Miracle-dz/UniFAR-FTUs huggingface dataset:
Digit Ratio (2D∶4D) Differences between 20 Strains of Inbred Mice

The second to fourth digit ratio (2D∶4D) is sexually differentiated in a variety of species, including humans, rats, birds, and lizards. In humans, this ratio tends to be lower in males than in females. Lower digit ratios are believed to indicate increased prenatal testosterone exposure, and are associated with more masculinized behavior across a range of traits. The story seems more complicated in laboratory mice. We have previously shown that there is no sex difference in the digit ratios of inbred mice, but found behavioral evidence to suggest that higher 2D∶4D is associated with more masculinized behaviors. Work examining intrauterine position effects show that neighbouring males raise pup digit ratio, suggesting again that higher digit ratios are associated with increased developmental androgens. Other work has suggested that masculinization is associated with lower digit ratios in lab mice. Here, we examine the fore- and hindlimb digit ratios of 20 inbred mouse strains. We find large inter-strain differences, but no sexual dimorphism. Digit ratios also did not correlate with mice behavioral traits. This result calls into question the use of this trait as a broadly applicable indicator for prenatal androgen exposure. We suggest that the inbred mice model presents an opportunity for researchers to investigate the genetic, and gene-environmental influence on the development of digit ratios.
Discrete-Time Adaptive Controller for Unfixed and Unknown Control Direction

An adaptive controller is proposed for unknown nonlinear discrete-time systems when the control direction is unknown and unfixed. Two fuzzy rules emulated networks are utilized to establish a system dynamic model which provides the control-gain and the control direction. The control law is developed according to the control direction including the following advantages: first, the relation between input and output of controlled plant cannot be generally Lipschitz with the zero-change of control effort; and second, the control direction is unfixed for both positive and negative values. Theoretical expressions are manifested to guarantee the convergence of model and tracking performance. The practical-validation is conducted by two experimental systems: first, dc motor current control for the case of fixed control direction and Lipschitz condition, and second, robotic system with opened architecture for the case of unfixed control direction and non-Lipschitz condition at constant input.
A preliminary investigation of the effect of relaxin on bone remodelling in suture expansion

Background and objectives Relaxin (RLN) is an insulin-like hormone associated with extracellular matrix degradation, osteoclastogenesis, and osteoblast differentiation. This study aimed to assess the effect of RLN during and after lateral expansion of murine calvarial sagittal sutures. Materials and methods RLN was injected topically using a nano-sized liposome carrier into the sagittal sutures of 8- to 10-week-old wild type mice just before lateral expansion. Suture morphology, bone mineral density (BMD), and bone volume were analysed by micro-computed tomography. Collagen deposition and osteoclast differentiation were observed by Verhoeff-Van Gieson (VVG) and tartrate-resistant acid phosphatase (TRAP) staining, respectively. Results Less collagen staining and higher tissue-specific relaxin/insulin-like family peptide receptor (Rxfp)-1 and -2 expression were observed in the RLN-treated samples after 48 hours. Increased BMD and volume, and thick well-organised osteoid tissue, with multinucleated TRAP-positive cells, were observed in RLN-treated samples after 1 week. Increased Rxfp-1 expression was observed in the sagittal sutures in the mid-suture fibrous tissue following RLN treatment. Rxfp-2 was only expressed in the calvarial bone under tensile stimulation and RLN treatment further increased its expression. Limitations RLN-liposomes were not detected at any instance under the current experimental conditions. This is a preliminary study and the sample number limits the power of its results. VVG staining cannot quantify collagen contents but can provide preliminary information on the presence of collagen fibres. Conclusions RLN treatment may modify bone remodelling and collagen metabolism during and after suture expansion.
Circulating microRNAs as novel biomarkers of ALK-positive non-small cell lung cancer and predictors of response to crizotinib therapy

Circulating microRNAs are potential diagnostic and predictive biomarkers, but have not been investigated for patients with anaplastic lymphoma kinase (ALK)-positive lung cancer. In this exploratory study, we sought to identify potential plasma biomarkers for ALK-positive non-small cell lung cancer (NSCLC). A microRNA microarray was used to select ALK-related microRNAs in ALK-positive NSCLC (n = 3), ALK-negative NSCLC (n = 3), and healthy subjects (n = 3). Plasma levels of 21 microRNAs were differentially expressed for ALK-positive and ALK-negative NSCLC, including 14 down-regulated and 7 up-regulated microRNAs. We also identified 5s rRNA as the most stable endogenous control gene using geNorm and NormFinder algorithms. Candidate microRNAs in plasma from ALK-positive (n = 41) and ALK-negative NSCLC patients (n = 32) were quantified using real-time reverse transcriptase quantitative polymerase chain reaction. The expression levels of miR-28-5p, miR-362-5p, and miR-660-5p were all down-regulated in ALK-positive NSCLC, compared with ALK-negative NSCLC. The areas under the receiver operating characteristic curves of miR-28-5p, miR-362-5p, miR-660-5p, and 3-microRNAs panel were 0.873, 0.673, 0.760, and 0.876, respectively. The positive predictive values of miR-28-5p, miR-362-5p, and miR-660-5p were 96.43%, 80.77%, and 83.87%, respectively. Increased plasma levels of miR-660-5p after crizotinib treatment predicted good tumor response (p = 0.012). The pre-crizotinib levels of miR-362-5p were significantly associated with progression-free survival (p = 0.015). Thus, in this preliminary investigation, we identified a potential panel of 3 microRNAs for distinguishing between patients with ALK-positive and ALK-negative NSCLC. We also identified miR-660-5p and miR-362-5p as potential predictors for response to crizotinib treatment.
Management of Ocular Cicatricial Pemphigoid with Intravenous Immunoglobulin Monotherapy

ABSTRACT Purpose: To assess the long-term efficacy and safety of IVIg monotherapy in patients with recalcitrant ocular cicatricial pemphigoid (OCP). Methods: A chart review of all OCP patients seen at the Massachusetts Eye Research and Surgery Institution (MERSI) between 2005 and 2015 was completed. Stage was graded by using the Foster grading system. IVIg infusion was 2g/kg/cycle administered in 3 consecutive days monthly. Results: Of 512 OCP patients, 17 patients (34 eyes) treated with IVIg monotherapy were identified. Seven were female and ten were male. The average age at diagnosis was 60.7-year-old. The follow up time ranged from 12 to 140 months. Twenty-six eyes (76.5%) achieved remission. Nine remission eyes received cataract surgeries, and 2 of them had relapse (22.2%). The other 17 eyes did not undergo ocular surgery and remained in remission. IVIg monotherapy showed high efficacy in stage 1 OCP (7/7, 100%). Ocular surgery can be associated with OCP relapse (Table 2). Conclusions: IVIg monotherapy is an effective and safe therapy in patients with recalcitrant OCP. Ocular surgery can be associated with OCP relapse.
Business-Related Determinants of Offshoring Intensity

Some researchers view information systems IS offshoring as extension of onshore IS outsourcing. However, others have the opinion that IS offshoring has its unique characteristics because of which, we cannot extend research made in onshore IS outsourcing without testing its applicability to the offshore context. This tension motivates our research to examine whether determinants of IS offshoring are indeed the same as determinants of onshore IS outsourcing? We examine the role of some firm level determinants of offshoring intensity. The four business related determinants that we analyze in this study are: business size, business cost, business financial leverage, and business performance. Results indicate a significant relationship between business size and offshoring intensity, and also between business financial leverage and offshoring intensity. Based on the results, we analyze similarities and differences between traditional onshore IS outsourcing and IS offshoring. Implications and contributions arising out of this study are also discussed.
Pattern Based Comprehensive Urdu Stemmer and Short Text Classification

Urdu language is used by approximately 200 million people for spoken and written communications. The bulk of unstructured Urdu textual data is available in the world. We can employ data mining techniques to extract useful information from such a large, potentially informative base data. There are many text processing systems available to process unstructured textual data. However, these systems are mostly language specific with the large proportion of systems applicable to English text. This is primarily due to language-dependent preprocessing systems, mainly the stemming requirement. Stemming is a vital preprocessing step in the text mining process and its primary aim is to reduce grammatical words form, e.g., parts of speech, gender, tense, and so on, to their root form. In the proposed work, we have developed a rule-based comprehensive stemming method for Urdu text. This proposed Urdu stemmer has the ability to generate the stem of Urdu words as well as loan words that belong to borrowed languages, such as Arabic, Persian, and Turkish, by removing prefix, infix, and suffix from the words. In the proposed stemming technique, we introduced six novel Urdu infix words classes and a minimum word length rule to generate the stem of Urdu text. In order to cope with the challenge of Urdu infix stemming, we have developed infix stripping rules for introduced infix words classes and generic stemming rules for prefix and suffix stemming. We also present a probabilistic classification approach to classify Urdu short text. Different experiments are performed to demonstrate the effectiveness and efficacy of the proposed approach. Comparison with existing state-of-the art approaches is also made. Stemming accuracy results demonstrate the adoptability of the proposed stemming approach for a variety text processing applications.
The cooling compound icilin attenuates autoimmune neuroinflammation through modulation of the T‐cell response

The synthetic supercooling drug, icilin, and its primary receptor target, the cation channel transient receptor potential (TRP) melastatin‐8 (TRPM8), have been described as potent negative regulators of inflammation in the colon. The aim of this study was to determine whether the anti‐inflammatory action of icilin could potentially be used to treat autoimmune neuroinflammatory disorders, such as multiple sclerosis (MS). During experimental autoimmune encephalomyelitis (EAE)—a CD4+ T cell‐driven murine model of MS—we found that both wild‐type (WT) and TRPM8‐deficient EAE mice were protected from disease progression during icilin treatment, as evidenced by delays in clinical onset and reductions in neuroinflammation. In vitro, icilin potently inhibited the proliferation of murine and human CD4+ T cells, with the peripheral expansion of autoantigen‐restricted T cells similarly diminished by the administration of icilin in mice. Attenuation of both TRPM8–/– and TRP ankyrin‐1–/– T‐cell proliferation by icilin was consistent with the WT phenotype, which suggests a mechanism that is independent of these channels. In addition, icilin treatment altered the expressional profile of activated CD4+ T cells to one that was indicative of restricted effector function and limited neuroinflammatory potential. These findings identify a potent antiinflammatory role for icilin in lymphocyte‐mediated neuroinflammation and highlight clear pleiotropic effects of the compound beyond classic TRP channel activation. —Ewanchuk, B. W. , Allan, E. R. O. , Warren, A. L. , Ramachandran, R. , Yates, R. M. The cooling compound icilin attenuates autoimmune neuroinflammation through modulation of the T‐cell response. FASEB J. 32,1236‐1249 (2018). www.fasebj. org
[Factors associated with length of stay and the risk of readmission in an acute psychiatric inpatient facility: A retrospective study].

OBJECTIVE to investigate factors in? uencing length of stay and predictors for the risk of readmission at an acute psychiatric inpatient unit. METHOD retrospective cross-sectional clinical fle audit ranging four years back, a random selection of 378 patients was reviewed, including 178 cases and 200 controls. A case control study was employed in the study of length of stay, and for predictors of risk of readmission a retrospective cohort study was used. RESULTS the 7 variables that were associated with length of stay were: 1- instruction level, 2- place of origin, 3- use of restraints, 4- gender, 5- marital status, 6- drug class, and 7- number of visits. The 9 variables associated with risk of readmission were: 1- history of previous admission, 2- cognitive status, 3- use of seclusion, 4- diagnostic category (personality cluster, bipolar disorder, substance use disorder, adaptive disorder, situational crisis, acute alcoholic intoxication), 5- risk to others at the time of index admission, 6- instruction level, 7- age at frst admission. Proactive and assertive treatment after discharge decreased the risk of readmission. CONCLUSIONS Length of stay has predictable multifactorial determinants which are diffcult to modify clinically, as inpatient quality of care was not associated with it. Good community network assisting practices appeared to be more likely to reduce risk of readmission.
Pixel or Paper? Validation of a Mobile Technology for Collecting Patient-Reported Outcomes in Rheumatoid Arthritis

Background In the management of chronic disease, new models for telemonitoring of patients combined with the choice of electronic patient-reported outcomes (ePRO) are being encouraged, with a clear improvement of both patients’ and parents’ quality of life. An Italian study demonstrated that ePRO were welcome in patients with rheumatoid arthritis (RA), with excellent matching data. Objective The aim of this study is to evaluate the level of agreement between electronic and paper-and-pencil questionnaire responses. Methods This is an observational prospective study. Patients were randomly assigned to first complete the questionnaire by paper and pencil and then by tablet or in the opposite order. The questionnaire consisted of 3 independent self-assessment visual rating scales (Visual Analog Scale, Global Health score, Patient Global Assessment of Disease Activity) commonly used in different adult patients, including those with rheumatic diseases. Results A total of 185 consecutive RA patients were admitted to hospital and were enrolled and completed the questionnaire both on paper and on electronic versions. For all the evaluated items, the intrarater degree of agreement between 2 approaches was found to be excellent (intraclass correlation coefficient>0.75, P<.001). Conclusions An electronic questionnaire is uploaded in a dedicated Web-based tool that could implement a telemonitoring system aimed at improving the follow-up of RA patients. High intrarater reliability between paper and electronic methods of data collection encourage the use of a new digital app with consequent benefit for the overall health care system.
The risk of nephrolithiasis is causally related to inactive matrix Gla protein, a marker of vitamin K status: a Mendelian randomization study in a Flemish population

Background Vitamin K (VK)-dependent γ-glutamate carboxylation and serine phosphorylation activate matrix Gla protein (MGP) to a potent locally acting inhibitor of calcification. Nephrolithiasis represents a process of unwanted calcification associated with substantial mortality and high recurrence rates. We hypothesized that the risk of nephrolithiasis increases with VK shortage, as exemplified by higher plasma levels of desphospho-uncarboxylated MGP (dp-ucMGP). Methods In 1748 randomly recruited Flemish individuals (51.1% women; mean age 46.8 years), we determined dp-ucMGP and the prevalence of nephrolithiasis at baseline (April 1996-February 2015) and its incidence during follow-up until March 2016. We estimated the multivariable-adjusted relative risk associated with the doubling of dp-ucMGP, using logistic or Cox regression. We did a Mendelian randomization analysis using four MGP genotypes as instrumental variables. Results With adjustments applied for sex, age and 24-h urinary volume and calcium excretion, the odds of having prevalent nephrolithiasis [n = 144 (8.2%)] associated with dp-ucMGP was 1.31 [95% confidence interval (CI) 1.04-1.64; P = 0.022]. dp-ucMGP levels were associated (P ≤ 0.001) with MGP variants rs2098435, rs4236 and rs2430692. In the Mendelian analysis, the causal odds ratio was 3.82 (95% CI 1.15-12.7; P = 0.029). The incidence of nephrolithiasis over 12.0 years (median) was 37 cases (0.2%). With similar adjustments as before, the hazard ratio in relation to dp-ucMGP was 2.48 (95% CI 1.71-3.61; P < 0.001). Additional adjustment for a nephrolithiasis propensity score produced consistent results. Conclusion Higher levels of inactive dp-ucMGP may be causally associated with the risk of nephrolithiasis. Whether or not VK deficiency plays a role in these observations remains to be firmly established.
Synthesis and Evaluation of the Antioxidant Activity of Lipophilic Phenethyl Trifluoroacetate Esters by In Vitro ABTS, DPPH and in Cell-Culture DCF Assays

Polyphenols are natural compounds showing a variety of health-promoting effects. Unfortunately, due to low lipid solubility, their applications in the pharmaceutical, food, and cosmetic industries are limited. With the aim of obtaining novel lipophilic derivatives, the present study reports the synthesis of a series of phenethyl trifluoroacetate esters containing up to two hydroxyl groups in the aromatic ring. Experimental logP values confirmed a greater lipophilicity of the novel compounds compared to the parent compounds. The radical scavenging capacity of all phenethyl trifluoroacetate esters was evaluated by in vitro assays (ABTS, DPPH) and in cultured cells (L6 myoblasts and THP-1 leukemic monocytes) using 2′,7′-dichlorodihydrofluorescein diacetate. These data revealed that the esters showed a good antioxidant effect that was strictly dependent on the grade of hydroxylation of the phenyl ring. The lack of toxicity, evaluated by the MTT assay and proliferation curves, makes these trifluoroacetates attractive derivatives for pharmaceutical, food, and cosmetic applications.
RON kinase inhibition reduces renal endothelial injury in sickle cell disease mice

Sickle cell disease patients are at increased risk of developing a chronic kidney disease. Endothelial dysfunction and inflammation associated with hemolysis lead to vasculopathy and contribute to the development of renal disease. Here we used a Townes sickle cell disease mouse model to examine renal endothelial injury. Renal disease in Townes mice was associated with glomerular hypertrophy, capillary dilation and congestion, and significant endothelial injury. We also detected substantial renal macrophage infiltration, and accumulation of macrophage stimulating protein 1 in glomerular capillary. Treatment of human cultured macrophages with hemin or red blood cell lysates significantly increased expression of macrophage membrane-associated protease that might cleave and activate circulating macrophage stimulating protein 1 precursor. Macrophage stimulating protein 1 binds to and activates RON kinase, a cell surface receptor tyrosine kinase. In cultured human renal glomerular endothelial cells, macrophage stimulating protein 1 induced RON downstream signaling, resulting in increased phosphorylation of ERK and AKT kinases, expression of Von Willebrand factor, increased cell motility, and re-organization of F-actin. Specificity of macrophage stimulating protein 1 function was confirmed by treatment with RON kinase inhibitor BMS-777607 that significantly reduced downstream signaling. Moreover, treatment of sickle cell mice with BMS-777607 significantly reduced glomerular hypertrophy, capillary dilation and congestion, and endothelial injury. Taken together, our findings demonstrated that RON kinase is involved in the induction of renal endothelial injury in sickle cell mice. Inhibition of RON kinase activation may provide a novel approach for prevention of the development of renal disease in sickle cell disease.
Distance to health services modifies the effect of an 11-valent pneumococcal vaccine on pneumonia risk among children less than 2 years of age in Bohol, Philippines.

Background Both vaccine trials and surveillance studies typically use passive surveillance systems to monitor study outcomes, which may lead to under-reporting of study outcomes in areas with poor access to care. This detection bias can have an adverse effect on conventional estimates of pneumonia risk derived from vaccine trials. Methods We conducted a secondary analysis of a randomized, placebo-controlled, double-blind vaccine trial that examined the efficacy of an 11-valent pneumococcal vaccine (PCV) among children less than 2 years of age in Bohol, Philippines. Trial data were linked to the residential location of each participant using a geographical information system. The study was conducted using 11 729 children who received three doses of any study vaccine (PCV11) or placebo. Multivariate Cox proportional hazards models were used to examine major risk factors for pneumonia diagnosis and the relationship between distance to Bohol Regional Hospital (BRH) and vaccination with PCV with risk for pneumonia diagnosis. Results There was a significant interaction effect between distance from BRH and vaccination with PCV11 on pneumonia risk. Among children living 12 km from BRH, vaccination with PCV11 was associated with a decreased hazard ratio for radiographic pneumonia, compared with vaccination with the study placebo [0.57, 95% confidence interval (CI) 0.37-0.86). However, for children living 1 km from BRH, there was little difference in risk of radiographic pneumonia diagnosis between children vaccinated with PCV11 and those given the study placebo. Conclusion Children living close to BRH had no documented reduction in the primary study outcome from PCV11, whereas those at greater distance experienced a substantial reduction. Because of detection bias caused by distance to BRH, in spatial analysis of vaccine trial results it may be necessary to adjust estimates of pneumonia risk and vaccine efficacy. Failure to consider the geographical dimension of trials may lead to underestimates of efficacy which might influence public health planning efforts.