Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical and in vivo confocal microscopic features of neuropathic corneal pain

Aims To describe clinical and in vivo confocal microscopy (IVCM) features of neuropathic corneal pain (NCP) without clinically visible signs. Methods Prospective, observational study of 27 eyes of 14 patients who had continuous severe ocular pain for one or more years, with minimal or no ocular surface signs and were non-responsive to topical lubricants, steroids and/or ciclosporin. All patients were evaluated using Ocular Surface Disease Index, Oxford grading scale, Schirmer test 1, Cochet Bonnet esthesiometry and response to topical anaesthesia. Central and paracentral regions of the cornea of patients and seven healthy controls were studied by IVCM. Corneal epithelial thickness and sub-basal nerve density were measured in patients and controls. Results Four patients responded to topical anaesthesia (responsive group (RG)), indicating peripheral NCP while 10 patients did not show any improvement (non-responsive group (NRG)), indicating central NCP. Schirmer-1 test was within normal limits in the RG but significantly greater in the NRG (p<0.001). None of the other clinical parameters nor corneal epithelial thickness were statistically significantly different. The sub-basal nerve density was significantly reduced (p<0.008) in patients compared with controls. Stroma of all patients demonstrated activated keratocytes and spindle, lateral and stump microneuromas. There was a statistically significant greater number of microneuromas (p<0.0001) and activated keratocytes in RG compared with NRG. Conclusion NCP without visible clinical signs does not represent typical dry eye disease. Distinct signs demonstrated on IVCM suggest that peripheral NCP, which responds to topical anaesthesia, and central NCP, which does not, are separate entities.
Dietary intake of fish and n-3 polyunsaturated fatty acids and risk of postpartum depression: a nationwide longitudinal study – the Japan Environment and Children's Study (JECS)

Abstract Background Pregnant women require increased levels of n-3 polyunsaturated fatty acids (PUFAs) due to the demands of the growing fetus. Although some evidence indicates that maternal intake of fish and n-3 PUFAs is associated with reduced risk of postpartum depression, the results are inconsistent. Methods We investigated whether dietary consumption of fish and/or n-3 PUFAs during pregnancy is associated with a reduced risk of maternal postpartum depression at 6 months after delivery and of serious mental illness at 1 year in a Japanese population. After exclusion and multiple imputation from a dataset comprising 103 062 pregnancies obtained in the Japan Environment and Children's Study, we evaluated 84 181 and 81 924 women at 6 months and 1 year after delivery, respectively. Results Multivariable logistic regression showed a reduced risk of postpartum depression at 6 months in the second to fifth quintiles v. the lowest quintile for fish and n-3 PUFA intake, with trend tests also revealing a significant linear association. At 1 year after delivery, fish intake was associated with a reduced risk of serious mental illness in the second to fifth quintiles v. the lowest quintile for fish and in the third to fifth quintiles v. the lowest quintile for n-3 PUFA intake, with trend tests also revealing a significant linear association. Conclusions Women with higher fish and/or n-3 PUFA intake showed reduced risk of postpartum depression at 6 months after delivery and of serious mental illness at 1 year after delivery.
Validating the Suicide Status Form for the Collaborative Assessment and Management of Suicidality in a Psychiatric Adolescent Sample.

BACKGROUND For adults, the Collaborative Assessment and Management of Suicidality (CAMS; Jobes, (2006, Managing suicidal risk: A collaborative approach, New York, Guilford) and Jobes, (2016, Managing suicidal risk: A collaborative approach, New York, Guilford)) is a treatment framework with replicated evidenced-based support for effectiveness. The current study is a psychometric validation of the Suicide Status Form (SSF-IV), the main assessment and treatment planning tool for CAMS, in an adolescent psychiatric sample. METHODS Data were collected from 100 adolescents, aged 12-17, in inpatient settings (mean age = 14.6; 67.5% female, 80% white). Adolescents were administered Part A of the SSF-IV, as well as measures of overall suicide risk (both explicit and implicit), mental pain, Stress, Agitation, reasons for living, and self-esteem. RESULTS Confirmatory factor analysis found a two-factor model to fit the data best, with Psychological Pain, Stress, and Agitation loading on one factor, and Hopelessness and Self-Hate on another. All of the core SSF constructs except Stress were significantly correlated with concurrent measures, and SSF overall suicide risk was significantly correlated with self-reported and implicit suicidality. Adolescents with suicide attempt history reported significantly higher scores on most core SSF items compared to no attempt history. CONCLUSIONS These results provide initial psychometric validation of the SSF for use with adolescents and indicate that it does not need to be adapted or modified for this age group.
Melatonin exerts oncostatic capacity and decreases melanogenesis in human MNT‐1 melanoma cells

Melanogenesis is a key parameter of differentiation in melanocytes and melanoma cells; therefore, search for factors regulating this pathway are strongly desired. Herein, we investigated the effects of melatonin, a ubiquitous physiological mediator that is found throughout animals and plants. In mammals, the pineal gland secretes this indoleamine into the blood circulation to exert an extensive repertoire of biological activities. Our in vitro assessment indicates an oncostatic capacity of melatonin in time‐dependent manner (24, 48, 72 hours) in highly pigmented MNT‐1 melanoma cells. The similar pattern of regulation regarding cell viability was observed in amelanotic Sk‐Mel‐28 cells. Subsequently, MNT‐1 cells were tested for the first time for evaluation of melanin/melatonin interaction. Thus primary, electron paramagnetic resonance (EPR) spectroscopy demonstrated that melatonin reduced melanin content. Artificially induced disturbances of melanogenesis by selected inhibitors (N‐phenylthiourea or kojic acid) were slightly antagonized by melatonin. Additionally, analysis using transmission electron microscopy has shown that melatonin, particularly at higher dose of 10−3 mol/L, triggered the appearance of premelanosomes (stage I‐II of melanosome) and MNT‐1 cells synthesize de novo endogenous melatonin shown by LC‐MS. In conclusion, these studies show a melanogenic‐like function of melatonin suggesting it as an advantageous agent for treatment of pigmentary disorders.
The emerging role of regulatory T cells following lung transplantation

Regulatory T cells (Treg) have proven to be a powerful immunologic force in nearly every organ system and hold therapeutic potential for a wide range of diseases. Insights gained from non‐transplant pathologies, such as infection, cancer, and autoimmunity, are now being translated to the field of solid organ transplantation, particularly for livers and kidneys. Recent insights from animal models of lung transplantation have established that Tregs play a vital role in suppressing rejection and facilitating tolerance of lung allografts, and such discoveries are being validated in human studies and preclinical trials. Given that long‐term outcomes following lung transplantation remain profoundly limited by chronic rejection, Treg therapy holds the potential to significantly improve patient outcomes and should be aggressively investigated.
The Symmetry of Generalized Rivalry Network Models Determines Patterns of Interocular Grouping in Four-Location Binocular Rivalry.

Previously, symmetry of network models has been proposed to account for interocular grouping during binocular rivalry. Here, we construct and analyze generalized rivalry network models with different types of symmetry (based on different kinds of excitatory coupling) to derive predictions of possible perceptual states in 12 experiments with four retinal locations. Percepts in binocular rivalry involving more than three locations have not been empirically investigated due to the difficulty in reporting simultaneous percepts at multiple locations. Here, we develop a novel reporting procedure in which the stimulus disappears when the subject is cued to report the simultaneously perceived colors in all four retinal locations. This procedure ensures that simultaneous rather than sequential percepts are reported. The procedure was applied in 12 experiments with six binocular rivalry stimulus configurations, all consisting of dichoptic displays of red and green squares at four locations. We call configurations with an even (resp.~odd) number of red squares even(resp. odd) configurations. In experiments using even stimulus configurations, we found that even percepts were more frequently observed than odd percepts, whereas in experiments using odd stimulus configurations even and odd percepts were observed with equal probability. The generalized rivalry network models in which couplings depend on stimulus features and spatial configurations was in better agreement with the empirical results. We conclude that the excitatory coupling strength in the horizontal and vertical configurations are different, and the coupling strengths between the same color and between different colors are different.
Spatio-Temporal Distribution of Tuberculosis in an Urban Setting in Germany

Abstract Background Big cities in Europe have the highest incidence rates of TB in otherwise low incidence settings. Understanding of the spatio-temporal patterns of TB incidence can support efforts for TB prevention and control in line with the End-TB Strategy of the WHO in such settings for low incidence settings. Methods Data from the municipal TB register of Cologne collected between 2006 and 2015 under the infection prevention legislation were retrieved, addresses geographically identified and all notified incident TB cases retrospectively analysed for their spatial and temporal distribution in this large German city using a geographic information system. Results During the analysed period 1,038 incident cases were reported, equivalent to an incidence rate of 10.03 cases per 100,000 inhabitants. Contagious pulmonary TB contributed 57 % of all cases. Distribution patterns changed over time with decreases in 37 and increases in 22 of the 77 urban sub-districts, three of which showing constant high rates of TB incidence. Conclusion The study presents a complementary method to monitor the distribution and development of incident TB cases at a disaggregated level of urban sub-districts. Identification of areas with comparatively high incidence can support identification of clusters respectively their prevention and allow better planning for targeted local TB services.
Feasibility of Conducting Nonpharmacological Interventions to Manage Dementia Symptoms in Community-Dwelling Older Adults: A Cluster Randomized Controlled Trial

This study assessed the feasibility of conducting 3 nonpharmacological interventions with older adults in dementia, exploring the effects of chair yoga (CY), compared to music intervention (MI) and chair-based exercise (CBE) in this population. Using a cluster randomized controlled trial (RCT), 3 community sites were randomly assigned 1:1:1 to CY, MI, or CBE. Participants attended twice-weekly 45-minute sessions for 12 weeks. Thirty-one participants were enrolled; 27 safely completed the interventions and final data collection (retention rate of 87%). Linear mixed modeling was performed to examine baseline and longitudinal group differences. The CY group improved significantly in quality of life compared to the MI group (CY mean = 35.6, standard deviation [SD] = 3.8; MI mean = 29.9, SD = 5.3, P = .010). However, no significant group differences were observed in physical function, behavioral, or psychological symptoms (eg, for mini-PPT: slopetime = 0.01, standard error [SE] = 0.3, P = .984 in the CBE group; slopetime = −0.1, SE = 0.3, P = .869 in the MI group; slopetime = −0.3, SE = 0.3, P = .361 in the CY group) over the 12-week intervention period. Overall, this pilot study is notable as the first cluster RCT of a range of nonpharmacological interventions to examine the feasibility of such interventions in older adults, most with moderate-to-severe dementia. Future clinical trials should be conducted to examine the effects of nonpharmacological interventions for older adults with dementia on health outcomes.
The conditional Fama-French model and endogenous illiquidity: A robust instrumental variables test

We investigate conditional specifications of the five-factor Fama-French (FF) model, augmented with traditional illiquidity measures. The motivation for this time-varying methodology is that the traditional static approach of the FF model may be misspecified, especially for the endogenous illiquidity measures. We focus on the time-varying nature of the Jensen performance measure α and the market systematic risk sensitivity β, as these parameters are essentially universal in asset pricing models. To tackle endogeneity and other specification errors, we rely on our robust instrumental variables (RIV) algorithm implemented via a GMM approach. In this dynamic or time-varying conditional context, we generally find that the most significant factor is the market one, but illiquidity may matter depending on which states or estimation methods we consider. In particular, sectors whose returns embed a market illiquidity premium are more exposed to a binding funding constraint in times of crisis, which leads to deleveraging and a resulting decrease in systematic risk.
Neonatal temperament and neuromotor differences are predictive of adolescent alcohol intake in rhesus monkeys (Macaca mulatta)

Identifying predictors of teenage alcohol use disorder (AUDs) is a major health initiative, with studies suggesting that there are distinct personality‐related traits that underlie patterns of alcohol intake. As temperament is biologically based, identifiable early in life, and stable across time, it is considered the foundation of personality. As such, we hypothesized that neonatal temperament traits would predict anxiety‐mediated adolescent alcohol consumption. To test this, N = 145 rhesus macaque (Macaca mulatta) infants (14 days of age), reared in a neonatal nursery (n = 82) or in a control condition with their mothers (n = 63) were assessed with a widely used standardized nonhuman primate testing battery, the Infant Behavioral Assessment Scale (IBAS), modeled after the Brazelton Neonatal Assessment Scale, evaluating visual orienting, temperament, motor maturity and, more recently, sensory sensitivity. As adolescents (3–4 years of age), these same subjects were allowed unfettered access to a sweetened‐alcohol solution for 1 hr/day, 4 days/week, over 5–7 weeks. Subjects were allowed to self‐administer alcohol while housed alone (n = 70) or socially in their home cage (n = 55). Linear regressions showed that alcohol intake was predicted by neonatal orienting ability (β = −.35; p = .01), state control (β = −.19; p = .04), and motor maturity (β = −.24; p = .01). Poor neonatal orienting, state control (ease of consolability), and motor maturity were associated with higher adolescent alcohol intake in rhesus monkeys. These findings suggest that neonatal temperament is predictive of patterns of adolescent alcohol intake. To the extent that these results generalize to humans, they provide evidence that early‐life temperament and neurodevelopment may be important risk factors for adolescent AUDs and that the IBAS may be used as an assessment tool for identifying such risk.
Comparison of the performance of paired urine and cervical samples for cervical cancer screening in screening population

The main objective of this work is to determine the performance of urine for human papillomavirus (HPV) detection in cervical cancer screening in screening population. Paired urine and cervical samples were collected from 2038 women (careHPV group: 1002, cobas4800 group: 1036) in 2015. Urine was tested by a new urine‐based HPV test and cervical samples by careHPV or cobas4800 HPV test. Women were triaged based on cervical results and then referred to colposcopy with biopsy as clinically indicated. In 2017, women were followed up and screened with cotesting strategy, women with any positive would be referred and biopsied if necessary. In careHPV group, the HPV prevalence of urine was 14.1%, and 16.4% for cervical samples. In cobas4800 group, it was 19.1% and 20.4%, correspondingly. The concordance of urine samples compared with cervical samples was moderate (careHPV group: 86.6%; κ = 0.48; cobas4800 group: 83%; κ = 0.46). The baseline sensitivity and specificity for urine against CIN2+ detection were 85.7%, 86.8% in careHPV group, and 69.2%, 82.3% in cobas4800 group, respectively. Cervical samples were 100% sensitive for both tests (careHPV and cobas4800) and 85.2% specific in careHPV group and 81.9% specific in cobas4800 group, respectively. The corresponding cumulative sensitivity and specificity were 68.8% and 87.1%, 58.8% and 81.9%, 87.5% and 85.5%, and 94.1% and 81.4%. Urine demonstrated certain potential in cervical cancer screening and could be an alternative if no better screening strategies available.
A complete additively manufactured (3D-printed) electrochemical sensing platform.

Herein, we report a complete additively manufactured (AM) electrochemical sensing platform. In this approach, a fully AM / 3D-printed electrochemical system, using a conventional low-cost 3D-printer (fused deposition modelling) fabricating both the conductive electrodes and non-conductive/chemically inert electrochemical cell is reported. The electrodes (working, counter, and pseudo-reference) are AM using a conductive fused-filament comprising of a mixture of carbon black nanoparticles and polylactic acid (CB/PLA). AM components partially coated with silver ink presented similar behavior to a conventional Ag/AgCl reference electrode. The performance of the AM working electrode was evaluated after a simple and fast polishing procedure on sandpaper and electrochemical activation in a NaOH solution (0.5 mol L-1). Following the electrochemical activation step, a considerable improvement in the electrochemical behavior (current intensity and voltammetric profile) was obtained for model analytes, such as dopamine, hexaammineruthenium (III) chloride, ferricyanide/ferrocyanide, uric acid, and ascorbic acid. Excellent repeatability (RSD = 0.4 %, N = 10) and limit of detection (0.1 µmol L 1) were obtained with the all complete AM electrochemical system for dopamine analysis. The electrochemical performance of the developed system (after simple electrochemical activation of the working electrode) was similar or better than those obtained using commercial glassy carbon and screen-printed carbon electrodes. The results shown here represents a significant advance in AM (3D-printing) technology for analytical chemistry.
Role of Transbronchial Cryobiopsy in Interstitial Lung Diseases: An Ongoing Tale

and we developed the temperature trajectory subphenotypes to be generalizable to past and future definitions; and 3) temperature trajectories derived only from patients with organ dysfunction on presentation would exclude patients with infection who later developed sepsis during hospitalization; because the development of organ dysfunction due to infection is likely in part related to the immune response, we did not want to exclude these patients from our analysis. On the suggestion of Dr. Maitra and Dr. Bhattacharjee, we tested the association between temperature trajectory membership andmortality adjusting for the Sequential Organ Failure Assessment (SOFA) score instead of the quick SOFA score. In logistic regression, when we controlled for age, comorbidities, SOFA, and time to antibiotics, membership in the “hyperthermic, fast resolvers” group remained associated with decreased mortality risk (odds ratio, 0.55; 95% confidence interval, 0.42–0.72; P, 0.001) compared with the “normothermic” group. Membership in the “hypothermic” group was associated with increased mortality risk (odds ratio, 1.56, 95% confidence interval, 1.30–1.88; P, 0.001). These results are similar to those we obtained in the primary analyses presented in our paper. Although the metric used to determine the accuracy of sepsis definitions is often risk of mortality, definitions developed based on that outcome may not capture the heterogeneity of the sepsis syndrome (2, 3). Developing a trajectory model based on body temperature (a biologically relevant clinical measurement) allowed us to establish subphenotypes that were disentangled from but still predictive of the outcome. Further studies are required to establish the precise biological significance of the temperature trajectory subphenotypes. n
Approaches to patients with variants in RAG genes: from diagnosis to timely treatment

ABSTRACT Introduction: Patients with primary immunodeficiency secondary to abnormal recombinase activating genes (RAG) can present with broad clinical phenotypes ranging from early severe infections to autoimmune complications and inflammation. Immunological phenotype may also vary from T−B− severe combined immunodeficiency to combined immunodeficiency or antibody deficiencies with near-normal T and B cell counts and even preserved specific antibody response to pathogens. It is not uncommon that RAG variants of uncertain significance are identified by serendipity during a broad genetic screening process and pathogenic RAG variants are increasingly recognized among all age groups, including adults. Establishing the pathogenicity and clinical relevance of novel RAG variants can be challenging since RAG genes are highly polymorphic. This review paper aims to summarize clinical phenotypes of RAG deficiencies and provide practical guidance for confirming the direct link between specific RAG variants and clinical disease. Lastly, we will review the current understanding of treatment option for patients with varying severity of RAG deficiencies. Area covered: This review discusses the different phenotypes and immunological aspects of RAG deficiencies, the diagnosis dilemma facing clinicians, and an overview of current and advancement in treatments. Expert opinion: A careful analysis of immunological and clinical data and their correlation with genetic findings helps to determine the significance of the genetic polymorphism. Advances in functional assays, as well as anti-cytokine antibodies, make it easier to resolve the diagnostic dilemma.