Miracle-dz/UniFAR-FTUs huggingface dataset:
Changes in immune cell populations following KappaMab, lenalidomide and low‐dose dexamethasone treatment in multiple myeloma

Lenalidomide (LEN) is used to treat multiple myeloma (MM) and shows in vitro synergy with KappaMab (KM), a chimeric antibody specific for Kappa Myeloma antigen, an antigen exclusively expressed on the surface of kappa‐restricted MM cells. Lenalidomide, dexamethasone (DEX) and KM control MM via multiple immunomodulatory mechanisms; however, there are several additional effects of the drug combination on immune cells. Lenalidomide can increase T cell and NKT cell cytotoxicity and dendritic cell (DC) activation in vitro. We investigated the immune cell populations in bone marrow of patients treated with KM, LEN and low‐dose DEX in kappa‐restricted relapsed/refractory MM ex vivo and assessed association of those changes with patient outcome.
Combinatorial analysis of ACE and ACE2 polymorphisms reveals protection against COVID-19 worsening: A genetic association study in Brazilian patients

Since angiotensin-converting enzyme 2, ACE2, was identified as the receptor for SARS-CoV-2 and considering the intense physiological interplay between the two angitensinases isoforms, ACE and ACE2, as counter-regulatory axis of the renin-angiotensin system, we proposed the evaluation of polymorphisms in these two key regulators in relation to COVID-19 severity. A genetic association study involving 621 COVID-19 hospitalized patients from Brazil was performed. All subjects had a confirmed diagnosis of COVID-19 via RT-PCR. Patients were categorized into two groups: the "mild" group (N = 296), composed of individuals hospitalized in ward beds who progressed to cure, and the "severe" group (N = 325), composed of individuals who required hospitalization in an intensive care unit (ICU), or who died. Blood samples were genotyped for ACE I/D polymorphism and ACE2 G8790A polymorphism by real-time PCR via TaqMan assay. The analysis of combined polymorphisms revealed a protective role for genotypic profile II/A_ (ORA = 0,26; p = 0,037) against the worsening of COVID-19 in women. The results indicate a protection profile to COVID-19 progression, in which the II/A_ carriers have almost four times less chance of a severe outcome. It is proposed that a decreased activity of ACE (deleterious effects) in conjunction with an increased ACE2 activity (protective effects), should be the underlying mechanism. The findings are unprecedented once other studies have not explored the genotypic combination analysis for ACE and ACE2 polymorphisms and bring perspectives and expectations for dealing with the COVID-19 pandemic based on definitions of genetically-based risk groups within the context of personalized medicine.
Dynamic prediction of survival via Landmark method using the asthma prevention trial in young children

This paper focuses on the applications of Landmark method for obtaining dynamic predictions of survival by using Landmark approach to the data of asthma prevention trial in young children. This work focuses on the different ways to model recurrent events by considering various time scales according to how subjects in the dataset experienced multiple events. Landmark models can be used to dynamically estimate the effect of treatments effects whilst also taken into consideration the history of previous asthma attacks. Our analysis show that the treatment effect should be modelled with a time varying effect and the effect of the previous attack reduces with the passage of time.
ACP Conversations with Chinese and South Asian Patients: Physicians’ Perspectives of Barriers and Facilitating Factors

Introduction/Objective Advance Care Planning (ACP) discussions are infrequently conducted with physicians, even fewer among minorities. We explored physicians’ experiences in engaging Chinese (CH) and South Asian (SA) patients in ACP conversations to understand initiation and participation patterns, topics covered, and barriers and facilitating factors. Method Twenty-two physicians with 15%+ SA patients aged 55+ and 19 with 15%+ CH patients aged 55+ were interviewed. Results SA- and CH-serving physicians described similar initiation patterns, cultural context, and need for standardized ACP routines. However, the SA-serving physicians described greater involvement of family members, while CH-serving physicians described more communication barriers and family members’ desire to hide the diagnosis from patients. Conclusion Cultural taboos surrounding discussion around death and dying appear to influence CH older adults and families strongly. Lack of familiarity with ACP amongst the SA population accounts more for their limited engagement in ACP discussions.
Lebanon Revisited: New Insights Into Triassic Hydrocarbon Prospects

A total of only six exploration wells have been drilled in Lebanon since World War II. The exposed succession consists predominantly of competent carbonates, with only minor occurrences of shales and marls. None of these wells penetrated formations older than the oldest exposed at the surface, which are of Liassic age. In the majority, reservoirs were invaded by meteoric waters as a result of the proximity of elevated, outcropping recharge areas, inefficient seals, or the proximity of major faults. Calculations based on gravity data indicate that the basement beneath the Lebanon uplift is some 3 km below sea level, providing for a sedimentary column over 5,000-m thick below the Upper Jurassic, most of which is unknown.
Reduced representation approaches produce similar results to whole genome sequencing for some common phylogeographic analyses

When designing phylogeographic investigations researchers can choose to collect many different types of molecular markers, including mitochondrial genes or genomes, SNPs from reduced representation protocols, large sequence capture data sets, and even whole genomes. Given that the statistical power and accuracy of various analyses are expected to differ depending on both the type of marker and the amount of data collected, an exploration of the variance across methodological results as a function of marker type should provide valuable information to researchers. Here we collect mitochondrial Cytochrome b sequences, whole mitochondrial genomes, single nucleotide polymorphisms (SNP)s isolated using a genotype by sequencing (GBS) protocol, sequences from ultraconserved elements, and low-coverage nuclear genomes from the North American water vole (Microtus richardsoni). We estimate genetic distances, population genetic structure, and historical demography using data from each of these datasets and compare the results across markers. As anticipated, the results exhibit differences across marker types, particularly in terms of the resolution offered by different analyses. A cost-benefit analysis indicates that SNPs collected using a GBS protocol are the most cost-effective molecular marker, with inferences that mirror those collected from the whole genome data at a fraction of the cost per sample.
Different PfEMP1-expressing Plasmodium falciparum variants induce divergent endothelial transcriptional responses during co-culture

The human malaria parasite Plasmodium falciparum is responsible for the majority of mortality and morbidity caused by malaria infection and differs from other human malaria species in the degree of accumulation of parasite-infected red blood cells in the microvasculature, known as cytoadherence or sequestration. In P. falciparum, cytoadherence is mediated by a protein called PfEMP1 which, due to its exposure to the host immune system, undergoes antigenic variation resulting in the expression of different PfEMP1 variants on the infected erythrocyte membrane. These PfEMP1s contain various combinations of adhesive domains, which allow for the differential engagement of a repertoire of endothelial receptors on the host microvasculature, with specific receptor usage associated with severe disease. We used a co-culture model of cytoadherence incubating human brain microvascular endothelial cells with erythrocytes infected with two parasite lines expressing different PfEMP1s that demonstrate different binding profiles to vascular endothelium. We determined the transcriptional profile of human brain microvascular endothelial cells (HBMEC) following different incubation periods with infected erythrocytes, identifying different transcriptional profiles of pathways previously found to be involved in the pathology of severe malaria, such as inflammation, apoptosis and barrier integrity, induced by the two PfEMP1 variants.
Monocyte to Lymphocyte ratio is highly specific in diagnosing latent tuberculosis and declines significantly following tuberculosis preventive therapy: A cross-sectional and nested prospective observational study

Background Interferon-gamma release assay and tuberculin skin test use is limited by costly sundries and cross-reactivity with non-tuberculous mycobacteria and Bacille Calmette-Guérin (BCG) vaccination respectively. We investigated the Monocyte to Lymphocyte ratio (MLR) as a biomarker to overcome these limitations and for use in monitoring response to tuberculosis preventive therapy (TPT). Methods We conducted a cross-sectional and nested prospective observational study among asymptomatic adults living with Human Immuno-deficiency Virus (HIV) in Kampala, Uganda. Complete blood count (CBC) and QuantiFERON-TB® Gold-plus were measured at baseline and CBC repeated at three months. Multivariable logistic regression was performed to identify factors associated with a high MLR and decline in MLR. Results We recruited 110 adults living with HIV and on antiretroviral therapy, of which 82.5% (85/110) had suppressed viral loads, 71.8% (79/110) were female, and 73.6% (81/110) had a BCG scar. The derived MLR diagnostic cut-off was 0.35, based on which the MLR sensitivity, specificity, positive predictive value, and negative predictive value were 12.8%, 91.6%, 45.5%, and 65.7% respectively. The average MLR declined from 0.212 (95% CI: 0.190–0.235) at baseline to 0.182 (95% CI: 0.166–0.198) after three months of TPT. A viral load of >50 copies/ml (aOR, 5.67 [1.12–28.60]) was associated with a high MLR while that of <50 copies/ml (aOR, 0.07 [0.007–0.832]) was associated with a decline in MLR. Conclusion MLR was highly specific in diagnosing latent TB and declined significantly following three months of TPT. Implications of a high MLR and decline in MLR after TPT need further evaluation in a larger cohort.
Incidence and predictors of virological failure among HIV infected children and adolescents on first-line antiretroviral therapy in East Shewa hospitals, Oromia Region, Ethiopia: A retrospective follow up study

Introduction Despite gains made from improved antiretroviral therapy coverage in resource limited countries, the occurrence of first line drug resistance remains a priority agenda. To reduce the emergence of resistant viruses, HIV viral load monitoring plays a critical role. However, many resource limited countries have difficulty of monitoring viral load due to economic constraints.There is also limited study regarding viral failure in developing countries. Therefore, this study aimed to assess the incidence and predictors of virological failure among HIV-infected children and adolescents on first-line ART Ethiopia, 2021. Methods Institution based retrospective follow-up study was employed on 492 children and adolescents. Data were collected by trained nurses who have experience working in ART clinics. Data were entered using Epi-data version 4.6 and exported to Stata version 14 for analysis. The proportional hazard assumption was checked, and the Weibull regression was fitted. Cox-Snell residual was used to test the goodness of fit, and the appropriate model was selected by AIC. Finally, an AHR with a 95% CI was computed, and variables with a P-value < 0.05 in the multivariable analysis were taken as significant predictors of virological failure. Results The overall incidence rate of virological failure was 4.2, (95% CI: 3.41, 5.22) per 1000 person-months of observation with 20,169 person-months follow-up time. In multivariable analysis living in rural area (AHR = 1.97, 95% CI: 1.15–3.36), poor adherence (AHR = 2.20, 95% CI: 1.24–3.91), lower CD4 Count <200 cells/mm3 (AHR = 2.57, 95% CI: 1.27–5.18) and 201–350 cells/mm3 (AHR = 2.44, 95% CI: 1.28–4.67) respectively, and recent OI (AHR = 4.60, 95% CI: 2.38–8.90) are significantly associated with virological failure. Conclusion The incidence rate of virological failure was high. Living in a rural, poor adherence, lower CD4 count, and recent opportunistic infection were independent risk factors associated with virological failure. Hence, it is better to give priority to strengthening the focused evaluation of important variables and managing accordingly.
Normative Data on Serum and Plasma Tryptophan and Kynurenine Concentrations from 8089 Individuals Across 120 Studies: A Systematic Review and Meta-Analysis

In this systematic review and meta-analysis, a normative dataset is generated from the published literature on the kynurenine pathway in control participants extracted from case-control and methodological validation studies. Study characteristics were mapped, and studies were evaluated in terms of analytical rigour and methodological validation. Meta-analyses of variance between types of instruments, sample matrices and metabolites were conducted. Regression analyses were applied to determine the relationship between metabolite, sample matrix, biological sex, participant age and study age. The grand mean concentrations of tryptophan in the serum and plasma were 60.52 ± 15.38 μM and 51.45 ± 10.47 μM, respectively. The grand mean concentrations of kynurenine in the serum and plasma were 1.96 ± 0.51 μM and 1.82 ± 0.54 μM, respectively. Regional differences in metabolite concentrations were observed across America, Asia, Australia, Europe and the Middle East. Of the total variance within the data, mode of detection (MOD) accounted for up to 2.96%, sample matrix up to 3.23%, and their interaction explained up to 1.53%; the latter of which was determined to be negligible. This review was intended to inform future empirical research and method development studies and successfully synthesised pilot data. The pilot data reported in this study will inform future precision medicine initiatives aimed at targeting the kynurenine pathway by improving the availability and quality of normative data.
Clinical spectrum of myelin oligodendrocyte glycoprotein antibody-associated disease in Brazil: a single-center experience

Abstract Background Anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibody-associated disease (MOGAD) is an immune-mediated neurological disorder with a broad spectrum of clinical presentation that is often difficult to distinguish from other demyelinating diseases, such as multiple sclerosis and neuromyelitis optica spectrum disorder. Objective To describe the clinical and paraclinical characteristics of MOGAD in a Brazilian tertiary center. Methods We retrospectively reviewed the records of adult and pediatric patients who tested positive for anti-MOG antibodies and presented with clinical and radiological diseases compatible with MOGAD. Results Forty-one patients (10 children) were included: 56% female, 58% Caucasian, mean age at onset 31 years (range 6-64), with a mean disease duration of 59.6 months (range 1-264 months). The most frequent onset presentation was optic neuritis (68%), acute disseminated encephalomyelitis (ADEM, 12%), and myelitis (10%). A monophasic disease course was observed in 49%. EDSS median was 2.1 at the last visit. Most patients (83%) were under continuous immunosuppressive treatment. Azathioprine was the first-line treatment in 59%. In all ADEM cases, conus, and root involvement was radiologically observed on MRI. Conclusion Brazilian MOGAD patients presented with a similar spectrum of previously reported MOGAD phenotypes. Conus and spinal root involvement seems to be frequently present in MOGAD-ADEM and could serve as radiologic characteristics of this clinical entity.
Analyzing drama metadata through machine learning to gain insights into social information dissemination patterns

TV drama, through synchronization with social phenomena, allows the audience to resonate with the characters and desire to watch the next episode. In particular, drama ratings can be the criterion for advertisers to invest in ad placement and a predictor of subsequent economic efficiency in the surrounding areas. To identify the dissemination patterns of social information about dramas, this study used machine learning to predict drama ratings and the contribution of various drama metadata, including broadcast year, broadcast season, TV stations, day of the week, broadcast time slot, genre, screenwriters, status as an original work or sequel, actors and facial features on posters. A total of 800 Japanese TV dramas broadcast during prime time between 2003 and 2020 were collected for analysis. Four machine learning classifiers, including naïve Bayes, artificial neural network, support vector machine, and random forest, were used to combine the metadata. With facial features, the accuracy of the random forest model increased from 75.80% to 77.10%, which shows that poster information can improve the accuracy of the overall predicted ratings. Using only posters to predict ratings with a convolutional neural network still obtained an accuracy rate of 71.70%. More insights about the correlations between drama metadata and social information dissemination patterns were explored.
Link prediction and feature relevance in knowledge networks: A machine learning approach

We propose a supervised machine learning approach to predict partnership formation between universities. We focus on successful joint R&D projects funded by the Horizon 2020 programme in three research domains: Social Sciences and Humanities, Physical and Engineering Sciences, and Life Sciences. We perform two related analyses: link formation prediction, and feature importance detection. In predicting link formation, we consider two settings: one including all features, both exogenous (pertaining to the node) and endogenous (pertaining to the network); and one including only exogenous features (thus removing the network attributes of the nodes). Using out-of-sample cross-validated accuracy, we obtain 91% prediction accuracy when both types of attributes are used, and around 67% when using only the exogenous ones. This proves that partnership predictive power is on average 24% larger for universities already incumbent in the programme than for newcomers (for which network attributes are clearly unknown). As for feature importance, by computing super-learner average partial effects and elasticities, we find that the endogenous attributes are the most relevant in affecting the probability to generate a link, and observe a largely negative elasticity of the link probability to feature changes, fairly uniform across attributes and domains.
Patient and Hospital Characteristics Associated With the Interhospital Transfer of Adult Patients With Sepsis

IMPORTANCE: The interhospital transfer (IHT) of patients with sepsis to higher-capability hospitals may improve outcomes. Little is known about patient and hospital factors associated with sepsis IHT. OBJECTIVES: We evaluated patterns of hospitalization and IHT and determined patient and hospital factors associated with the IHT of adult patients with sepsis. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: A total of 349,938 adult patients with sepsis at 329 nonfederal hospitals in California, 2018–2019. MAIN OUTCOMES AND MEASURES: We evaluated patterns of admission and outward IHT between low sepsis-, intermediate sepsis-, and high sepsis-capability hospitals. We estimated odds of IHT using generalized estimating equations logistic regression with bootstrap stepwise variable selection. RESULTS: Among the cohort, 223,202 (66.4%) were initially hospitalized at high-capability hospitals and 10,870 (3.1%) underwent IHT. Nearly all transfers (98.2%) from low-capability hospitals were received at higher-capability hospitals. Younger age (< 65 yr) (adjusted odds ratio [aOR] 1.54; 95% CI, 1.40–1.69) and increasing organ dysfunction (aOR 1.22; 95% CI, 1.19–1.25) were associated with higher IHT odds, as were admission to low-capability (aOR 2.79; 95% CI, 2.33–3.35) or public hospitals (aOR 1.35; 95% CI, 1.09–1.66). Female sex (aOR 0.88; 95% CI, 0.84–0.91), Medicaid insurance (aOR 0.59; 95% CI, 0.53–0.66), home to admitting hospital distance less than or equal to 10 miles (aOR 0.92; 95% CI, 0.87–0.97) and do-not-resuscitate orders (aOR 0.48; 95% CI, 0.45–0.52) were associated with lower IHT odds, as was admission to a teaching hospital (aOR 0.83; 95% CI, 0.72–0.96). CONCLUSIONS AND RELEVANCE: Most patients with sepsis are initially hospitalized at high-capability hospitals. The IHT rate for sepsis is low and more likely to originate from low-capability and public hospitals than from high-capability and for-profit hospitals. Transferred patients with sepsis are more likely to be younger, male, sicker, with private medical insurance, and less likely to have care limitation orders. Future studies should evaluate the comparative benefits of IHT from low-capability hospitals.
Nutrient Requirements and Optimal Nutrition Winter Cholecalciferol Supplementation at 51 ° N Has No Effect on Markers of Cardiometabolic Risk in Healthy Adolescents Aged 14 – 18 Years

Background: Epidemiologic studies have supported inverse associations between low serum 25-hydroxyvitamin D [25(OH)D] and cardiometabolic risk markers, but few randomized trials have investigated the effect of vitamin D supplementation on these markers in adolescents. Objective: The objective of this study was to investigate the effect of winter-time cholecalciferol (vitamin D3) supplementation on cardiometabolic risk markers in white, healthy 14to 18-y-old adolescents in the UK (51°N) as part of the ODIN Project. Methods: In a dose-response trial, 110 adolescents (mean ± SD age: 15.9 ± 1.4 y; 43%male; 81% normal weight) were randomly assigned to receive 0, 10 or 20 μg/d vitamin D3 for 20 wk (October–March). Cardiometabolic risk markers including BMI-for-age z score (BMIz), waist circumference, systolic and diastolic blood pressure, fasting plasma triglycerides, cholesterol (total, HDL, LDL, and total:HDL), and glucose were measured at baseline and endpoint as secondary outcomes, together with serum 25(OH)D. Intervention effects were evaluated in linear regression models as betweengroup differences at endpoint, adjusted for the baseline value of the outcome variable and additionally for age, sex, Tanner stage, BMIz, and baseline serum 25(OH)D. Results: Mean ± SD baseline serum 25(OH)D was 49.1 ± 12.3 nmol/L and differed between groups at endpoint with concentrations of 30.7 ± 8.6, 56.6 ± 12.4, and 63.9 ± 10.6 nmol/L in the 0, 10, and 20 μg/d groups, respectively (P ≤ 0.001). Vitamin D3 supplementation had no effect on any of the cardiometabolic risk markers (all P > 0.05), except for lower HDL (−0.12 mmol/L; 95% CI: −0.21, 0.04 mmol/L; P = 0.003) and total cholesterol (−0.21 mmol/L; 95% CI: −0.42, 0.00 mmol/L; P = 0.05) in the 20 μg/d than in the 10 μg/d group, which disappeared in the fully adjusted analysis (P = 0.27 and P = 0.30, respectively). Conclusions: Supplementation with vitamin D3 at 10 and 20 μg/d, which increased serum 25(OH)D concentrations during the winter-time, had no effect on markers of cardiometabolic risk in healthy 14to 18-y-old adolescents. This trial was registered at clinicaltrials.gov as NCT02150122. J Nutr 2018;148:1–7.