Miracle-dz/UniFAR-FTUs huggingface dataset:
Kaposi's sarcoma‐associated herpesvirus and extracellular vesicles

Kaposi's sarcoma‐associated herpesvirus (KSHV) represents the etiological agent for several human malignancies, including Kaposi's Sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD), which develop mainly in immunocompromised patients. KSHV has established many strategies to hijack and thwart the host's immune responses, including through the use of extracellular vesicles (EVs). EVs represent a significant mode of intercellular communication as they carry a variety of molecules that can be delivered from cell‐to‐cell. EVs are now recognized as one of the major players in immune system development and function during both innate and adaptive immune responses. In the current mini‐review, we summarize recent findings on how KSHV utilizes EVs to create favorable environments for viral spread and persistence while evading immune responses. We also discuss the limitations and unanswered questions in this field and the potential areas for related immunotherapies.
Mortality Among Young Adults Born Preterm and Early Term in 4 Nordic Nations

Key Points Question Are all-cause and noncommunicable disease (NCD) mortality risks higher amomg adults born preterm and early term compared with those born at full term? Findings This cohort study of more than 6.1 million individuals from 4 Nordic birth cohorts provided found all degrees of preterm birth and early-term birth are associated with increased risk of premature adult death. Excess mortality associated with shorter gestation was pronounced for death from NCDs, such as cardiovascular diseases, chronic lung disease, and diabetes. Meaning These findings suggest that increased early adult mortality associated with shorter gestation includes excess risk in the large group of adults born late preterm and early term and is pronounced for NCD deaths.
A municipality-level analysis of excess mortality in Italy in the period January-April 2020.

BACKGROUND the first confirmed cases of COVID-19 in WHO European Region was reported at the end of January 2020 and, from that moment, the epidemic has been speeding up and rapidly spreading across Europe. The health, social, and economic consequences of the pandemic are difficult to evaluate, since there are many scientific uncertainties and unknowns. OBJECTIVES the main focus of this paper is on statistical methods for profiling municipalities by excess mortality, directly or indirectly caused by COVID-19. METHODS the use of excess mortality for all causes has been advocated as a measure of impact less vulnerable to biases. In this paper, observed mortality for all causes at municipality level in Italy in the period January-April 2020 was compared to the mortality observed in the corresponding period in the previous 5 years (2015-2019). Mortality data were made available by the Ministry of Internal Affairs Italian National Resident Population Demographic Archive and the Italian National Institute of Statistics (Istat). For each municipality, the posterior predictive distribution under a hierarchical null model was obtained. From the posterior predictive distribution, we obtained excess death counts, attributable community rates and q-values. Full Bayesian models implemented via MCMC simulations were used. RESULTS absolute number of excess deaths highlights the burden paid by major cities to the pandemic. The Attributable Community Rate provides a detailed picture of the spread of the pandemic among the municipalities of Lombardy, Piedmont, and Emilia-Romagna Regions. Using Q-values, it is clearly recognizable evidence of an excess of mortality from late February to April 2020 in a very geographically scattered number of municipalities. A trade-off between false discoveries and false non-discoveries shows the different values of public health actions. CONCLUSIONS despite the variety of approaches to calculate excess mortality, this study provides an original methodological approach to profile municipalities with excess deaths accounting for spatial and temporal uncertainty.
Development and Validation of a Machine Learning Model to Predict Near-Term Risk of Iatrogenic Hypoglycemia in Hospitalized Patients

Key Points Question Can the risk of iatrogenic hypoglycemia resulting from insulin or insulin secretagogues be predicted continuously throughout hospitalization without the use of continuous glucose monitors? Findings In this cohort study of 54 978 admissions in a large US health care system, a stochastic gradient boosting machine learning model using 43 static and time-varying clinical predictors available in the electronic medical record accurately predicted the risk of iatrogenic hypoglycemia in a prediction horizon of 24 hours from the time of each point-of-care and serum glucose measurement throughout a patient’s hospital admission. Meaning These findings suggest that translating this machine learning prediction model into a real-time informatics alert embedded in the electronic medical record has the potential to reduce the incidence of iatrogenic hypoglycemia, a serious adverse event.
Effects of Inspiratory Muscle Training on Respiratory Muscle Strength, Trunk Control, Balance and Functional Capacity in Stroke Patients: A single-blinded randomized controlled study

ABSTRACT Objective Aim of the study was to examine the effects of inspiratory muscle training (IMT) on respiratory function, respiratory muscle strength, trunk control, balance, and functional capacity in stroke patients. Methods 21 stroke individuals were randomly divided into two groups as control group and treatment group. Respiratory function test, Maximal Inspiratory Pressure (MIP) and Maximal Expiratory Pressure (MEP) were evaluated. Also, Trunk Impairment Scale (TIS), Timed Up and Go Test (TUG) Berg Balance Scale (BBS), and Six-Minute Walk Test (6MWT) were performed. Neurodevelopmental treatment program was performed in both groups for 5 days a week for 6 weeks, and IMT was given to the treatment group. IMT was started from 40% of MIP. Results After treatment, respiratory functions, respiratory muscle strength, and trunk control and balance improved in the treatment group. In the control group; however, only the balance level was improved. When the changes in the evaluation parameters between the groups were compared, there were only statistically significant differences in the TIS, Peak Expiratory Flow (PEF) and MIP in the treatment group (p˂0.05), the change amounts in other evaluation parameters were similar (p˃0.05). When the effect size of the groups was compared, the effect size of the variables in the treatment group was found to be higher. Conclusion As a conclusion, IMT, which was given in addition to the neurological physiotherapy and rehabilitation program to our patients, improved inspiratory muscle strength and trunk control. We believe that this result will raise awareness for physiotherapists working in the field of neurological rehabilitation about including respiratory muscle training in the rehabilitation program of stroke patients.
Smithsonite Flotation from Zinc Oxide Ore using Alkyl Amine Acetate Collectors

Flotation of smithsonite from tailing coming from a cerussite flotation circuit was investigated using Armac C and Armac T as alkyl amine acetate collectors. The results showed that the dosage of Na2S, collector type and dosage, collector's mixture ratio, and desliming are the main affecting parameters on the Zn grade and recovery of smithsonite flotation concentrate. The contact angle measurement on smithsonite and calcite minerals indicated that Armac T acts more selectively than Armac C and enhances the Zn grade of the concentrate. At the mixture ratio of Armac C:Armac T, 1:6, the collectors' consumption are decreased significantly and an optimal concentrate with 94.4% recovery and 42.3% Zn grade is obtained without any gangue depressant reagents. Nevertheless, using NaOH as a pH regulator, the dosage of Na2S is decreased significantly but the flotation results are affected negatively. The recovery of Zn in the concentrate is more sensitive to the slime than Zn grade. The Zn minerals lost in the tailing are mostly in the form of very fine disseminated particles. About 11% of smithsonite with particle sizes finer than 10 µm is lost in the slime. Overall Zn flotation recovery is estimated to be about 84%.
Antagonistic effects of finerenone and spironolactone on the aldosterone‐regulated transcriptome of human kidney cells

Aldosterone, the main mineralocorticoid hormone in humans, plays a pivotal role in the control of water and salt reabsorption via activation of the mineralocorticoid receptor (MR). Alterations in MR signaling pathway lead to renal dysfunction, including chronic kidney disease and renal fibrosis, that can be prevented or treated with mineralocorticoid receptor antagonists (MRAs). Here, we used RNA‐Sequencing to analyze effects of two MRAs, spironolactone and finerenone, on the aldosterone‐induced transcriptome of a human renal cell line stably expressing the MR. Bioinformatics analysis of the data set reveals the identity of hundreds of genes induced or repressed by aldosterone. Their regulation is modulated in a time‐dependent manner and, for the induced genes, depends on the aldosterone‐driven direct binding of the MR onto its genomic targets that we have previously characterized. Although both MRAs block aldosterone‐induced as well as aldosterone‐repressed genes qualitatively similarly, finerenone has a quantitatively more efficient antagonism on some aldosterone‐induced genes. Our data provide the first complete transcriptome for aldosterone on a human renal cell line and identifies pro‐inflammatory markers (IL6, IL11, CCL7, and CXCL8) as aldosterone‐repressed genes.
Meningococcal carriage among Hajj pilgrims, risk factors for carriage and records of vaccination: a study of pilgrims to Mecca

The Saudi government requires that all pilgrims receive a quadrivalent meningococcal vaccine at least 10 days before the Hajj. We conducted a study to determine the uptake of meningococcal vaccine and antibiotic use. We also investigated risk factors of meningococcal carriage and carriage of Neisseria meningitidis pathogenic serogroups A, C, W and Y.
A nationwide study on Borrelia burgdorferi s.l. infection rates in questing Ixodes ricinus: a six‐year snapshot study in protected recreational areas in England and Wales

Understanding the variation in Borrelia burgdorferi s.l. infection rates in Ixodes ricinus ticks is important for assessing the potential for Lyme borreliosis transmission. This study aimed to investigate infection rates of B. burgdorferi s.l. bacteria in I. ricinus across 24 field sites in England and Wales, focussing on protected recreational areas in National Parks (NPs) and Areas of Outstanding Natural Beauty (AONBs), to provide comparable data across multiple years to assess spatio‐temporal changes in B. burgdorferi s.l. infection. Working with park rangers, questing ticks were collected each spring from 2014 to 2019. A subset of ticks, 4104 nymphs, were analysed using a pan‐Borrelia qPCR assay, as well as a Borrelia miyamotoi‐specific qPCR, and sequenced to determine Borrelia burgdorferi s.l. genospecies. Site‐specific B. burgdorferi s.l. infection rates in I. ricinus nymphs varied from 0% to 24%, with overall infection rates ranging from 2.5% to 5.1% across the years. Genospecies composition of sequenced samples was 62.5% B. garinii, 20.3% B. valaisiana and 17.2% B. afzelii. Borrelia miyamotoi was detected in 0.2% of ticks. This study increases our knowledge on B. burgdorferi s.l. infection in areas used by the public for outdoor activity across England and Wales, highlighting the spatial and temporal variability which can impact the changing risk to humans from infected tick bites.
Congenital Mirror Movements Associated With Brain Malformations

Background: Congenital mirror movements are involuntary movements of a side of the body imitating intentional movements on the opposite side, appearing in early childhood and persisting beyond 7 years of age. Congenital mirror movements are usually idiopathic but have been reported in association with various brain malformations. Methods: We describe clinical, genetic, and radiologic features in 9 individuals from 5 families manifesting congenital mirror movements. Results: The brain malformations associated with congenital mirror movements were: dysplastic corpus callosum in father and daughter with a heterozygous p.Met1* mutation in DCC; hypoplastic corpus callosum, dysgyria, and malformed vermis in a mother and son with a heterozygous p.Thr312Met mutation in TUBB3; dysplastic corpus callosum, dysgyria, abnormal vermis, and asymmetric ventricles in a father and 2 daughters with a heterozygous p.Arg121Trp mutation in TUBB; hypoplastic corpus callosum, dysgyria, malformed basal ganglia and abnormal vermis in a patient with a heterozygous p.Glu155Asp mutation in TUBA1A; hydrocephalus, hypoplastic corpus callosum, polymicrogyria, and cerebellar cysts in a patient with a homozygous p.Pro312Leu mutation in POMGNT1. Conclusion: DCC, TUBB3, TUBB, TUBA1A, POMGNT1 cause abnormal axonal guidance via different mechanisms and result in congenital mirror movements associated with brain malformations.
Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932

Purpose: AALL0932 evaluated two randomized maintenance interventions to optimize disease-free survival (DFS) while reducing the burden of therapy in children with newly diagnosed NCI standard-risk (SR) B-acute lymphoblastic leukemia (B-ALL). Methods: AALL0932 enrolled 9,229 patients with B-ALL; 2,364 average-risk (AR) patients were randomly assigned (2 × 2 factorial design) at the start of maintenance therapy to vincristine/dexamethasone pulses every 4 (VCR/DEX4) or every 12 (VCR/DEX12) weeks, and a starting dose of weekly oral methotrexate of 20 mg/m2 (MTX20) or 40 mg/m2 (MTX40). Results: Five-year event-free survival and overall survival (OS) from enrollment (with 95% CIs), for all eligible and evaluable SR B-ALL patients (n = 9,226), were 92.0% (91.1% and 92.8%) and 96.8% (96.2% and 97.3%), respectively. The 5-year DFS and OS from the start of maintenance for randomly assigned AR patients were 94.6% (93.3% and 95.9%) and 98.5% (97.7% and 99.2%), respectively. The 5-year DFS and OS for patients randomly assigned to receive VCR/DEX4 (n = 1,186) versus VCR/DEX12 (n = 1,178) were 94.1% (92.2% and 96.0%) and 98.3% (97.2% and 99.4%) v 95.1% (93.3% and 96.9%) and 98.6% (97.7% and 99.6%), respectively (P = .86 and .69). The 5-year DFS and OS for AR patients randomly assigned to receive MTX20 versus MTX40 were 95.1% (93.3% and 96.8%) and 98.8% (97.9% and 99.7%) v 94.2% (92.2% and 96.1%) and 98.1% (97.0% and 99.2%), respectively (P = .92 and .89). Conclusions: The 0NCI-SR AR B-ALL who received VCR/DEX12 had outstanding outcomes despite receiving one third of the vincristine/dexamethasone pulses previously used as standard of care on Children's Oncology Group (COG) trials. The higher starting dose of MTX of 40 mg/m2/week did not improve outcomes when compared with 20 mg/m2/week. The decreased frequency of vincristine/dexamethasone pulses has been incorporated into frontline COG B-ALL trials to decrease the burden of therapy for patients and their families.
Combining botanical collections and ecological data to better describe plant community diversity

In this age of rapid biodiversity loss, we must continue to refine our approaches to describing variation in life on Earth. Combining knowledge and research tools from multiple disciplines is one way to better describe complex natural systems. Understanding plant community diversity requires documenting both pattern and process. We must first know which species exist, and where (i.e., taxonomic and biogeographic patterns), before we can determine why they exist there (i.e., ecological and evolutionary processes). Floristic botanists often use collections-based approaches to elucidate biodiversity patterns, while plant ecologists use hypothesis-driven statistical approaches to describe underlying processes. Because of these different disciplinary histories and research goals, floristic botanists and plant ecologists often remain siloed in their work. Here, using a case study from an urban greenway in Colorado, USA, we illustrate that the collections-based, opportunistic sampling of floristic botanists is highly complementary to the transect- or plot-based sampling of plant ecologists. We found that floristic sampling captured a community species pool four times larger than that captured using ecological transects, with rarefaction and non-parametric species estimation indicating that it would be prohibitive to capture the “true” community species pool if constrained to sampling within transects. We further illustrate that the discrepancy in species pool size between approaches led to a different interpretation of the greenway’s ecological condition in some cases (e.g., transects missed uncommon cultivated species escaping from nearby gardens) but not others (e.g., plant species distributions among functional groups were similar between species pools). Finally, we show that while using transects to estimate plant relative abundances necessarily trades off with a fuller assessment of the species pool, it is an indispensable indicator of ecosystem health, as evidenced by three non-native grasses contributing to 50% of plant cover along the highly modified urban greenway. We suggest that actively fostering collaborations between floristic botanists and ecologists can create new insights into the maintenance of species diversity at the community scale.
Epigenetic Regulatory Enzymes: mutation Prevalence and Coexistence in Cancers

Abstract Epigenetic regulation is an important layer of transcriptional control with the particularity to affect the broad spectrum of genome. Over the years, largely due to the substantial number of recurrent mutations, there have been hundreds of novel driver genes characterized in various cancers. Additionally, the relative contribution of two dysregulated epigenomic entities (DNA methylation and histone modifications) that gradually drive the cancer phenotype remains in the research focus. However, a complex scenario arises when the disease phenotype does not harbor any relevant mutation or an abnormal transcription level. Although the cancer landscape involves the contribution of multiple genetic and non-genetic factors, herein, we discuss specifically the mutation spectrum of epigenetically-related enzymes in cancer. In addition, we address the coexistence of these two epigenetic entities in malignant human diseases, especially cancer. We suggest that the study of epigenetically-related somatic mutations in the early cellular differentiation stage of embryonic development might help to understand their later-staged footprints in the cancer genome. Furthermore, understanding the co-occurrence and/or inverse association of different disease types and redefining the general definition of “healthy” controls could provide insights into the genome reorganization.
Dual trajectories of fatigue and disease activity in an inception cohort of adults with systemic lupus erythematosus over 10 years

Objectives Fatigue is one of the most common symptoms reported in patients living with SLE. We aim to: 1) determine if different trajectories of fatigue associate with specific latent classes of disease activity and 2) define the patient characteristics and associated factors in different latent classes. Methods Data from an inception cohort of adult patients from the Toronto Lupus Clinic from 1997-2018 were analyzed. Fatigue levels were measured using Fatigue Severity Scale (FSS) and disease activity by the Adjusted Mean Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) (AMS). Dual latent class trajectory analysis, for fatigue and AMS, was performed. Univariable and multivariable logistic regression analyses assessed the association of baseline variables with class membership. Results Among 280 patients, 4 dual classes (C) of fatigue and disease activity were identified: C1- lowest disease activity and second highest fatigue trajectory (27%); C2- second highest disease activity and highest fatigue trajectory (30%); C3-moderate disease activity and lowest fatigue trajectory (33%); and C4- highest disease activity and moderate fatigue trajectory (10%). Conclusion 4 distinct latent classes of dual fatigue and disease activity trajectories were identified. Fatigue and disease activity follow distinct trajectories and disease activity alone cannot fully explain fatigue trajectories. Trajectories with higher FSS scores were associated with more fibromyalgia and trajectories with higher disease activity were associated with higher cumulative glucocorticoid use. Higher baseline glucocorticoid use was more likely associated with more fatigue while older age at SLE diagnosis was associated with less fatigue.
A Comprehensive Self-Management Program With Diet Education Does Not Alter Microbiome Characteristics in Women With Irritable Bowel Syndrome

Background and Purpose: Changes in diet and lifestyle factors are frequently recommended for persons with irritable bowel syndrome (IBS). It is unknown whether these recommendations alter the gut microbiome and/or whether baseline microbiome predicts improvement in symptoms and quality of life following treatment. Therefore, the purpose of this study was to explore if baseline gut microbiome composition predicted response to a Comprehensive Self-Management (CSM) intervention and if the intervention resulted in a different gut microbiome composition compared to usual care. Methods: Individuals aged 18–70 years with IBS symptoms ≥6 months were recruited using convenience sampling. Individuals were excluded if medication use or comorbidities would influence symptoms or microbiome. Participants completed a baseline assessment and were randomized into the eight-session CSM intervention which included dietary education and cognitive behavioral therapy versus usual care. Questionnaires included demographics, quality of life, and symptom diaries. Fecal samples were collected at baseline and 3-month post-randomization for 16S rRNA-based microbiome analysis. Results: Within the CSM intervention group (n = 30), Shannon diversity, richness, and beta diversity measures at baseline did not predict benefit from the CSM intervention at 3 months, as measured by change in abdominal pain and quality of life. Based on both alpha and beta diversity, the change from baseline to follow-up microbiome bacterial taxa did not differ between CSM (n = 25) and usual care (n = 25). Conclusions and Inferences: Baseline microbiome does not predict symptom improvement with CSM intervention. We do not find evidence that the CSM intervention influences gut microbiome diversity or composition over the course of 3 months.