Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of Advance Care Planning on the Hospitalization-Associated Utilization and Cost of Patients with Alzheimer’s Disease-Related Disorders Receiving Primary Care via Telehealth in a Provider Shortage Area: A Quantitative Pre-Study

Telehealth has been adopted as an alternative to in-person primary care visits. With multiple participants able to join remotely, telehealth can facilitate the discussion and documentation of advance care planning (ACP) for those with Alzheimer’s disease-related disorders (ADRDs). We measured hospitalization-associated utilization outcomes, instances of hospitalization and 90-day re-hospitalizations from payors’ administrative databases and verified the data via electronic health records. We estimated the hospitalization-associated costs using the Nevada State Inpatient Dataset and compared the estimated costs between ADRD patients with and without ACP documentation in the year 2021. Compared to the ADRD patients without ACP documentation, those with ACP documentation were less likely to be hospitalized (mean: 0.74; standard deviation: 0.31; p < 0.01) and were less likely to be readmitted within 90 days of discharge (mean: 0.16; standard deviation: 0.06; p < 0.01). The hospitalization-associated cost estimate for ADRD patients with ACP documentation (mean: USD 149,722; standard deviation: USD 80,850) was less than that of the patients without ACP documentation (mean: USD 200,148; standard deviation: USD 82,061; p < 0.01). Further geriatrics workforce training is called for to enhance ACP competencies for ADRD patients, especially in areas with provider shortages where telehealth plays a comparatively more important role.
A Genome-Wide Analysis of a Sudden Cardiac Death Cohort: Identifying Novel Target Variants in the Era of Molecular Autopsy

Sudden cardiac death (SCD) is an unexpected natural death due to cardiac causes, usually happening within one hour of symptom manifestation or in individuals in good health up to 24 h before the event. Genomic screening has been increasingly applied as a useful approach to detecting the genetic variants that potentially contribute to SCD and helping the evaluation of SCD cases in the post-mortem setting. Our aim was to identify the genetic markers associated with SCD, which might enable its target screening and prevention. In this scope, a case–control analysis through the post-mortem genome-wide screening of 30 autopsy cases was performed. We identified a high number of novel genetic variants associated with SCD, of which 25 polymorphisms were consistent with a previous link to cardiovascular diseases. We ascertained that many genes have been already linked to cardiovascular system functioning and diseases and that the metabolisms most implicated in SCD are the lipid, cholesterol, arachidonic acid, and drug metabolisms, suggesting their roles as potential risk factors. Overall, the genetic variants pinpointed herein might be useful markers of SCD, but the novelty of these results requires further investigations.
In Situ Inactivation of Selected Bacillus Strains in Brewer’s Spent Grain during Fermentation by Lactococcus lactis ATCC 11454—The Possibility of Post-Production Residues Management

The safety and quality of post-production residues is essential before they can be reused. Both to explore the possibility of reuse as a fermentation medium and the context of pathogens’ inactivation, the research aimed to characterize the fermentation system of L. lactis ATCC 11454 and brewer’s spent grain, malt and barley, especially to in situ inactivation of selected Bacillus strains during the fermentation and storage. Barley products were milled, autoclaved, hydrated and fermented with L. lactis ATCC 11454. Then, the co-fermentation with Bacillus strains was carried out. The amount of polyphenols in the samples ranged from 483.5 to 718.4 ug GAE g−1 and increased after 24 h fermentation with L. lactis ATCC 11454. The high viability of LAB in the fermented samples and after 7 days of storage at 4 °C (8 log CFU g−1) indicates the high nutrients bioavailability during the storage. Also, this co-fermentation on different barley products indicated a high reduction level (2 to 4 logs) of Bacillus due to the biosuppression effect of the LAB strain in this fermentation system. Brewer’s spent grain (BSG) fermented with L. lactis ATCC 25 11454 produces a highly effective cell-free supernatant (CFS) for suppressing Bacillus strains. This was evident in both the inhibition zone and fluorescence analysis of bacteria viability. In conclusion, the obtained results justify the use of brewer’s spent grain in selected food products, increasing their safety and nutritional value. This finding is highly beneficial in the sustainable management of post-production residues when current waste material can still serve as a source of food.
Effects of Sex and Hunting Season on Carcass and Meat Quality Characteristics of the Brown Hare (Lepus europaeus)

The objective of the study was to determine the effects of sex and hunting season on the carcass, meat and fat quality of hunted brown hares (Lepus europaeus). Twenty-two hares of both sexes hunted in winter (December) during two hunting seasons in accordance with the law on hunting in Lithuania were evaluated using reference methods The data were subjected to two-factor analysis of variance in the general linear (GLM) procedure. No significant differences in carcass measurements and muscularity or internal organs between the sexes of brown hares were found; however, the hunting season appeared to affect the size of hares. The biceps femoris (BF) thigh muscle of males had lower (p < 0.05) dry matter content and higher (p < 0.05) drip loss compared with females. The hunting season demonstrated an effect (p < 0.001) on protein and hydroxyproline contents in the longissimus thoracis et lumborum (LTL) and affected dry matter, protein and hydroxyproline contents (p < 0.05, p < 0.001 and p < 0.01, respectively) in BF muscles, and differences in the colour of muscles were also observed. The shear force in the Warner–Bratzler (WB) test was higher (p < 0.001 and p < 0.01, respectively) for LTL and BF muscles during the first hunting season. The hunting season did not affect the total SFA in the intramuscular fat (IMF) of all the tissues, but it affected levels of monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids in the muscles. No differences were found in the total saturated fatty acids (SFA) of both muscles between the sexes, but females demonstrated lower (p < 0.05 and p < 0.01, respectively) and more favourable n-6/n-3 PUFA ratios in the muscles and fat and a lower (p < 0.05) thrombogenic (TI) index in the LTL compared with males.
Deep-Learning-Based Segmentation of Extraocular Muscles from Magnetic Resonance Images

In this study, we investigated the performance of four deep learning frameworks of U-Net, U-NeXt, DeepLabV3+, and ConResNet in multi-class pixel-based segmentation of the extraocular muscles (EOMs) from coronal MRI. Performances of the four models were evaluated and compared with the standard F-measure-based metrics of intersection over union (IoU) and Dice, where the U-Net achieved the highest overall IoU and Dice scores of 0.77 and 0.85, respectively. Centroid distance offset between identified and ground truth EOM centroids was measured where U-Net and DeepLabV3+ achieved low offsets (p > 0.05) of 0.33 mm and 0.35 mm, respectively. Our results also demonstrated that segmentation accuracy varies in spatially different image planes. This study systematically compared factors that impact the variability of segmentation and morphometric accuracy of the deep learning models when applied to segmenting EOMs from MRI.
Survival Benefit of Renin-Angiotensin System Blockers in Critically Ill Cancer Patients: A Retrospective Study

Simple Summary The involvement of the renin-angiotensin pathway in both the regulation of the cardiovascular system and in tumorigenesis raises the question of the prognostic impact of renin-angiotensin system blockers (RABs) in cancer patients experiencing life-threatening complications. The aim of our retrospective study was to assess this impact in solid tumor patients requiring unplanned ICU admission over a 14-year period. Among 1845 patients mainly diagnosed with gastrointestinal and lung cancers, 414 (22.4%) were treated with RABs: 220 (53.1%) with angiotensin-receptor blockers (ARBs) and 194 (46.9%) with angiotensin-converting enzyme inhibitors (ACEis). ARBs use and ACEis use were both associated with improved in-ICU survival, whereas only ARBs use was associated with improved one-year survival. Abstract Increasing evidence argues for the promotion of tumorigenesis through activation of the renin-angiotensin system pathway. Accordingly, a benefit of renin-angiotensin system blockers (RABs) treatments has been suggested in patients with solid cancers in terms of survival. We aimed to evaluate in-ICU survival and one-year survival in cancer patients admitted to the ICU with respect to the use of RABs. We conducted a retrospective observational single-center study in a 24-bed medical ICU. We included all solid cancer patients (age ≥ 18 years) requiring unplanned ICU admission. From 2007 to 2020, 1845 patients with solid malignancies were admitted (median age 67 years (59–75), males 61.7%). The most frequent primary tumor sites were the gastrointestinal tract (26.8%), the lung (24.7%), the urological tract (20.1%), and gynecologic and breast cancers (13.9%). RABs were used in 414 patients, distributed into 220 (53.1%) with angiotensin-receptor blockers (ARBs) and 194 (46.9%) with angiotensin-converting enzyme inhibitors (ACEis). After multivariate adjustment, ARBs use (OR = 0.62, 95%CI (0.40–0.92), p = 0.03) and ACEis use (OR = 0.52, 95%CI (0.32–0.82), p = 0.006) were both associated with improved in-ICU survival. Treatment with ARBs was independently associated with decreased one-year mortality (OR = 0.6, 95%CI (0.4–0.9), p = 0.02), whereas treatment with ACEis was not. In conclusion, this study argues for a beneficial impact of RABs use on the prognosis of critically ill cancer patients.
Age and Gender-Specific Pattern of Cardiovascular Disease Risk Factors in Saudi Arabia: A Subgroup Analysis from the Heart Health Promotion Study

Objective: To investigate gender and age-specific distribution patterns of cardiovascular disease risk factors in the Saudi population for tailored health policies. Methods: From the heart health promotion study, 3063 adult Saudis were included in this study. The study cohort was divided into five age groups (less than 40 years, 40–45 years, 46–50 years, 51–55 years and ≥56 years). The prevalence of metabolic, socioeconomic, and cardiac risk was compared between the groups. Anthropometric and biochemical data were gathered using the World Health Organization stepwise approach to chronic disease risk factors. The cardiovascular risk (CVR) was determined using the Framingham Coronary Heart Risk Score. Results: The prevalence of CVR risk increased with age in both genders. Both Saudi men and women exhibit similar propensities for sedentary lifestyles and unhealthy food habits. The prevalence of tobacco smoking was significantly higher and from an early age in males compared to females (28% and 2.7%, respectively, at age 18–29 years). There is no significant difference in either the prevalence of diabetes, hypertension, or metabolic syndrome between men and women before the age of 60 years. Old Saudi females (≥60 years) have a higher prevalence of diabetes (50% vs. 38.7%) and metabolic syndrome (55.9% versus 43.5%). Obesity was more prevalent in females aged 40–49 years onwards (56.2% vs. 34.9% males), with 62.9% of females aged ≥60 years being obese compared to 37.9% of males. Dyslipidaemia prevalence increased with the progression of age, significantly more in males than females. Framingham high-risk scores showed that 30% of males were at high risk of cardiovascular diseases at the age group of 50–59 years, while only 3.7% of the females were considered as such. Conclusions: Both Saudi men and women exhibit similar propensities for sedentary lifestyles and unhealthy food habits, with a marked increase in cardiovascular and metabolic risk factors with age. Gender differences exist in risk factor prevalence, with obesity as the main risk factor in women, while smoking and dyslipidaemia were the main risk factors in men.
The Effects of Growth Modification on Pollen Development in Spring Barley (Hordeum vulgare L.) Genotypes with Contrasting Drought Tolerance

Drought stress inducing pollen sterility can reduce crop yield worldwide. The regulatory crosstalk associated with the effects of drought on pollen formation at the cellular level has not been explored in detail so far. In this study, we performed morphological and cytoembryological analysis of anther perturbations and examined pollen development in two spring barley genotypes that differ in earliness and drought tolerance. The Syrian breeding line CamB (drought-tolerant) and the European cultivar Lubuski (drought-sensitive) were used as experimental materials to analyze the drought-induced changes in yield performance, chlorophyll fluorescence kinetics, the pollen grain micromorphology and ultrastructure during critical stages of plant development. In addition, fluctuations in HvGAMYB expression were studied, as this transcription factor is closely associated with the development of the anther. In the experiments, the studied plants were affected by drought, as was confirmed by the analyses of yield performance and chlorophyll fluorescence kinetics. However, contrary to our expectations, the pollen development of plants grown under specific conditions was not severely affected. The results also suggest that growth modification, as well as the perturbation in light distribution, can affect the HvGAMYB expression. This study demonstrated that the duration of the vegetation period can influence plant drought responses and, as a consequence, the processes associated with pollen development as every growth modification changes the dynamics of drought effects as well as the duration of plant exposition to drought.
Use of Automated Machine Learning for Classifying Hemoperitoneum on Ultrasonographic Images of Morrison’s Pouch: A Multicenter Retrospective Study

This study evaluated automated machine learning (AutoML) in classifying the presence or absence of hemoperitoneum in ultrasonography (USG) images of Morrison’s pouch. In this multicenter, retrospective study, 864 trauma patients from trauma and emergency medical centers in South Korea were included. In all, 2200 USG images (1100 hemoperitoneum and 1100 normal) were collected. Of these, 1800 images were used for training and 200 were used for the internal validation of AutoML. External validation was performed using 100 hemoperitoneum images and 100 normal images collected separately from a trauma center that were not included in the training and internal validation sets. Google’s open-source AutoML was used to train the algorithm in classifying hemoperitoneum in USG images, followed by internal and external validation. In the internal validation, the sensitivity, specificity, and area under the receiver operating characteristic (AUROC) curve were 95%, 99%, and 0.97, respectively. In the external validation, the sensitivity, specificity, and AUROC were 94%, 99%, and 0.97, respectively. The performances of AutoML in the internal and external validation were not statistically different (p = 0.78). A publicly available, general-purpose AutoML can accurately classify the presence or absence of hemoperitoneum in USG images of the Morrison’s pouch of real-world trauma patients.
Fundamental Characterization of Antibody Fusion-Single-Chain TNF Recombinant Proteins Directed against Costimulatory TNF Receptors Expressed by T-Lymphocytes

The costimulatory signal regulated by the members of the tumor necrosis factor receptor (TNFR) superfamily expressed by T cells plays essential roles for T cell responses and has emerged as a promising target for cancer immunotherapy. However, it is unclear how the difference in TNFR costimulation contributes to T cell responses. In this study, to clarify the functional significance of four different TNFRs, OX40, 4-1BB, CD27 and GITR, we prepared corresponding single-chain TNF ligand proteins (scTNFLs) connected to IgG Fc domain with beneficial characteristics, i.e., Fc−scOX40L, Fc−sc4-1BBL, Fc−scCD27L (CD70) and Fc−scGITRL. Without intentional cross-linking, these soluble Fc−scTNFL proteins bound to corresponding TNFRs induced NF-kB signaling and promoted proliferative and cytokine responses in CD4+ and CD8+ T cells with different dose-dependencies in vitro. Mice injected with one of the Fc−scTNFL proteins displayed significantly augmented delayed-type hypersensitivity responses, showing in vivo activity. The results demonstrate that each individual Fc−scTNFL protein provides a critical costimulatory signal and exhibits quantitatively distinct activity toward T cells. Our findings provide important insights into the TNFR costimulation that would be valuable for investigators conducting basic research in cancer immunology and also have implications for T cell-mediated immune regulation by designer TNFL proteins.
Low-Abundance Protein Enrichment for Medical Applications: The Involvement of Combinatorial Peptide Library Technique

The discovery of low- and very low-abundance proteins in medical applications is considered a key success factor in various important domains. To reach this category of proteins, it is essential to adopt procedures consisting of the selective enrichment of species that are present at extremely low concentrations. In the past few years pathways towards this objective have been proposed. In this review, a general landscape of the enrichment technology situation is made first with the presentation and the use of combinatorial peptide libraries. Then, a description of this peculiar technology for the identification of early-stage biomarkers for well-known pathologies with concrete examples is given. In another field of medical applications, the determination of host cell protein traces potentially present in recombinant therapeutic proteins, such as antibodies, is discussed along with their potentially deleterious effects on the health of patients on the one hand, and on the stability of these biodrugs on the other hand. Various additional applications of medical interest are disclosed for biological fluids investigations where the target proteins are present at very low concentrations (e.g., protein allergens).
Enhancement of Tumor Cell Immunogenicity and Antitumor Properties Derived from Platinum-Conjugated Iron Nanoparticles

Simple Summary The immune system has been shown to play a critical role in controlling tumor development. Therefore, therapeutic strategies based on targeting tumors from this point of view are becoming increasingly important. One of the approaches offered by nanotechnology and small molecules in this context is the induction of immunogenic cell death (ICD). In this work, a characterization of the antitumor response of paramagnetic iron nanoparticles conjugated with a platinum compound is presented. A highlight of this work is the significant improvement in the antitumor properties of the nanoconjugate comparing it with the platinum compound. Moreover, the conjugation has been shown to have crucial properties for the induction of ICD, such as the activation of cellular endoplasmic reticulum stress. Our results emphasize the relevance of nanotechnology as a fundamental strategy for the development of new approaches with onco-immunotherapy activity. Abstract From chemistry design to clinical application, several approaches have been developed to overcome platinum drawbacks in antitumoral therapies. An in-depth understanding of intracellular signaling may hold the key to the relationship of both conventional drugs and nanoparticles. Within these strategies, first, nanotechnology has become an essential tool in oncotherapy, improving biopharmaceutical properties and providing new immunomodulatory profiles to conventional drugs mediated by activation of endoplasmic reticulum (ER) stress. Secondly, functional proteomics techniques based on microarrays have proven to be a successful method for high throughput screening of proteins and profiling of biomolecule mechanisms of action. Here, we conducted a systematic characterization of the antitumor profile of a platinum compound conjugated with iron oxide nanoparticles (IONPs). As a result of the nano-conjugation, cytotoxic and proteomics profiles revealed a significant improvement in the antitumor properties of the starting material, providing selectivity in certain tumor cell lines tested. Moreover, cell death patterns associated with immunogenic cell death (ICD) response have also been identified when ER signaling pathways have been triggered. The evaluation in several tumor cell lines and the analysis by functional proteomics techniques have shown novel perspectives on the design of new cisplatin-derived conjugates, the high value of IONPs as drug delivery systems and ICD as a rewarding approach for targeted oncotherapy and onco-immunotherapies.
The RHOA Mutation G17V Does Not Lead to Increased Migration of Human Malignant T Cells but Is Associated with Matrix Remodelling

Simple Summary The aim of this study was to understand if the presence of a RHOA-G17V mutation in angioimmunoblastic T-cell lymphoma is responsible for the typical clinical presentation with early dissemination of tumor cells. Overexpression of RHOA-G17V in malignant T cells did not enhance their migration capacity neither in microfluidics microchannels, 3D collagen gel or primary human lymphoid tissue. In contrast, RHOA-G17V overexpressing cells from the HH cell line presented increased numbers of cells surrounded by cleaved collagen. Primary AITL cases showed a correlation between RHOA-G17V mutation allele frequency and collagen fibrosis of the tissue, suggesting that mechanisms leading to extracellular matrix degradation contribute to the early spread of AITL tumor cells. Abstract Nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (AITL), is characterized by constitutional symptoms, advanced-stage disease, and generalized lymphadenopathy. A genetic hallmark of this lymphoma is the frequent occurrence of the RHOA mutation G17V in neoplastic cells, which is observed in around 60% of patients. Because RHOA is involved in both T-cell receptor downstream signalling and cell migration, we hypothesized that the characteristic presentation of AITL could be the result of enhanced tumor cell migration. Therefore, this study aimed to elucidate the impact of the RHOA variant G17V on the migration of neoplastic T cells. We transfected the T-cell lymphoma cell lines HH and HuT78 to stably express the RHOA-G17V variant. RHOA-G17V-expressing T cells did not exhibit enhanced motility compared to empty-vector-transfected cells in microchannels, a 3D collagen gel, or primary human lymphatic tissue. Cells of the HH cell line expressing RHOA-G17V had an increased number of cells with cleaved collagen compared with the empty-vector-transfected cells. Therefore, we hypothesized that the early spread of AITL tumor cells may be related to remodelling of the extracellular matrix. Accordingly, we observed a significant negative correlation between the relative area of collagen in histological sections from 18 primary AITL and the allele frequency of the RHOA-G17V mutation. In conclusion, our results suggest that the characteristic presentation of AITL with early, widespread dissemination of lymphoma cells is not the result of an enhanced migration capacity due to the RHOA-G17V mutation; instead, this feature may rather be related to extracellular matrix remodelling.