Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhancement in the Therapeutic Efficacy of In Vivo BNCT Mediated by GB-10 with Electroporation in a Model of Oral Cancer

Boron neutron capture therapy (BNCT) combines preferential tumor uptake of 10B compounds and neutron irradiation. Electroporation induces an increase in the permeability of the cell membrane. We previously demonstrated the optimization of boron biodistribution and microdistribution employing electroporation (EP) and decahydrodecaborate (GB-10) as the boron carrier in a hamster cheek pouch oral cancer model. The aim of the present study was to evaluate if EP could improve tumor control without enhancing the radiotoxicity of BNCT in vivo mediated by GB-10 with EP 10 min after GB-10 administration. Following cancerization, tumor-bearing hamster cheek pouches were treated with GB-10/BNCT or GB-10/BNCT + EP. Irradiations were carried out at the RA-3 Reactor. The tumor response and degree of mucositis in precancerous tissue surrounding tumors were evaluated for one month post-BNCT. The overall tumor response (partial remission (PR) + complete remission (CR)) increased significantly for protocol GB-10/BNCT + EP (92%) vs. GB-10/BNCT (48%). A statistically significant increase in the CR was observed for protocol GB-10/BNCT + EP (46%) vs. GB-10/BNCT (6%). For both protocols, the radiotoxicity (mucositis) was reversible and slight/moderate. Based on these results, we concluded that electroporation improved the therapeutic efficacy of GB-10/BNCT in vivo in the hamster cheek pouch oral cancer model without increasing the radiotoxicity.
Broadband Circularly-polarized Crossed-dipole Antenna with Good Gain Stability

A broadband Circularly Polarized (CP) cross-dipole antenna with the merit of stable gain is proposed. The designed antenna consists of crossed dipoles, parasitic patches, reflectors, and vertical parasitic plates. By adding parasitic patches and parasitic plates, the circular polarization performance of the antenna is significantly improved. Furthermore, the gain value becomes stable in the entire operating frequency band by modifying the structure of the parasitic plates. The final dimension of the presented antenna is 0. 76λ0 X 0. 76λ0 X 0. 28λ0 (λ0 is the wavelength at the center frequency point in the circularly polarized working frequency band). The measured results depict that the Impedance Bandwidth (IBW) is 80.8% (2.03GHz~4.78GHz) and the Axial Ratio Bandwidth(ARBW) is 68.5% (2.35GHz~4.8GHz). Stable gain values, ranging from 6dBic to 7.5dBic, are obtained in the working frequency band, and the average gain can reach 7dBic.
Broadband Optical Properties of Bi2Se3

Materials with high optical constants are of paramount importance for efficient light manipulation in nanophotonics applications. Recent advances in materials science have revealed that van der Waals (vdW) materials have large optical responses owing to strong in-plane covalent bonding and weak out-of-plane vdW interactions. However, the optical constants of vdW materials depend on numerous factors, e.g., synthesis and transfer method. Here, we demonstrate that in a broad spectral range (290–3300 nm) the refractive index n and the extinction coefficient k of Bi2Se3 are almost independent of synthesis technology, with only a ~10% difference in n and k between synthesis approaches, unlike other vdW materials, such as MoS2, which has a ~60% difference between synthesis approaches. As a practical demonstration, we showed, using the examples of biosensors and therapeutic nanoparticles, that this slight difference in optical constants results in reproducible efficiency in Bi2Se3-based photonic devices.
A Clinically Applicable Gene-Expression Classifier Reveals Intrinsic and Extrinsic Contributions to Consensus Molecular Subtypes in Primary and Metastatic Colon Cancer

Purpose: Four consensus molecular subtypes (CMS1–4) of colorectal cancer were identified in primary tumors and found to be associated with distinctive biological features and clinical outcomes. Given that distant metastasis largely accounts for colorectal cancer–related mortality, we examined the molecular and clinical attributes of CMS in metastatic colorectal cancer (mCRC). Experimental Design: We developed a colorectal cancer–focused NanoString-based CMS classifier that is ideally suited to interrogate archival tissues. We successfully used this panel in the CMS classification of formalin-fixed paraffin-embedded (FFPE) tissues from mCRC cohorts, one of which is composed of paired primary tumors and metastases. Finally, we developed novel mouse implantation models to enable modeling of colorectal cancer in vivo at relevant sites. Results: Using our classifier, we find that the biological hallmarks of mCRC, including CMS, are in general highly similar to those observed in nonmetastatic early-stage disease. Importantly, our data demonstrate that CMS1 has the worst outcome in relapsed disease, compared with other CMS. Assigning CMS to primary tumors and their matched metastases reveals mostly concordant subtypes between primary and metastasis. Molecular analysis of matched discordant pairs reveals differences in stromal composition at each site. The development of two novel in vivo orthotopic implantation models further reinforces the notion that extrinsic factors may impact on CMS identification in matched primary and metastatic colorectal cancer. Conclusions: We describe the utility of a NanoString panel for CMS classification of FFPE clinical samples. Our work reveals the impact of intrinsic and extrinsic factors on colorectal cancer heterogeneity during disease progression.
Should we discontinue RAS-inhibitor therapy in patients with advanced CKD?

The 2021 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines provide a strong (Level 1B) recommendation that among patients with hypertension, chronic kidney disease (CKD) and severely increased albuminuria, renin-angiotensin-system (RAS)-inhibitors should be administered as first-line antihypertensive agents [1]. This guidance is based on solid clinical-trial evidence demonstrating that among patients with albuminuric CKD, angiotensin-converting-enzyme-inhibitors (ACEIs) or angiotensin-receptor-blockers (ARBs) are superior to placebo or activetreatment with other antihypertensive drug classes in mitigating the risk of kidney failure [2–5]. In addition, these landmark clinical trials showed that the kidney protective effect of RAS-blockade is paralleled with a clinically meaningful reduction in the risk of hospitalization for decompensated heart failure [2–5]. However, it is less clear whether these benefits are similarly applicable to patients with advanced CKD. In this subgroup of high-risk patients, there is the concern that the use of ACEIs or ARBs may aggravate the risk of adverse events, such as hyperkalemic events or episodes of acute deterioration in kidney function leading to unplanned initiation of dialysis [6]. Accordingly, the KDIGO guidelines provide a clinical practice recommendation for down-titration of the dose or discontinuation of RAS-inhibitors when managing patients with kidney failure with the aim to reduce uremic symptoms and gain the necessary time for the preparation of kidney replacement therapy [1]. In this article, we explore the question whether RAS-inhibitor therapy should be continued or stopped in patients with advanced and progressive CKD. We provide an overview of the available data from observational studies and post-hoc analyses of prior clinical trials. We conclude with more conclusive evidence from the recently published STOP-ACEi (Multi-center Randomized Controlled Trial of ACEI/ARB withdrawal in advanced renal disease) trial [7].
Effects of probiotics on strength and power performance in a trained population

The main purpose of this systematic review and meta-analysis was to evaluate the effects of probiotics intake on strength and power performance in a trained population. This study was designed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines. The review was registered in PROSPERO with the following registration number: CRD42021248173. PubMed/MEDLINE, Web of Science, and Scopus databases were searched from their inception to the 18th March 2022 to find original research studies evaluating the effects of probiotic supplementation on strength and power performance tests in a trained population. The following inclusion criteria were applied to select studies: probiotics supplementation; trained population; strength and power performance measurements; human experimental trial; controlled with a placebo group; peer-reviewed and original articles written in English language. Random effects model and standardized mean differences (SMD) were used following Hedges’ G for the meta-analysis. Seven studies were finally included after the inclusion/exclusion criteria were applied (n=142 participants). Results of the meta-analysis identified a significant benefit of probiotics compared to placebo treatments (p=.04), with a small pooled effect size (SMD=0.36 [0.02-0.70]; I2=43%), and no funnel plot asymmetry was present. In summary, this systematic review and meta-analysis demonstrated that probiotic supplementation could effectively enhance strength and power performance in a trained population.
Prevalence and Family Determinants of Geriatric Depression Among Elderly People in Elderly Support Groups in Rwanda

Background The 1994 Tutsi genocide in Rwanda significantly impacted family structure, with many people growing old alone and lacking social bonds and connections with family members. However, little is known about the contribution of the family environment to geriatric depression which was highlighted by WHO as a psychological problem with a 10% to 20% prevalence rate among the elderly worldwide. This study aims to investigate geriatric depression and associated family determinants among the elderly in Rwanda. Methods With a community-based cross-sectional study design, we assessed geriatric depression (GD), quality-of-life enjoyment and satisfaction (QLES), family support (FS), loneliness, neglect, and attitude toward grief in a convenience sample of 107 participants (M=72.32, SD=8.79) aged between 60 and 95 years who were recruited from three groups of elderly people supported by the NSINDAGIZA organization in Rwanda. SPSS (version 24) was used for statistical data analysis; differences across various sociodemographic variables were tested for significance by an independent t-test; the relationship between study variables was tested by Pearson correlation analysis; and multiple regression analysis was performed to model the contribution of independent variables to dependent variables. Results A total of 64.5% of the elderly scored above the threshold of the normal range of geriatric depression (SDS>49), with higher symptoms in women than in men. Multiple regression analysis indicated that family support and quality-of-life enjoyment and satisfaction were contributors to geriatric depression in the participants. Conclusion Geriatric depression was relatively common in our participants. It is associated with the quality of life and family support received. Hence, adequate family-based interventions are needed to improve the well-being of geriatric people in their respective families.
IGH::CD274 (PD‐L1) rearrangement in diffuse large B cell lymphoma and its therapeutic implication

Diffuse large B cell lymphoma (DLBCL) expresses abundant programmed death ligand 1 (PD‐L1), which shields tumor cells from immune attacks through the PD‐L1/PD‐1 signaling axis. The mechanism of PD‐L1 overexpression includes the deletion of the 3′end of PD‐L1, which increases its mRNA stability, and the gain or amplification of PD‐L1. Previous studies found two cases of DLBCL carrying an IGH::PD‐L1 by whole genome sequencing. We describe two more such cases by a targeted DNA next‐generation sequencing (NGS) capable of detecting IGH rearrangements, leading to PD‐L1 overexpression. DLBCL with PD‐L1 overexpression is often resistant to R‐CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine and prednisolone). Our patients responded to a combination of R‐CHOP and a PD‐1 inhibitor.
SNP-Based Heritability of Osteochondrosis Dissecans in Hanoverian Warmblood Horses

Simple Summary The heritability of a trait is the proportion of phenotypic variance explained via genetic variance. Prior to the advent of genomics, heritability was estimated using extensive pedigree analyses. With the availability of genome-wide genotyping arrays, an alternative method became available to estimate heritability using genomic relationship matrices derived from genotype data. We used approaches that consider patterns of linkage disequilibrium and relatedness to estimate heritability of osteochondrosis dissecans in Hanoverian Warmblood horses based on genotype data from SNP arrays and imputed genotype data. Taking into account linkage disequilibrium patterns and relatedness in the data, heritability estimates on the linear scale for fetlock-, hock- and stifle-OCD were 0.41–0.43, 0.62–0.63, and 0.23–0.25, respectively, with standard errors of 0.11–0.14. In summary, SNP-based approaches are able to capture a greater proportion of additive genetic variance than previous estimates based on pedigree data. Abstract Before the genomics era, heritability estimates were performed using pedigree data. Data collection for pedigree analysis is time consuming and holds the risk of incorrect or incomplete data. With the availability of SNP-based arrays, heritability can now be estimated based on genotyping data. We used SNP array and 1.6 million imputed genotype data with different minor allele frequency restrictions to estimate heritabilities for osteochondrosis dissecans in the fetlock, hock and stifle joints of 446 Hanoverian warmblood horses. SNP-based heritabilities were estimated using a genomic restricted maximum likelihood (GREML) method and accounting for patterns of regional linkage disequilibrium in the equine genome. In addition, we employed GREML for family data to account for different degrees of relatedness in the study population. Our results indicate that we were able to capture a larger proportion of additive genetic variance compared to pedigree-based estimates in the same population of Hanoverian horses. Heritability estimates on the linear scale for fetlock-, hock- and stifle-osteochondrosis dissecans were 0.41–0.43, 0.62–0.63, and 0.23–0.25, respectively, with standard errors of 0.11–0.14. Accounting for linkage disequilibrium patterns had an upward effect on the imputed data and a downward impact on the SNP array genotype data. GREML for family data resulted in higher heritability estimates for fetlock-osteochondrosis dissecans and slightly higher estimates for hock-osteochondrosis dissecans, but had no effect on stifle-osteochondrosis dissecans. The largest and most consistent heritability estimates were obtained when we employed GREML for family data with genomic relationship matrices weighted through patterns of regional linkage disequilibrium. Estimation of SNP-based heritability should be recommended for traits that can only be phenotyped in smaller samples or are cost-effective.
Microhabitat conditions remedy heat stress effects on insect activity

Anthropogenic global warming has major implications for mobile terrestrial insects, including long‐term effects from constant warming, for example, on species distribution patterns, and short‐term effects from heat extremes that induce immediate physiological responses. To cope with heat extremes, they either have to reduce their activity or move to preferable microhabitats. The availability of favorable microhabitat conditions is strongly promoted by the spatial heterogeneity of habitats, which is often reduced by anthropogenic land transformation. Thus, it is decisive to understand the combined effects of these global change drivers on insect activity. Here, we assessed the movement activity of six insect species (from three orders) in response to heat stress using a unique tracking approach via radio frequency identification. We tracked 465 individuals at the iDiv Ecotron across a temperature gradient up to 38.7°C. In addition, we varied microhabitat conditions by adding leaf litter from four different tree species to the experimental units, either spatially separated or well mixed. Our results show opposing effects of heat extremes on insect activity depending on the microhabitat conditions. The insect community significantly decreased its activity in the mixed litter scenario, while we found a strong positive effect on activity in the separated litter scenario. We hypothesize that the simultaneous availability of thermal refugia as well as resources provided by the mixed litter scenario allows animals to reduce their activity and save energy in response to heat stress. Contrary, the spatial separation of beneficial microclimatic conditions and resources forces animals to increase their activity to fulfill their energetic needs. Thus, our study highlights the importance of habitat heterogeneity on smaller scales, because it may buffer the consequences of extreme temperatures of insect performance and survival under global change.
Favorable Effect of High-Density Lipoprotein Cholesterol on Gastric Cancer Mortality by Sex and Treatment Modality

Simple Summary Studies on the effects of high-density lipoprotein cholesterol (HDL-C) on gastric cancer mortality are few, and the results are inconsistent. In this study, we investigated the effects of HDL-C on gastric cancer mortality and conducted sub-group analysis by sex and treatment modality. In this cohort study including patients with gastric cancer (n = 22,468), HDL-C was inversely related with mortality with a dose-dependent manner. In validation cohort (n = 3379), HDL-C was also inversely associated with mortality with a dose-dependent manner. The two cohorts demonstrated consistent favorable effects of higher HDL-C on mortality in both sexes. In validation cohort, the beneficial effect of HDL-C was observed in both gastrectomy and endoscopic resection (p for trend < 0.001) as more remarkable in endoscopic resection group. In this study, we explored that an increased HDL-C reduced mortality in both sexes and curative resection group. Abstract Studies on the effects of high-density lipoprotein cholesterol (HDL-C) on gastric cancer mortality are few, and the results are inconsistent. In this study, we investigated the effects of HDL-C on gastric cancer mortality and conducted sub-group analysis by sex and treatment modality. Newly diagnosed patients with gastric cancer (n = 22,468) who underwent gastric cancer screening between January 2011 and December 2013 were included and followed up until 2018. A validation cohort (n = 3379) that had newly diagnosed gastric cancer from 2005 to 2013 at a university hospital, was followed up until 2017. HDL-C was inversely related with mortality; adjusted hazard ratio (aHR) 0.90 (95% confidence interval [CI], 0.83–0.98) for HDL-C of 40–49 mg/dL, 0.86 (0.79–0.93) for HDL-C of 50–59 mg/dL, 0.82 (0.74–0.90) for HDL-C of 60–69 mg/dL, and 0.78 (0.69–0.87) for HDL-C ≥ 70 mg/dL compared to HDL-C < 40 mg/dL. In the validation cohort, HDL-C was also inversely associated with mortality; aHR 0.81 (0.65–0.99) for HDL-C of 40–49 mg/dL, 0.64 (0.50–0.82) for HDL-C of 50–59 mg/dL, and 0.46 (0.34–0.62) for HDL-C ≥ 60 mg/dL compared to HDL-C < 40 mg/dL. The two cohorts demonstrated that higher HDL-C was associated with a low risk of mortality in both sexes. In validation cohort, this association was observed in both gastrectomy and endoscopic resection (p for trend < 0.001) as more remarkable in endoscopic resection group. In this study, we explored that an increased HDL-C reduced mortality in both sexes and curative resection group.
A Novel Two-Gene Expression-Based Prognostic Score in Malignant Pleural Mesothelioma

Background: Malignant pleural mesothelioma (MPM) is a rare cancer type with an increasing incidence worldwide. We aimed to develop a rational gene expression-based prognostic score in MPM using publicly available datasets. Methods: We developed and validated a two-gene prognostic score (2-PS) using three independent publicly available gene expression datasets. The 2-PS was built using the Robust Likelihood-Based Survival Modeling with Microarray Data method. Results: We narrowed down the model building to the analysis of 179 genes, which have been shown previously to be of importance to MPM development. Our statistical approach showed that a model including two genes (GOLT1B and MAD2L1) was the best predictor for overall survival (OS) (p < 0.0001). The binary score based on the median of the continuous score stratified the patients into low and high score groups and also showed statistical significance in uni- and multivariate models. The 2-PS was validated using two independent transcriptomic datasets. Furthermore, gene set enrichment analysis using training and validation datasets showed that high score patients had distinct gene expression profiles. Our 2-PS also showed a correlation with the estimated infiltration by some immune cell fractions such as CD8+ T cells and M1/2 macrophages. Finally, 2-PS correlated with sensitivity or resistance to some commonly used chemotherapeutic drugs. Conclusion: This is the first study to demonstrate good performance of only two-gene expression-based prognostic scores in MPM. Our initial approach for features selection allowed for an increased likelihood for the predictive value of the developed score, which we were also able to demonstrate.
Polarimetric Variability of Classic Supercell Storms as a Function of Environment

AbstractClassic supercell storms occur in a generally well understood environment characterized by instability and vertical wind shear. Within this broadly favorable environment, large day-to-day variability in environmental parameters may lead to widely varying radar presentation of storms. Of interest here is whether specific storm structures exhibit repeatable characteristics in similar environments and whether radar presentation can be predicted with knowledge of environmental characteristics. Specifically, this paper focuses on (i) updraft characteristics inferred using differential reflectivity ZDR columns, (ii) characteristics of storm-relative inflow inferred using ZDR arcs, and (iii) areal extent and cyclicality of polarimetrically inferred hailfall at low levels. Variability of these radar features is compared among storms in similar environments and among a larger subset of storms across highly varying environments. The similarity of storms in similar and different environments is quantified, a.
Acoustic receptivity simulations of flow past a flat plate with elliptic leading edge

We present results of numerical simulations of leading-edge acoustic receptivity for acoustic waves impinging on the leading edge of a finite-thickness flat plate. We use both compressible and incompressible flow solvers fitted with high-order high-accuracy numerical methods and independent methods of estimating the receptivity coefficient. The results show that the level of acoustic receptivity in the existing literature appears to be one order of magnitude too high. Our review of previous numerical simulations and experiments clearly identifies some contradictory trends. In the limit of an infinitely thin flat plate, our results are consistent with asymptotic theory and numerical simulations.