Miracle-dz/UniFAR-FTUs huggingface dataset:
Deep neural network classification based on somatic mutations potentially predicts clinical benefit of immune checkpoint blockade in lung adenocarcinoma

ABSTRACT Although several biomarkers have been proposed to predict the response of patients with lung adenocarcinoma (LUAD) to immune checkpoint blockade (ICB) therapy, existing challenges such as test platform uniformity, cutoff value definition, and low frequencies restrict their effective clinical application. Here, we attempted to use deep neural networks (DNNs) based on somatic mutations to predict the clinical benefit of ICB to LUAD patients undergoing immunotherapy. We used DNNs to train and validate the predictive model in three cohorts. Kaplan-Meier estimates determined the overall survival (OS) and progression-free survival (PFS) between specific subgroups. Then, we performed a relevant analysis on the multiple-dimension data types including immune cell infiltration, programmed death receptor 1 ligand (PD-L1) expression, and tumor mutational burden (TMB) from cohorts of LUAD public database and immunotherapeutic patients. Two classification groups (C1 and C2) in the training and two validation sets were identified for the efficacy of ICB via the DNN algorithm. Patients in C1 showed remarkably long OS and PFS to programmed death 1 (PD-1) inhibitors. The C1 group was significantly associated with increased expression of immune cell infiltration, immune checkpoints, activated T-effectors, and interferon gamma signature. C1 group also exhibited significantly higher TMB, neoantigens, transversion, or transition than the C2 group. This work provides novel insights that classification of DNNs using somatic mutations in LUAD could serve as a potentially predictive approach in developing a strategy for anti-PD-1/PD-L1 immunotherapy.
Optimization of Artificial Intelligence System by Evolutionary Algorithm for Prediction of Axial Capacity of Rectangular Concrete Filled Steel Tubes under Compression

Concrete filled steel tubes (CFSTs) show advantageous applications in the field of construction, especially for a high axial load capacity. The challenge in using such structure lies in the selection of many parameters constituting CFST, which necessitates defining complex relationships between the components and the corresponding properties. The axial capacity (Pu) of CFST is among the most important mechanical properties. In this study, the possibility of using a feedforward neural network (FNN) to predict Pu was investigated. Furthermore, an evolutionary optimization algorithm, namely invasive weed optimization (IWO), was used for tuning and optimizing the FNN weights and biases to construct a hybrid FNN–IWO model and improve its prediction performance. The results showed that the FNN–IWO algorithm is an excellent predictor of Pu, with a value of R2 of up to 0.979. The advantage of FNN–IWO was also pointed out with the gains in accuracy of 47.9%, 49.2%, and 6.5% for root mean square error (RMSE), mean absolute error (MAE), and R2, respectively, compared with simulation using the single FNN. Finally, the performance in predicting the Pu in the function of structural parameters such as depth/width ratio, thickness of steel tube, yield stress of steel, concrete compressive strength, and slenderness ratio was investigated and discussed.
First look at emergency medical technician wellness in India: Application of the Maslach Burnout Inventory in an unstudied population

Introduction Professional wellness is critical to developing and maintaining a health care workforce. Previous work has identified burnout as a significant challenge to professional wellness facing emergency medical technicians (EMTs) in many countries worldwide. Our study fills a critical gap by assessing the prevalence of burnout among emergency medical technicians (EMTs) in India. Methods This was a cross-sectional survey of EMTs within the largest prehospital care organization in India. We used the Maslach Burnout Inventory (MBI) to measure wellness. All EMTs presenting for continuing medical education between July-November 2017 from the states of Gujarat, Karnataka, and Telangana were eligible. Trained, independent staff administered anonymous MBI-Medical Personnel Surveys in local languages. Results Of the 327 EMTs eligible, 314 (96%) consented to participate, and 296 (94%) surveys were scorable. The prevalence of burnout was 28.7%. Compared to EMTs in other countries, Indian EMTs had higher levels of personal accomplishment but also higher levels of emotional exhaustion and moderate levels of depersonalization. In multivariate regression, determinants of burnout included younger age, perceived lack of respect from colleagues and administrators, and a sense of physical risk. EMTs who experienced burnout were four times as likely to plan to quit their jobs within one year. Conclusion This is the first assessment of burnout in EMTs in India and adds to the limited body of literature among low- and middle-income country (LMIC) prehospital providers worldwide. Burnout was strongly associated with an EMT’s intention to quit within a year, with potential implications for employee turnover and healthcare workforce shortages. Burnout should be a key focus of further study and possible intervention to achieve internationally recognized targets, including Sustainable Development Goal 3C and WHO’s 2030 Milestone for Human Resources.
The Effect of DHA Supplementation on Cognition in Patients with Bipolar Disorder: An Exploratory Randomized Control Trial

Bipolar disorder (BD) is a severe mental disorder with a wide range of cognitive deficits, both in the euthymic and acute phase of the disease. Interestingly, in recent years, there has been a growing interest in investigating the impact of ω-3 polyunsaturated fatty acids on cognition in BD. In this context, the aim of this study is to evaluate the effect of docosahexaenoic acid (C22:6 ω-3, DHA) supplementation on cognitive performances in euthymic BD patients. This is an exploratory, single-centre, double-blind randomized controlled trial evaluating 12 weeks DHA supplementation (1250 mg daily) vs. a placebo (corn oil) in 31 euthymic BD patients compared to 15 healthy controls (HCs) on cognitive functions, assessed by the Brief Assessment of Cognition in Affective Disorder (BAC-A). Plasma levels of DHA were measured. After 12 weeks of treatment, no significant group differences were observed in all neuropsychological tests between the four groups, except for the emotion inhibition test, where HCs with DHA had higher scores compared to either BD with DHA (z = 3.9, p = 0.003) or BD with placebo (t = 3.7, p = 0.005). Although our results showed that DHA could be effective for ameliorating cognition in healthy subjects, future studies are still needed to clarify the impact of DHA on cognition in BD.
Cell-mediated and humoral immune profile to hydatidosis among naturally infected farm animals

Background and Aim: Cystic echinococcosis (CE) is a widespread parasitic disease caused by Echinococcus granulosus tapeworm infect different intermediate hosts including sheep, cattle, and camels. The intermediate host’s immune response to the hydatid cyst is still conflict and complex. The current study was designed to evaluate the immune response in sera of hydatid naturally infected sheep, cattle, and camels in the form of features of inflammatory cell infiltrations, levels of Th1 and Th2 cytokines, besides the humoral specific immunoglobulin G (IgG) responses. Materials and Methods: Thirty-nine sheep, 74 cattle, and 79 camels’ sera were collected and considered as CE naturally infected and ten samples from each species were graded as non-infected. Lung specimens were collected for histopathological examination. The quantitative concentrations of tumor necrosis factor-α, interleukin (IL)-6, IL-4, and IL-10 were determined. Different antigens were prepared from hydatid cyst; hydatid cyst fluid of lung origin hydatid cyst fluid of liver origin, hydatid cyst protoscoleces of lung origin (HCP-g), hydatid cyst protoscoleces of liver origin, hydatid cyst germinal layer of lung origin, and hydatid cyst germinal layer of liver origin; and characterized by gel electrophoresis and Western blotting analysis. The total specific IgG level against E. granulosus infection was measured using an indirect enzyme-linked immunosorbent assay. Results: The results indicated that the cellular immune response in the infected tissues was characterized by inflammatory cell penetration. The pro-inflammatory Th1 cytokine profile was predominant in infected animals in comparison with non-infected ones. However, the humoral immune response was seen as a high level of IgG in infected animals. The presented data approved that the HCP-g antigen could be considered as a delegate antigen for all other prepared antigens with an immunoreactive band at molecular weights 32 kDa. Conclusion: This study provides a fundamental insight into the events that manipulate cellular and humoral immune profiles in an intermediate host; sheep, cattle, and camel that naturally infected with CE. Hence, it was concluded that CE is a constant disease and confirm the reactivity Th1 in combating hydatid cyst. Besides, it could lead to the activation of the humoral immune response in the form of a high level of IgG.
HCV cure in HIV coinfection dampens inflammation and improves cognition through multiple mechanisms.

BACKGROUND Chronic inflammation in HIV/HCV coinfection increases cognitive impairment. With newer direct-acting antiviral therapies for HCV, our objective was to determine if chronic inflammation would be decreased and cognition improved with HCV sustained viral response (SVR) in coinfection. METHODS We studied 4 groups longitudinally, 7 HCV monoinfected and12 HIV/HCV coinfected before and after treatment for HCV, 12 HIV monoinfected and 9 healthy controls. We measured monocyte activation and gene expression, monocyte-derived exosome miRNAs expression, plasma inflammation and cognitive impairment before and after therapy. RESULTS Plasma sCD163 and neopterin were decreased in HCV mono and coinfected persons. Blood CD16+ monocytes were decreased in coinfection after HCV treatment. Global deficit score improved 25% in coinfection with the visual learning/memory domain the most improved. HCV SVR decreased monocyte interferon genes MX1, IFI27 and CD169 in coinfection and MX1, LGALS3BP and TNFAIP6 in HCV monoinfection. Monocyte exosomes from coinfected persons increased in miR-19a, miR-221 and miR-223, all associated with decreasing inflammation and NF-κB activation. CONCLUSIONS HCV cure in coinfection brings monocyte activation to levels of HIV alone. Cognitive impairment is significantly improved with cure but not better than HIV infection alone strongly suggesting that cognitive impairment was driven by both HIV and HCV.
Factors associated with abnormal left ventricular ejection fraction (decreased or increased) in patients with sepsis in the intensive care unit

Background Sepsis-induced cardiomyopathy (SIC) is known to show cardiac dysfunction in patients with sepsis. Both a decrease or an increase in ejection fraction (EF), an indicator of cardiac function, can occur. The purpose of this study was to identify factors associated with abnormal left ventricular (LV) function measured by EF in patients with sepsis in the intensive care unit (ICU). Methods This was a retrospective study performed from November 2016 to December 2018. Three-hundred and sixty-six patients (mean age, 73 ± 13 years; 191 [52%] men) admitted to the ICU with sepsis were included. Patients were classified into three categories according to LV EF (group 1 –[EF<50%, n = 36], group 2 –[50≤EF<70%, n = 252], and group 3 –[EF≥70%, n = 78]). Echocardiographic assessment was performed within 48 hours of diagnosis of sepsis. We analyzed clinical factors including mortality, echocardiographic findings, and laboratory parameters. Results Decreased LV EF occurred in 36 (10%) patients and hyper-dynamic EF developed in 78 (21%) patients. Of 366 patients, 103 (28%) patients died. Baseline characteristics were similar in the three groups, except female sex an indicator of abnormal EF. Mortality rates were also similar in the three groups; however, mortality rates were significantly higher in patients with abnormal EF (decreased or increased vs. normal). Echocardiographic parameters were significantly different in the three groups, in terms of LV systolic parameters and chamber size. Small left atrium (LA) and small LV were significantly associated with abnormal EF (especially in patients with increased EF). High brain natriuretic peptide was associated with decreased EF. Among these factors, female sex and small LA were significantly associated with abnormal EF in the multiple regression analysis. Conclusion Our findings highlight that female sex and small cardiac size are associated with abnormal EF, and therefore, death. Therefore, female patients and patients with small LA should be monitored closely when they present with sepsis.
In the context of romantic attraction, beautification can increase assertiveness in women

Can beautification empower women to act assertively? Some women report that beautification is an agentic and assertive act, whereas others find beautification to be oppressive and disempowering. To disentangle these effects, in the context of romantic attraction we conducted the first experimental tests of beautification—on psychological and behavioral assertiveness. Experiment 1 (N = 145) utilized a between-subjects design in which women used their own clothing, make-up, and accessories to adjust their appearance as they normally would for a “hot date” (beautification condition) or a casual day at home with friends (control condition). We measured implicit, explicit, and behavioral assertiveness, as well as positive affect and sexual motivation. Experiment 2 (N = 40) sought to conceptually replicate Experiment 1 using a within-subject design and different measures of assertiveness. Women completed measures of explicit assertiveness and assertive behavioral intentions in three domains, in whatever clothing they were wearing that day then again after extensively beautifying their appearance. In Experiment 1, we found that women demonstrated higher psychological assertiveness after beautifying their appearance, and that high sexual motivation mediated the effect of beautification on assertive behavior. All effects were independent of positive affect. Experiment 2 partially replicated Experiment 1. These experiments provide novel insight into the effects of women’s appearance-enhancing behaviors on assertiveness by providing evidence that beautification may positively affect assertiveness in women under some circumstances.
Immune Response Dysfunction in Chronic Lymphocytic Leukemia: Dissecting Molecular Mechanisms and Microenvironmental Conditions

Representing the major cause of morbidity and mortality for chronic lymphocytic leukemia (CLL) patients, immunosuppression is a common feature of the disease. Effectors of the innate and the adaptive immune response show marked dysfunction and skewing towards the generation of a tolerant environment that favors disease expansion. Major deregulations are found in the T lymphocyte compartment, with inhibition of CD8+ cytotoxic and CD4+ activated effector T cells, replaced by exhausted and more tolerogenic subsets. Likewise, differentiation of monocytes towards a suppressive M2-like phenotype is induced at the expense of pro-inflammatory sub-populations. Thanks to their B-regulatory phenotype, leukemic cells play a central role in driving immunosuppression, progressively inhibiting immune responses. A number of signaling cascades triggered by soluble mediators and cell–cell contacts contribute to immunomodulation in CLL, fostered also by local environmental conditions, such as hypoxia and derived metabolic acidosis. Specifically, molecular pathways modulating T-cell activity in CLL, spanning from the best known cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed cell death 1 (PD-1) to the emerging T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT)/CD155 axes, are attracting increasing research interest and therapeutic relevance also in the CLL field. On the other hand, in the microenvironment, the B cell receptor (BCR), which is undoubtedly the master regulator of leukemic cell behavior, plays an important role in orchestrating immune responses, as well. Lastly, local conditions of hypoxia, typical of the lymphoid niche, have major effects both on CLL cells and on non-leukemic immune cells, partly mediated through adenosine signaling, for which novel specific inhibitors are currently under development. In summary, this review will provide an overview of the molecular and microenvironmental mechanisms that modify innate and adaptive immune responses of CLL patients, focusing attention on those that may have therapeutic implications.
High resolution computed tomography patterns in interstitial lung disease (ILD): prevalence and prognosis

ABSTRACT Objective To correlate the prevalence and prognosis of each HRCT pattern of typical, probable, and indeterminate usual interstitial pneumonia (UIP) with the clinical multidisciplinary diagnosis of interstitial lung disease (ILD). Methods We included all patients with a multidisciplinary diagnosis of ILD with an HRCT pattern of typical UIP, probable UIP, or indeterminate for UIP. Clinical and histopathological data, pulmonary function tests, and survival status were retrospectively obtained. The final diagnosis was validated by a multidisciplinary team. Results A total of 244 patients were included in the study, with a mean age of 68 ±13 years and being 52.5% males. In a total of 106 patients with typical UIP pattern, 62% had the multidisciplinary diagnosis of IPF, 20% had chronic hypersensitivity pneumonitis (CHP), and 10% had connective tissue disease-related ILD (CTD-ILD). Out of the 114 cases with probable UIP, CTD-ILD corresponded to 39%, IPF to 31%, desquamative interstitial pneumonia to 11%, drug-related lung disease to 9%, and CHP to 8%. In the 24 patients with CT indeterminate for UIP, CTD-ILD was the final diagnosis in 33%, followed by desquamative interstitial pneumonia (21%), and IPF (13%). Patients with typical UIP were more likely to die or had lung transplantation in the follow-up (17.9% and 11.3%, respectively). Conclusion IPF, CHP, and CTD-ILD were the main differential diagnoses in patients with HRCT patterns of typical, probable and indeterminate UIP. Patients with HRCT typical UIP pattern were more likely to die or had lung transplantation in the follow-up.
The Influences of Quality of Work Life and Organizational Justice on the Employees Performance of the State Owned Enterprises (SOEs) in South Sulawesi

This research aims to analyze: a) the effect of quality of work life on job satisfaction; b) the effect of organizational justice on job satisfaction; c) the effect of quality of work life on employees performance; d) the effect of organizational justice on employees performance; e) the effect of job satisfaction on employees performance. This analysis method used on this research is path analysis which is included Structural Equation Modeling (SEM) AMOS versi 5.00. The unit analysis of this study was the employees of the State owned Enterprises (SOEs), locally called BUMN, consisting of PT. Perusahaan Listrik Negara (Persero), PT. Pertamina (Persero), PT. Telekomunikasi Indonesia, Tbk. (Persero), PT. Pelindo IV (Persero), PT. Bank Negara Indonesia, Tbk (Persero) located in the South Sulawesi. The sample in this study was 255 employees collected by using convenience sampling method. The data was collected by using questionnaire. The study found that the quality of work life and organizational justice have significant positive influences on the job satisfaction and employees performance of the SOEs in Sulawesi Selatan.
Impaired O-glycosylation at consecutive threonine TTX motifs in mucins generates conformationally restricted cancer neoepitopes.

Autoantibody signatures to circulating mucin fragments stem from cancer tissues and the microenvironments are promising biomarkers for cancer diagnosis and therapy. The present study highlights dynamic epitopes generated by aberrantly truncated immature O-glycosylation at consecutive threonine motifs (TTX) found in mucins and intrinsically disordered proteins (IDPs). NMR analysis of synthetic mucin models having glycosylated TTX motifs and colonic MUC2 tandem repeats (TRs) containing TTP and TTL moieties unveils a general principle that O-glycosylation at TTX motifs generates highly extended and rigid conformation in IDPs. We demonstrate that the specific conformation of glycosylated TTX motifs in MUC2 TRs is rationally rearranged by concerted motions of multiple dihedral angles and non-covalent interactions between carbohydrate and peptide region. Importantly, this canonical conformation of glycosylated TTX motifs minimizes steric crowding of glycans attached to threonine residues, in which O-glycans possess restricted orientations permitting further sugar extension. Antiadhesive microarray displaying synthetic MUC2 derivatives elicited presence of natural autoantibodies to MUC2 with impaired O-glycosylation at TTX motifs in sera of healthy volunteers and patients diagnosed as early stage colorectal cancer (CRC). Interestingly, autoantibody levels in sera of the late stage CRC patients were distinctly lower than those of early stage CRC and normal individuals, indicating that anti-MUC2 humoral response to MUC2 neoepitopes correlates inversely with CRC stage of patients. Our results uncovered structural basis in the creation of dynamic epitopes by immature O-glycosylation at TTX motifs in mucins that facilitates determination of highly potential targets for cancer diagnosis and therapy.
Serological testing for Lyme Borreliosis in general practice: A qualitative study among Dutch general practitioners

Abstract Background Concerns are raised about missed, delayed and inappropriate diagnosis of Lyme Borreliosis. Quantitative descriptive studies have demonstrated non-adherence to the guidelines for testing for Lyme Borreliosis. Objectives To gain insight into the diagnostic practices that general practitioners apply for Lyme Borreliosis, their motives for ordering tests and how they act upon test results. Methods A qualitative study among 16 general practitioners using semi-structured interviews and thematic content analysis. Results Five themes were distinguished: (1) recognising localised Lyme Borreliosis and symptoms of disseminated disease, (2) use of the guideline, (3) serological testing in patients with clinically suspect Lyme Borreliosis, (4) serological testing without clinical suspicion of Lyme Borreliosis, and (5) dealing with the limited accuracy of the serological tests. Whereas the national guideline recommends using serological tests for diagnosing, general practitioners also use them for ruling out disseminated Lyme Borreliosis. Reasons for non-adherence to the guideline for testing were to reassure patients with non-specific symptoms or without symptoms who feared to have Lyme disease, confirmation of localised Lyme Borreliosis and routine work-up in patients with continuing unexplained symptoms. Some general practitioners referred all patients who tested positive to medical specialists, where others struggled with the explanation of the results. Conclusion Both diagnosis and ruling out of disseminated Lyme Borreliosis can be difficult for general practitioners. General practitioners use serological tests to reassure patients and rule out Lyme Borreliosis, thereby deviating from the national guideline. Interpretation of test results in these cases can be difficult.