Miracle-dz/UniFAR-FTUs huggingface dataset:
Value Frameworks: Adaptation of Korean Versions of Value Frameworks for Oncology

This study sought to adapt the existing value framework (VF) to produce a reliable and valid Korean oncology VF. Two VFs developed by The American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) were selected for examination in the present study. Forward and backward translations were conducted for six high-priced drugs indicated for non-small-cell lung cancer and multiple myeloma. Inter-rater reliability was measured based on the intraclass correlation coefficient (ICC) and variation was described using the coefficient of variation. The relative weights of factors critically considered by Korean oncologists were derived following the analytic hierarchy process (AHP), and focus group interviews (FGIs) were used to obtain qualitative data regarding the applications of these two VFs in the Korean setting. The ICCs of the Korean VFs were 0.895 (0.654–0.983) for ASCO and 0.726 (0–0.982) for ESMO translations, suggesting excellent reliability for ASCO and good reliability for ESMO. AHP demonstrated that clinical benefit has the highest priority, which is consistent with the ASCO VF. The FGIs suggested that the result for AHP is acceptable and that both ESMO and ASCO VFs should be used complementarily. Although further evaluation with a larger sample size is needed, the Korean versions of ESMO/ASCO VFs are valid and reliable tools and are acceptable to Korean stakeholders, yet they should be applied with caution.
TRPM4 Participates in Aldosterone-Salt-Induced Electrical Atrial Remodeling in Mice

Aldosterone plays a major role in atrial structural and electrical remodeling, in particular through Ca2+-transient perturbations and shortening of the action potential. The Ca2+-activated non-selective cation channel Transient Receptor Potential Melastatin 4 (TRPM4) participates in atrial action potential. The aim of our study was to elucidate the interactions between aldosterone and TRPM4 in atrial remodeling and arrhythmias susceptibility. Hyperaldosteronemia, combined with a high salt diet, was induced in mice by subcutaneously implanted osmotic pumps during 4 weeks, delivering aldosterone or physiological serum for control animals. The experiments were conducted in wild type animals (Trpm4+/+) as well as Trpm4 knock-out animals (Trpm4-/-). The atrial diameter measured by echocardiography was higher in Trpm4-/- compared to Trpm4+/+ animals, and hyperaldosteronemia-salt produced a dilatation in both groups. Action potentials duration and triggered arrhythmias were measured using intracellular microelectrodes on the isolated left atrium. Hyperaldosteronemia-salt prolong action potential in Trpm4-/- mice but had no effect on Trpm4+/+ mice. In the control group (no aldosterone-salt treatment), no triggered arrythmias were recorded in Trpm4+/+ mice, but a high level was detected in Trpm4-/- mice. Hyperaldosteronemia-salt enhanced the occurrence of arrhythmias (early as well as delayed-afterdepolarization) in Trpm4+/+ mice but decreased it in Trpm4-/- animals. Atrial connexin43 immunolabelling indicated their disorganization at the intercalated disks and a redistribution at the lateral side induced by hyperaldosteronemia-salt but also by Trpm4 disruption. In addition, hyperaldosteronemia-salt produced pronounced atrial endothelial thickening in both groups. Altogether, our results indicated that hyperaldosteronemia-salt and TRPM4 participate in atrial electrical and structural remodeling. It appears that TRPM4 is involved in aldosterone-induced atrial action potential shortening. In addition, TRPM4 may promote aldosterone-induced atrial arrhythmias, however, the underlying mechanisms remain to be explored.
Selective Proliferation of Highly Functional Adipose-Derived Stem Cells in Microgravity Culture with Stirred Microspheres

Therapeutic effects of adult stem-cell transplantations are limited by poor cell-retention in target organs, and a reduced potential for optimal cell differentiation compared to embryonic stem cells. However, contemporary studies have indicated heterogeneity within adult stem-cell pools, and a novel culturing technique may address these limitations by selecting those for cell proliferation which are highly functional. Here, we report the preservation of stemness in human adipose-derived stem cells (hASCs) by using microgravity conditions combined with microspheres in a stirred suspension. The cells were bound to microspheres (100−300 μm) and cultured using a wave-stirring shaker. One-week cultures using polystyrene and collagen microspheres increased the proportions of SSEA-3(+) hASCs 4.4- and 4.3-fold (2.7- and 2.9-fold increases in their numbers), respectively, compared to normal culture conditions. These cultured hASCs expressed higher levels of pluripotent markers (OCT4, SOX2, NANOG, MYC, and KLF), and had improved abilities for proliferation, colony formation, network formation, and multiple-mesenchymal differentiation. We believe that this novel culturing method may further enhance regenerative therapies using hASCs.
Antenna Protein Clustering In Vitro Unveiled by Fluorescence Correlation Spectroscopy

Antenna protein aggregation is one of the principal mechanisms considered effective in protecting phototrophs against high light damage. Commonly, it is induced, in vitro, by decreasing detergent concentration and pH of a solution of purified antennas; the resulting reduction in fluorescence emission is considered to be representative of non-photochemical quenching in vivo. However, little is known about the actual size and organization of antenna particles formed by this means, and hence the physiological relevance of this experimental approach is questionable. Here, a quasi-single molecule method, fluorescence correlation spectroscopy (FCS), was applied during in vitro quenching of LHCII trimers from higher plants for a parallel estimation of particle size, fluorescence, and antenna cluster homogeneity in a single measurement. FCS revealed that, below detergent critical micelle concentration, low pH promoted the formation of large protein oligomers of sizes up to micrometers, and therefore is apparently incompatible with thylakoid membranes. In contrast, LHCII clusters formed at high pH were smaller and homogenous, and yet still capable of efficient quenching. The results altogether set the physiological validity limits of in vitro quenching experiments. Our data also support the idea that the small, moderately quenching LHCII oligomers found at high pH could be relevant with respect to non-photochemical quenching in vivo.
Hormetic Responses of Photosystem II in Tomato to Botrytis cinerea

Botrytis cinerea, a fungal pathogen that causes gray mold, is damaging more than 200 plant species, and especially tomato. Photosystem II (PSII) responses in tomato (Solanum lycopersicum L.) leaves to Botrytis cinerea spore suspension application were evaluated by chlorophyll fluorescence imaging analysis. Hydrogen peroxide (H2O2) that was detected 30 min after Botrytis application with an increasing trend up to 240 min, is possibly convening tolerance against B. cinerea at short-time exposure, but when increasing at relative longer exposure, is becoming a damaging molecule. In accordance, an enhanced photosystem II (PSII) functionality was observed 30 min after application of B. cinerea, with a higher fraction of absorbed light energy to be directed to photochemistry (ΦPSΙΙ). The concomitant increase in the photoprotective mechanism of non-photochemical quenching of photosynthesis (NPQ) resulted in a significant decrease in the dissipated non-regulated energy (ΦNO), indicating a possible decreased singlet oxygen (1O2) formation, thus specifying a modified reactive oxygen species (ROS) homeostasis. Therefore, 30 min after application of Botrytis spore suspension, before any visual symptoms appeared, defense response mechanisms were triggered, with PSII photochemistry to be adjusted by NPQ in a such way that PSII functionality to be enhanced, but being fully inhibited at the application spot and the adjacent area, after longer exposure (240 min). Hence, the response of tomato PSII to B. cinerea, indicates a hormetic temporal response in terms of “stress defense response” and “toxicity”, expanding the features of hormesis to biotic factors also. The enhanced PSII functionality 30 min after Botrytis application can possible be related with the need of an increased sugar production that is associated with a stronger plant defense potential through the induction of defense genes.
Comprehensive Genomic Characterization of Fifteen Early-Onset Lynch-Like Syndrome Colorectal Cancers

Simple Summary The most prevalent type of hereditary colorectal cancer is called Lynch syndrome and it is characterized by a tumor phenotype called microsatellite instability (MSI). This disease is a consequence of germline (inheritable) variants in any of the four mismatch repair (MMR) DNA genes, being their identification essential to ensure their appropriate diagnosis and implementation of preventive measurements. Nevertheless, only 50% of patients with MSI and suspected Lynch syndrome actually carry a germline pathogenic variant in an MMR gene that explains the clinical entity. The remaining 50% are termed Lynch-like syndrome, and their causes remain unknown. In this work, we tried to elucidate the molecular mechanisms that underlie this rare entity in a group of early-onset Lynch-like syndrome colorectal cancer, through whole-exome sequencing of germline and tumor samples. We observed that one-third of these patients have somatic alterations in genes associated with the MMR system and that these could be the mechanism causing their unexplained MSI. Furthermore, we found that patients who showed biallelic somatic alterations also carried germline variants in new candidate genes associated with DNA repair functions and that this could be, partly, the cause of the early onset in this cohort. Abstract Lynch-like syndrome (LLS) is an increasingly common clinical challenge with an underlying molecular basis mostly unknown. To shed light onto it, we focused on a very young LLS early-onset colorectal cancer (CRC) cohort (diagnosis ≤ 40 y.o.), performing germline and tumor whole-exome sequencing (WES) of 15 patients, and additionally analyzing their corresponding tumor mutational burden (TMB) and mutational signatures. We identified four cases (27%) with double somatic putative variants in mismatch repair (MMR) core genes, as well as three additional cases (20%) with double MSH3 somatic alterations in tumors with unexplained MSH2/MSH6 loss of expression, and two cases (13%) with POLD1 potential biallelic alterations. Average TMB was significantly higher for LLS cases with double somatic alterations. Lastly, nine predicted deleterious variants in genes involved in the DNA repair functions and/or previously associated with CRC were found in nine probands, four of which also showed MMR biallelic somatic inactivation. In conclusion, we contribute new insights into LLS CRC, postulating MSH3 and POLD1 double somatic alterations as an underlying cause of a microsatellite instability (MSI) phenotype, proposing intrinsic biological differences between LLS with and without somatic alterations, and suggesting new predisposing candidate genes in this scenario.
Halal Food Performance and Its Influence on Patron Retention Process at Tourism Destination

Muslim tourism is one of the most rapidly developing sectors in the international tourism industry. Nevertheless, halal food performance and its relationship with international Muslim traveler decision-making and behaviors have not been sufficiently examined. The present research explored the influence of halal food performance, which encompasses availability, health/nutrition, accreditation, and cleanness/safety/hygiene factors, on the Muslim traveler retention process at a non-Islamic destination. A survey methodology with a quantitative data analytic approach was employed to achieve research goals. Our findings indicated that halal food performance increased destination trust and destination attachment, which in turn influenced Muslim traveler retention. Additionally, the efficacy of the higher-order framework of halal food performance was defined. Both destination trust and attachment mediated the effect of halal food performance on retention. A halal-friendly destination image included a moderating influence on the retention process. The effectiveness of the proposed theoretical framework for explicating Muslim traveler behaviors was uncovered. This research better introduces the importance of halal food performance and its attributes for the elicitation of Muslim traveler approach responses and behaviors at a non-Islamic destination to researchers and practitioners.
A Reinforcement Learning Approach to View Planning for Automated Inspection Tasks

Manual inspection of workpieces in highly flexible production facilities with small lot sizes is costly and less reliable compared to automated inspection systems. Reinforcement Learning (RL) offers promising, intelligent solutions for robotic inspection and manufacturing tasks. This paper presents an RL-based approach to determine a high-quality set of sensor view poses for arbitrary workpieces based on their 3D computer-aided design (CAD). The framework extends available open-source libraries and provides an interface to the Robot Operating System (ROS) for deploying any supported robot and sensor. The integration into commonly used OpenAI Gym and Baselines leads to an expandable and comparable benchmark for RL algorithms. We give a comprehensive overview of related work in the field of view planning and RL. A comparison of different RL algorithms provides a proof of concept for the framework’s functionality in experimental scenarios. The obtained results exhibit a coverage ratio of up to 0.8 illustrating its potential impact and expandability. The project will be made publicly available along with this article.
Graphene Oxide–Silver Nanoparticle Nanocomposites Induce Oxidative Stress and Aberrant Methylation in Caprine Fetal Fibroblast Cells

Graphene oxide–silver nanoparticle (GO-AgNPs) nanocomposites have drawn much attention for their potential in biomedical uses. However, the potential toxicity of GO-AgNPs in animals and humans remains unknown, particularly in the developing fetus. Here, we reported the GO-AgNP-mediated cytotoxicity and epigenetic alteration status in caprine fetal fibroblast cells (CFFCs). In brief, the proliferation and apoptosis rate of GO-AgNP-treated CFFCs (4 and 8 µg/mL of GO-AgNPs) were measured using the cell-counting kit (CCK-8) assay and the annexin V/propidium iodide (PI) assay, respectively. In addition, the oxidative stress induced by GO-AgNPs and detailed mechanisms were studied by evaluating the generation of reactive oxygen species (ROS), superoxide dismutase (SOD), lactate dehydrogenase (LDH), malondialdehyde (MDA), and caspase-3 and abnormal methylation. The expression of pro- and anti-apoptotic genes and DNA methyltransferases was measured using reverse transcription followed by RT-qPCR. Our data indicated that GO-AgNPs cause cytotoxicity in a dose-dependent manner. GO-AgNPs induced significant cytotoxicity by the loss of cell viability, production of ROS, increasing leakage of LDH and level of MDA, increasing expression of pro-apoptotic genes, and decreasing expression of anti-apoptotic genes. GO-AgNPs incited DNA hypomethylation and the decreased expression of DNMT3A. Taken together, this study showed that GO-AgNPs increase the generation of ROS and cause apoptosis and DNA hypomethylation in CFFCs. Therefore, the potential applications of GO-AgNPs in biomedicine should be re-evaluated.
Schemes for Drug-Induced Treatment of Osteonecrosis of Jaws with Particular Emphasis on the Influence of Vitamin D on Therapeutic Effects

Drugs that inhibit bone resorption are prescribed most often by orthopedists, hematologists, or oncologists. Dental practice rarely draws attention to their importance and the effects they carry. The problem concerns mainly older people owing to oncological problems or postmenopausal consequences, but everyone can be at risk. Carefully conducted interviews and analysis of history and disease should always be performed before any action is taken by patients taking this type of medicine. Further action should consider possible complications and, above all, the risk of their occurrence. In this article, the most important issues related to the treatment of drug-induced osteonecrosis of the jaws (ONJ) are raised, including medication-related osteonecrosis of the jaw (MRONJ); conservative treatment, including the use of laser; and the impact of vitamin D supplementation on the overall treatment, prognosis, and prevention before complication, which is osteonecrosis of the jaw in the course of treatment with bisphosphonates and other drugs predisposing to MRONJ, such as denosumab and angiogenesis inhibitors. The degree of osteonecrosis is also critical, as it is possible to avoid surgical procedures for only conservative methods that sometimes bring good results. Surgical treatment of advanced stages is complicated and carries a high risk of error and complications. MRONJ is a disease that is easy to avoid, but it is difficult to treat and treatment sometimes leads only to a partial remission of the disease, not a complete cure.
Genotyping-by-Sequencing in Vigna unguiculata Landraces and Its Utility for Assessing Taxonomic Relationships

Genotyping by sequencing (GBS) was used to analyze relationships among cowpea and asparagus bean landraces from southern Italy and to assess the utility of this technology to study taxonomy in a wider panel, including V. unguiculata cultigroups, subspecies, and other Vigna species. The analysis of SNPs derived from GBS highlighted that, among the cowpea landraces, the African samples were separated from the other material, while, for the Italian landraces, a certain clustering depending on seed color/pattern was observed in the dendrogram. When examining the V. unguiculata species complex, a clear separation between the two groups of wild subspecies, i.e., the allogamous wild perennials and the perennial out/inbreds, could be observed, the former representing the more ancestral wild progenitors of V. unguiculata. The species V. vexillata appeared more closely related to V. unguiculata than to the other Vigna species analyzed.
Surgical Outcome of Trigeminal Schwannomas

Simple Summary Trigeminal schwannomas are the most common among non-vestibular schwannomas. Treatment of trigeminal schwannomas may be challenging due to critical anatomical relations and involvement of different aspects of the skull base. Advances in microsurgery have led to improved outcomes over the last decades, whereas in contrast, some advocate stereotactic radiotherapy as an effective therapy, controlling the tumor volume with few complications. In this manuscript, we present outcome and adverse events in a contemporary cohort of trigeminal schwannomas and discuss surgical advantages and disadvantages of different performed classic skull-base approaches. Abstract (1) Background: As resection of trigeminal schwannomas is challenging, due to anatomical involvement of the anterior, middle and posterior fossa, the appropriate approach is important. We report our experience with surgical resection of trigeminal schwannomas by simple and classic skull-base approaches. (2) Methods: We performed a retrospective single-center study including patients who underwent surgery for trigeminal schwannoma tumors between June 2007 and May 2020, concentrating on surgical technique, extent of resection, postoperative outcome and complications. (3) Results: We included 13 patients (median age 57.5 with range of 36-83 years, 53.8% (7/13) female. The most common preoperative clinical presentations were facial pain in six (46.2%), hypoacusis in four (30.8%), trigeminal nerve hypesthesia in 11 (V1 46.2% (6/13), V2 (61.5% (8/13), V3 46.2% (6/13)) and headache in three (23.1%) patients. In three cases, the tumor was resected in a two-stage technique. The intradural subtemporal approach was performed in six cases, the extradural technique in two cases, the retrosigmoid approach in five cases, a Kawase approach in two cases and the transnasal endoscopic approach in one case. The gross total resection rate was 76.9% (10/13) and the median follow-up time 24.0 (0–136) months. Three (23.1%) patients developed postoperative anesthesia in at least one branch of the trigeminal nerve. Trigeminal motor function was preserved in 11 (84.6%) patients. Ten of the 11 patients (76.9%) who reported decreased gustation, cerebellar ataxia, visual impairment, or headache improved postoperatively. Two (15.4%) patients exhibited minimal facial palsy (House and Brackmann II–III), which resolved during the follow-up. The total adverse event rate requiring surgical intervention during follow-up was 7.7%. Surgery-related mortality was 0%. (4) Conclusions: Trigeminal schwannomas are rare benign lesions with intra- and extracranial extension. Considering the low operative morbidity and satisfying functional outcome, gross total resection of trigeminal schwannomas is achievable by classic, but also individually tailored approaches. More invasive or combined techniques were not needed with meticulous surgical planning.
Effects of Pulsed Electric Field Processing and Sous Vide Cooking on Muscle Structure and In Vitro Protein Digestibility of Beef Brisket

Pulsed electric fields (PEF) in conjunction with sous vide (SV) cooking has been explored for meat tenderisation. The aim of this experiment was to study the effect of PEF–SV treatment on the muscle structure and in vitro protein digestibility of beef brisket. Pulsed electric field treatment (specific energy of 99 ± 5 kJ/kg) was applied to bovine Deep and Superficial pectoral muscles in combination with sous vide (SV) cooking (60 °C for 24 h). A similar micro- and ultrastructure was detected between the control SV-cooked and PEF-treated SV-cooked pectoral muscles. The combined PEF–SV treatment increased the in vitro protein digestibility of the pectoral muscles by approximately 29%, in terms of ninhydrin-reactive free amino nitrogen released at the end of simulated digestion. An increment in proteolysis of the PEF-treated SV-cooked meat proteins (e.g., myosin heavy chains and C-protein) during simulated digestion was also observed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. More damaged muscle micro- and ultrastructure was detected in PEF-treated SV-cooked muscles at the end of in vitro digestion, showing its enhanced digestive proteolysis compared to the control cooked meat.
Effect of a Brain–Computer Interface Based on Pedaling Motor Imagery on Cortical Excitability and Connectivity

Recently, studies on cycling-based brain–computer interfaces (BCIs) have been standing out due to their potential for lower-limb recovery. In this scenario, the behaviors of the sensory motor rhythms and the brain connectivity present themselves as sources of information that can contribute to interpreting the cortical effect of these technologies. This study aims to analyze how sensory motor rhythms and cortical connectivity behave when volunteers command reactive motor imagery (MI) BCI that provides passive pedaling feedback. We studied 8 healthy subjects who performed pedaling MI to command an electroencephalography (EEG)-based BCI with a motorized pedal to receive passive movements as feedback. The EEG data were analyzed under the following four conditions: resting, MI calibration, MI online, and receiving passive pedaling (on-line phase). Most subjects produced, over the foot area, significant event-related desynchronization (ERD) patterns around Cz when performing MI and receiving passive pedaling. The sharpest decrease was found for the low beta band. The connectivity results revealed an exchange of information between the supplementary motor area (SMA) and parietal regions during MI and passive pedaling. Our findings point to the primary motor cortex activation for most participants and the connectivity between SMA and parietal regions during pedaling MI and passive pedaling.