Miracle-dz/UniFAR-FTUs huggingface dataset:
Whole-Exome Sequencing of Rare Site Endometriosis-Associated Cancer

Malignant transformation of extraovarian endometriosis is rare, with the carcinogenesis mechanism unclear. To clarify the actionable variants of rare-site endometriosis-associated cancer (RSEAC), we performed whole-exome sequencing for the tumor, in two patients. The intestine was affected in both cases, although the histology was that of clear cell carcinoma and undifferentiated carcinoma, respectively. Therefore, the cases were referred to as endometriosis-associated intestinal tumors (EIATs). Actionable variants (all frameshift mutations) were identified in tumor suppressor genes ARID1A, PTEN, and p53; however, no oncogenic variants were identified. Both cases were microsatellite stable. The patient with undifferentiated carcinoma exhibited hypermutator and homologous recombination deficiency phenotypes. The dominant mutation signatures were signature 30 (small subset of breast cancers) and 19 (pilocytic astrocytoma) in patient 1, and signature 5 (small subset of breast cancers) and 3 (breast, ovarian, and pancreatic cancers) in patient 2. Immunohistochemistry revealed positive CD8 and PD-1 expression in both patients; patient 1 also showed positive PDL-1 expression. Our results suggest that RSEAC is associated with variants of tumor suppressor genes as epigenetic alterations. Mutation signature-based whole-exome sequencing could be useful to select an adjuvant chemotherapy regimen. High CD8 and PD-1 expression in RSEAC suggests that immune checkpoint inhibitors are useful for treatment.
Peptide Vaccination against Cytomegalovirus Induces Specific T Cell Response in Responses in CMV Seronegative End-Stage Renal Disease Patients

Introduction: Cytomegalovirus (CMV) reactivation occurs in seronegative patients after solid organ transplantation (SOT) particularly from seropositive donors and can be lethal. Generation of CMV-specific T cells helps to prevent CMV reactivation. Therefore, we initiated a clinical phase I CMVpp65 peptide vaccination trial for seronegative end-stage renal disease patients waiting for kidney transplantation. Methods: The highly immunogenic nonamer peptide NLVPMVATV derived from CMV phosphoprotein 65(CMVpp65) in a water-in-oil emulsion (Montanide™) plus imiquimod (Aldara™) as an adjuvant was administered subcutaneously four times biweekly. Clinical course as well as immunological responses were monitored using IFN-γ ELISpot assays and flow cytometry for CMV-specific CD8+ T cells. Results: Peptide vaccination was well tolerated, and no drug-related serious adverse events were detected except for Grade I–II local skin reactions. Five of the 10 patients (50%) mounted any immune response (responders) and 40% of the patients presented CMV-specific CD8+ T cell responses elicited by these prophylactic vaccinations. No responders experienced CMV reactivation in the 18 months post-transplantation, while all non-responders reactivated. Conclusion: CMVpp65 peptide vaccination was safe, well tolerated, and clinically encouraging in seronegative end-stage renal disease patients waiting for kidney transplantation. Further studies with larger patient cohorts are planned.
The mitochondrial localized CISD-3.1/CISD-3.2 proteins are required to maintain normal germline structure and function in Caenorhabditis elegans

Reproductive organs and developing tissues have high energy demands that require metabolic functions primarily supported by mitochondria function. The highly conserved CISD/NEET iron-sulfur (Fe-S) protein family regulates iron and reactive oxygen homeostasis, both of which are important for mitochondrial function. Disruption of iron and reactive oxygen homeostasis typically leads to detrimental effects. In humans, CISD dysfunction is associated with human health issues including Wolfram syndrome 2. Using C. elegans, we previously determined that the cisd-1, cisd-3.1 and cisd-3.2 have an overlapping role in the regulation of physiological germline apoptosis through the canonical programmed cell death pathway. Here, we isolated the cisd-3.2(pnIs68) mutant that resulted in physiological and fitness defects including germline abnormalities that are associated with abnormal stem cell niche and disrupted formation of bivalent chromosomes. The cisd-3.2(pnIs68) mutation led to complete disruption of the cisd-3.2 gene expression and a decrease in expression of genetically intact cisd-1 and cisd-3.1 genes suggesting an indirect impact of the cisd-3.2(pnIs68) allele. The CISD-3.2 and CISD-3.1 proteins localize to the mitochondria in many tissues throughout development. The cisd-3.2(pnIs68) mutant displays phenotypes associated with mitochondrial dysfunction, including disruption of the mitochondrial network within the germline. These results further support the idea that the CISD protein family is required for mitochondrial function that supports important functions in animals including overall fitness and germline viability.
Minimum Reporting Standards for in vivo Magnetic Resonance Spectroscopy (MRSinMRS): Experts' consensus recommendations

The translation of MRS to clinical practice has been impeded by the lack of technical standardization. There are multiple methods of acquisition, post‐processing, and analysis whose details greatly impact the interpretation of the results. These details are often not fully reported, making it difficult to assess MRS studies on a standardized basis. This hampers the reviewing of manuscripts, limits the reproducibility of study results, and complicates meta‐analysis of the literature. In this paper a consensus group of MRS experts provides minimum guidelines for the reporting of MRS methods and results, including the standardized description of MRS hardware, data acquisition, analysis, and quality assessment. This consensus statement describes each of these requirements in detail and includes a checklist to assist authors and journal reviewers and to provide a practical way for journal editors to ensure that MRS studies are reported in full.
Cryogenic trapping with a packed cold finger trap for the determination and speciation of arsenic by flow injection/hydride generation/atomic absorption spectrometry

An innovative analytical system based on the combination of cryogenic trapping and unambiguous gas chromatographic separation performed within a packed cold finger trap (PCFT) has been developed here. In this hydride generation-packed cold finger trap-atomic absorption spectrometric (HG-PCFT-AAS) system, the carrier gas (He) and heating voltage were optimized from a complete factorial experiment and in accordance with a base-line resolution (RS > 1.4) between monomethylarsonic acid (MMA) and dimethylarsenic acid (DMA); the sheath gas argon (Ar) flow rate, on the other hand, was optimized from a single factorial experiment to obtain the highest signal-to-noise (S/N) ratio. Here, for MMA and DMA analysis, compromised levels of the parameters for hydride generation were determined from an L16(4)5 orthogonal array experimental design following the principle of the larger-is-better S/N ratio. The hydride evolution after the addition of a citrate buffer was employed to selectively measure arsenite (AsIII). With an atomic absorption spectrometer (AAS) serving as the detector, the limits of detection were 0.9, 0.8, 0.5, and 0.6 ng for AsIII, AsV (arsenate), MMA and DMA, respectively. The results of the application of the method in freshwater and seawater showed spike recovery ranges from 82∼113% and relative standard deviation of triplicate analysis ranges from 3∼10%, depending on the arsenic species. Accuracy of the established method was also validated by analyzing two standard reference materials, NASS-5 and SLEW-3, in which two arsenic species, AsIII and AsV, are detected.
Male‐biased sexual selection, but not sexual dichromatism, predicts speciation in birds

Sexual selection is thought to shape phylogenetic diversity by affecting speciation or extinction rates. However, the net effect of sexual selection on diversification is hard to predict because many of the hypothesized effects on speciation or extinction have opposing signs and uncertain magnitudes. Theoretical work also suggests that the net effect of sexual selection on diversification should depend strongly on ecological factors, though this prediction has seldom been tested. Here, we test whether variation in sexual selection can predict speciation and extinction rates across passerine birds (up to 5812 species, covering most genera) and whether this relationship is mediated by environmental factors. Male‐biased sexual selection, and specifically sexual size dimorphism, predicted two of the three measures of speciation rates that we examined. The link we observed between sexual selection and speciation was independent of environmental variability, though species with smaller ranges had higher speciation rates. There was no association between any proxies of sexual selection and extinction rate. Our findings support the view that male‐biased sexual selection, as measured by frequent predictors of male‐male competition, has shaped diversification in the largest radiation of birds.
Two step yielding in attractive colloids: transition from gels to attractive glasses

Steady and oscillatory rheology was utilized to study the mechanical response of colloidal glasses and gels with particular emphasis in their yielding behaviour. We used a suspension of hard sphere colloidal particles with short-range depletion attractions induced by the addition of non-adsorbing linear polymer. While high volume fraction hard sphere glasses exhibit a single yield point due to cage breaking, attraction dominated glasses show a two-step yielding reflecting bond and cage breaking, respectively. Here we investigated the yielding behaviour of frustrated colloid–polymer systems with equal attraction strength and range, varying the particle volume fraction, φ, spanning the region from an attractive glass (φ = 0.6) to a low volume fraction (φ = 0.1) attractive gel. Yielding throughout this range, probed both by oscillatory and steady shear, is found to remain a two step process until very low φ's. The first yield strain related with in-cage or inter-cluster bond braking remains constant for φ > 0.3 while the second yield strain, attributed to braking of cages or clusters into smaller constituents, increases as volume fraction is decreased due to enhancement of structural inhomogeneities in the gel. Steady shear tests indicated distinct shear rate regimes: At steady state, low and intermediate shear rates create denser or smaller flowing clusters, whereas high rates may lead to complete break-up into independent particles. When the range of attraction was increased, both yield strains increased scaling with the range of attraction and accompanied structural changes. Finally, ageing leads to an overall strengthening of both the gel and the attractive glass accompanied by an enhancement of the second stress overshoot in steady shear, while the attractive glass also becomes more brittle.
Soft tissue abnormalities in Wassel Type VI radial polydactyly: a detailed anatomical study

Wassel VI radial polydactyly is associated with metacarpal adduction and radial deviation of the metacarpophalangeal joint of the ulnar duplicate. The soft tissue abnormalities responsible for these deformities were characterized using preoperative multi-planar three-dimensional ultrasound and intraoperative observation in four patients. In all patients, the abductor pollicis brevis and superficial head of the flexor pollicis brevis inserted into the radial first metacarpal, whereas the adductor pollicis and deep head of the flexor pollicis brevis inserted into the ulnar thumb. Aberrant location of the flexor pollicis longus and absence of the A1 pulley system was associated with severe radial deviation. An additional superficial thenar muscle along the ulnar metacarpal was associated with minimal metacarpal adduction. Uneven forces on the ulnar duplicate could be associated with these characteristic deformities and joint instability. Knowledge of these abnormalities allows better planning of surgery and further insight into this rare radial polydactyly configuration. Level of evidence: II
Chimeric antigen receptor T-cell therapy for HIV cure

Purpose of review Cell-based immunotherapies have made enormous progress over the last decade with the approval of several anti-CD19-chimeric antigen receptor (CAR)-T cell therapies for haemato-oncological diseases. CARs are synthetic receptors comprising an antigen-specific extracellular domain fused to a hinge, transmembrane and intracellular signalling domains. The success obtained with CD19 CAR-T cells rekindled interest in using CAR-T cells to treat HIV seropositive patients. The purpose of this review is to discuss historical and recent developments of anti-HIV CARs. Recent findings Since the first description of CD4+-based CARs in the early 90s, new generations of anti-HIV CARs were developed. They target the hetero-trimeric glycoprotein gp120/gp41 and consist of either a CD4+ extracellular domain or a VH/VL segment derived from broadly neutralizing antibodies. Recent efforts were employed in multiplexing CAR specificities, intracellular signalling domains and T cells resistance to HIV. Summary Several new-anti HIV CAR-T cells were successfully tested in preclinical mice models and are now waiting to be evaluated in clinical trials. One of the key parameters to successfully using CAR-T cells in HIV treatment will depend on their capacity to control the HIV reservoir without causing off-targeting activities.
Insight into chemical mechanisms of sepal color development and variation in hydrangea

Hydrangea (Hydrangea macrophylla) is a unique flower because it is composed of sepals rather than true petals that have the ability to change color. In the early 20th century, it was known that soil acidity and Al3+ content could intensify the blue hue of the sepals. In the mid-20th century, the anthocyanin component 3-O-glucosyldelphinidin (1) and the copigment components 5-O-caffeoylquinic, 5-O-p-coumaroylquinic, and 3-O-caffeoylquinic acids (2–4) were reported. Interestingly, all hydrangea colors from red to purple to blue are produced by the same organic components. We were interested in this phenomenon and the chemical mechanisms underlying hydrangea color variation. In this review, we summarize our recent studies on the chemical mechanisms underlying hydrangea sepal color development, including the structure of the blue complex, transporters involved in accumulation of aluminum ion (Al3+), and distribution of the blue complex and aluminum ions in living sepal tissue.
Cross-Cultural Adaptation and Evaluation of the Participation and Environment Measure for Children and Youth to the Indian Context—A Mixed-Methods Study

Culturally appropriate measures enable knowledge transfer and quality improvement of rehabilitation services in diverse contexts. The Applied Cultural Equivalence Framework (ACEF) was used in a two-phased mixed methods study to adapt and evaluate the Participation and Environment Measure-Children and Youth (PEM-CY) in India. Cognitive interviews with caregivers of children with disabilities (n = 15) aged 5–17 years established conceptual, item, semantic, and operational equivalence of the Indian PEM-CY. Construct validity was assessed by comparing PEM-CY scores of children with and without disabilities (n = 130) using a case-control design. Cognitive interviews resulted in operational (60.3%), semantic (26.4%), and item-level (13.2%) modifications in the PEM-CY with no changes at the conceptual level. Internal consistency (n = 130) was acceptable to excellent (0.61–0.87) on most scales. Test–retest reliability (n = 30) was good to excellent (ICC ≥ 0.75, Kappa 0.6–1.0) for most scales. Significant differences in all PEM-CY summary scores were found between children with and without disabilities, except for environmental supports. Children with disabilities had lower scores on frequency and involvement in activities across all settings; their caregivers desired greater change in participation and reported experiencing more environmental barriers across settings. Findings suggest the adapted PEM-CY is a valid and reliable measure for assessing the participation of Indian children.
The Glomerular Filtration Rate Estimators in the Pharmacokinetic Modelling in Acute Kidney Injury: An Observational Study

The glomerular filtration rate (GFR), according to which the drug dose for patients with chronic kidney disease (CKD) is adjusted, is computed with estimators (eGFR) that are developed specifically for CKD. These particular types of estimators are also used in population pharmacokinetic (pop PK) modelling in drug development. Similar approaches without scientific validation have been proposed for patients with acute kidney injury (AKI), yet it is uncertain which specific eGFR should be used for drug dosing or in pop PK models in patients with AKI. In our study, we included 34 patients with AKI and vancomycin (VCM) treatment, and we built both individual PK and pop PK (non-linear mixed-effects, one-compartment) models to see which eGFR estimator is the best covariate. In these models different eGFRs (Cockcroft-Gault, MDRD, CKD-EPI 2009, Jelliffe and Jelliffe, Chen et al., and Yashiro et al. 2013) were used. We included six additional patients to validate the final pop PK model. All eGFRs underrate the true renal clearance in the AKI, so we created pop PK models for VCM dosing in AKI with all eGFRs, to discover that the most accurate model was the one with the Cockcroft-Gault estimator. Since the eGFRs underestimate the true renal clearance in AKI, they are inaccurate for clinical drug dosing decisions, with the exception of the Cockcroft-Gault one, which is appropriate for the pop PK models intended for drug development purposes in AKI.
Ethylene Response Factors regulate expression of HbSUT3, the sucrose influx carrier in laticifers of Hevea brasiliensis.

Natural rubber is an important industrial raw material and commercially produced by rubber tree (Hevea brasiliensis). The sucrose transporter HbSUT3 plays an essential role in rubber production. Its expression in latex (cytoplasm of rubber-producing laticifers) is induced by bark treatment with Ethrel, an ethylene releaser, and the inducing effect correlates well with Ethrel-stimulated rubber yield increase. However, the mechanisms of ethylene induction on HbSUT3 expression are not known. Here, five Ethylene Response Factor (ERF) genes were identified from the cDNA library of Hevea latex by yeast one-hybrid screening with the promoter of HbSUT3 gene as bait. As revealed in a tobacco protoplast transient expression system, these HbERFs were mainly localized in the nucleus and four of them exhibited apparent transactivation activity. Of the five HbERF genes, HbERF-IXc4 was the most frequently screened in yeast one-hybrid, accounting for 65% of the ERF clones obtained. Moreover, among the five HbERFs, HbERF-IXc4 showed the strongest transactivation capacity when expressed in tobacco protoplast, the highest transcript abundance in latex, and a close expressional correlation with its target gene, HbSUT3, in response to the Ethrel treatment. Taken together, our results indicate that ERFs, especially HbERF-IXc4 is critically involved in the activation of HbSUT3 expression in latex after the Ethrel treatment on Hevea bark, and thus the stimulated latex yield.
A Review on the Life Cycle Assessment of Cellulose: From Properties to the Potential of Making It a Low Carbon Material

The huge plastic production and plastic pollution are considered important global issues due to environmental aspects. One practical and efficient way to address them is to replace fossil-based plastics with natural-based materials, such as cellulose. The applications of different cellulose products have recently received increasing attention because of their desirable properties, such as biodegradability and sustainability. In this regard, the current study initially reviews cellulose products’ properties in three categories, including biopolymers based on the cellulose-derived monomer, cellulose fibers and their derivatives, and nanocellulose. The available life cycle assessments (LCA) for cellulose were comprehensively reviewed and classified at all the stages, including extraction of cellulose in various forms, manufacturing, usage, and disposal. Finally, due to the development of low-carbon materials in recent years and the importance of greenhouse gases (GHG) emissions, the proposed solutions to make cellulose a low carbon material were made. The optimization of the cellulose production process, such as the recovery of excessive solvents and using by-products as inputs for other processes, seem to be the most important step toward making it a low carbon material.
Comparative study of fertility parameters in vitrified human spermatozoa in the presence or absence of EmbryORP®: A novel antioxidant

The cryopreservation of spermatozoa has the main purpose of preserving male fertility. However, current preservation techniques have shown to produce lesions in the structure and alter sperm functions, probably due to the production of reactive oxygen species (ROS) during cryopreservation. To overcome the damage provoked by ROS, we introduced a novel antioxidant called EmbryORP® in a vitrification protocol and compared eight fertility parameters: motility, viability, morphology, concentration, the semen pH, the oxidation‐reduction potential (ORP), the spontaneous acrosomal reaction (AR) and the mitochondrial membrane potential (MMP), in the presence or absence of EmbryORP®. We analysed 20 samples from healthy human sperm donors and observed that the antioxidant significantly decreased the semen pH as well as the MMP and the ORP affecting the balance of ROS. The antioxidant also lowered the motility and viability of the cells, but preserved the acrosome and sperm morphology in general. We concluded that EmbryORP® lowered the ORP, but to a suboptimal level that may be harmful to spermatozoa. Despite these results, our work opens new perspectives on how to improve cryopreservation media. Therefore, we recommend exploring the EmbryORP® potential benefit by reducing its concentration or changing the exposure time during the cryopreservation protocol.