Miracle-dz/UniFAR-FTUs huggingface dataset:
Tofacitinib, an Oral Janus Kinase Inhibitor: Analysis of Malignancy (Excluding Nonmelanoma Skin Cancer) Events Across the Ulcerative Colitis Clinical Program

Abstract Background Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Here, we performed an integrated analysis of malignancy events from the tofacitinib phase 3 UC clinical development program (excluding nonmelanoma skin cancer [NMSC]). Methods Data (up to May 2019) were pooled from two phase 3 induction studies, a phase 3 maintenance study, and an ongoing, open-label, long-term extension (OLE) study, and analyzed as 3 cohorts: induction (N = 1139), maintenance (N = 592), and overall (induction, maintenance, and ongoing OLE study; N = 1124). Proportions and incidence rates (IRs; unique patients with events per 100 patient-years [PY] of exposure) for malignancies confirmed by adjudication were calculated. Results The overall cohort consisted of patients who received at least 1 dose of tofacitinib at 5 or 10 mg twice daily, for up to 6.8 years, with an exposure of 2576.4 PY. Of the 1124 overall cohort tofacitinib-treated patients, 20 developed a malignancy (excluding NMSC; IR, 0.75; 95% confidence interval, 0.46–1.16), of which 17 occurred in patients treated with tofacitinib 10 mg twice daily; importantly, more than 80% of patients predominantly received this dose. Furthermore, there was no apparent clustering of malignancy types, and IRs were stable over time. Conclusions In the tofacitinib UC clinical development program, malignancy events were infrequent, and rates were comparable with those in the tofacitinib rheumatoid arthritis and psoriatic arthritis clinical development programs, and for biologic UC treatments. ClinicalTrials.gov: NCT01465763, NCT01458951, NCT01458574, and NCT01470612.
Patterns of multimorbidity and pharmacotherapy: a total population cross-sectional study

Abstract Background Treatment of multimorbid patients can be improved. Development of patient-centred care of high-quality requires context-bound understanding of the multimorbid population’s patterns of demographics, co-morbidities and medication use. Objective The aim of this study was to identify patterns of multimorbidity in the total population of Region Stockholm, Sweden, by exploring demographics, claimed prescription drugs, risk of mortality and non-random association of conditions. Methods In this cross-sectional descriptive population-based cohort study, we extracted data from the Swedish VAL database (N = 2 323 667) including all consultations in primary and specialized outpatient care, all inpatient care and all prescriptions claimed during 2017. We report number of chronic conditions and claimed prescription drugs, physical and mental co-morbidity, and 1-year mortality. We stratified the analyses by sex. We examined non-random associations between diseases using cluster analysis. Results In total, 21.6% had multimorbidity (two or more chronic conditions) and 24.1% had polypharmacy (more than five claimed prescription drugs). Number of claimed drugs, co-occurrence of mental and physical conditions, and 1-year mortality increased as multimorbidity increased. We identified seven multimorbidity clusters with clinically distinct characteristics. The smallest cluster (7% of individuals) had prominent cardiovascular disease, the highest 1-year mortality rate, high levels of multimorbidity and polypharmacy, and was much older. The largest cluster (27% of individuals) was younger and heterogenous, with primarily mental health problems. Conclusions Individuals with chronic conditions often show clinical complexity with both concordant and discordant conditions and polypharmacy. This study indicates that clinical guidelines addressing clustering of conditions may be one strategy for managing complexity.
Long range effects in gravity theories with Vainshtein screening

In this paper we study long range modifications of gravity in the consistent framework of bigravity, which introduces a second massive spin-2 field and allows to continuously interpolate between the regime of General Relativity (mediated by a massless spin-2 field) and massive gravity (mediated by a massive spin-2 field). In particular we derive for the first time the equations for light deflection in this framework and study the effect on the lensing potential of galaxy clusters. By comparison of kinematic and lensing mass reconstructions, stringent bounds can be set on the parameter space of the new spin-2 fields. Furthermore, we investigate galactic rotation curves and the effect on the observable dark matter abundance within this framework.
Sex Hormone Therapy and Tenofovir Diphosphate Concentration in Dried Blood Spots: Primary Results of the iBrEATHe Study.

BACKGROUND Pilot studies showed lower tenofovir plasma concentrations during PrEP use among transgender women (TGW) using feminizing hormones compared with cisgender men (CGM). Tenofovir diphosphate (TFV-DP) concentrations in TGW and transgender men (TGM) using gender affirming hormones and on directly observed dosing of PrEP have not been studied. METHODS TGM and TGW on at least 6 months of stable sex hormone therapy containing testosterone or estradiol (respectively) were enrolled in a 4-week study of directly observed dosing of daily oral co-formulated emtricitabine and tenofovir disoproxil fumarate (FTC/TDF). TFV-DP in dried blood spots and sex hormones in serum were measured at weekly intervals. TFV-DP was compared with 2 and 4 week samples from DOT-DBS (NCT02022657). RESULTS From May 2017 to June 2018, 24 TGM and 24 TGW were enrolled; one TGM withdrew prior to 4 weeks of PrEP. Ethnicity (non-exclusive) was 27 (57%) white, 10 (21%) black, and 15 (32%) latinx. The median age was 31 (IQR 28 to 40). Of TGW, 9 (38%) took spironolactone in addition to estradiol. Testosterone (total and free) and estradiol concentrations were comparable before and after 4 weeks of PrEP use in TGM and TGW respectively. Historical controls comprised of 17 cisgender women (CGW) and 15 CGM. TFV-DP concentrations at week 4 were comparable between TGW and TGM (mean difference -6%; 95% CI -21% to 12%; P=0.47), comparable between TGW and CGM (mean difference -12%; 95% CI -27% to 7%; P=0.21) and were lower among TGM compared with CGW (mean difference -23%; 95% CI -36% to -7%; P=0.007). All persons in all groups were projected to reach the TFV-DP threshold that has been associated with high protection from HIV. There were no associations between serum estradiol or free testosterone concentrations and TFV-DP. CONCLUSION CGM, TGM, and TGW had comparable TFV-DP concentrations in DBS after 4 weeks of directly observed daily FTC/TDF PrEP use. Serum hormone concentrations were not affected by FTC/TDF PrEP use.
Endothelial Dysfunction and Thrombosis in Patients With COVID-19—Brief Report

Supplemental Digital Content is available in the text. Objective: Alveolar-capillary endothelial cells can be activated by severe acute respiratory syndrome coronavirus 2 infection leading to cytokine release. This could trigger endothelial dysfunction, pyroptosis, and thrombosis, which are the vascular changes, commonly referred to as coronavirus disease 2019 (COVID-19) endotheliopathy. Thus, this study aimed to identify tissue biomarkers associated with endothelial activation/dysfunction and the pyroptosis pathway in the lung samples of patients with COVID-19 and to compare them to pandemic influenza A virus H1N1 subtype 2009 and control cases. Approach and Results: Postmortem lung samples (COVID-19 group =6 cases; H1N1 group =10 cases, and control group =11 cases) were analyzed using immunohistochemistry and the following monoclonal primary antibodies: anti-IL (interleukin)-6, anti-TNF (tumor necrosis factor)-α, anti-ICAM-1 (intercellular adhesion molecule 1), and anticaspase-1. From the result, IL-6, TNF-α, ICAM-1, and caspase-1 showed higher tissue expression in the COVID-19 group than in the H1N1 and control groups. Conclusions: Our results demonstrated endothelial dysfunction and suggested the participation of the pyroptosis pathway in the pulmonary samples. These conditions might lead to systemic thrombotic events that could impair the clinical staff’s efforts to avoid fatal outcomes. One of the health professionals’ goals should be to identify the high risk of thrombosis patients early to block endotheliopathy and its consequences.
Exploring the pedagogic relation - Supporting six-year-olds in making sense of physical motion

This article explores how verbal relations between child and researcher may support the child’s reasoning and making sense of physical motion. In an earlier study, 64 children aged 6–14 participated in one-to-one reflective dialogues. Some of them developed their reasoning during the dialogue, and used an exploring approach to make sense of physical motion. For the present study, 6 transcripts were re-analyzed concerning the interplay between the researcher and the 6-year-olds who used this approach, aiming to explore the pedagogic relation, namely how the children used language to understand physical motion and how they were supported by the researcher. The analysis revealed some conditions for a pedagogic relation: the adult uses an inviting approach, directing the child’s awareness by framing the phenomenon, directing and reflecting the child’s awareness towards their use of language, and asking for the child’s perspective. Children who used an exploring approach spoke of the phenomenon ‘as’, expressed awareness of their own use of language, and tested and developed meanings. The results are discussed in relation to science education in early childhood settings, and ways of helping children expand their reasoning using an exploring approach to scientific phenomena.
Capturing open ocean biodiversity: Comparing environmental DNA metabarcoding to the continuous plankton recorder

Environmental DNA (eDNA) metabarcoding is emerging as a novel, objective tool for monitoring marine metazoan biodiversity. Zooplankton biodiversity in the vast open ocean is currently monitored through continuous plankton recorder (CPR) surveys, using ship‐based bulk plankton sampling and morphological identification. We assessed whether eDNA metabarcoding (2 L filtered seawater) could capture similar Southern Ocean zooplankton biodiversity as conventional CPR bulk sampling (~1,500 L filtered seawater per CPR sample). We directly compared eDNA metabarcoding with (a) conventional morphological CPR sampling and (b) bulk DNA metabarcoding of CPR collected plankton (two transects for each comparison, 40 and 44 paired samples, respectively). A metazoan‐targeted cytochrome c oxidase I (COI) marker was used to characterize species‐level diversity. In the 2 L seawater eDNA samples, this marker amplified large amounts of non‐metazoan picoplanktonic algae, but eDNA metabarcoding still detected up to 1.6 times more zooplankton species than morphologically analysed bulk CPR samples. COI metabarcoding of bulk DNA samples mostly avoided nonmetazoan amplifications and recovered more zooplankton species than eDNA metabarcoding. However, eDNA metabarcoding detected roughly two thirds of metazoan species and identified similar taxa contributing to community differentiation across the subtropical front separating transects. We observed a diurnal pattern in eDNA data for copepods which perform diel vertical migrations, indicating a surprisingly short temporal eDNA signal. Compared to COI, a eukaryote‐targeted 18S ribosomal RNA marker detected a higher proportion, but lower diversity, of metazoans in eDNA. With refinement and standardization of methodology, eDNA metabarcoding could become an efficient tool for monitoring open ocean biodiversity.
Lizard blues: blue body colouration and ultraviolet polychromatism in lacertids

Understanding the evolution of conspicuous colour patterns has been a major challenge in evolutionary biology since Darwin’s formulation of natural and sexual selection 150 years ago. A striking case of conspicuous colouration is the structural blue colour found in lizards belonging to several families, including lacertids (Lacertidae). Blue colouration can be restricted to discrete patches, as those found in the flanks or head of many lacertids, or can extend over large areas of the integument as in several insular populations of Lacertini. Recent research has shown that the blue flank and head patches of many lacertids have their peak of reflectance in the ultraviolet (UV) range. It has been suggested that these UV-blue patches may be part of a private (i.e. available only to receptors with UV vision) communication system. In contrast, nothing is known about the spectral characteristics of those species in which all or large portions of the body surface are blue. Using objective methods of colour measurement and analysis, we studied the spectral characteristics of blue colouration in Podarcis lilfordi kuligae and compared them with those from other blue lacertids. The ventral surface and flank patches of P. lilfordi kuligae are both UV-blue, but their spectral shape is strikingly different, possibly reflecting different underlying selective pressures and colour production mechanisms. To our knowledge, this is the first recorded case of polychromatism in the UV part of the electromagnetic spectrum. Our results show that a wide range of spectrally different colourations belie human-perceived blues in lacertids. We analyse visual interactions among lizard colours and habitat natural backgrounds and propose some hypothesis for the evolution of lizard blue and UV-blue colourations.
Artificial Intelligence for the Financial Services Industry: What Challenges Organizations to Succeed

As a research field, artificial intelligence (AI) exists for several years. More recently, technological break-throughs, coupled with the fast availability of data, have brought AI closer to commercial use. Internet giants such as Google, Amazon, Apple or Facebook invest significantly into AI, thereby underlining its relevance for business models worldwide. For the highly data driven finance industry, AI is of intensive interest within pilot projects, still, few AI applications have been implemented so far. This study analyzes drivers and inhibitors of a successful AI adoption in the finance industry based on panel data comprising 22 semi-structured interviews with experts in AI in finance. As theoretical lens, we structured our results using the TOE framework. Guidelines for applying AI successfully reveal AI-specific role models and process competencies as crucial, before trained algorithms will have reached a quality level on which AI applications will operate without human intervention and moral concerns.
Prevalence, associated factors and perspectives of HIV testing among men in Uganda

Background Despite overall increase in HIV testing, more men than women remain untested. In 2018, 92% of Ugandan women but only 67% of men had tested for HIV. Understanding men’s needs and concerns for testing could guide delivery of HIV testing services (HTS) to them. We assessed the prevalence of testing, associated factors and men’s perspectives on HIV testing in urban and peri-urban communities in Central Uganda. Methods and findings We conducted a parallel-convergent mixed-methods study among men in Kampala and Mpigi districts from August to September 2018. Using two-stage sampling, we selected 1340 men from Mpigi. We administered a structured questionnaire to collect data on HIV testing history, socio-demographics, self-reported HIV risk-related behaviors, barriers and facilitators to HIV testing. We also conducted 10 focus-groups with men from both districts to learn their perspectives on HIV testing. We used modified Poisson regression to assess factors associated with HIV testing and inductive thematic analysis to identify barriers and facilitators. Though 84.0% of men reported having tested for HIV, only 65.7% had tested in the past 12-months despite nearly all (96.7%) engaging in at least one HIV risk-related behavior. Men were more likely to have tested if aged 25–49 years, Catholic, with secondary or higher education and circumcised. Being married was associated with ever-testing while being widowed or divorced was associated with testing in past 12-months. Men who engaged in HIV risk-related behavior were less likely to have tested in the past 12-months. Qualitative findings showed that men varied in their perspectives about the need for testing, access to HTS and were uncertain of HIV testing and its outcomes. Conclusions Recent HIV testing among men remains low. Modifying testing strategies to attract men in all age groups could improve testing uptake, reduce gender disparity and initiate risk reduction interventions.
Rapid Implementation of a Diabetes Telemedicine Clinic During the Coronavirus Disease 2019 Outbreak: Our Protocol, Experience, and Satisfaction Reports in Saudi Arabia

Background: The importance of telemedicine in diabetes care became more evident during the coronavirus disease 2019 (COVID-19) pandemic as many people with diabetes, especially those in areas without well-established telemedicine, lost access to their health care providers (HCPs) during this pandemic. Subjects and Methods: We describe a simplified protocol of a Diabetes Telemedicine Clinic that utilizes technological tools readily available to most people with diabetes and clinics around the world. We report the satisfaction of 145 patients and 14 HCPs who participated in the virtual clinic and 210 patients who attended the virtual educational sessions about “Diabetes and Ramadan. ” Results: The majority of patients agreed or strongly agreed that the use of telemedicine was essential in maintaining a good glucose control during the pandemic (97%) and they would use the clinic again in the future (86%). A similar high satisfaction was reported by patients who attended the “Diabetes and Ramadan” virtual educational session and 88% of them recommended continuing this activity as a virtual session every year. Majority of the HCPs (93%) thought the clinic protocol was simple and did not require a dedicated orientation session prior to implementing. Conclusions: The simplicity of our Diabetes Telemedicine Clinic protocol and the high satisfaction reported by patients and HCPs make it a suitable model to be adopted by clinics, especially during pandemics or disasters in resource-limited settings. This clinic model can be quickly implemented and does not require technological tools other than those widely available to most people with diabetes, nowadays. We were able to successfully reduce the number of patients, HCPs, and staff physically present in the clinics during the COVID-19 pandemic without negatively impacting the patients’ nor the HCPs’ satisfaction with the visits.
A reduction theory of second order meromorphic differential equations. II

On etudie des equations differentielles meromorphes X'(Z)=A(Z)×X(Z) de dimension 2×2 dont le comportement exponentiel pres de la singularite a l'infini est gouverne par une matrice diagonale Q(Z) contenant un polynome en Z 1/2 et non en Z
Development and application of ultrasensitive fluorescence spectroscopy and microscopy for biomolecular interaction studies

This thesis describes the development of sensitive and high-resolution fluorescence spectroscopic and microscopic techniques and their application to probe biomolecules and their interactions in solution, lipid membrane model systems and in cells. Paper I-IV are largely focused on methodological developments. In paper I, a new fluorescence method based on fluorescence correlation spectroscopy (FCS) for detecting single particles was realized, requiring no fluorescent labeling of the particles. The method can yield information both about the diffusion properties of the particles as well as about their volumes. In paper II, a modified fluorescence cross correlation spectroscopy procedure with well characterized instrumental calibration was developed and applied to study cis interactions between an inhibitory receptor and its Major Histocompatibility Complex class I ligand molecule, both within the same cellular membranes. The quantitative analysis brought new insights into the Nature killer cell’s self-regulating of tolerance and aggressiveness for immune responses. Paper III describes a multi-color STED (STimulated Emission Depletion) microscopy procedure, capable of imaging four different targets in the same cells at ∼40nm optical resolution, which was developed and successfully demonstrated on platelets. In paper IV, a modified co-localization algorithm for fluorescence images analysis was proposed, which is essentially insensitive to resolutions and molecule densities. Further, the performance of this algorithm and of using STED microscopy for co-localization analysis was evaluated using both simulated and experimentally acquired images. Papers V-VII have their main emphasis on the application side. In paper V, transient state imaging was demonstrated on live cells to image intra-cellular oxygen concentration and successfully differentiated different breast cancer cell lines and the different metabolic pathways they adopted to under different culturing conditions. Paper VI describes a FCS-based study of proton exchange at biological membranes, the size-dependence of the membrane proton collecting antenna effect as well as effects of external buffer solutions on the proton exchange, in a nanodisc lipid membrane model system. These findings provide insights for understanding proton transport at and across membranes of live cells, which has a central biological relevance. In paper VII, STED imaging and co-localization analysis was applied to analyze cell adhesion related protein interactions, which are believed to have an important modulating role for the proliferation, differentiation, survival
Discarded plasma obtained after cord blood volume reduction as an alternative for fetal calf serum in mesenchymal stromal cells cultures

Utilization of the fetal calf serum (FCS) carries a potential health risk and raises growing economic and ethical problems. Umbilical cord blood volume reduction, required for banking, provides clinical‐grade umbilical cord blood plasma (UCBP) discarded as a waste. The aim of this study was to test whether serum derived from UCBP could replace FCS for the amplification of mesenchymal stromal cells (MSCs).
In vivo quantitative analysis of advanced glycation end products in atopic dermatitis—Possible culprit for the comorbidities?

Advanced glycation end products (AGEs) interact with the membrane‐bound receptor for AGEs (RAGE), consequently amplifying the inflammatory response. Soluble receptor for AGE (sRAGE) and endogenous secretory RAGE (esRAGE) act as decoys for AGE and competitively sequester RAGE ligands, thereby serving a cytoprotective role. Our objective was to investigate AGE expression and their receptors in the serum and skin of patients with atopic dermatitis (AD). In this case‐control study, the levels of AGE, sRAGE and esRAGE were measured in the blood samples and corneocytes of 29 adult patients with AD and 12 healthy controls by ELISA. Corneocyte AGE levels increased in the AD group (P = .002). Higher corneocyte AGE levels were observed in the severe AD than in the milder form of AD. No significant difference in serum AGE level was observed in patients with AD and healthy controls. Serum sRAGE markedly decreased in patients with AD (P = .007) and serum esRAGE followed a similar trend. In conclusion, dermal accumulation of AGE in AD may have a role in fuelling skin inflammation. The potential after‐effects of reduced neutralizer on systemic risk need further evaluation.