Miracle-dz/UniFAR-FTUs huggingface dataset:
New risk model is able to identify patients with a low risk of progression in systemic sclerosis

Objectives To develop a prediction model to guide annual assessment of systemic sclerosis (SSc) patients tailored in accordance to disease activity. Methods A machine learning approach was used to develop a model that can identify patients without disease progression. SSc patients included in the prospective Leiden SSc cohort and fulfilling the ACR/EULAR 2013 criteria were included. Disease progression was defined as progression in ≥1 organ system, and/or start of immunosuppression or death. Using elastic-net-regularisation, and including 90 independent clinical variables (100% complete), we trained the model on 75% and validated it on 25% of the patients, optimising on negative predictive value (NPV) to minimise the likelihood of missing progression. Probability cutoffs were identified for low and high risk for disease progression by expert assessment. Results Of the 492 SSc patients (follow-up range: 2–10 years), disease progression during follow-up was observed in 52% (median time 4.9 years). Performance of the model in the test set showed an AUC-ROC of 0.66. Probability score cutoffs were defined: low risk for disease progression (<0.197, NPV:1.0; 29% of patients), intermediate risk (0.197–0.223, NPV:0.82; 27%) and high risk (>0.223, NPV:0.78; 44%). The relevant variables for the model were: previous use of cyclophosphamide or corticosteroids, start with immunosuppressive drugs, previous gastrointestinal progression, previous cardiovascular event, pulmonary arterial hypertension, modified Rodnan Skin Score, creatine kinase and diffusing capacity for carbon monoxide. Conclusion Our machine-learning-assisted model for progression enabled us to classify 29% of SSc patients as ‘low risk’. In this group, annual assessment programmes could be less extensive than indicated by international guidelines.
Divergent and overlapping hippocampal and cerebellar transcriptome responses following developmental ethanol exposure during the secondary neurogenic period

Abstract Background The developing hippocampus and cerebellum, unique among brain regions, exhibit a secondary surge in neurogenesis during the third trimester of pregnancy. Ethanol (EtOH) exposure during this period is results in a loss of tissue volume and associated neurobehavioral deficits. However, mechanisms that link EtOH exposure to teratology in these regions are not well understood. We therefore analyzed transcriptomic adaptations to EtOH exposure to identify mechanistic linkages. Methods Hippocampi and cerebella were microdissected at postnatal day (P)10, from control C57BL/6J mouse pups, and pups treated with 4 g/kg of EtOH from P4 to P9. RNA was isolated and RNA‐seq analysis was performed. We compared gene expression in EtOH‐ and vehicle‐treated control neonates and performed biological pathway‐overrepresentation analysis. Results While EtOH exposure resulted in the general induction of genes associated with the S‐phase of mitosis in both cerebellum and hippocampus, overall there was little overlap in differentially regulated genes and associated biological pathways between these regions. In cerebellum, EtOH additionally induced gene expression associated with the G2/M‐phases of the cell cycle and sonic hedgehog signaling, while in hippocampus, EtOH‐induced the pathways for ribosome biogenesis and protein translation. Moreover, EtOH inhibited the transcriptomic identities associated with inhibitory interneuron subpopulations in the hippocampus, while in the cerebellum there was a more pronounced inhibition of transcripts across multiple oligodendrocyte maturation stages. Conclusions These data indicate that during the delayed neurogenic period, EtOH may stimulate the cell cycle, but it otherwise results in widely divergent molecular effects in the hippocampus and cerebellum. Moreover, these data provide evidence for region‐ and cell‐type‐specific vulnerability, which may contribute to the pathogenic effects of developmental EtOH exposure.
Childhood maltreatment and within-person associations between cortisol and affective experience

Abstract Glucocorticoids exert profound effects on the brain and behavior, but cortisol concentrations are rarely linked to subjectively reported emotional states in humans. This study examined whether the link between cortisol and subjective anxiety varied by childhood maltreatment history. To do this, 97 individuals (60.8% female) participated in a standardized stress task in the laboratory (Trier Social Stress Test, TSST) while providing serial ratings of their feelings of anxiety as well as cortisol samples in blood. These measurements were collected nine times across the laboratory visit, from immediately before the TSST to 65 minutes after stress initiation. We estimated the within-person association between cortisol concentrations and momentary feelings of anxiety for individuals with and without exposure to childhood maltreatment, measured via self-report on the Childhood Trauma Questionnaire (CTQ). Individuals exposed to maltreatment during childhood reported the greatest feelings of anxiety when cortisol concentrations were lowest. This pattern was exaggerated among female participants, those with posttraumatic stress disorder (PTSD), and those exposed to emotional neglect relative to other forms of maltreatment. Early life adversity, such as parental maltreatment, may alter the role of cortisol in affective experiences. This observation may provide preliminary, translational evidence of a novel pathway through which stress may lead to and maintain internalizing symptoms in humans. More studies accounting for the moderating role of childhood maltreatment in biobehavioral pathways are needed.
Edwardsiella piscicida Interferes with Classical Endocytic Trafficking and Replicates in a Specialized Replication-Permissive Niche in Nonphagocytic Cells

E. piscicida is a facultative intracellular bacterium associated with septicemia and fatal infections in many animals, including fish and humans. However, little is known about its intracellular life, which is important for successful invasion of the host. ABSTRACT Edwardsiella piscicida is an intracellular pathogen within a broad spectrum of hosts. Essential to E. piscicida’s virulence is its ability to invade and replicate inside host cells, yet the survival mechanisms and the nature of the replicative compartment remain unknown. Here, we characterized its intracellular lifestyle in nonphagocytic cells and showed that the intracellular replication of E. piscicida in nonphagocytic cells is dependent on its type III secretion system (T3SS) but not its type VI secretion system. Following internalization, E. piscicida is contained in vacuoles that transiently mature into early endosomes but subsequently bypasses the classical endosome pathway and fusion with lysosomes, which depend on its T3SS. Following rapid escape from the degradative pathway, E. piscicida was found to create a specialized replication-permissive niche characterized by endoplasmic reticulum (ER) markers. Furthermore, we found that a T3SS effector, EseJ, is responsible for the intracellular replication of E. piscicida by preventing endosome/lysosome fusion. In vivo experiments also confirmed that EseJ is necessary for bacterial colonization by E. piscicida in the epithelial layer, followed by systemic dissemination in both zebrafish and mice. Thus, this work elucidates the tactics used by E. piscicida to survive and proliferate within host nonphagocytic cells. IMPORTANCE E. piscicida is a facultative intracellular bacterium associated with septicemia and fatal infections in many animals, including fish and humans. However, little is known about its intracellular life, which is important for successful invasion of the host. The present study is the first comprehensive characterization of E. piscicida’s intracellular lifestyle in host cells. Upon internalization, E. piscicida is transiently contained in Rab5-positive vacuoles, but the pathogen prevents further endosome maturation and fusion with lysosomes by utilizing a T3SS effector, EseJ. In addition, the bacterium creates a specialized replication niche for rapid growth via an interaction with the ER. Our study provides new insights into the strategies used by E. piscicida to successfully establish an intracellular lifestyle that contributes to its survival and dissemination during infection.
Serum levels of ARMS2, COL8A1, RAD51B, and VEGF and their correlations in Age-Related Macular Degeneration.

BACKGROUND Many factors including genetic and environmental are responsible for the incidence of age-related macular degeneration (AMD). However, its pathogenesis has not been clearly elucidated yet. OBJECTIVE This study aimed to estimate the Age-Related Maculopathy Susceptibility 2 (ARMS2), Collagen type VIII Alpha 1 chain (COL8A1), Rad 51 paralog(RAD51B), and Vascular Endothelial Growth Factor (VEGF) protein levels in serum of AMD and control participants and to further investigate their correlation to understand AMD pathogenesis. METHODS For this cross-sectional study, 31 healthy control and 57 AMD patients were recruited from Advanced Eye Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India. A blood sample was taken and serum was isolated from it. ELISA(enzyme-linked immunosorbent assay)was used for the estimation of proteins in the serum of patients. RESULTS ARMS2 and COL8A1 levels were significantly elevated in the AMD group than in the control group. The highest levels of ARMS2, COL8A1, and VEGF proteins were recorded for the wet AMD sub-group. The study results endorsed significant positive correlation between these following molecules; ARMS2 and COL8A1 (r=0.933, p<0.0001), ARMS2 and RAD51B (r=0.704, p<0.0001), ARMS2 and VEGF (r=0.925, p<0.0001), COL8A1 and RAD51B (r=0.736, p<0.0001), COL8A1 and VEGF (r=0.879, p<0.0001),and RAD51B and VEGF (r=0.691, p<0.0001). CONCLUSION The ARMS2 and COL8A1 levels were significantly higher and RAD51B was significantly lower in the AMD group than controls. Also, a significant statistical correlation was detected between these molecules, indicating that their interaction may be involved in the pathogenesis of AMD.
Intimate partner sexual violence and violent victimisation among women living homeless in Madrid (Spain).

The purpose of this paper is to discover the extent to which women living homeless in Madrid (Spain) have been victims of intimate partner sexual violence (IPSV), analysing the connection between stressful life events (SLE) relating to violent victimisation and having suffered sexual assault by a partner. This study took place using a sample of women living homeless in Madrid (n = 136). The results obtained show that a high percentage of the women living homeless who were questioned had been victims of IPSV. The women interviewed, who had been victims of IPSV, had suffered, to a greater extent, SLEs relating to situations of violent victimisation, both during childhood and adolescence as well as in adulthood. The episodes of violent victimisation that seem to be the most common forerunners to IPSV are incidents of sexual abuse in childhood and adolescence.
New findings bearing on the prevention, detection and management of high blood pressure

Purpose of review Hypertension is the foremost risk factor for cardiovascular disease (CVD) and death. This review highlights recent findings that apply to the prevention, detection, and management of high blood pressure (BP), in the context of the 2017 American College of Cardiology/American Heart Association BP guideline. Recent findings Several new findings on the association of BP measurement with CVD outcomes are now available. (1) Beginning with a systolic BP (SBP) as low as 90 mm Hg, coronary artery calcium deposition and the risk of incident atherosclerotic CVD (ASCVD) increased in stepwise fashion with increasing SBP levels within the normal range in adults at low risk for ASCVD. (2) Isolated diastolic hypertension was not associated with ASCVD, heart failure, or chronic kidney disease. (3) Nocturnal BP appeared to be better associated with CVD outcomes than office or daytime BP. (4) In a head-to-head comparison, home BP monitoring had higher reliability and predictive value than office or ambulatory BP to detect left ventricular hypertrophy, an intermediate form of hypertension-related target organ damage. In addition, new information indicates that autonomous aldosterone production is present in a substantially larger percentage of adults with hypertension than previously recognized. Finally, intensive BP lowering is associated with a significant reduction in the incidence of mild cognitive impairment, a precursor of dementia. Summary Ongoing research has made significant progress in the prevention, detection, and management of high BP, clarifying, amplifying, and/or supporting the 2017 ACC/AHA BP guideline recommendations.
Feasibility of Model-Assisted Probability of Detection Principles for Structural Health Monitoring Systems Based on Guided Waves for Fiber-Reinforced Composites

In many industrial sectors, structural health monitoring (SHM) is considered as an addition to nondestructive testing (NDT) that can reduce maintenance effort during the lifetime of a technical facility, structural component, or vehicle. A large number of SHM methods are based on ultrasonic waves, whose properties change depending on structural health. However, the wide application of SHM systems is limited due to the lack of suitable methods to assess their reliability. The evaluation of the system performance usually refers to the determination of the probability of detection (POD) of a test procedure. Up until now, only a few limited methods exist to evaluate the POD of SHM systems, which prevents them from being standardized and widely accepted in the industry. The biggest hurdle concerning the POD calculation is the large number of samples needed. A POD analysis requires data from numerous identical structures with integrated SHM systems. Each structure is then damaged at different locations and with various degrees of severity. All of these are connected to high costs. Therefore, one possible way to tackle this problem is to perform computer-aided investigations. In this work, the POD assessment procedure established in NDT according to the Berens model is adapted to guided wave-based SHM systems. The approach implemented here is based on solely computer-aided investigations. After efficient modeling of wave propagation phenomena across an automotive component made of a carbon-fiber-reinforced composite, the POD curves are extracted. Finally, the novel concept of a POD map is introduced to look into the effect of damage position on system reliability.
A Virtual Cardiovascular Care Program for Prevention of Heart Failure Readmissions in a Skilled Nursing Facility Population: Retrospective Analysis

Background Patients with heart failure (HF) in skilled nursing facilities (SNFs) have 30-day hospital readmission rates as high as 43%. A virtual cardiovascular care program, consisting of patient selection, initial televisit, postconsultation care planning, and follow-up televisits, was developed and delivered by Heartbeat Health, Inc., a cardiovascular digital health company, to 11 SNFs (3510 beds) in New York. The impact of this program on the expected SNF 30-day HF readmission rate is unknown, particularly in the COVID-19 era. Objective The aim of the study was to assess whether a virtual cardiovascular care program could reduce the 30-day hospital readmission rate for patients with HF discharged to SNF relative to the expected rate for this population. Methods We performed a retrospective case review of SNF patients who received a virtual cardiology consultation between August 2020 and February 2021. Virtual cardiologists conducted 1 or more telemedicine visit via smartphone, tablet, or laptop for cardiac patients identified by a SNF care team. Postconsult care plans were communicated to SNF clinical staff. Patients included in this analysis had a preceding index admission for HF. Results We observed lower hospital readmission among patients who received 1 or more virtual consultations compared with the expected readmission rate for both cardiac (3% vs 10%, respectively) and all-cause etiologies (18% vs 27%, respectively) in a population of 3510 patients admitted to SNF. A total of 185/3510 patients (5.27%) received virtual cardiovascular care via the Heartbeat Health program, and 40 patients met study inclusion criteria and were analyzed, with 26 (65%) requiring 1 televisit and 14 (35%) requiring more than 1. Cost savings associated with this reduction in readmissions are estimated to be as high as US $860 per patient. Conclusions The investigation provides initial evidence for the potential effectiveness and efficiency of virtual and digitally enabled virtual cardiovascular care on 30-day hospital readmissions. Further research is warranted to optimize the use of novel virtual care programs to transform delivery of cardiovascular care to high-risk populations.
Lung squamous cell carcinoma with severe hypomagnesemia due to cisplatin plus gemcitabine in combination with necitumumab therapy: A case report

Abstract A 72‐year‐old man, diagnosed with advanced lung squamous cell carcinoma, was administered of cisplatin plus gemcitabine with necitumumab, a human monoclonal antibody that binds to the epidermal growth factor receptor (EGFR), as a sixth‐line treatment. Tumor shrinkage was observed, but asymptomatic grade 4 hypomagnesemia occurred on day 8 of the second cycle. He received magnesium replenishment and hypomagnesemia recovered on day 40, but tumor progression was observed during the period of magnesium correction. Hypomagnesemia is known as a major adverse event of treatment with anti‐EGFR antibodies, but there have been no case reports of severe hypomagnesemia or its clinical course.
Mean Arterial Pressure and Chronic Kidney Disease Progression in the CKiD Cohort

Supplemental Digital Content is available in the text. Consensus blood pressure guidelines vary in their recommended ambulatory blood pressure targets for children with chronic kidney disease (CKD) because of limited research in this area. We analyzed longitudinal ambulatory blood pressure monitoring data from 679 children with moderate CKD enrolled in the observational CKiD (Chronic Kidney Disease in Children) cohort by time-varying mean arterial pressure (MAP) percentile categories based on the highest wake or sleep MAP percentile. Analyses were stratified by nonglomerular and glomerular diagnoses, with 3 models constructed: unadjusted, adjusted for age, sex, and race, and additional adjustment for proteinuria. The outcome of interest was time to renal replacement therapy or 50% decline in baseline renal function. We found that among children with nonglomerular CKD, MAP percentile was not associated with accelerated disease progression risk until after 4 years of follow-up at which point a high MAP (>90th percentile) was associated with a higher risk of progression to the composite end point (HR, 1.88 [CI, 1.03–3.44]). Among those with glomerular CKD, differential risk for progression began from baseline with the highest risk in those with MAP >90th percentile (HR, 3.23 [CI, 1.34–7.79]). These relationships were attenuated somewhat after adjustment for level of proteinuria, but the trend for higher MAP being associated with higher risk of progression remained significant. Thus, in children with CKD, having ambulatory wake or sleep MAP >90th percentile was associated with higher risk of kidney disease progression with the highest levels of MAP associated with the greatest risk of progression. Registration: URL: https://www.clinicaltrials. gov; Unique identifier: NCT00327860
Effect of Augmentative Technology on Communication and Quality of Life After Tracheostomy or Total Laryngectomy

Objective Surgical procedures that render patients acutely aphonic can cause them to experience significant anxiety and distress. We queried patient perceptions after tracheostomy or laryngectomy and investigated whether introducing augmentative technology was associated with improvement in patient-reported outcomes. Methods Participants included hospitalized patients who acutely lost the ability to speak due to tracheostomy or total laryngectomy from April 2018 to December 2019. We distributed questions regarding the patient communication experience and relevant questions from the validated V-RQOL questionnaire (Voice-Related Quality of Life). Patients were offered a tablet with the electronic communication application Verbally. Pre- and postintervention groups were compared with chi-square analyses. Results Surveys were completed by 35 patients (n = 18, preintervention; n = 17, postintervention). Prior to using augmentative technology, 89% of patients who were aphonic reported difficulty communicating, specifically noting breathing or suctioning (56%), treatment and discharge plans (78%), or immediate needs, such as pain and using the bathroom (39%). Communication difficulties caused anxiety (55%), depression (44%), or frustration (62%), and 92% of patients were interested in using an electronic communication device. Patients reported less trouble communicating after the intervention versus before (53% vs 89%, P = .03), including less difficulty communicating about treatment or discharge plans (35% vs 78%, P < .01). V-RQOL scores were unchanged. Discussion Acute loss of phonation arising from surgery can be highly distressing for patients, and use of augmentative technology may alleviate some of these challenges by improving communication. Further studies are needed to identify what additional strategies may improve overall well-being. Implications for Practice Electronic communication devices may benefit patients with acute aphonia.
DOES INSURANCE MARKET ACTIVITY PROMOTE ECONOMIC GROWTH? A CROSS-COUNTRY STUDY

Insurance market activity may contribute to economic growth, both as financial intermediary and provider of risk transfer and indemnification, by allowing different risks to be managed more efficiently and by mobilizing domestic savings. During the last decade, there has been faster growth in insurance market activity, particularly in emerging markets, given the process of financial liberalization and integration, which raises questions about the overall impact on economic growth. This article tests whether there is a causal relationship between insurance market activity (life and nonlife insurance) and economic growth. Using the generalized method of moments (GMM) for dynamic models of panel data for 55 countries between 1976 and 2004, I find robust evidence for this relationship. Both life and nonlife insurance have a positive and significant causal effect on economic growth. For life insurance, high-income countries drive the results, and for nonlife insurance, both high-income and developing countries drive the results.
Where is my hand in space? The internal model of gravity influences proprioception

Knowing where our limbs are in space is crucial for a successful interaction with the external world. Joint position sense (JPS) relies on both cues from muscle spindles and joint mechanoreceptors, as well as the effort required to move. However, JPS may also rely on the perceived external force on the limb, such as the gravitational field. It is well known that the internal model of gravity plays a large role in perception and behaviour. Thus, we have explored whether direct vestibular-gravitational cues could influence JPS. Participants passively estimated the position of their hand while they were upright and therefore aligned with terrestrial gravity, or pitch-tilted 45° backwards from gravity. Overall participants overestimated the position of their hand in both upright and tilted postures; however, the proprioceptive bias was significantly reduced when participants were tilted. Our findings therefore suggest that the internal model of gravity may influence and update JPS in order to allow the organism to interact with the environment.