Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunogenomic identification and characterization of granulocytic myeloid derived suppressor cells in multiple myeloma.

Granulocytic myeloid-derived suppressor cells (G-MDSCs) promote tumor growth and immunosuppression in multiple myeloma (MM). However, their phenotype is not well-established for accurate monitoring and clinical translation. Here, we aimed at providing the phenotypic profile of G-MDSCs based on their prognostic significance in MM, immunosuppressive potential, and molecular program. The pre-established phenotype of G-MDSCs was evaluated in bone marrow samples from controls and MM patients using multidimensional flow cytometry and, surprisingly, we found that CD11b+CD14-CD15+CD33+HLADR- cells overlapped with common eosinophils and neutrophils, which were not expanded in MM patients. Thus, we relied on automated clustering to unbiasedly identify all granulocytic subsets in the tumor microenvironment: basophils, eosinophils, immature, intermediate and mature neutrophils. In a series of 267 newly-diagnosed MM patients (GEM2012MENOS65 trial), only the frequency of mature neutrophils at diagnosis was significantly associated with patients' outcome, and a high mature-neutrophils/T-cell ratio resulted in inferior progression-free survival (P<.001). Upon FACSorting of each neutrophil subset, T cell proliferation decreased in presence of mature neutrophils (0.5-fold; P=.016) and the cytotoxic potential of T cells engaged by a BCMAxCD3 bispecific antibody increased notably with the depletion of mature neutrophils (4-fold; P=.0007). Most interestingly, RNAseq of the three subsets revealed that G-MDSCs-related genes were specifically upregulated in mature neutrophils from MM patients vs controls due to differential chromatin accessibility. Taken together, we established a correlation between the clinical significance, immunosuppressive potential and transcriptional network of well-defined neutrophil subsets, providing for the first time, a set of optimal markers (CD11b/CD13/CD16) for accurate monitoring of G-MDCSs in MM.
Impact of Telerehabilitation for Stroke-Related Deficits.

Background: Stroke is the leading cause of serious long-term disability in the United States. Barriers to rehabilitation include cost, transportation, lack of trained personnel, and equipment. Telerehabilitation (TR) has emerged as a promising modality to reduce costs, improve accessibility, and retain patient independence. TR allows providers to remotely administer therapy, potentially increasing access to underserved regions. Objectives: To describe types of stroke rehabilitation therapy delivered through TR and to evaluate whether TR is as effective as traditional in-person outpatient therapy in improving satisfaction and poststroke residual deficits such as motor function, speech, and disability. Methods: A literature search of the term "telerehabilitation and stroke" was conducted across three databases. Full-text articles with results pertaining to TR interventions were reviewed. Articles were scored for methodological quality using the PEDro scale. Results: Thirty-four articles with 1,025 patients were included. Types of TR included speech therapy, virtual reality (VR), robotic, community-based, goal setting, and motor training exercises. Frequently measured outcomes included motor function, speech, disability, and satisfaction. All 34 studies reported improvement from baseline after TR therapy. PEDro scores ranged from 2 to 8 with a mean of 4.59 ± 1.94 (on a scale of 0-10). Studies with control interventions, randomized allocation, and blinded assessment had significantly higher PEDro scores. All 15 studies that compared TR with traditional therapy showed equivalent or better functional outcomes. Home-based robotic therapy and VR were less costly than in-person therapy. Patient satisfaction with TR and in-person clinical therapy was similar. Conclusions: TR is less costly and equally as effective as clinic-based rehabilitation at improving functional outcomes in stroke patients. TR produces similar patient satisfaction. TR can be combined with other therapies, including VR, speech, and robotic assistance, or used as an adjuvant to direct in-person care.
The Study of Health-Related Fitness Normative Scores for Nepalese Older Adults

Physical fitness tests are important to maintain and promote the health status of people. The purpose of this study was to develop health-related fitness evaluation norms according to the age and gender of Nepalese older adults. One thousand nine subjects (449 males, 560 females) above 60 years, residing in 19 wards (rural and urban) of Dhangadhi Sub-Metropolitan City participated in this study. The test included the PAR-Q (Physical Activity Readiness Questionnaire), social aspects questionnaire, blood pressure test, height, weight, BMI (body mass index), percent body fat, and four physical fitness components (grip strength, 1-minute sit-to-stand, sit and reach, and 2-minute step tests). Mean, SD, and fitness evaluation norms for each component were obtained after the main test and statistical analyses. This study showed higher BMI and percent body fat in female age groups than in male age groups. Grip strength, relative grip strength, sit-to-stand, and 2-minute steps scores were better in male age groups than in female age groups, but in contrast, flexibility was better in female age groups. This study may help the related sectors to assess physical fitness, identify fitness levels, and develop appropriate physical activities or exercise programs for older adults based on age.
Shape Memory Alloys for Aerospace, Recent Developments, and New Applications: A Short Review

Shape memory alloys (SMAs) show a particular behavior that is the ability to recuperate the original shape while heating above specific critical temperatures (shape memory effect) or to withstand high deformations recoverable while unloading (pseudoelasticity). In many cases the SMAs play the actuator’s role. Starting from the origin of the shape memory effect, the mechanical properties of these alloys are illustrated. This paper presents a review of SMAs applications in the aerospace field with particular emphasis on morphing wings (experimental and modeling), tailoring of the orientation and inlet geometry of many propulsion system, variable geometry chevron for thrust and noise optimization, and more in general reduction of power consumption. Space applications are described too: to isolate the micro-vibrations, for low-shock release devices and self-deployable solar sails. Novel configurations and devices are highlighted too.
Functional Characterization of PHEX Gene Variants in Children With X‐Linked Hypophosphatemic Rickets Shows No Evidence of Genotype–Phenotype Correlation

X‐linked hypophosphatemia (XLHR) is caused by loss‐of‐function mutations in the phosphate regulating endopeptidase homolog X‐linked (PHEX) gene. Considerable controversy exists regarding genotype–phenotype correlations in XLHR. The present study describes the clinical features and molecular genetic bases of 53 pediatric patients with XLHR. Overall, 47 different mutations were identified, of which 27 were not previously described in the literature or entered in the Human Gene Mutation Database (HGMD). A high prevalence (72.34%) of truncating variants was observed in XLHR patients. The clinical presentation and severity of XLHR did not show an evident correlation between the truncating and non‐truncating mutation types in our cohort. To further delineate the characteristics of PHEX variants underlying this nonsignificant trend, we assessed the effects of 10 PHEX variants on protein expression, cellular trafficking, and endopeptidase activity. Our results showed that the nonsense mutations p.Arg567*, p.Gln714*, and p.Arg747* caused a reduction of protein molecular weight and a trafficking defect. Among seven non‐truncating mutations, the p.Cys77Tyr, p.Cys85Ser, p.Ile281Lys, p.Ile333del, p.Ala514Pro, and p.Gly572Ser mutants were not secreted into the medium and remained trapped inside cells in an immature form, whereas the p.Gly553Glu mutant was terminally glycosylated and secreted into the medium. We further assessed the endopeptidase activity of the p.Gly553Glu mutant using a quenched fluorogenic peptide substrate and revealed that the activity of p.Gly553Glu significantly reduced to 13% compared with the wild type, which indicated disruption of catalytic function. These data not only support the clinical results showing no correlation between disease severity and the type of PHEX mutation but also provide helpful molecular insights into the pathogenesis of XLHR. © 2020 American Society for Bone and Mineral Research.
Relaxation Dynamics of Chlorophyll b in the Sub-ps Ultrafast Timescale Measured by 2D Electronic Spectroscopy

A thorough characterization of the early time sub-100 fs relaxation dynamics of biologically relevant chromophores is of crucial importance for a complete understanding of the mechanisms regulating the ultrafast dynamics of the relaxation processes in more complex multichromophoric light-harvesting systems. While chlorophyll a has already been the object of several investigations, little has been reported on chlorophyll b, despite its pivotal role in many functionalities of photosynthetic proteins. Here the relaxation dynamics of chlorophyll b in the ultrafast regime have been characterized using 2D electronic spectroscopy. The comparison of experimental measurements performed at room temperature and 77 K allows the mechanisms and the dynamics of the sub-100 fs relaxation dynamics to be characterized, including spectral diffusion and fast internal conversion assisted by a specific set of vibrational modes.
Association between Rumen Microbiota and Marbling Score in Korean Native Beef Cattle

Simple Summary The ruminal microbiome affects various metabolic processes associated with animal development; however, few studies have focused on its correlation with marbling. Results of the present study show differences in ruminal microbiomes among Hanwoo Korean beef cattle, which have low or high marbling scores. By elucidating the effect of the ruminal microbiome on the marbling of Hanwoo, differentially abundant microbial taxa, ruminal taxonomic drivers of lipid metabolism, and the correlation with meat quality indices, the present study provides insights into the potential effects of microbial factors on marbling in beef cattle. Abstract This study demonstrated the potential effects of the rumen microbiota on the deposition of intramuscular fat, known as marbling. Previous studies on fatty acid metabolism in beef cattle have mostly focused on biohydrogenating rumen bacteria, whereas those on the overall rumen microbiota—to understand their roles in marbling—have not been systematically performed. The rumen microbiota of 14 Korean beef cattle (Hanwoo), which showed similar carcass characteristics and blood metabolites but different marbling scores, were analyzed by 16S rRNA gene sequencing. The rumen samples were grouped into two extreme marbling score groups of host animals as follows: LMS, marbling score≤ 4 or HMS, marbling score ≥7. Species richness tended to be higher in the HMS group, whereas the overall microbiota differed between LMS and HMS groups. RFP12, Verrucomicrobia, Oscillospira, Porphyromonadaceae, and Paludibacter were differentially abundant in the HMS group, whereas Olsenella was abundant in the LMS group. Some marbling-associated bacterial taxa also contributed to the enrichment of two lipid metabolic pathways including “alpha-linolenic acid metabolism” and “fatty acid biosynthesis” in the HMS microbiome. Taxonomic drivers of fatty acid biosynthesis, particularly in the rumen microbiome of high-marbled meat, could thus be further studied to increase the intramuscular fat content.
Stress-Sensing Method via Laser-Generated Ultrasound Wave Using Candle Soot Nanoparticle Composite

This article aims to develop a semi-noncontact stress-sensing system using a laser-generated ultrasound (LGU) wave assisted by candle soot nanoparticle (CSNP) composite. While the acoustoelastic effect is commonly targeted to measure the stress level, efforts to combine it with the LGU wave signal have been lacking due to weak signal intensity. In this study, the CSNP-based transducer is designed to potentiate the photoacoustic energy conversion. To demonstrate the wave propagation with the designed parameters, a numerical simulation was first conducted. The experimental results showed that a laser intensity of 6.5 mJ/cm2 was enough to generate the subsurface longitudinal (SSL) wave from the CSNP composite transducer. The normal beam projection is the most effective wave-generation method, exhibiting the highest signal magnitude compared with inclined projection cases. Finally, the laser-assisted stress-sensing system was assessed by increasing the internal pressure of an air tank. The sensitivity of the developed sensor system was estimated to be 0.296 ns/MPa, showing a correlation of 0.983 with the theoretical prediction. The proposed sensing system can be used to monitor the structural integrity of nuclear power plants.
Amino Acid Deletions in p6Gag Domain of HIV-1 CRF07_BC Ameliorate Galectin-3 Mediated Enhancement in Viral Budding

HIV-1 CRF07_BC is a recombinant virus with amino acid (a.a.) deletions in p6Gag, which are overlapped with the Alix-binding domain. Galectin-3 (Gal3), a β-galactose binding lectin, has been reported to interact with Alix and regulate HIV-1 subtype B budding. This study aims to evaluate the role of Gal3 in HIV-1 CRF07_BC infection and the potential effect of a.a. deletions on Gal3-mediated regulation. A total of 38 HIV-1+ injecting drug users (IDUs) were enrolled in the study. Viral characterization and correlation of Gal3 were validated. CRF07_BC containing 7 a.a. deletions and wild-type in the p6Gag (CRF07_BC-7d and -wt) were isolated and infectious clones were generated. Viral growth kinetic and budding assays using Jurkat-CCR5/Jurkat-CCR5-Gal3 cells infected with CRF07_BC were performed. Results indicate that 69.4% (25/38) of the recruited patients were identified as CRF07_BC, and CRF07_BC-7d was predominant. Slow disease progression and significantly higher plasma Gal3 were noted in CRF07_BC patients (p < 0.01). Results revealed that CRF07_BC infection resulted in Gal3 expression, which was induced by Tat. Growth dynamic and budding assays indicated that Gal3 expression in Jurkat-CCR5 cells significantly enhanced CRF07_BC-wt replication and budding (p < 0.05), while the promoting effect was ameliorated in CRF07_BC-7d. Co-immunoprecipitation found that deletions in the p6Gag reduced Gal-3-mediated enhancement of the Alix–Gag interaction.
Predictors of Need for Non-Invasive Mechanical Ventilation in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Background: COPD remains a common cause of morbidity and mortality worldwide. NIV has been well established as the gold standard therapy for treatment of acute decompensated respiratory failure complicating an acute exacerbation of COPD (AECOPD) with reduced mortality and intubation rates compared to standard therapy. Objective: to evaluate the predictors for the need for NIV in management of AECOPD. Methods: Eighty adult patients previously diagnosed as COPD presented with AECOPD were assessed with recording of demographic and clinical data, arterial blood gases (ABGs), C-reactive protein (CRP), serum electrolytes (sodium (Na)&potassium (K)) with previously performed spirometry. Results: The current study showed higher smoking frequency and smoking index in group II patients that were treated with NIV, BMI mean ± SD. was significantly higher in group I who were treated without need for NIV. Group II was presented by more frequent AECOPD, higher heart rate and respiratory rate and longer duration of hospital stay. More cases of group II showed positive CRP (60%) versus 46.7% of group I cases, while mean ± SD of CRP showed insignificant differences between both groups. Serum Na and K were significantly lower in group II. There was significant differences between both groups as regards PH and PaO2/FiO2 as these values were significantly lower in group II patients. Univariate regression analysis elucidated that higher smoking index (SI), PaCO2, and frequent AECOPD were independent positive predictors of the need for NIV in treating cases of AECOPD and higher PaO2 and PaO2/FiO2 were negative predictors of its requirement. Conclusions: Higher smoking index and frequency, more frequent COPD exacerbations, higher heart rate and respiratory rate,lower serum electrolytes (Na & K),lower PH and PaO2/FiO2 can significantly indicate a more severe AECOPD and higher smoking index (SI), PaCO2, frequent AECOPD, or lower PaO2 and Pao2/FiO2 can be used as independent predictors for the need for NIV.
Insights into Genetic Susceptibility to Melanoma by Gene Panel Testing: Potential Pathogenic Variants in ACD, ATM, BAP1, and POT1

The contribution of recently established or candidate susceptibility genes to melanoma missing heritability has yet to be determined. Multigene panel testing could increase diagnostic yield and better define the role of candidate genes. We characterized 273 CDKN2A/ARF and CDK4-negative probands through a custom-designed targeted gene panel that included CDKN2A/ARF, CDK4, ACD, BAP1, MITF, POT1, TERF2IP, ATM, and PALB2. Co-segregation, loss of heterozygosity (LOH)/protein expression analysis, and splicing characterization were performed to improve variant classification. We identified 16 (5.9%) pathogenic and likely pathogenic variants in established high/medium penetrance cutaneous melanoma susceptibility genes (BAP1, POT1, ACD, MITF, and TERF2IP), including two novel variants in BAP1 and 4 in POT1. We also found four deleterious and five likely deleterious variants in ATM (3.3%). Thus, including potentially deleterious variants in ATM increased the diagnostic yield to about 9%. Inclusion of rare variants of uncertain significance would increase the overall detection yield to 14%. At least 10% of melanoma missing heritability may be explained through panel testing in our population. To our knowledge, this is the highest frequency of putative ATM deleterious variants reported in melanoma families, suggesting a possible role in melanoma susceptibility, which needs further investigation.
Reproductive tract diseases in female backyard chickens (Gallus gallus domesticus) – diagnostic imaging and final outcome during a decade

Abstract Objective Female reproductive tract disorders are common conditions of backyard poultry with an increasing demand for individual veterinary care. However, only limited case reports are available on diagnostic workup and outcomes of individual cases. This study aims at giving an overview of usually presented reproductive tract disorders, comparing diagnostic imaging findings with final diagnoses, and summarizing the outcome of the respective diseases. Material and methods The digital medical records archive of the University for Veterinary Medicine in Vienna was searched for chickens that were finally diagnosed with diseases of the reproductive tract, including all patients from May 1st, 2009 to May 31st, 2019. Information such as patient age, medical history, results of diagnostic imaging, final confirmed diagnosis, outcome, surgical protocol and necropsy findings was extracted. Results Finally confirmed reproductive tract diseases were found in 57 of 315 female chickens. The most common conditions were egg-related coelomitis along with salpingitis or impacted salpinx (25/57), followed by ovarian or oviductal neoplasia (17/57). Clinical findings were unspecific in the majority of cases, but most conspicuous were chickens presented with a distended coelomic cavity and apathy. Coelomic ultrasonography as well as computed tomography proved to be valuable tools for distinguishing between the respective conditions. However, ultrasonography alone mainly failed (10/11) to differentiate between ovary or oviductal neoplasia and egg-related coelomitis with salpingitis or impacted salpinx, respectively. Computed tomography was perceived as a superior tool for final diagnosis. In total 6/6 CT-scans correctly made a definitive diagnosis. Nevertheless, accurate diagnosis was only possible after celiotomy with the necessity of consecutive surgery for most of the reported cases. As an overall outcome 34 of 57 patients were either euthanised or died, whereas only 23 chickens could be successfully treated and discharged. Several hens were reported to be doing well at home, according to regular check-up procedures within 4 years post-surgery. Conclusion and clinical relevance Diagnostic work-up and treatment of hens with reproductive tract diseases can be challenging. Clinical presentation and diagnostic imaging provide important information, still celiotomy is often required for final diagnosis. The condition of the chickens is usually serious. Within our study, 40 % of the hens could be treated successfully. Therefore, a realistic assessment of each individual case and clarification for the owners are important.
Feeling safe, avoiding harm: Safety priorities of children and young people with disability and high support needs

This study explored what helped and constrained children and young people with disability and high support needs, in feeling and being safe in institutional settings. Through adapted qualitative methods, 22 children and young people aged 7–25 years shared their conceptualizations of safety, along with facilitators and barriers to interpersonal safety in their everyday lives. Key themes were feeling safe and known in relationships, minimizing risk, having strategies and the opportunity to practice these, opportunities to learn about safety and supported transitions. The living patterns and environments of children and young people were different to their non-disabled peers, and they faced systemic barriers to activating safety strategies. Building meaningful prevention strategies for children and young people with disability requires specific skill in design and implementation. Without focused attention to their specific circumstances, measures promoting child safety may overlook the experiences of children and young people with intellectual disability.
A Single Nucleotide Mutation in Adenylate Cyclase Affects Vegetative Growth, Sclerotial Formation and Virulence of Botrytis cinerea

Botrytis cinerea is a pathogenic fungus that causes gray mold disease in a broad range of crops. The high intraspecific variability of B. cinerea makes control of this fungus very difficult. Here, we isolated a variant B05.10M strain from wild-type B05.10. The B05.10M strain showed serious defects in mycelial growth, spore and sclerotia production, and virulence. Using whole-genome resequencing and site-directed mutagenesis, a single nucleotide mutation in the adenylate cyclase (BAC) gene that results in an amino acid residue (from serine to proline, S1407P) was shown to be the cause of various defects in the B05.10M strain. When we further investigated the effect of S1407 on BAC function, the S1407P mutation in bac showed decreased accumulation of intracellular cyclic AMP (cAMP), and the growth defect could be partially restored by exogenous cAMP, indicating that the S1407P mutation reduced the enzyme activity of BAC. Moreover, the S1407P mutation exhibited decreased spore germination rate and infection cushion formation, and increased sensitivity to cell wall stress, which closely related to fungal development and virulence. Taken together, our study indicates that the S1407 site of bac plays an important role in vegetative growth, sclerotial formation, conidiation and virulence in B. cinerea.