Miracle-dz/UniFAR-FTUs huggingface dataset:
Architecture of the Triceps Surae Muscles Complex in Patients with Spastic Hemiplegia: Implication for the Limited Utility of the Silfverskiöld Test

The Silfverskiöld test has long been used as an important tool for determining the affected muscles of the triceps surae in patients with equinus deformity. However, the test may not reflect the altered interactions between the muscles of the triceps which are affected by spasticity. The purpose of this study was to compare the architectural properties of the triceps surae muscles complex using ultrasonography, between hemiplegic patients and typically-developing children. Specifically, we wished to examine any differences in the architecture of the three muscles with various angle configurations of the knee and ankle joints. Ultrasound images of the medial gastrocnemius, lateral gastrocnemius, and soleus were acquired from paretic (group I) and non-paretic (group II) legs of ten patients and the legs (group III) of 10 age-matched normal children. A mixed model was used to evaluate the differences in the measurements of muscle architecture among the groups and the effects of various joint configurations on the measurements within the muscles. Compared to the results of measurements in groups II and III, the fascicle length was not different in the medial gastrocnemius of a paretic leg but it was longer in the lateral gastrocnemius and shorter in the soleus; the pennation angle was smaller in both medial and lateral gastrocnemii and was not different in the soleus; and the muscle thickness was found to be reduced in the three muscles of the paretic leg. Contrary to the observations in both the medial and lateral gastrocnemii, the fascicle length was increased and the pennation angle was decreased in the soleus with an increase of knee flexion. Through the current simulation study of the Silfverskiöld test using ultrasonography, we found that the changes detected in the architectural properties of the three muscles induced by systematic variations of the position at the ankle and the knee joints were variable. We believe that the limited utility of the Silfverskiöld test should be considered in determining an appropriate operative procedure to correct the equinus deformity in patients with altered architecture of the muscles in conditions such as cerebral palsy, as the differing muscle architectures of the triceps surae complex may affect the behavior of the muscles during the Silfverskiöld test.
Surveillance of HIV / AIDS epidemic in India [editorial]

HIV/AIDS pandemic is posing serious challenges the world over Number of people living with HIV/AIDS (Dec. 2002) are estimated to be 42 millions. Sub- Saharan-Africa is worst affected as it is home for 29.4 million of HIV/AIDS South and South East Asia contributed 6.0 million and share of India alone in this continent is 4.0 million which is next only to Sub Saharan Africa. Therefore the threat of HIV/AIDS looms large over India; necessitating adequate and effective response to meet this unabated scourge. The activities of screening of blood for HIV commenced in India way back in 1985 at National AIDS Research Institute Pune and Christian Medical College Vellore. During this phase of restricted surveillance the purpose was to validate the presence of HIV infection in India First HIV positive was detected in 1986 from commercial sex workers in Madras. Soon thereafter HIV reporting system was set up under the aegis of ICMR with sero-surveillance and reference centres spread over throughout the country with a view to identify the geographical spread of HIV infection and determining the major modes of HIV transmission. Most of these testing centres were located in Medical Colleges and activities of screening were confined to high risk and institutional population. This activity indicated that HIV was widespread in the country and every state reported the presence of HIV infection by the end of year 1997. (excerpt)
Response of Trichogramma spp. (Hymenoptera: Trichogrammatidae) to Insecticides at Concentrations Sublethal to Cnaphalocrocis medinalis (Lepidoptera: Pyralidae)

Abstract Trichogramma japonicum Ashmead (Hymenoptera: Trichogrammatidae) and Trichogramma dendrolimi Matsumura (Hymenoptera: Trichogrammatidae) are important parasitoids of Lepidopteran pests and are used for biological control in rice fields. In this study, the response of two of these parasitoids to four insecticides (chlorpyrifos, chlorantraniliprole, emamectin benzoate, and spinosad) were evaluated at target sublethal concentrations (TSC10 and TSC25, representing the LC10 and LC25 to the target pest) of the important rice pest, Cnaphalocrocis medinalis (Guenée). Each of the insecticides led to the mortality of adult T. japonicum and T. dendrolimi at TSC10 and TSC25, whereas no significant differences in the mortality of T. japonicum between TSC10 of chlorantraniliprole and control groups occurred. The parasitic capacity increased at F0 of T. japonicum at the two TSCs of spinosad treated host eggs, whereas the TSC10 was lower for emamectin benzoate at F1 for T. japonicum. The TSCs of chlorpyrifos treated host eggs negatively influenced the emergence rates of T. japonicum at F1. Emamectin benzoate with TSC10 reduced the female ratio of T. japonicum at F1. For T. dendrolimi, the TSCs of chlorpyrifos treated host eggs negatively influenced the emergence rates at F1. These findings indicate that T. japonicum and T. dendrolimi are affected by insecticides at TSCs, and among the four insecticides, chlorantraniliprole had the lowest mortality rates for T. japonicum and T. dendrolimi at TSCs.
Ultrasound and Clinical Preoperative Characteristics for Discrimination Between Ovarian Metastatic Colorectal Cancer and Primary Ovarian Cancer: A Case-Control Study

The aim of this study was to describe the clinical and sonographic features of ovarian metastases originating from colorectal cancer (mCRC), and to discriminate mCRC from primary ovarian cancer (OC). We conducted a multi-institutional, retrospective study of consecutive patients with ovarian mCRC who had undergone ultrasound examination using the International Ovarian Tumor Analysis (IOTA) terminology, with the addition of evaluating signs of necrosis and abdominal staging. A control group included patients with primary OC. Clinical and ultrasound data, subjective assessment (SA), and an assessment of different neoplasias in the adnexa (ADNEX) model were evaluated. Fisher’s exact and Student’s t-tests, the area under the receiver–operating characteristic curve (AUC), and classification and regression trees (CART) were used to conduct statistical analyses. In total, 162 patients (81 with OC and 81 with ovarian mCRC) were included. None of the patients with OC had undergone chemotherapy for CRC in the past, compared with 40% of patients with ovarian mCRC (p < 0.001). The ovarian mCRC tumors were significantly larger, a necrosis sign was more frequently present, and tumors had an irregular wall or were fixed less frequently; ascites, omental cake, and carcinomatosis were less common in mCRC than in primary OC. In a subgroup of patients with ovarian mCRC who had not undergone treatment for CRC in anamnesis, tumors were larger, and had fewer papillations and more locules compared with primary OC. The highest AUC for the discrimination of ovarian mCRC from primary OC was for CART (0.768), followed by SA (0.735) and ADNEX calculated with CA-125 (0.680). Ovarian mCRC and primary OC can be distinguished based on patient anamnesis, ultrasound pattern recognition, a proposed decision tree model, and an ADNEX model with CA-125 levels.
Allergic Rhinitis to Weed Pollen in Germany: Dominance by Plantain, Rising Prevalence, and Polysensitization Rates over 20 Years

Background: In contrast to the 3 major aeroallergens tree pollen, grass pollen, and house dust mites, allergic rhinitis caused by herbal pollen has received comparatively little attention in recent clinical studies. Since various weeds flower during summer until fall, allergic rhinitis to weeds may be underdiagnosed and/or mistakenly diagnosed as grass pollen allergy. Objective: To investigate (i) the currently most frequent weed allergy between mugwort, ragweed, plantain, chamomile, nettle, and oilseed rape and (ii) time trends in prevalence of sensitization to weed pollen in the middle of Germany over the last 20 years. Methods: This study, the largest of its kind to date, monocentrically evaluated the prick test results of a total of 6,220 patients with suspected RCA over a period of 20 years (1998–2017). Results: In the study cohort, sensitization rates to plantain almost doubled from 26.6% in the decade 1998–2007 to 50.5% in 2008–2017. Identical increases were observed for ragweed, while sensitization rates for mugwort stayed largely unchanged. The most prominent increase in positive skin prick tests to plantain and ragweed pollen was mainly observed in younger patients. Further, we identified a trend toward polysensitization, currently dominated by plantain and ragweed. Sensitization to weed pollen was found to be highly associated with additional sensitizations to grass and/or birch pollen. Conclusion: Plantain is currently the best choice to screen rhinitis patients for weed allergy which identifies 86% of all weed-sensitized individuals, at least in Germany. Over the last 20 years, we demonstrate a significant rise in the total number of weed pollen sensitization as well as increases in polysensitization, predominantly in younger patients.
A general mechanism for signal propagation in the nicotinic acetylcholine receptor family.

Nicotinic acetylcholine receptors (nAChRs) modulate synaptic activity in the central nervous system. The α7 subtype, in particular, has attracted considerable interest in drug discovery as a target for several conditions, including Alzheimer's disease and schizophrenia. Identifying agonist-induced structural changes underlying nAChR activation is fundamentally important for understanding biological function and rational drug design. Here, extensive equilibrium and nonequilibrium molecular dynamics simulations, enabled by cloud-based high-performance computing, reveal the molecular mechanism by which structural changes induced by agonist unbinding are transmitted within the human α7 nAChR. The simulations reveal the sequence of coupled structural changes involved in driving conformational change responsible for biological function. Comparison with simulations of the α4β2 nAChR subtype identifies features of the dynamical architecture common to both receptors, suggesting a general structural mechanism for signal propagation in this important family of receptors.
Modeling DNA Flexibility: Comparison of Force Fields from Atomistic to Multiscale Levels.

Accurate parameterization of force fields (FF) is of ultimate importance for computer simulations to be reliable and to possess a predictive power. In this work we analyzed, in multi-microsecond simulations of a 40 base pairs DNA fragment, the performance of four force fields, namely the two recent major updates of CHARMM and two from the AMBER family. We focused on description of double-helix DNA flexibility and dynamics both at atomistic and at mesoscale level in coarse-grained (CG) simulations. In addition to the traditional analysis of different base pair and base step parameters, we extended our analysis to investigate ability of the force field to parameterize a CG DNA model by structure-based bottom-up coarse-graining, computing DNA persistence length as a function of ionic strength. Our simulations unambiguously showed that the CHARMM36 force field is unable to preserve DNA's structural stability at over-microsecond time scale. Both versions of the AMBER FF, parmbsc0 and parmbsc1 showed good agreement with experiment, with some bias of parmbsc0 parameters for intermediate A/B form DNA structures. The CHARMM27 force field provides stable atomistic trajectories, and overall (among the considered force fields) the best fit to experimentally determined DNA flexibility parameters both at atomistic and at mesoscale level.
Benchmark of long non-coding RNA quantification for RNA sequencing of cancer samples

Abstract Background Long non-coding RNAs (lncRNAs) are emerging as important regulators of various biological processes. While many studies have exploited public resources such as RNA sequencing (RNA-Seq) data in The Cancer Genome Atlas to study lncRNAs in cancer, it is crucial to choose the optimal method for accurate expression quantification. Results In this study, we compared the performance of pseudoalignment methods Kallisto and Salmon, alignment-based transcript quantification method RSEM, and alignment-based gene quantification methods HTSeq and featureCounts, in combination with read aligners STAR, Subread, and HISAT2, in lncRNA quantification, by applying them to both un-stranded and stranded RNA-Seq datasets. Full transcriptome annotation, including protein-coding and non-coding RNAs, greatly improves the specificity of lncRNA expression quantification. Pseudoalignment methods and RSEM outperform HTSeq and featureCounts for lncRNA quantification at both sample- and gene-level comparison, regardless of RNA-Seq protocol type, choice of aligners, and transcriptome annotation. Pseudoalignment methods and RSEM detect more lncRNAs and correlate highly with simulated ground truth. On the contrary, HTSeq and featureCounts often underestimate lncRNA expression. Antisense lncRNAs are poorly quantified by alignment-based gene quantification methods, which can be improved using stranded protocols and pseudoalignment methods. Conclusions Considering the consistency with ground truth and computational resources, pseudoalignment methods Kallisto or Salmon in combination with full transcriptome annotation is our recommended strategy for RNA-Seq analysis for lncRNAs.
The Impact of Dust/Gas Ratios on Chromospheric Activity in Red Giant and Supergiant Stars

Abstract Stencel et al. (1986) analyzed IUE spectra of a modest set of cool stars and found that they continue to produce chromospheres even in the presence of high dust levels in their outer atmospheres. This reversed the previous results of Jennings (1973) and Jennings & Dyck (1972). We describe an on-going extension of these studies to a sample of stars representing a broader range in dust/gas ratios, using archival IUE and archival and new HST data on both RGB and AGB stars. Surface fluxes in emission lines will be analyzed to assess the chromospheric activity and obscuration by dust in each star, as those fluxes will follow a different pattern for reduced activity (temperature/density dependent) vs. dust obscuration (wavelength dependent). Wind characteristics will be measured by modeling of wind-reversed chromospheric emission lines.
Myeloid Cell-Targeted miR-146a Mimic Inhibits NF-kB-Driven Inflammation and Leukemia Progression in Vivo.

NF-κB is a key regulator of inflammation and cancer progression, with important role in leukemogenesis. Despite therapeutic potential, targeting NF-κB using pharmacologic inhibitors proved challenging. Here, we describe a myeloid cell-selective NF-κB inhibitor using miR146a mimic oligonucleotide conjugated to a scavenger receptor (SR)/Toll-like receptor 9 (TLR9) agonist (C-miR146a). Unlike an unconjugated miR-146a, C-miR146a was rapidly internalized and delivered to cytoplasm of target myeloid cells and leukemic cells. C-miR146a reduced expression of classic miR-146a targets, IRAK1 and TRAF6, thereby blocking NF-κB activation in target cells. Intravenous injections of C-miR146a mimic to miR-146-deficient mice prevented excessive NF-κB activation in myeloid cells, thereby alleviating myeloproliferation and mice hypersensitivity to bacterial challenge. Importantly, C-miR146a showed efficacy in dampening severe inflammation in clinically relevant models of chimeric antigen receptor (CAR) T-cell-induced cytokine release syndrome (CRS). Systemic administration of C-miR146a oligonucleotide alleviated human monocyte-dependent release of IL-1 and IL-6 in xenotransplanted B-cell lymphoma model without affecting CD19-specific CAR T-cell antitumor activity. Beyond anti-inflammatory functions, miR146a is a known tumor suppressor commonly deleted or expressed at reduced levels in human myeloid leukemia. Using TCGA AML dataset, we found inverse correlation of miR-146 levels with NF-κB-related genes and with patients' survival. Correspondingly, C-miR146a induced cytotoxic effects in human MDSL, HL-60 and MV4-11 leukemia cells in vitro. The repeated intravenous administration of C-miR146a inhibited expression of NF-κB target genes and thereby thwarted progression of disseminated HL-60 leukemia. Our results demonstrate potential of using myeloid cell-targeted miR146a mimics for treatment of inflammatory and myeloproliferative disorders.
Status, kinship, and place of burial at Early Bronze Age Bab adh-Dhra': A biogeochemical comparison of charnel house human remains.

OBJECTIVES The Early Bronze Age (EBA; ca. 3,600-2000 BCE) of the southern Levant underwent considerable transformation as agro-pastoral communities began to utilize their land more intensively, constructing larger, fortified towns prior to site abandonment at the end of the third millennium. At the site of Bab adh-Dhra' in Jordan, the dead of the Early Bronze (EB) II-III (ca. 3,100-2,500 BCE) period were communally interred within charnel houses, but important disparities between these structures and their contents may be reflective of ownership and use by particular extended kin groups whose activity patterns, subsistence strategies, and even social status may have differed from one another. Subsequently, we hypothesized that differences in mobility and dietary intake may differentiate tomb groups from one another. MATERIALS AND METHODS Dental enamel from 31 individuals interred in three different Early Bronze Age charnel houses (A56, A22, A55) at Bab adh-Dhra', Jordan were analyzed for strontium, oxygen, and carbon isotope values. RESULTS Strontium isotope ratios (range: 0.70793-0.70842) possessed medians that did not differ statistically from one another, but had ranges that exhibited significant differences in variance. Carbon isotope values ( x ¯ = -13.2 ± 0.5‰, 1σ) were not significantly different. DISCUSSION General similarities in human isotopic signatures between EB II-III charnel houses A22 and A55 suggest that their activities were likely similar to one another and agree with findings from excavated domestic spaces with little archaeological evidence for economic, social, or political differentiation. More variable strontium isotope ratios and lower carbon isotope values from A22 could reflect a greater involvement with pastoralist practices or regional trade, including the consumption of more 13 C-depleted foods, while those in A55 may have led a more sedentary lifestyle with greater involvement in cultivating orchard crops. All charnel houses contained nonlocal individuals likely originating from other Dead Sea Plain sites with no EB II-III cemeteries of their own, supporting the idea that extended kin groups throughout the region returned to Bab adh-Dhra' to bury their dead.
Tolerance to arsenic trioxide combined with all‐trans‐retinoic acid in children with acute promyelocytic leukaemia in France

Acute promyelocytic leukaemia (APL) is characterized by the reciprocal translocation t(15;17). The classical treatment strategy for APL features chemotherapy (anthracyclines) combined with all-trans-retinoic acid (ATRA). A phase 3 study showed that treatment associating ATRA and arsenic trioxide (ATO) was at least equivalent to ATRA plus chemotherapy, in patients aged between 18 and 71 years with standard-risk APL (Burnett et al., 2015). Commencing in 2015, while awaiting a formal biomedical research protocol, the Soci et e Franc aise de Lutte contre les Cancers et les Leuc emies de l’Enfant et de l’Adolescent (SFCE), in conjunction with a European consortium, recommended ATRA combined with ATO for children with standard-risk (SR) APL, but only few safety data for children or adolescents are available (Iland et al., 2015; Creutzig et al., 2017; Kutny et al., 2017; Kayser et al., 2018). First objective was to evaluate the tolerance and adverse events related to ATO/ATRA therapy in children with APL treated in SFCE centres. Secondary objectives were evaluation of molecular residual disease development in those receiving ATO/ATRA therapy, and the survival of children and adolescents with APL treated since 2015.
Spatial EGFR Dynamics and Metastatic Phenotypes Modulated by Upregulated EphB2 and Src Pathways in Advanced Prostate Cancer

Advanced prostate cancer is a very heterogeneous disease reflecting in diverse regulations of oncogenic signaling pathways. Aberrant spatial dynamics of epidermal growth factor receptor (EGFR) promote their dimerization and clustering, leading to constitutive activation in oncogenesis. The EphB2 and Src signaling pathways are associated with the reorganization of the cytoskeleton leading to malignancy, but their roles in regulating EGFR dynamics and activation are scarcely reported. Using single-particle tracking techniques, we found that highly phosphorylated EGFR in the advanced prostate cancer cell line, PC3, was associated with higher EGFR diffusivity, as compared with LNCaP and less aggressive DU145. The increased EGFR activation and biophysical dynamics were consistent with high proliferation, migration, and invasion. After performing single-cell RNA-seq on prostate cancer cell lines and circulating tumor cells from patients, we identified that upregulated gene expression in the EphB2 and Src pathways are associated with advanced malignancy. After dasatinib treatment or siRNA knockdowns of EphB2 or Src, the PC3 cells exhibited significantly lower EGFR dynamics, cell motility, and invasion. Partial inhibitory effects were also found in DU145 cells. The upregulation of parts of the EphB2 and Src pathways also predicts poor prognosis in the prostate cancer patient cohort of The Cancer Genome Atlas. Our results provide evidence that overexpression of the EphB2 and Src signaling pathways regulate EGFR dynamics and cellular aggressiveness in some advanced prostate cancer cells.
Estimating Penetration-Related X-Band InSAR Elevation Bias: A Study over the Greenland Ice Sheet

Accelerating melt on the Greenland ice sheet leads to dramatic changes at a global scale. Especially in the last decades, not only the monitoring, but also the quantification of these changes has gained considerably in importance. In this context, Interferometric Synthetic Aperture Radar (InSAR) systems complement existing data sources by their capability to acquire 3D information at high spatial resolution over large areas independent of weather conditions and illumination. However, penetration of the SAR signals into the snow and ice surface leads to a bias in measured height, which has to be corrected to obtain accurate elevation data. Therefore, this study purposes an easy transferable pixel-based approach for X-band penetration-related elevation bias estimation based on single-pass interferometric coherence and backscatter intensity which was performed at two test sites on the Northern Greenland ice sheet. In particular, the penetration bias was estimated using a multiple linear regression model based on TanDEM-X InSAR data and IceBridge laser-altimeter measurements to correct TanDEM-X Digital Elevation Model (DEM) scenes. Validation efforts yielded good agreement between observations and estimations with a coefficient of determination of R2 = 68% and an RMSE of 0.68 m. Furthermore, the study demonstrates the benefits of X-band penetration bias estimation within the application context of ice sheet elevation change detection.