Miracle-dz/UniFAR-FTUs huggingface dataset:
Risks of undernutrition and depression in hospitalized patients: A cross-sectional study

Undernutrition in hospitalized patients is a significant healthcare burden worldwide. Depression is a major global health problem characterized by symptoms such as altered mood, loss of interest and pleasure, and impairment in cognitive and physical functions. Patients hospitalized for medical conditions have a higher risk of depression than the general population. The purpose of this study was to explore the relationship between undernutrition risk and depression risk in hospitalized patients. The design of this study was an observational cross-sectional analytic. A questionnaire form created by the investigator including sociodemographic data, dietary patterns, presence of chronic diseases and anthropometric measurements, Nutritional Risk Screening and Patient Health Questionnaire-2 were applied to the patients. All quantitative data were expressed as the median and interquartile range and qualitative data were expressed as numbers and percentage. Mann–Whitney U test and Kruskal–Wallis test were used to analyze nonparametric data; Chi-square and Fisher Exact test were used to analyze qualitative data. P < . 05 was considered statistically significant. A total of 308 patients who met the criteria were reached. Undernutrition was detected in 28.6% of the participants, and depression was present in 37.3%. A statistically significant relationship was found between the risk of undernutrition and the risk of depression, with individuals without a risk of depression being found to have a lower risk of undernutrition. (P < .001). The risk of undernutrition was found to increase with advancing age. Moreover, individuals with higher values for arm muscle area, arm muscle circumference, mid-upper arm circumference, triceps skinfold thickness, calf circumference, and body mass index had a lower risk of undernutrition. No relationship was found between gender and the risk of depression. However, a statistically significant relationship was observed between age and the risk of depression, indicating that older patients had a higher risk of depression. In this study, a statistically significant relationship was found between the risk of undernutrition and the risk of depression in hospitalized patients. It was observed that the risk of undernutrition was lower in individuals without risk of depression.
Correlation study and clinical value analysis between cerebral microbleeds and white matter hyperintensity with high-field susceptibility-weighted imaging

This study aimed to investigate the relationship between white matter hyperintensity (WMH) and cerebral microbleeds (CMBs) using susceptibility-weighted imaging (SWI) with high resolution. Additionally, it sought to analyze the clinical significance of SWI with high resolution and its potential to guide intravenous thrombolysis in stroke patients. In this retrospective analysis, we examined 96 patients with hypertension after acute stroke in our hospital using SWI. Demographic and medical data of these 96 patients were collected. Spearman correlation analysis was performed to investigate the relationship between CMBs and the grading of WMH. A significant positive correlation was observed between CMBs and the grade of WMH (R = 0.593, P < .05). The data also revealed a superior ROC area under the curve for the modified Fazekas grading of WMH, which was 0.814 (P < .05). There is a positive correlation between CMBs and the grading of leukoaraiosis in patients with acute stroke and hypertension. The higher the degree of WMH, the more severe the microvascular lesions, increasing the likelihood of intracranial hemorrhage. SWI can provide valuable guidance for administering intravenous thrombolysis in patients with acute stroke.
Sustainable coffee certification programs and coffee cooperatives in Guatemala : a small-scale producer perspective

This descriptive, phenomenological case study presents the perspectives of smallscale coffee producers in Guatemala regarding cooperative membership, sustainable coffee certification programs and the role of ANACAFE. The viewpoints of two producer cooperatives are described based on participant observation, semi-structured interviews and focus groups. Through content analysis the transcribed data were categorized and summarized, and emergent themes are discussed. Advantages to cooperative membership include access to finances, information, cost sharing and expanding direct-trade relationships. Challenges identified are securing finances and attracting new membership. Certification programs may be desirable, but access to information regarding program types is limited. Participants feel that standards do not reflect cultural differences, and the producers question who actually receives the advertised price premiums. The use of bestpractices incorporating the social, environmental and economic principles of certification programs is preferred. ANACAFE is a source of technical information and funding but resource access is selective and limited.
Outcomes of adding cognitive behavioral therapy to medication-assisted treatment for opioid use disorder

ABSTRACT Background: With increasing rates of opioid overdose deaths throughout the United States, there is an urgent need to implement interventions to mitigate this trend. Psychosocial interventions are reported to improve retention rates in rehabilitation centers with medication-assisted treatment (MAT) programs for opioid use. Local problem: In 2020, 14% (187 of 1,309) of opioid overdose deaths in Georgia were in Dougherty County where an intensive outpatient MAT program had historically used twice weekly group therapy plus individual cognitive behavioral therapy (CBT) with an inconsistent duration and frequency. Method: Using existing clinical data, a quality-improvement project was designed and implemented to determine whether 60 min of CBT every other week, in addition to weekly group therapy, and prescription medication would result in higher opioid use disorder treatment retention rates. Intervention: A 6-month data analysis of monthly MAT reports compared program retention rates from the 3 months before to 3 months after the policy change. Results: The retention rate significantly increased from 8% to 56% (χ2 = 8.93, p = .01) following the policy change, adding consistent (98%) individual CBT every other week. Conclusions: Implementing a policy with a consistent 60 min of individual CBT every other week in addition to the group counseling twice a week and the prescribed medication was associated with an increased retention rate among patients engaged in MAT for opioid use.
Poor sleep quality is an overlooked risk for geriatric syndromes in older adults with type 2 diabetes mellitus

ABSTRACT Background Aging and type 2 diabetes mellitus (DM) are two different conditions that impair sleep quality. The primary objective of this study was to investigate the impact of sleep quality on geriatric syndromes in older diabetic adults. Methods Comprehensive geriatric assessment was performed on 236 patients. The assessment included the Geriatric Depression Scale (GDS), Beck Anxiety Inventory (BAI), European Quality of Life Questionnaire (EQ-5D), Mini Mental Statement Examination (MMSE), Pittsburgh Sleep Quality Index (PSQI), Mini Nutritional Assessment, and measurement of handgrip strength (HGS). Results Of the participants, 55% had DM, and 61.4% had poor sleep quality. Poor sleep prevalence was higher in diabetic patients (68.5%) than in non-diabetics (52.8%). Diabetic patients with poor sleep quality had higher frequencies of chronic pain, recurrent urinary tract infections, confirmed sarcopenia, and frailty (p = 0.015, p < 0.001, p = 0.027, and p < 0.001, respectively), a higher number of comorbidities and higher GDS and BAI scores (p = 0.046, p < 0.001 and p < 0.001, respectively), and lower scores of activities of daily living, HGS, and EQ-5D index (p = 0.023, p = 0.004, and p < 0.001, respectively) compared to diabetic patients with good sleep quality. According to the correlation analysis results, PSQI score had a positive correlation with GDS score (r = 0.461, p < 0.001) and a negative correlation with Mini Nutritional Assessment score (r = –0.317, p < 0.001), skeletal muscle mass index (r = –0.283, p = 0.002) and HGS (r = –0.307, p < 0.001) scores in diabetic older adults. Conclusion Poor sleep quality in older diabetic patients has a negative impact on several geriatric syndromes. Our findings suggest that poor sleep quality is an independent risk factor for depression, malnutrition, and lower muscle mass in older diabetic adults. Improving sleep quality may play a crucial role in preventing and managing geriatric syndromes in this population.
Deepening the role of excitation/inhibition balance in human iPSCs-derived neuronal networks coupled to MEAs during long-term development

Objective. The purpose of this study is to investigate whether and how the balance between excitation and inhibition (‘E/I balance’) influences the spontaneous development of human-derived neuronal networks in vitro. To achieve that goal, we performed a long-term (98 d) characterization of both homogeneous (only excitatory or inhibitory neurons) and heterogeneous (mixed neuronal types) cultures with controlled E/I ratios (i.e. E:I 0:100, 25:75, 50:50, 75:25, 100:0) by recording their electrophysiological activity using micro-electrode arrays. Approach. Excitatory and inhibitory neurons were derived from human induced pluripotent stem cells (hiPSCs). We realized five different configurations by systematically varying the glutamatergic and GABAergic percentages. Main results. We successfully built both homogeneous and heterogeneous neuronal cultures from hiPSCs finely controlling the E/I ratios; we were able to maintain them for up to 3 months. Homogeneity differentially impacted purely inhibitory (no bursts) and purely excitatory (few bursts) networks, deviating from the typical traits of heterogeneous cultures (burst dominated). Increased inhibition in heterogeneous cultures strongly affected the duration and organization of bursting and network bursting activity. Spike-based functional connectivity and image-based deep learning analysis further confirmed all the above. Significance. Healthy neuronal activity is controlled by a well-defined E/I balance whose alteration could lead to the onset of neurodevelopmental disorders like schizophrenia or epilepsy. Most of the commonly used in vitro models are animal-derived or too simplified and thus far from the in vivo human condition. In this work, by performing a long-term study of hiPSCs-derived neuronal networks obtained from healthy human subjects, we demonstrated the feasibility of a robust in vitro model which can be further exploited for investigating pathological conditions where the E/I balance is impaired.
Evolution and neutralization escape of the SARS-CoV-2 BA.2.86 subvariant

Omicron BA.2. 86 subvariant differs from Omicron BA.2 as well as recently circulating variants by over 30 mutations in the spike protein alone. Here we report on the first isolation of the live BA.2. 86 subvariant from a diagnostic swab collected in South Africa which we tested for escape from neutralizing antibodies and viral replication properties in cell culture. BA.2. 86 did not have significantly more escape than Omicron XBB.1. 5 from neutralizing immunity elicited by infection of Omicron subvariants ranging from BA.1 to XBB, either by infection alone or as breakthrough infection in vaccinated individuals. Neutralization escape was present relative to earlier strains: BA.2. 86 showed extensive escape both relative to ancestral virus in sera from pre-Omicron vaccinated individuals and relative to Omicron BA.1 in sera from Omicron BA.1 infected individuals. We did not observe substantial differences in viral properties in cell culture relative to XBB.1. 5. Both BA.2. 86 and XBB.1. 5 produced infection foci of similar size, had similar cytopathic effect (both lower than ancestral SARS-CoV-2), and had similar replication dynamics. We also investigated the relationship of BA.2. 86 to BA.2 sequences and found that the closest were BA.2 samples from Southern Africa circulating in early 2022. These observations suggest that BA.2. 86 is more closely related to sequences from Southern Africa than other regions and so may have evolved there, and that evolution led to escape from neutralizing antibodies similar in scale to recently circulating strains of SARS-CoV-2.
Prediction of systemic free and total valproic acid by off-line analysis of exhaled breath in epileptic children and adolescents

Therapeutic drug monitoring (TDM) of medications with a narrow therapeutic window is a common clinical practice to minimize toxic effects and maximize clinical outcomes. Routine analyses rely on the quantification of systemic blood concentrations of drugs. Alternative matrices such as exhaled breath are appealing because of their inherent non-invasive nature. This is especially the case for pediatric patients. We have recently showcased the possibility of predicting systemic concentrations of valproic acid (VPA), an anti-seizure medication by real-time breath analysis in two real clinical settings. This approach, however, comes with the limitation of the patients having to physically exhale into the mass spectrometer. This restricts the possibility of sampling from patients not capable or available to exhale into the mass spectrometer located on the hospital premises. In this work, we developed an alternative method to overcome this limitation by collecting the breath samples in customized bags and subsequently analyzing them by secondary electrospray ionization coupled to high-resolution mass spectrometry (SESI-HRMS). A total of n = 40 patients (mean ± SD, 11.5 ± 3.5 y.o.) diagnosed with epilepsy and taking VPA were included in this study. The patients underwent three measurements: (i) serum concentrations of total and free VPA, (ii) real-time breath analysis and (iii) off-line analysis of exhaled breath collected in bags. The agreement between the real-time and the off-line breath analysis methods was evaluated using Lin’s concordance correlation coefficient (CCC). CCC was computed for ten mass spectral predictors of VPA concentrations. Lin’s CCC was >0.6 for all VPA-associated features, except for two low-signal intensity isotopic peaks. Finally, free and total serum VPA concentrations were predicted by cross validating the off-line data set. Support vector machine algorithms provided the most accurate predictions with a root mean square error of cross validation of 29.0 ± 7.4 mg l−1 and 3.9 ± 1.4 mg l−1 for total and free VPA (mean ± SD), respectively. As a secondary analysis, we explored whether exhaled metabolites previously associated with side-effects and response to medication could be rendered by the off-line analysis method. We found that five features associated with side effects showed a CCC > 0.6, whereas none of the drug response-associated peaks reached this cut-off. We conclude that the clinically relevant free fraction of VPA can be predicted by this combination of off-line breath collection with rapid SESI-HRMS analysis. This opens new possibilities for breath based TDM in clinical settings.
Progress in building clinically relevant patient‐derived tumor xenograft models for cancer research

Patient‐derived tumor xenograft (PDX) models, a method involving the surgical extraction of tumor tissues from cancer patients and subsequent transplantation into immunodeficient mice, have emerged as a pivotal approach in translational research, particularly in advancing precision medicine. As the first stage of PDX development, the patient‐derived orthotopic xenograft (PDOX) models implant tumor tissue in mice in the corresponding anatomical locations of the patient. The PDOX models have several advantages, including high fidelity to the original tumor, heightened drug sensitivity, and an elevated rate of successful transplantation. However, the PDOX models present significant challenges, requiring advanced surgical techniques and resource‐intensive imaging technologies, which limit its application. And then, the humanized mouse models, as well as the zebrafish models, were developed. Humanized mouse models contain a human immune environment resembling the tumor and immune system interplay. The humanized mouse models are a hot topic in PDX model research. Regarding zebrafish patient‐derived tumor xenografts (zPDX) and patient‐derived organoids (PDO) as promising models for studying cancer and drug discovery, zPDX models are used to transplant tumors into zebrafish as novel personalized medical animal models with the advantage of reducing patient waiting time. PDO models provide a cost‐effective approach for drug testing that replicates the in vivo environment and preserves important tumor‐related information for patients. The present review highlights the functional characteristics of each new phase of PDX and provides insights into the challenges and prospective developments in this rapidly evolving field.
Synthesis of copaiba (Copaifera officinalis) oil nanoemulsion and the potential against Zika virus: An in vitro study

Zika virus (ZIKV) has spread all over the world since its major outbreak in 2015. This infection has been recognized as a major global health issue due to the neurological complications related to ZIKV infection, such as Guillain–Barré Syndrome and Zika virus Congenital Syndrome. Currently, there are no vaccines or specific treatments for ZIKV infection, which makes the development of specific therapies for its treatment very important. Several studies have been developed to analyze the potential of compounds against ZIKV, with the aim of finding new promising treatments. Herein, we evaluate the ability of a copaiba (Copaifera officinalis) oil nanoemulsion (CNE) to inhibit ZIKV. First, the highest non-cytotoxic concentration of 180 μg/mL was chosen since this concentration maintains 80% cell viability up to 96h after treatment with CNE in VERO cells resulted from MTT assay. The intracellular uptake assay was performed, and confirmed the internalization of the nanoemulsion in cells at all times analyzed. VERO cells were infected with ZIKV and simultaneously treated with CNE and the nanoformulation without oil (ENE) at the highest non-toxic concentration. The results evaluated by plaque assay revealed a viral inhibition of 80% for CNE and 70% for ENE. A dose-dependence assay revealed that the CNE treatment demonstrated a dose-dependent response in the viral RNA levels, whereas all ENE tested concentrations exhibited a similar degree of reduction. Taken together, our results suggest CNE as a promising nano-sized platform to be further studied for antiviral treatments.
Mocetinostat activates Krüppel-like factor 4 and protects against tissue destruction and inflammation in osteoarthritis

Osteoarthritis (OA) is the most common joint disorder, and disease-modifying OA drugs (DMOADs) represent a major need in OA management. Krüppel-like factor 4 (KLF4) is a central transcription factor upregulating regenerative and protective functions in joint tissues. This study was aimed to identify small molecules activating KLF4 expression and to determine functions and mechanisms of the hit compounds. High-throughput screening (HTS) with 11,948 clinical-stage compounds was performed using a reporter cell line detecting endogenous KLF4 activation. Eighteen compounds were identified through the HTS and confirmed in a secondary screen. After testing in SW1353 chondrosarcoma cells and human chondrocytes, mocetinostat — a class I selective histone deacetylase (HDAC) inhibitor — had the best profile of biological activities. Mocetinostat upregulated cartilage signature genes in human chondrocytes, meniscal cells, and BM-derived mesenchymal stem cells, and it downregulated hypertrophic, inflammatory, and catabolic genes in those cells and synoviocytes. I.p. administration of mocetinostat into mice reduced severity of OA-associated changes and improved pain behaviors. Global gene expression and proteomics analyses revealed that regenerative and protective effects of mocetinostat were dependent on peroxisome proliferator-activated receptor γ coactivator 1-α. These findings show therapeutic and protective activities of mocetinostat against OA, qualifying it as a candidate to be used as a DMOAD.
Action Selection for Hammer Shots in Curling: Optimization of Non-convex Continuous Actions With Stochastic Action Outcomes

Optimal decision making in the face of uncertainty is an active area of research in artificial intelligence. In this thesis, I present the sport of curling as a novel application domain for research in optimal decision making. I focus on one aspect of the sport, the hammer shot, the last shot taken before a score is given, and how selecting this shot can be modelled as a lowdimensional optimization problem with a continuous action space and stochastic transitions. I explore the unique research challenges that are brought forth when optimizing in a setting where there is uncertainty in the action outcomes. I then survey several existing optimization strategies and describe a new optimization algorithm called Delaunay Sampling, adapted from a method based on Delaunay triangulation. I compare the performance of Delaunay Sampling with the other algorithms using our curling physics simulator and show that it outperforms these other algorithms. I also show that, with a few caveats, Delaunay Sampling exceeds the performance of Olympic-level humans when selecting strategies for hammer shots.
Rapid in vitro assessment of the immunogenicity potential of engineered antibody therapeutics through detection of CD4+ T cell interleukin-2 secretion

ABSTRACT Therapeutic antibodies sometimes elicit anti-drug antibodies (ADAs) that can affect efficacy and safety. Engineered antibodies that contain artificial amino acid sequences are potentially highly immunogenic, but this is currently difficult to predict. Therefore, it is important to efficiently assess immunogenicity during the development of complex antibody-based formats. Here, we present an in vitro peripheral blood mononuclear cell-based assay that can be used to assess immunogenicity potential within 3 days. This method involves examining the frequency and function of interleukin (IL)-2-secreting CD4+ T cells induced by therapeutic antibodies. IL-2-secreting CD4+ T cells seem to be functionally relevant to the immunogenic potential due to their proliferative activity and the expression of several cytokines. The rates of the donors responding to low and high immunogenic proteins, mAb1, and keyhole limpet hemocyanin were 1.3% and 93.5%, respectively. Seven antibodies with known rates of immunogenicity (etanercept, emicizumab, abciximab, romosozumab, blosozumab, humanized anti-human A33 antibody, and bococizumab) induced responses in 1.9%, 3.8%, 6.4%, 10.0%, 29.2%, 43.8%, and 89.5% of donors, respectively. These data are comparable with ADA incidences in clinical settings. Our results show that this assay can contribute to the swift assessment and mechanistic understanding of the immunogenicity of therapeutic antibodies.