO.2003. 05.062 3. Chang GJ, RodriguezBigas MA, Skibber JM, Moyer VA. Lymph node evaluation and survival after curative resection of colon cancer: systematic review. J Natl Cancer Inst. 2007;99(6):433– 41. https://doi.org/10.1093/jnci/djk092 4. Hashiguchi Y, Muro K, Saito Y, Ito Y, Ajioka Y, Hamaguchi T, et al. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2019 for the treatment of colorectal cancer. Int J Clin Oncol. 2020;25(1):1– 42. https://doi.org/10.1007/s1014 701901485 z 5. Cheong CK, Nistala KRY, Ng CH, Syn N, Chang HSY, Sundar R, et al. Neoadjuvant therapy in locally advanced colon cancer: a metaanalysis and systematic review. J Gastrointest Oncol. 2020;11(5):847– 57. https://doi.org/10.21037/ jgo20220 6. Arredondo J, Pastor E, Simó V, Beltrán M, Castañón C, Magdaleno MC, et al. Neoadjuvant chemotherapy in locally advanced colon cancer: a systematic review. Tech Coloproctol. 2020;24(10):1001– 15. https://doi.org/10.1007/s1015 102002289 4 7. Gosavi R, Chia C, Michael M, Heriot AG, Warrier SK, Kong JC. Neoadjuvant chemotherapy in locally advanced colon cancer: a systematic review and metaanalysis. Int J Colorectal Dis. 2021;36(10):2063– 70. https://doi.org/10.1007/s0038 402103945 3 8. Crafa F, Vanella S, Neola B, Miro A, Coppola BE. Hemicolectomy with complete mesocolic excision: description of an open and laparoscopic approach— A video vignette. Colorectal Dis. 2021;23(5):1280– 1. https://doi.org/10.1111/codi.15565 9. Takeda Y, Eto K, Neki K, Ohkuma M, Kosuge M, Ikegami T. Laparoscopic complete mesocolic excision and pelvic lymphadenectomy for locally advanced, T4b, rightsided colon cancer: a video vignette. Colorectal Dis. 2021;23(10):2777.
Method of Bus-load Forecasting Using BP Neural Network Optimized by PSO

Due to the big difference among different buses,the small base number of bus load and the weak stability,a bus load forecasting method based on particle swarm optimization optimized multi-layered forward feed neural network is proposed,and the particle swarm optimization(PSO) algorithm is used to optimize the weight and the threshold value of the back propagation(BP) network.The method combines characteristics of the overall random searching optimal solution and advantages of the gradient descent partial careful search superiority,that prevent from falling into local minimum,uses the initial value of the bus load as the value of particles,optimizes the BP neural network weights and threshold,enhances the bus-load forecast accuracy and improves the generalization.The proposed method is tested on the 110 kV and 220 kV bus load in Hunan area,and the results show validity and the superiority of the proposed method.
Risk factors associated with acute respiratory illnesses in athletes: a systematic review by a subgroup of the IOC consensus on ‘acute respiratory illness in the athlete’

Objective To review risk factors associated with acute respiratory illness (ARill) in athletes, including non-infectious ARill and suspected or confirmed acute respiratory infections (ARinf). Design Systematic review. Data sources Electronic databases: PubMed-Medline, EbscoHost and Web of Science. Eligibility criteria Original research articles published between January 1990 and July 2020 in English were searched for prospective and retrospective full text studies that reported quantitative data on risk factors associated with ARill/ARinf in athletes, at any level of performance (elite/non-elite), aged 15–65 years. Results 48 studies (n=19 390 athletes) were included in the study. Risk factors associated with ARill/ARinf were: increased training monotony, endurance training programmes, lack of tapering, training during winter or at altitude, international travel and vitamin D deficits. Low tear-(SIgA) and salivary-(IgA) were immune biomarkers associated with ARill/ARinf. Conclusions Modifiable training and environmental risk factors could be considered by sports coaches and athletes to reduce the risk of ARill/ARinf. Clinicians working with athletes can consider assessing and treating specific nutritional deficiencies such as vitamin D. More research regarding the role and clinical application of measuring immune biomarkers in athletes at high risk of ARill/ARinf is warranted. PROSPERO registration number CRD42020160928.
Stroke Among SARS-CoV-2 Vaccine Recipients in Mexico

Background and Objectives Information on stroke among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines remains scarce. We report stroke incidence as an adverse event following immunization (AEFI) among recipients of 79,399,446 doses of 6 different SARS-CoV-2 vaccines (BNT162b2, ChAdOx1 nCov-19, Gam-COVID-Vac, CoronaVac, Ad5-nCoV, and Ad26.COV2-S) between December 24, 2020, and August 31, 2021, in Mexico. Methods This retrospective descriptive study analyzed stroke incidence per million doses among hospitalized adult patients (≥18 years) during an 8-month interval. According to the World Health Organization, AEFIs were defined as clinical events occurring within 30 days after immunization and categorized as either nonserious or serious, depending on severity, treatment, and hospital admission requirements. Acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and cerebral venous thrombosis (CVT) cases were collected through a passive epidemiologic surveillance system in which local health providers report potential AEFI to the Mexican General Board of Epidemiology. Data were captured with standardized case report formats by an ad hoc committee appointed by the Mexican Ministry of Health to evaluate potential neurologic AEFI against SARS-COV-2. Results We included 56 patients (31 female patients [55.5%]) for an overall incidence of 0.71 cases per 1,000,000 administered doses (95% CI 0.54–0.92). Median age was 65 years (interquartile range [IQR] 55–76 years); median time from vaccination to stroke (of any subtype) was 2 days (IQR 1–5 days). In 27 (48.2%) patients, the event was diagnosed within the first 24 hours after immunization. The most frequent subtype was AIS in 43 patients (75%; 0.54 per 1,000,000 doses, 95% CI 0.40–0.73), followed by ICH in 9 (16.1%; 0.11 per 1,000,000 doses, 95% CI 0.06–0.22) and SAH and CVT, each with 2 cases (3.6%; 0.03 per 1,000,000 doses, 95% CI 0.01–0.09). Overall, the most common risk factors were hypertension in 33 (58.9%) patients and diabetes in 22 (39.3%). Median hospital length of stay was 6 days (IQR 4–13 days). At discharge, functional outcome was good (modified Rankin Scale score 0–2) in 41.1% of patients; in-hospital mortality rate was 21.4%. Discussion Stroke is an exceedingly rare AEFI against SARS-CoV-2. Preexisting stroke risk factors were identified in most patients. Further research is needed to evaluate causal associations between SARS-COV-2 vaccines and stroke.
Efficacy and safety of lurasidone in schizophrenia: pooled analysis of European results from double-blind, placebo-controlled 6-week studies

The objective of this study is to confirm the efficacy and safety of lurasidone in the acute treatment of schizophrenia in European patients. Data were pooled from three studies of patients randomized to 6 weeks of double-blind, placebo-controlled, fixed-dose (40/80 mg and 120/160 mg) lurasidone. The primary efficacy endpoint was a week 6 change in the Positive and Negative Syndrome Scale (PANSS) total score and secondary endpoints included the Clinical Global Impression, Severity scale (CGI-S). In total 328 safety patients were enrolled; 72.6% were completers. Endpoint change was significantly greater in patients treated with 40–80 mg/d and 120–160 mg/d compared to placebo on the PANSS total score (P < 0.001) and the CGI-Severity score (P < 0.001) for all comparisons. For PANSS total scores, endpoint effect sizes for lurasidone 40–80 mg/d and 120–160 mg/d were 0.68 to 0.77, respectively. Adverse events with a frequency ≥5% (and were greater than for combined lurasidone) were insomnia (11.7%), akathisia (11.3%), headache (7.4%), Parkinsonism (6.5%) and nausea (5.7%). Median changes (in mg/dL) at endpoint were minimal for total cholesterol (−8.0); triglycerides (−8.5) and glucose (−2.0) and in mean weight (−0.2 kg). In European patients with schizophrenia, short-term treatment with lurasidone in doses of 40–160 mg/d was generally safe, well-tolerated and effective with minimal effects on weight and metabolic parameters.
Threshold Equalizing Noise Test Reveals Suprathreshold Loss of Hearing Function, Even in the “Normal” Audiogram Range

Objectives: The threshold equalizing noise (TEN(HL)) is a clinically administered test to detect cochlear “dead regions” (i.e., regions of loss of inner hair cell [IHC] connectivity), using a “pass/fail” criterion based on the degree of elevation of a masked threshold in a tone-detection task. With sensorineural hearing loss, some elevation of the masked threshold is commonly observed but usually insufficient to create a “fail” diagnosis. The experiment reported here investigated whether the gray area between pass and fail contained information that correlated with factors such as age or cumulative high-level noise exposure (>100 dBA sound pressure levels), possibly indicative of damage to cochlear structures other than the more commonly implicated outer hair cells. Design: One hundred and twelve participants (71 female) who underwent audiometric screening for a sensorineural hearing loss, classified as either normal or mild, were recruited. Their age range was 32 to 74 years. They were administered the TEN test at four frequencies, 0.75, 1, 3, and 4 kHz, and at two sensation levels, 12 and 24 dB above their pure-tone absolute threshold at each frequency. The test frequencies were chosen to lie either distinctly away from, or within, the 2 to 6 kHz region where noise-induced hearing loss is first clinically observed as a notch in the audiogram. Cumulative noise exposure was assessed by the Noise Exposure Structured Interview (NESI). Elements of the NESI also permitted participant stratification by music experience. Results: Across all frequencies and testing levels, a strong positive correlation was observed between elevation of TEN threshold and absolute threshold. These correlations were little-changed even after noise exposure and music experience were factored out. The correlations were observed even within the range of “normal” hearing (absolute thresholds ≤15 dB HL). Conclusions: Using a clinical test, sensorineural hearing deficits were observable even within the range of clinically “normal” hearing. Results from the TEN test residing between “pass” and “fail” are dominated by processes not related to IHCs. The TEN test for IHC-related function should therefore only be considered for its originally designed function, to generate a binary decision, either pass or fail.
Facile Melting-Crystallization Synthesis of Cs2NaxAg1-xInCl6: Bi Double Perovskites for White Light-Emitting Diodes.

Lead-free double perovskites (DPs) have outstanding luminescent properties, which make them excellent candidates for wide use in optoelectronics. Herein, a solvent-free melting-crystallization technique, which can produce kilogram-scale DP microcrystals (DP-MCs) in one batch, is invented to synthesize the Cs2NaxAg1-xInCl6: Bi (x = 0, 0.2, 0.4, 0.6, 0.8, and 1) DP-MCs. The structure and composition analysis confirmed the products are pure Cs2NaxAg1-xInCl6 DP-MCs. Affected by Jahn-Teller distortion of AgCl6 octahedra, self-trapped excitons appear in the excited state, resulting in the broadband emission (400-850 nm) of Cs2Ag1-xNaxInCl6: Bi DP-MCs. The enhancement of the photoluminescence quantum yield can be realized by introducing Na+ to break the parity-forbidden transition in the Cs2AgInCl6 DP. Optimized Cs2Na0.4Ag0.6InCl6: Bi DP-MC phosphors combined with commercial blue and green phosphors were coated on ultraviolet chips (365 nm) to fabricate white light-emitting diodes (WLEDs) from warm white (2930 K) to cold white (6957 K). An ultrahigh color rendering index of 97.1 and a CCT of 5548 K as well as Commission Internationale de l'Eclairage color coordinates of (0.331, 0.339) have been demonstrated. This kilogram-scale synthesis technique could stimulate the industrial development of WLEDs for general lighting based on DP-MC phosphors.
Multi-Well Array Culture of Primary Human Hepatocyte Spheroids for Clearance Extrapolation of Slowly Metabolized Compounds

Accurate prediction of human pharmacokinetics using in vitro tools is an important task during drug development. Albeit, currently used in vitro systems for clearance extrapolation such as microsomes and primary human hepatocytes in suspension culture show reproducible turnover, the utility of these systems is limited by a rapid decline of activity of drug metabolizing enzymes. In this study, a multi-well array culture of primary human hepatocyte spheroids was compared to suspension and single spheroid cultures from the same donor. Multi-well spheroids remained viable and functional over the incubation time of 3 days, showing physiological excretion of albumin and α-AGP. Their metabolic activity was similar compared to suspension and single spheroid cultures. This physiological activity, the high cell concentration, and the prolonged incubation time resulted in significant turnover of all tested low clearance compounds (n = 8). In stark contrast, only one or none of the compounds showed significant turnover when single spheroid or suspension cultures were used. Using multi-well spheroids and a regression offset approach (log(CLint) = 1.1 × + 0.85), clearance was predicted within 3-fold for 93% (13/14) of the tested compounds. Thus, multi-well spheroids represent a novel and valuable addition to the ADME in vitro tool kit for the determination of low clearance and overall clearance prediction. Graphical Abstract Graphical Abstract