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Background: Pancreatic ductal carcinoma (PDAC) is an extremely poor prognostic disease. Even though multidisciplinary treatment for PDAC has developed, supportive therapies, such as nutritional therapy or perioperative rehabilitation to sustain and complete aggressive treatment, have not yet been well-established in PDAC. The aim of this study was to elucidate the relationship between the combined index using psoas muscle mass index (PMI) values and controlling nutritional status (CONUT) score and prognosis. Methods: We included 101 patients diagnosed with PDAC who underwent radical pancreatectomy with regional lymphadenectomy. The cut-off value was set at the first quartile (male, 6.3 cm2/m2; female 4.4 cm2/m2), and patients were classified into high PMI and low PMI groups. A CONUT score of 0 to 1 was classified as the normal nutritional status group, and 2 or more points as the malnutritional status group. Patients were further divided into three groups: high PMI and normal nutrition (good general condition group), low PMI and low nutrition (poor general condition group), and none of the above (moderate general condition group). We performed a prognostic analysis of overall survival (OS), stratified according to PMI values and CONUT scores. Results: In the poor general condition group, the proportion of elderly people over 70 years of age was significantly higher than that in the other groups (p < 0.001). The poor general condition group had a significantly worse prognosis than the good and moderate general condition groups (p = 0.012 and p = 0.037). The 5-year survival rates were 10.9%, 22.3%, and 36.1% in the poor, moderate, and good general condition groups, respectively. In multivariate analysis, poor general condition, with both low PMI and malnutrition status, was an independent poor prognostic factor for postoperative OS (hazard ratio 2.161, p = 0.031). Conclusions: The combination of PMI and CONUT scores may be useful for predicting the prognosis of patients with PDAC after radical surgery. [ABSTRACT FROM AUTHOR]

Background/objectives: We investigated whether dietary interventions, i.e. a fasting mimicking diet (FMD, Prolon®) or glycocalyx mimetic supplementation (EndocalyxTM) could stabilize microvascular function in Surinamese South-Asian patients with type 2 diabetes (SA-T2DM) in the Netherlands, a patient population more prone to develop vascular complications. Subjects/methods: A randomized, placebo controlled, 3-arm intervention study was conducted in 56 SA-T2DM patients between 18 and 75 years old, for 3 consecutive months, with one additional follow up measurement 3 months after the last intervention. Sublingual microcirculation was assessed with SDF-imaging coupled to the GlycoCheckTM software, detecting red blood cell velocity, capillary density, static and dynamic perfused boundary region (PBR), and the overall microvascular health score (MVHS). Linear mixed models and interaction analysis were used to investigate the effects the interventions had on microvascular function. Results: Despite a temporal improvement in BMI and HbA1c after FMD the major treatment effect on microvascular health was worsening for RBC-velocity independent PBRdynamic, especially at follow-up. Glycocalyx supplementation, however, reduced urinary MCP-1 presence and improved both PBRdynamic and MVHSdynamic, which persisted at follow-up. Conclusions: We showed that despite temporal beneficial changes in BMI and HbA1c after FMD, this intervention is not able to preserve microvascular endothelial health in Dutch South-Asian patients with T2DM. In contrast, glycocalyx mimetics preserves the microvascular endothelial health and reduces the inflammatory cytokine MCP-1. Clinical study registration: NCT03889236. [ABSTRACT FROM AUTHOR]

Xenotransplantation is emerging as a vital solution to the critical shortage of organs available for transplantation, significantly propelled by advancements in genetic engineering and the development of sophisticated immunosuppressive treatments. Specifically, the transplantation of kidneys from genetically engineered pigs into human patients has made significant progress, offering a potential clinical solution to the shortage of human kidney supply. Recent trials involving the transplantation of these modified porcine kidneys into deceased human bodies have underscored the practicality of this approach, advancing the field towards potential clinical applications. However, numerous challenges remain, especially in the domains of identifying suitable donor-recipient matches and formulating effective immunosuppressive protocols crucial for transplant success. Critical to advancing xenotransplantation into clinical settings are the nuanced considerations of anesthesia and surgical practices required for these complex procedures. The precise genetic modification of porcine kidneys marks a significant leap in addressing the biological and immunological hurdles that have traditionally challenged xenotransplantation. Yet, the success of these transplants hinges on the process of meticulously matching these organs with human recipients, which demands thorough understanding of immunological compatibility, the risk of organ rejection, and the prevention of zoonotic disease transmission. In parallel, the development and optimization of immunosuppressive protocols are imperative to mitigate rejection risks while minimizing side effects, necessitating innovative approaches in both pharmacology and clinical practices. Furthermore, the post-operative care of recipients, encompassing vigilant monitoring for signs of organ rejection, infectious disease surveillance, and psychological support, is crucial for ensuring post-transplant life quality. This comprehensive care highlights the importance of a multidisciplinary approach involving transplant surgeons, anesthesiologists, immunologists, infectiologists and psychiatrists. The integration of anesthesia and surgical expertise is particularly vital, ensuring the best possible outcomes of those patients undergoing these novel transplants, through safe procedural practices. As xenotransplantation moving closer to clinical reality, establishing consensus guidelines on various aspects, including donor-recipient selection, immunosuppression, as well as surgical and anesthetic management of these transplants, is essential. Addressing these challenges through rigorous research and collective collaboration will be the key, not only to navigate the ethical, medical, and logistical complexities of introducing kidney xenotransplantation into mainstream clinical practice, but also itself marks a new era in organ transplantation. [ABSTRACT FROM AUTHOR]

The vagus nerve is the only pathway for transmitting parasympathetic signals between the brain and thoracoabdominal organs, thereby exhibiting anti-inflammatory functions through the cholinergic anti-inflammatory pathway. Despite often being resected during lymph node dissection in upper gastrointestinal cancer surgery, the impact of vagotomy on postoperative outcomes in gastric cancer patients remains unclear. Sub-diaphragmatic vagotomy was performed on C57BL/6 mice. Three weeks later, syngeneic murine gastric cancer cell line YTN16P was injected into the peritoneal cavity, and the number of peritoneal metastases (PM) on the mesentery and omentum compared with control mice. The phenotypes of immune cells in peritoneal lavage and omental milky spots one day after tumor inoculation were analyzed using flow cytometry and immunohistochemistry. Intraperitoneal transfer of 3 × 105 YTN16P significantly increased the number of metastatic nodules on the mesentery in the vagotomy group compared to the control group. The omental metastasis grade was also significantly higher in the vagotomy group. Phenotypic analysis of immune cells in peritoneal lavage did not reveal significant differences after vagotomy. However, vagotomized mice exhibited a notable increase in milky spot area, with a higher presence of cytokeratin(+) tumor cells, F4/80(+) macrophages, and CD3(+) T cells. Vagus nerve signaling appears to regulate the immune response dynamics within milky spots against disseminated tumor cells and inhibits the development of PM. Preserving the vagus nerve may offer advantages in advanced gastric cancer surgery to reduce peritoneal recurrence. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a debilitating neurodegenerative disease characterized by the accumulation of extracellular amyloid-β peptides (Aβ) within the cerebral parenchyma and vasculature, which is known as cerebral amyloid angiopathy (CAA). This study utilized confocal imaging to investigate heparan sulfate (HS) expression within the cerebrovasculature and its associations with Aβ, gender, and ApoE4 genotype in AD. Our investigation revealed elevated levels of HS in the cerebrovasculature of AD patients with severe CAA. Additionally, these patients exhibited higher HS colocalization with Aβ in the cerebrovasculature, including both endothelial and vascular smooth muscle cell compartments. Intriguingly, a reversal in the polarized expression of HS within the cerebrovasculature was detected in AD patients with severe CAA. Furthermore, male patients exhibited lower levels of both parenchymal and cerebrovascular HS. Additionally, ApoE4 carriers displayed heightened cerebrovascular Aβ expression and a tendency of elevated cerebrovascular HS levels in AD patients with severe CAA. Overall, these findings reveal potential intricate interplay between HS, Aβ, ApoE, and vascular pathology in AD, thereby underscoring the potential roles of cerebrovascular HS in CAA development and AD pathology. Further study of the underlying mechanisms may present novel therapeutic avenues for AD treatment. [ABSTRACT FROM AUTHOR]

The good insulation properties and the low carbon footprint of vegetal concretes make them promising materials whose use tends to grow continuously. To produce optimized building materials, a better understanding of the interfacial transition zone (ITZ) between vegetal particles and cement paste in terms of the reactions involved and the size of the impacted surface was investigated. This research led to the setting of a reliable visual test to observe ITZ, which enables the monitoring of its appearance and development. Different combinations of vegetal particles and cement pastes were tested to compare the formed ITZ: hemp, rapeseed, and bamboo into Portland and Prompt cement. Finally, a clear link was drawn between the sugar concentration and the size of ITZ. Thanks to image analysis, it was shown that ITZ is due to physico-chemical reactions, with the extraction of free saccharide molecules from the vegetal and water suction followed by their release into the cement paste. [ABSTRACT FROM AUTHOR]

A series of integral experiments was conducted to evaluate the fission and the capture cross-sections of transuranic (TRU) nuclides at the fast critical facility FCA of the Japan Atomic Energy Agency (JAEA). The experiments were carried out using seven uranium-fueled assemblies of the FCA. The neutron energy spectra of the core regions were adjusted so as to change from an intermediate neutron spectrum to a fast neutron spectrum on an assembly-by-assembly basis. The integral data measured with these experimental configurations provide some neutron energy characteristics: 1) fission rate ratios (FRRs) of 237Np, 238Pu, 242Pu, 241Am, 243Am, and 244Cm relative to 239Pu by using absolutely calibrated fission chambers, 2) small sample reactivity worths (SRWs) of 237Np, 238Pu, 240Pu, 241Am, and 243Am where oxide powders of around 15 to 20 grams were used, 3) criticalities, and 4) spectral indices such as fission rate ratios of 238U relative to 235U. In this paper, details of the SRW measurements are reported, and the latest Japanese Evaluated Nuclear Data Library JENDL-5 is tested by using the integral data obtained in systematically varied neutron energy spectra. [ABSTRACT FROM AUTHOR]

The diverse freshwater fish fauna of the Japanese archipelago is distributed among four main island landmasses, which include Hokkaido in the north, with many diadromous species. One relatively well-preserved river drainage along the southern coast of Central Hokkaido is the Mukawa River. Fish fauna surveys in the Mukawa River were mostly in downstream areas and the fish diversity is not well-documented among the upper, lower river, and coastal environments. Fish communities in the river, estuary, and sea were sampled using eDNA analysis to evaluate upstream and downstream species detections, and tidal and spatial detection variation near the river mouth. The number of species was higher at the river mouth and nearshore sites compared to the river and offshore. Fish detections reflected life history categories (freshwater resident, diadromous, brackish, or marine) and the environments. Similarity analysis showed that fish species compositions were divided into (1) upstream and midstream, (2) downstream and river mouth, (3) adjacent shore, and (4) offshore. Salmonid, cyprinid, loach, and sculpin species were detected in the river, compared to a mixture of species downstream and along the coast. This rapid assessment type study demonstrated that eDNA survey methodology would be effective for multiple river comparative surveys, seasonality studies, or evaluating possible effects of cross-river weirs or dams. [ABSTRACT FROM AUTHOR]

Allergic reactions are the most frequent adverse events in blood transfusion, and anaphylactic shock, although less frequent, is systemic and serious. The cause of allergic reactions to blood transfusions are largely unknown, but deficiencies in serum proteins such as haptoglobin (Hp) can lead to anaphylactic shock. A complete deletion of the haptoglobin gene (HPdel) was first identified in families with anomalous inheritance and then verified as a genetic variant that can cause anaphylactic shock because homozygotes for HPdel have complete Hp deficiency. Thereby, they may produce antibodies against Hp from blood transfusions. HPdel is found in East and Southeast Asian populations, with a frequency of approximately 0.9% to 4%, but not in other populations. Diagnosis of Hp deficiency due to HPdel prior to transfusion is advisable because severe adverse reactions can be prevented by washing the red blood cells and/or platelets with saline or by administering plasma products obtained from an Hp-deficient donor pool. This review outlines the background of the identification of HPdel and several genetic and immunological methods developed for diagnosing Hp deficiency caused by HPdel. [ABSTRACT FROM AUTHOR]

Background: Despite the expanding use of orthopedic devices and the application of strict pre- and postoperative protocols, the elimination of postoperative implant-related infections remains a challenge. Objectives: To identify and assess the in vitro and in vivo properties of antimicrobial-, silver- and iodine-based implants, as well as to present novel approaches to surface modifications of orthopedic implants. Methods: A systematic computer-based review on the development of these implants, on PubMed and Web of Science databases, was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Overall, 31 in vitro and 40 in vivo entries were evaluated. Regarding the in vitro studies, antimicrobial-based coatings were assessed in 12 entries, silver-based coatings in 10, iodine-based in 1, and novel-applied coating technologies in 8 entries. Regarding the in vivo studies, antimicrobial coatings were evaluated in 23 entries, silver-coated implants in 12, and iodine-coated in 1 entry, respectively. The application of novel coatings was studied in the rest of the cases (4). Antimicrobial efficacy was examined using different bacterial strains, and osseointegration ability and biocompatibility were examined in eukaryotic cells and different animal models, including rats, rabbits, and sheep. Conclusions: Assessment of both in vivo and in vitro studies revealed a wide antimicrobial spectrum of the coated implants, related to reduced bacterial growth, inhibition of biofilm formation, and unaffected or enhanced osseointegration, emphasizing the importance of the application of surface modification techniques as an alternative for the treatment of orthopedic implant infections in the clinical settings. [ABSTRACT FROM AUTHOR]

Lipid droplets (LDs) are cellular organelles derived from the endoplasmic reticulum (ER), serving as lipid storage sites crucial for maintaining cellular lipid homeostasis. Recent attention has been drawn to their roles in viral replication and their interactions with viruses. However, the precise biological functions of LDs in viral replication and pathogenesis remain incompletely understood. To elucidate the interaction between LDs and viruses, it is imperative to comprehend the biogenesis of LDs and their dynamic interactions with other organelles. In this review, we explore the intricate pathways involved in LD biogenies within the cytoplasm, encompassing the uptake of fatty acid from nutrients facilitated by CD36-mediated membranous protein (FABP/FATP)-FA complexes, and FA synthesis via glycolysis in the cytoplasm and the TCL cycle in mitochondria. While LD biogenesis primarily occurs in the ER, matured LDs are intricately linked to multiple organelles. Viral infections can lead to diverse consequences in terms of LD status within cells post-infection, potentially involving the breakdown of LDs through the activation of lipophagy. However, the exact mechanisms underlying LD destruction or accumulation by viruses remain elusive. The significance of LDs in viral replication renders them effective targets for developing broad-spectrum antivirals. Moreover, considering that reducing neutral lipids in LDs is a strategy for anti-obesity treatment, LD depletion may not pose harm to cells. This presents LDs as promising antiviral targets for developing therapeutics that are minimally or non-toxic to the host. [ABSTRACT FROM AUTHOR]

The germline provides the genetic and non-genetic information that passes from one generation to the next. Given this important role in species propagation, egg and sperm precursors, called primordial germ cells (PGCs), are one of the first cell types specified during embryogenesis. In fact, PGCs form well before the bipotential somatic gonad is specified. This common feature of germline development necessitates that PGCs migrate through many tissues to reach the somatic gonad. During their journey, PGCs must respond to select environmental cues while ignoring others in a dynamically developing embryo. The complex multi-tissue, combinatorial nature of PGC migration is an excellent model for understanding how cells navigate complex environments in vivo. Here, we discuss recent findings on the migratory path, the somatic cells that shepherd PGCs, the guidance cues somatic cells provide, and the PGC response to these cues to reach the gonad and establish the germline pool for future generations.We end by discussing the fate of wayward PGCs that fail to reach the gonad in diverse species. Collectively, this field is poised to yield important insights into emerging reproductive technologies. [ABSTRACT FROM AUTHOR]

Chondroitin sulfate/dermatan sulfate (CS/DS) is a member of glycosaminoglycans (GAGs) found in animal tissues. Major CS/DS subclasses, O, A, C, D, and E units, exist based on the sulfation pattern in d-glucuronic acid (GlcA) and N-acetyl-d-galactosamine repeating units. DS is formed when GlcA is epimerized into l-iduronic acid. Our study aimed to analyze the CS/DS profile in 3 T3-L1 cells before and after adipogenic induction. CS/DS contents, molecular weight (Mw), and sulfation pattern were analyzed by using high-performance liquid chromatography. CS/DS synthesis- and sulfotransferase-related genes were analyzed by reverse transcription real-time PCR. CS/DS amount was significantly decreased in the differentiated (DI) group compared to the non-differentiated (ND) group, along with a lower expression of CS biosynthesis-related genes, chondroitin sulfate N-acetylgalactosaminyltransferase 1 and 2, as well as chondroitin polymerizing factor. GAGs in the DI group also showed lower Mw than those of ND. Furthermore, the A unit was the major CS/DS in both groups, with a proportionally higher CS-A in the DI group. This was consistent with the expression of carbohydrate sulfotransferase 12 that encodes chondroitin 4-O-sulfotransferase, for CS-A formation. These qualitative and quantitative changes in CS/DS and CS/DS-synthases before and after adipocyte differentiation reveal valuable insights into adipocyte development., (© 2023 Japanese Society of Animal Science.)

In this study, we present the design of an integrated transverse electric mode isolator realized by the epitaxial growth of a cobalt ferrite (CFO) film on a silicon micro-ring resonator structure. Exploiting the large magneto-optical activity of CFO along with the good characteristics of resonator structures, we numerically demonstrated isolator designs with ultra-compact sizes. The use of ring resonator structures with the reduced size is appealing because of lower insertion loss values. The nonreciprocal phase shift was maximized by optimizing the ring cross-section and was further studied in terms of the ring radius employing a transformation optics theory. Finally, we analyzed the optical isolator characteristics in terms of ring size and ring-waveguide power coupling ratio. The computed results pointed out that decreasing the ring size improves the device performance and can ease the device design and fabrication process. [ABSTRACT FROM AUTHOR]

Machine learning is a promising research topic that has recently achieved remarkable results, leading to the substitution of more traditional methods with automatically learned solutions. Some recent works have begun to highlight how a machine-learned model can be tricked by just applying small variations to the data, resulting in completely erroneous outcomes. Such behaviour can be traced to two elements: the lack of any metrological characterization of the inputs passed to the model, such as the uncertainty of the data, and the lack of an assessment of the reliability of the results. This paper tackles both these elements, considering the case of random forest model and proposing a method for assessing a confidence probability as an estimator for classification reliability. This considers the original classification structure, leaving it untouched, and the distribution of the training datasets. An overlaying structure statistically combines the two, and also includes in the process the propagation of feature uncertainties as a further element deriving from input measurements. The new classification outcome is a vector of probabilities that define how reliably a feature entry can be assigned, or not, to each of the considered classes, independently of others. In this new structure, an additional classification result naturally becomes available: the unclassifiable feature entry. [ABSTRACT FROM AUTHOR]

Musculocontractural Ehlers-Danlos syndrome caused by dermatan sulfate epimerase deficiency (mcEDS-DSE) is a rare connective tissue disorder. This is the first report describing the detailed and comprehensive clinical and pathophysiological features of mcEDS-DSE. The patient, with a novel homozygous nonsense variant (NM&#95;013352.4:c.2601C>A:p.(Tyr867*)), exhibited mild skin hyperextensibility without fragility and small joint hypermobility, but developed recurrent large subcutaneous hematomas. Dermatan sulfate (DS) moieties on chondroitin sulfate/DS proteoglycans were significantly decreased, but remained present, in skin fibroblasts. Electron microscopy examination of skin specimens, including cupromeronic blue-staining to visualize glycosaminoglycan (GAG) chains, revealed coexistence of normally assembled collagen fibrils with attached curved GAG chains and dispersed collagen fibrils with linear GAG chains from attached collagen fibrils across interfibrillar spaces to adjacent fibrils. Residual activity of DS-epi1, encoded by DSE, and/or compensation by DS-epi2, a minor homolog of DS-epi1, may contribute to the mild skin involvement through this "mosaic" pattern of collagen fibril assembly., (© 2022 Wiley Periodicals LLC.)

Introduction: The expression and localization of the water channel transporters, aquaporins (AQPs), in the brain are substantially modified in gliomas during tumorigenesis, cell migration, edema formation, and resolution. We hypothesized that the molecular changes associated with AQP1 and AQP4 in the brain may potentially be anticancer therapeutic targets. To test this hypothesis, a bioinformatics analysis of publicly available data from international consortia was performed. Methods: We used RNA-seq as an experimental strategy and identified the number of differential AQP1 and AQP4 transcript expressions in glioma tissue compared to normal brain tissue. Results: AQPs genes are overexpressed in patients with glioma. Among the glioma subtypes, AQP1 and AQP4 were overexpressed in astrocytoma (low-grade glioma) and classical (high-grade glioma). Overall survival analysis demonstrated that both AQP genes can be used as prognostic factors for patients with low-grade glioma. Additionally, we observed a correlation between the expression of genes involved in the tyrosine and thyroid hormone pathways and AQPs, namely: PNMT, ALDH1A3, AOC2, HGDATP1B1, ADCY5, PLCB4, ITPR1, ATP1A3, LRP2, HDAC1, MED24, MTOR, and ACTB1 (Spearman's coefficient = geq 0.20 and p-value = 0.05). Conclusion: Our findings indicate that the thyroid hormone pathways and AQPs 1 and 4 are potential targets for new anti-tumor drugs and therapeutic biomarkers for malignant gliomas. [ABSTRACT FROM AUTHOR]

This paper presents a comparative analysis of classification approaches in the Japanese discourse relation analysis (DRA) task. In the Japanese DRA task, it is difficult to resolve implicit relations where explicit discourse phrases do not appear. To understand implicit relations further, we compared the four approaches by incorporating a special token to encode the relations of the given discourses. Our four approaches included inserting a special token at the beginning of a sentence, end of a sentence, conjunctive position, and random position to classify the relation between the two discourses into one of the following categories: CAUSE/REASON, CONCESSION, CONDITION, PURPOSE, GROUND, CONTRAST, and NONE. Our experimental results revealed that special tokens are available to encode the relations of given discourses more effectively than pooling-based approaches. In particular, the random insertion of a special token outperforms other approaches, including pooling-based approaches, in the most numerous CAUSE/REASON category in implicit relations and categories with few instances. Moreover, we classified the errors in the relation analysis into three categories: confounded phrases, ambiguous relations, and requiring world knowledge for further improvements. [ABSTRACT FROM AUTHOR]

Background: Recently, bean ferritin has been attracting considerable attention as a new source of iron, that is available to vegetarians. Although high rates of iron absorption and bioavailability from this protein have been reported, clinical data on its efficacy remain scarce. Objective: In this study, we administered bean ferritin iron to premenopausal Japanese women for nine weeks, starting immediately after menstruation, to evaluate their recovery from low hemoglobin levels as one sign of anemia. Methods: Participants in the test supplement group received an iron intake of 5 mg from one capsule containing bean extract (SloIron®) for five weeks, which was increased to 10 mg (i.e., two capsules) from the 6th to the 9th week. The study evaluated the change in hemoglobin levels as the primary endpoint, and hematocrit, red blood cell count, serum iron, MCH (mean corpuscular hemoglobin), MCHC (mean corpuscular hemoglobin concentration), serum ferritin, TSAT (TIBC), serum zinc, serum copper, anemia symptoms questionnaire, OSA sleep inventory, and the anti-fatigue questionnaire as the secondary endpoints. Results: Our results showed a significant difference (P=0.03) in the change in hemoglobin levels between the groups after nine weeks of intake, confirming the restorative effect of bean ferritin on low hemoglobin levels caused by menstruation. Moreover, a significant difference (P=0.01) was observed in the amount of change in MCHC between the two groups after five weeks of intake, and after nine weeks of intake, a significant difference in the change in both MCH (P=0.02) and MCHC P<0.01) was observed between the groups. A significant difference (P=0.03) was observed in the change in serum ferritin levels after nine weeks of intake. Conclusion: The study confirmed that iron supplementation from bean ferritin is an effective treatment for low hemoglobin and low ferritin levels caused by menstruation. [ABSTRACT FROM AUTHOR]

Retroperitoneal sarcomas (RPS) are rare tumours of mesenchymal origin, commonly presented as a large tumour mass at time of diagnosis. We investigated the impact of body composition on outcome in patients operated on for primary localized RPS. We retrospectively analysed data for all patients operated on for primary RPS at our institution between 1999 and 2020. Preoperative skeletal muscle area (SMA), visceral and subcutaneous adipose tissue area (VAT and SAT) and muscle radiation attenuation (MRA) were calculated using computed tomography scans at the level of third lumbar vertebra. European Working Group on Sarcopenia in Older People (EWGSOP2) criteria were applied to define myopenia. Using maximum log-rank statistic method we determined the optimal cut-off values of body composition parameters. Myosteatosis was defined based on determined MRA cut-offs. In total 58 patient were eligible for the study. With a median follow-up of 116 months, the estimated 5-year overall survival (OS) and local-recurrence free survival (LRFS) were 66.8% and 77.6%, respectively. Patients with myopenia had significantly lower 5-year OS compared to non-myopenic (p = 0.009). Skeletal muscle index and subcutaneous adipose tissue index predicted LRFS on univariate analysis (p = 0.052 and p = 0.039, respectively). In multivariate analysis high visceral-to-subcutaneous adipose tissue area ratio (VSR) independently predicted higher postoperative complication rate (89.2% vs. 10.8%, p = 0.008). Myosteatosis was associated with higher postoperative morbidity. Myopenia affected survival, but not postoperative outcome in RPS. Visceral obesity, VSR (> 0.26) and myosteatosis were associated with higher postoperative morbidity. VSR was better prognostic factor than VAT in RPS. [ABSTRACT FROM AUTHOR]

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Background/Aim: Sarcopenia accompanied by systemic inflammation is associated with poor prognosis in patients with cancer. This study evaluated the prognostic significance of sarcopenia (myopenia and myosteatosis) and systemic inflammatory markers in older patients (aged =80 years) with resected biliary tract cancer. Patients and Methods: Patients who underwent resection for biliary tract cancer between July 2010 and January 2023 at the NHO Fukuyama Medical Center were retrospectively reviewed. Preoperative computed tomography measured myopenia and myosteatosis, using the psoas muscle index and modified intramuscular adipose tissue content. Associations between clinicopathological characteristics, inflammation-based prognostic scores, and overall survival were analyzed using Cox proportional hazards models. Results: Univariate analysis revealed low C-reactive protein-to-albumin ratio (<0.125), low prognostic nutritional index (<42), low modified intramuscular adipose tissue content, higher T-stage (T3-4), lymph node metastasis, and postoperative complications associated with worse overall survival in older patients (aged = 80 years) with resected biliary tract cancer (n=48). Multivariate analysis identified low prognostic nutritional index (<42) (p=0.007), low modified intramuscular adipose tissue content (p=0.015), higher Tstage (T3-4) (p<0.001), lymph node metastasis (p=0.001), and postoperative complications (p=0.017) as independent predictors of overall survival. Conclusion: Preoperative myosteatosis and low prognostic nutritional index are independent prognostic factors for overall survival in older patients (aged =80 years) with resected biliary tract cancer. These factors may be useful for risk stratification and clinical decision-making. Early interventions, such as nutritional support and physical exercise, may improve outcomes after resection of biliary tract cancer. [ABSTRACT FROM AUTHOR]

Persons with inborn errors of immunity (IEI) are at risk not only of recurrent and severe infections and autoimmunity, but also of malignancy. Malignancies arise from numerous mechanisms, ranging from persistent infection with oncogenic organisms and impaired immunologic surveillance of somatic cells with malignant potential to defective DNA repair mechanisms. This article highlights key current concepts regarding the epidemiology of cancer in persons with IEI and the mechanisms by which cancer may arise in these persons. Furthermore, we explore strategies of screening for and prevention of cancer in persons with IEI, and challenges imposed by the treatment of cancer in persons with IEI. Key concepts of cancer in the context of IEI are illustrated using 22 q11.2 deletion syndrome, ataxia telangiectasia, common variable immunodeficiency, selective IgA deficiency, severe combined immunodeficiency and Wiskott-Aldrich syndrome as illustrative IEI conditions. [ABSTRACT FROM AUTHOR]

Desbuquois dysplasia type 2 (DBQD2) and spondylo-ocular syndrome (SOS) are autosomal recessive disorders affecting the extracellular matrix (ECM) and categorized as glycosaminoglycan (GAG) linkeropathies. Linkeropathies result from mutations within glycosyltransferases involved in the synthesis of the tetrasaccharide linker, a linker between the core protein of proteoglycan (PG) and GAG. DBQD2 and SOS are caused by the isolated mutations of the xylosyltransferase (XT) isoforms. In this work, we successfully generated XYLT1- as well as XYLT2-deficient GAG linkeropathy model systems in human dermal fibroblasts using a ribonucleoprotein-based CRISPR/Cas9-system. Furthermore, it was possible to generate a complete XYLT-knockdown. Short- and long-term XT activity deficiency led to the mutual reduction in all linker transferase-encoding genes, suggesting a potential multienzyme complex with mutual regulation. Fibroblasts compensated for ECM misregulation initially by overexpressing ECM through the TGFβ1 signaling pathway, akin to myofibroblast differentiation patterns. The long-term reduction in one XT isoform induced a stress response, reducing ECM components. The isolated XYLT1-knockout exhibited α-smooth muscle actin overexpression, possibly partially compensated by unaltered XT-II activity. XYLT2-knockout leads to the reduction in both XT isoforms and a strong stress response with indications of oxidative stress, induced senescence and apoptotic cells. In conclusion, introducing XYLT-deficiency revealed temporal and isoform-specific regulatory differences. [ABSTRACT FROM AUTHOR]

To measure the quality of student learning, teachers must conduct evaluations. One of the most efficient modes of evaluation is the short answer question. However, there can be inconsistencies in teacher-performed manual evaluations due to an excessive number of students, time demands, fatigue, etc. Consequently, teachers require a trustworthy system capable of autonomously and accurately evaluating student answers. Using hybrid transfer learning and student answer dataset, we aim to create a reliable automated short answer scoring system called Hybrid Transfer Learning for Automated Short Answer Scoring (HTL-ASAS). HTL-ASAS combines multiple tokenizers from a pretrained model with the bidirectional encoder representations from transformers. Based on our evaluation of the training model, we determined that HTL-ASAS has a higher evaluation accuracy than models used in previous studies. The accuracy of HTL-ASAS for datasets containing responses to questions pertaining to introductory information technology courses reaches 99.6%. With an accuracy close to one hundred percent, the developed model can undoubtedly serve as the foundation for a trustworthy ASAS system. [ABSTRACT FROM AUTHOR]

Background: The specific dimensions of learners that have been impacted by educational programs related to social determinants of health (SDoH) remain unknown. This study aims to elucidate how learners are affected by postgraduate education (a single 90‐min educational session) regarding tool‐guided clinical assessment of patients' social backgrounds. Methods: A pretest‐posttest design was utilized in which residents (postgraduate year (PGY) 1 or 2) and fellows in family medicine (PGY over 3) were recruited. Likert‐type questions were developed based on previous qualitative findings. Participants answered these questions before, immediately after, and 1.5 months after the educational session on tool‐guided clinical SDoH assessment. Paired‐sample t‐tests were used, and effect size was measured using Cohen's d. Results: A total of 114 residents and fellows participated. After the session, participants expressed more interest in knowing their patients' social backgrounds when considering how to address their patients and were more open to embracing a pre‐established assessment framework. Participants also considered clinical skills related to SDoH as learnable and improved their attitude toward patients. They reported that they did not perform specific interventions related to SDoH within 1.5 months after the session. Unlike previous qualitative findings, their concern about the implementation of SDoH‐related practices did not increase significantly. Conclusion: An educational session on tool‐guided SDoH assessment may have a positive impact on learners' attitudes related to addressing patients' social backgrounds without fostering concerns. [ABSTRACT FROM AUTHOR]

Hepatic hemangiomas are the most common benign liver tumors. Typically, small- to medium-sized hemangiomas are asymptomatic and discovered incidentally through the widespread use of imaging techniques. Giant hemangiomas (>5 cm) have a higher risk of complications. A variety of imaging methods are used for diagnosis. Cavernous hemangioma is the most frequent type, but radiologists must be aware of other varieties. Conservative management is often adequate, but some cases necessitate targeted interventions. Although surgery was traditionally the main treatment, the evolution of minimally invasive procedures now often recommends transarterial chemoembolization as the treatment of choice. [ABSTRACT FROM AUTHOR]

High-performance magneto-optical materials are in urgent demand for high-power Faraday isolators. The traditional Tb3Ga5O12 crystal presents a relatively low Verdet constant and large absorption coefficient, which makes it difficult to meet the continuous development of high-power lasers. In this work, novel Tb3(AlxGa1)5O12 (TAGG) single crystals are grown by the Czochralski method. High-quality TAGG crystals with Al-substitution of up to 75% are obtained for the first time. The optical, thermal, and magneto-optical properties are significantly enhanced through high Al incorporation. This work demonstrates that the highly Al-substituted TAGG single crystals are remarkable magneto-optical materials for Faraday isolators. [ABSTRACT FROM AUTHOR]

Simple Summary: Evolution provided animals with efficient predatory and defense mechanisms that may include the secretion of bioactive molecules, referred to as toxins, that disrupt physiological processes in their recipients. Owing to their reactivity and, often, relative specificity, toxins hold biotechnological interest, especially proteinaceous toxins, which may be more easily manipulated and synthetized in vitro. Here, we investigated putative cysteine-rich neurotoxins from the marine worm Eulalia ('phyllotoxins') and other bioactive proteins by isolating their full coding sequence and analyzing their potential mode of action using computational methods. The findings suggest that some of these toxins can be highly bioactive and that their specificity may render them interesting for further investigation as painkillers, anticoagulative drugs, or even as a method of enhancing the effect of other drugs. Proteinaceous toxins are peptides or proteins that hold great biotechnological value, evidenced by their ecological role, whether as defense or predation mechanisms. Bioprospecting using bioinformatics and omics may render screening for novel bioactives more expeditious, especially considering the immense diversity of toxin-secreting marine organisms. Eulalia sp. (Annelida: Phyllodocidae), a toxin bearing marine annelid, was recently shown to secrete cysteine-rich protein (Crisp) toxins (hitherto referred to as 'phyllotoxins') that can immobilize its prey. By analyzing and validating transcriptomic data, we narrowed the list of isolated full coding sequences of transcripts of the most abundant toxins or accompanying bioactives secreted by the species (the phyllotoxin Crisp, hyaluronidase, serine protease, and peptidases M12A, M13, and M12B). Through homology matching with human proteins, the biotechnological potential of the marine annelid's toxins and related proteins was tentatively associated with coagulative and anti-inflammatory responses for the peptidases PepM12A, SePr, PepM12B, and PepM13, and with the neurotoxic activity of Crisp, and finally, hyaluronidase was inferred to bear properties of an permeabilizing agent. The in silico analysis succeeded by validation by PCR and Sanger sequencing enabled us to retrieve cDNAs can may be used for the heterologous expression of these toxins. [ABSTRACT FROM AUTHOR]

As automated essay scoring (AES) has progressed from handcrafted techniques to deep learning, holistic scoring capabilities have merged. However, specific trait assessment remains a challenge because of the limited depth of earlier methods in modeling dual assessments for holistic and multi‐trait tasks. To overcome this challenge, we explore providing comprehensive feedback while modeling the interconnections between holistic and trait representations. We introduce the DualBERT‐Trans‐CNN model, which combines transformer‐based representations with a novel dual‐scale bidirectional encoder representations from transformers (BERT) encoding approach at the document‐level. By explicitly leveraging multi‐trait representations in a multi‐task learning (MTL) framework, our DualBERT‐Trans‐CNN emphasizes the interrelation between holistic and trait‐based score predictions, aiming for improved accuracy. For validation, we conducted extensive tests on the ASAP++ and TOEFL11 datasets. Against models of the same MTL setting, ours showed a 2.0% increase in its holistic score. Additionally, compared with single‐task learning (STL) models, ours demonstrated a 3.6% enhancement in average multi‐trait performance on the ASAP++ dataset. [ABSTRACT FROM AUTHOR]

Traditional Radiation Therapy (RT) predominantly comprises a targeted therapeutic strategy focused on improving localised tumour control and achieving a cure while minimising the occurrence of adverse side effects. It could be feasible to take advantage of the better dose distribution by enabling larger RT dosages to the malignancy while preventing a rise in the toxicity of RT-induced healthy tissue, or by reducing adverse reactions to manageable levels. Poor local disease control and important dose-limiting normal tissue, which prevent safe dosage increase with conventional photon RT, have been the key justifications for RT. Proton treatment, on the other hand, delivers therapeutic protons or positive particles using proton beams. The potential advantage of protons' physical properties allows for more localised RT delivery. By increasing the dosage to equitoxic levels, it is also possible to take advantage of the potential improvement in normal tissue sparing to support local tumour management and, ideally, longevity. Proton treatment preserves more important structures than photon therapy because of its unique physics. Thus, there is a need for wide usage of Proton Therapy (PT) for successive cancer treatment. The present review focuses on PT based on tumour site, clinical studies, biological barriers, instrumentation of PT, significance, and limitations. [ABSTRACT FROM AUTHOR]

Sound source approaching is a typical task for the robot with auditory sensing. Many existing methods are based on sound source localization (SSL), and utilize the explicit location as the control input. To reduce the localization computation cost and improve the robustness against noise and reverberation, we propose a novel auditory feature driven model predictive control (AFD-MPC) method, which directly uses the auditory feature as the control input. First, a new convolution-ternarization based interaural time difference (CT-ITD) estimation method is proposed, which is more robust to noise and reverberation by eliminating signal spikes and irrelevant components. Second, a new system model is derived and established, which directly links the robot motions and the interaural time difference (ITD) feature. Third, AFD-MPC is realized based on the proposed CT-ITD feature estimation and system model. The states at multiple future time steps are predicted based on the system model, and a control objective function considering both target approaching and motion smoothness is designed. By involving the multi-step future states in the control objective function, the control outcome is more smooth on motion trajectory and more robust to instantaneous interferences. A series of experiments such as static and dynamic sound source approaching are conducted on a mobile robot equipped with a small-sized 6-microphone array to validate the effectiveness of our methods. [ABSTRACT FROM AUTHOR]