Miracle-dz/UniFAR-FTUs huggingface dataset:
SCGAN: Sparse CounterGAN for Counterfactual Explanations in Breast Cancer Prediction

Imaging phenotypes extracted via radiomics of magnetic resonance imaging have shown great potential in predicting the treatment response in breast cancer patients after administering neoadjuvant systemic therapy (NST). Understanding the causal relationships between Imaging phenotypes, Clinical information, and Molecular (ICM) features, and the treatment response are critical in guiding treatment strategies and management plans. Counterfactual explanations provide an interpretable approach to generating causal inference; however, existing approaches are either computationally prohibitive for high dimensional problems, generate unrealistic counterfactuals, or confound the effects of causal features. This paper proposes a new method called Sparse CounteRGAN (SCGAN) for generating counterfactual instances to establish causal relationships between ICM features and the treatment response after NST. The generative approach learns the distribution of the original instances and, therefore, ensures that the new instances are realistic. Further, we propose a loss function that regularizes the counterfactuals to minimize the distance between original instances and counterfactuals (to promote sparsity) and the distances among generated counterfactuals to promote diversity. We evaluate the proposed method on two publicly available datasets, followed by the breast cancer dataset, and compare their performance with existing methods in the literature. Finally, we demonstrate the causal relationships from generated counterfactual instances. Results show that SCGAN generates plausible and realistic counterfactual instances with small changes in only a few features, making it a valuable tool for understanding the causal relationships between ICM features and treatment response.
TB disease yield from household contact screening of tuberculosis index patients; a cohort study from Karachi, Pakistan

Nearly 40% of people affected by TB in Pakistan are not diagnosed each year. Guidelines recommend screening household contacts however, not all index patients or contacts are eligible. Therefore, many contacts who may have TB disease, remain unscreened. We conducted a prospective cohort study under programmatic conditions in Karachi, Pakistan from January 2018 - December 2019, to screen all household contacts of all TB index patients. We disaggregated these according to guidelines into eligible (those with bacteriologically confirmed pulmonary TB or children <5 years) or ineligible (those with clinically diagnosed or extrapulmonary TB [≥]5 years) index patients, and eligible (children <5 years or symptomatic individuals) or ineligible (asymptomatic individuals [≥]5 years) contacts. We calculated TB disease yields for different groups of index patients and contacts. Of 39,168 household contacts from 6,362 index patients, 21,035 completed clinical assessments for TB disease with a medical officer, and 416 were diagnosed with all forms TB disease. Household contacts of clinically diagnosed pulmonary TB patients were 26% more likely to be diagnosed with TB compared to the household contacts of bacteriologically confirmed pulmonary TB (adjusted Odds Ratio 1.26 [1.01 - 1.59] p-value:0.03). The yield of TB disease among child contacts (3.4%) was significantly higher than the yield among adult contacts (0.5%) (p-value:<0.001). Broadening TB contact screening guidelines to include clinically diagnosed and extrapulmonary index patients [≥]5 years could double the number of patients detected at a similar level of effort.
On the Least Significant 2-Adic and Ternary Digits of Certain Stirling Numbers

Our main goal is to effectively calculate the p-ary digits of certain Stirling numbers of the second kind. We base our study on an observation regarding these numbers: as m increases, more and more p-adic digits match in S(i(p− 1)pm, k) with integer i ≥ 1.
A New and Simpler Approximation for ANOVA Under Variance Heterogeneity

A new approximation is proposed for testing the equality of k independent means in the face of heterogeneity of variance. Monte Carlo simulations show that the new procedure has Type I error rates that are very nearly nominal and Type II error rates that are quite close to those produced by James’s (1951) second-order approximation. In addition, it is computationally the simplest approximation yet to appear, and it is easily applied to Scheffé (1959)-type multiple contrasts and to the calculation of approximate tail probabilities.
Estimation of the optimal time needed for weaning of Intensive Care Unit tracheostomized patients on mechanical ventilation. a prospective observational study

Background and aim: Determining the time that is required for weaning, as well as the factors that influence it can be used for the appropriate planning of patient’s medical and nursing care. The aim of this study is to estimate the optimal time an Intensive Care Unit (ICU) patient with tracheostomy needs to wean from mechanical ventilation. Methods: This prospective observational study was conducted on 162 patients from two general hospitals in Athens, Greece. A specially designed recording form was created to conduct the study. The Statistical Package for the Social Sciences (SPSS) v.25 for Windows was used to record and analyze the data. The level of statistical significance was set at α=5%. Results: Results were found after comparing and associating the demographic and clinical characteristics and medical history of patients with the duration of weaning, the length of post-tracheostomy ICU stay and the time from intubation to tracheostomy. Conclusions: According to the results of our study, there are various factors that affect success and duration of weaning. More specifically, there seems to be an association between duration of weaning and age, number of closure attempts, success of closure, time from intubation to tracheostomy, length of the patient’s post-tracheostomy ICU stay and diagnosis upon admission. The shorter the duration of weaning, the greater the benefits for the patients themselves, such us avoiding respiratory damage, reduction of mortality and morbidity and preventing of length of patient’s ICU stay. (www.actabiomedica.it)
Brain transcriptome-wide association study implicates novel risk genes underlying schizophrenia risk

Abstract Background To identify risk genes whose expression are regulated by the reported risk variants and to explore the potential regulatory mechanism in schizophrenia (SCZ). Methods We systematically integrated three independent brain expression quantitative traits (eQTLs) (CommonMind, GTEx, and BrainSeq Phase 2, a total of 1039 individuals) and GWAS data (56 418 cases and 78 818 controls), with the use of transcriptome-wide association study (TWAS). Diffusion magnetic resonance imaging was utilized to quantify the integrity of white matter bundles and determine whether polygenic risk of novel genes linked to brain structure was present in patients with first-episode antipsychotic SCZ. Results TWAS showed that eight risk genes (CORO7, DDAH2, DDHD2, ELAC2, GLT8D1, PCDHA8, THOC7, and TYW5) reached transcriptome-wide significance (TWS) level. These findings were confirmed by an independent integrative approach (i.e. Sherlock). We further conducted conditional analyses and identified the potential risk genes that driven the TWAS association signal in each locus. Gene expression analysis showed that several TWS genes (including CORO7, DDAH2, DDHD2, ELAC2, GLT8D1, THOC7 and TYW5) were dysregulated in the dorsolateral prefrontal cortex of SCZ cases compared with controls. TWS genes were mainly expressed on the surface of glutamatergic neurons, GABAergic neurons, and microglia. Finally, SCZ cases had a substantially greater TWS genes-based polygenic risk (PRS) compared to controls, and we showed that fractional anisotropy of the cingulum-hippocampus mediates the influence of TWS genes PRS on SCZ. Conclusions Our findings identified novel SCZ risk genes and highlighted the importance of the TWS genes in frontal-limbic dysfunctions in SCZ, indicating possible therapeutic targets.
The associations between prognostic awareness and health-related quality of life among patients with advanced cancer: A systematic review

Background: Prognostic awareness among patients with advanced cancer is important for better palliative and end-of-life care. However, the relationships between prognostic awareness and patient health-related quality of life outcomes remain inconsistent across studies. Critically synthesizing empirical literature will allow for a better understanding of these associations. Aim: To investigate the associations between prognostic awareness and health-related quality of life outcomes among patients with advanced cancer. Design: This study was a systematic review, prospectively registered on PROSPERO (CRD42020177228). Data sources: Seven databases (PubMed/Medline, Embase, Scopus, Cochrane Central, PsycINFO, CINAHL, and Web of Science) were searched in March 2022. Cross-sectional and longitudinal empirical studies in English were included regardless of cancer type or publication date. Results: We identified 1338 articles and included 36 for review. A substantial proportion of patients remained prognostically unaware (50%). Prognostic awareness was either not significantly associated (48%) or associated with worsened (40%) outcomes. These associations were found to vary (e.g., be differently associated with improved, worsened, or non-significant health-related quality of life outcomes) based on the definition of prognostic awareness used and the population sampled (Asian vs Western). Few structured, validated questionnaires were used and only three studies investigated how the associations evolved over time. Conclusions: To facilitate better understanding of the relationships between prognostic awareness and health-related quality of life, future research must focus on developing a standardized, “gold standard” measurement of prognostic awareness. Research should also examine the influence of culture and the evolution of these relationships longitudinally.
FRC transplantation restores lymph node conduit defects in laminin α4–deficient mice

Fibroblastic reticular cells (FRCs) play important roles in tolerance by producing laminin α4 (Lama4) and altering lymph node (LN) structure and function. The present study revealed the specific roles of extracellular matrix Lama4 in regulating LN conduits using FRC-specific KO mouse strains. FRC-derived Lama4 maintained conduit fiber integrity, as its depletion altered conduit morphology and structure and reduced homeostatic conduit flow. Lama4 regulated the lymphotoxin β receptor (LTβR) pathway, which is critical for conduit and LN integrity. Depleting LTβR in FRCs further reduced conduits and impaired reticular fibers. Lama4 was indispensable for FRC generation and survival, as FRCs lacking Lama4 displayed reduced proliferation but upregulated senescence and apoptosis. During acute immunization, FRC Lama4 deficiency increased antigen flow through conduits. Importantly, adoptive transfer of WT FRCs to FRC Lama4–deficient mice rescued conduit structure, ameliorated Treg and chemokine distribution, and restored transplant allograft acceptance, which were all impaired by FRC Lama4 depletion. Single-cell RNA sequencing analysis of LN stromal cells indicated that the laminin and collagen signaling pathways linked crosstalk among FRC subsets and endothelial cells. This study demonstrated that FRC Lama4 is responsible for maintaining conduits by FRCs and can be harnessed to potentiate FRC-based immunomodulation.
Aperture compensated radon and fourier transforms

In seismic data analysis, recorded data often are transformed to various domains to discriminate against coherent and incoherent noise. For instance, by mapping a shot record from time-space domain to frequency-wavenumber domain, coherent linear noise can be attenuated. Similarly, by mapping a common-midpoint gather from time-space to timevelocity domain (velocity stacks) multiples are separated from primaries based on moveout discrimination. In these procedures the correct identification of seismic events with similar moveout can be severely affected by the aperture of the array and the discrete sampling of the wavefield. Economic and/or logistic reasons usually dictate the cable length and spatial sampling of the seismic experiment. This thesis examines how the resolution (the ability to distinguish close events) of slant stack and parabolic stack operators deteriorates under limited aperture. An algorithm is developed to increase the resolution of the aforementioned operators. This procedure constructs an operator that collapses each seismic signal in the transform domain, thus diminishing truncation artifacts. The overall procedure is equivalent to the simulation of a longer array of receivers. Slant stacks and the parabolic stacks are linear operations used to map the seismic data into another domain, the transform domain (τ−p or τ−q). In this thesis an inverse problem is posed. This is accomplished by considering the data as the result of a linear operation onto the transform domain. This approach permits one to incorporate prior information into the problem which is utilized to attenuate truncation artifacts. The prior information is incorporated into the inverse problem by means of the Bayesian formalism. The observational errors and the prior information are combined ix
Thermal Equilibrium of the Atmosphere with a Given Distribution of Relative Humidity

Abstract Radiative convective equilibrium of the atmosphere with a given distribution of relative humidity is computed as the asymptotic state of an initial value problem. The results show that it takes almost twice as long to reach the state of radiative convective equilibrium for the atmosphere with a given distribution of relative humidity than for the atmosphere with a given distribution of absolute humidity. Also, the surface equilibrium temperature of the former is almost twice as sensitive to change of various factors such as solar constant, CO2 content, O3 content, and cloudiness, than that of the latter, due to the adjustment of water vapor content to the temperature variation of the atmosphere. According to our estimate, a doubling of the CO2 content in the atmosphere has the effect of raising the temperature of the atmosphere (whose relative humidity is fixed) by about 2C. Our model does not have the extreme sensitivity of atmospheric temperature to changes of CO2 content which was adduced by M.
Group independent components underpin responses to items from a depression scale.

OBJECTIVE The aim of the presents study is to investigate the brain circuits or networks which underpin diagnostically specific tasks by means of group independent component analysis for FMRI toolbox (GIFT). We hypothesized that there will be neural network patterns of activation and deactivation, which correspond to real time performance on clinical self-evaluation scales. METHODS There have been included 20 healthy controls and 22 patients with major depressive episode. All subjects were scanned with functional MRI with paradigm comprised of diagnostic clinical self-assessment depression scale contrasted to neutral scale. The data were processed with group independent component analysis for functional MRI toolbox and statistical parametric mapping. RESULTS The results have demonstrated that there exist positively or negatively modulated brain networks during processing of diagnostic specific task questions for depressive disorder. There have also been confirmed differences in the networks processing diagnostic versus off blocks between patients and controls in anterior cingulate cortex and middle frontal gyrus. Diagnostic conditions (depression scale) when contrasted to neutral conditions demonstrate differential activity of right superior frontal gyrus and right middle cingulate cortex in the comparison of patients with healthy controls. CONCLUSION Potential neuroimaging state dependent-biomarkers has been directly linked with clinical assessment self-evaluation scale, administered as stimuli simultaneously with the fMRI acquisition. It may be regarded as further evidence in support of the convergent capacity of both methods to distinguish groups by means of incremental translational cross-validation.
Vitamin D Insufficiency in Children with Chronic Neurological Diseases: Frequency and Causative Factors

Objective Vitamin D insufficiency/rickets is a metabolic bone disease that leads to insufficient mineralization of bone. Chronic neurological diseases, including cerebral palsy (CP), convulsive disorders, neural tube defects, myopathy, immobility, lack of sun exposure, inadequate nutrition, and antiepileptic drugs (AEDs) can cause vitamin D insufficiency and osteopenia in children. Materials & Methods In this study, the authors searched the frequency and causative factors of vitamin D insufficiency in children with chronic neurological diseases such as CP, hypoxic-ischemic encephalopathy, mental motor retardation, epilepsy, neurodegenerative and neuromuscular diseases, meningitis-encephalitis sequelae, neural tube defects, paralysis, and paresis. This cross-sectional study included 108 children (forty-five (41.6%) females; sixty-three (58.4%) males), aged between one and 18 years with chronic neurological diseases, and a control group of thirty age-matched healthy children (16 (53.3%) females; 14 (46.7%) males. Results Vitamin D levels were significantly lower, and parathyroid hormone (PTH) levels were significantly higher in the patient group than in the control group (p<0.05). The patient group was divided into four subgroups: (i) Epilepsy (n=41; 38%), (ii) Neural tube defects (n=14; 13%), (iii) CP (n=21; 19%), and (iv) other diseases (neurodegenerative and neuromuscular diseases, meningitis sequelae, intracranial hemorrhage, psychomotor retardation, hypoxic-ischemic. encephalopathy) (n=32; 30%) to identify any differences in the measured levels. In the patient group, eighty-three (76.9%) had vitamin D deficiency, and 17 (15.7%) had vitamin D insufficiency, while in the control group, twenty-one (70%) had vitamin D insufficiency. The use of AEDs had no significant effect on serum Ca, P, ALP, PTH, or vitamin D levels (p>0.05), and serum Ca levels were significantly higher in ambulant patients than in non-ambulant patients (p<0.05). Vitamin D levels were significantly higher in the non-ambulant than in the ambulant patients (p<0.05). No rickets was determined in the control group, while in the patient group, nine (8.3%) had level-1 rickets, six (5.6%) had level-2 rickets, and two (1.9%) had level-3 rickets. Conclusion Children with chronic neurological diseases have low serum vitamin D levels, and vitamin D prophylaxis is essential in this group.
The Effect of Occupation-Based Modified Constraint-Induced Movement Therapy on the Participation of Children with Cerebral Palsy: A Single-Blind Randomized Controlled Trial

Objective This study investigates the impact of modified constraint-induced movement therapy (m-CIMT), accompanied by occupation-based and activity analysis, on the participation of children with hemiplegia. Materials & Methods Twenty-three participants were randomly assigned to the intervention and control groups. The intervention group received occupation-based m-CIMT (m-CIMT along with occupation-based and activity analysis), while the control group received m-CIMT without occupation-based and activity analysis. The intervention was conducted one hour per day, three days a week, for four weeks. Results The primary outcomes revealed no significant differences between groups in promoting the participation of children with hemiplegia in the activities of daily living (ADL). However, scores were higher in the intervention group with a medium to large effect size (Canadian occupational performance measure: F(1,19)=2.14, P=0.160, η2P=0.101, Canadian occupational performance measure-satisfaction: F(1,19)=1.53, P=0.231, η2P=0.075, Goal attainment scaling: F(1,19)=5.55, P=0.029, η2P=0.226). This effect remained during the follow-up period. The secondary outcomes indicated no significant differences between groups in improving the manual ability of the children. However, scores were higher in the intervention group with a medium to large effect size (ABILHAND-Kids: F(1,19)=0.64, P=0.434, η2P=0.033, pediatric motor activity log- how long: F(1,19)=3.53, P=0.076, η2P=0.157, pediatric motor activity log- how well: F(1,19)=2.59, P=0.124, η2P=0.120). This effect was sustainable during the follow-up period. Conclusion m-CIMT accompanied by occupation-based and activity analysis and the client-centered paradigm substantially enhances the manual ability of children with hemiplegia and their participation in the ADL.
Hematopoietic stem cell–derived Tregs are essential for maintaining favorable B cell lymphopoiesis following posttransplant cyclophosphamide

Posttransplant cyclophosphamide (PTCy) is associated with a low incidence of chronic graft-versus-host disease (cGVHD) following hematopoietic stem cell (HSC) transplantation. Previous studies have shown the important roles of B cell immunity in cGVHD development. Here, we investigated the long-term reconstitution of B lymphopoiesis after PTCy using murine models. We first demonstrated that the immune homeostatic abnormality leading to cGVHD is characterized by an initial increase in effector T cells in the bone marrow and subsequent B and Treg cytopenia. PTCy, but not cyclosporine A or rapamycin, inhibits the initial alloreactive T cell response, which restores intra-bone marrow B lymphogenesis with a concomitant vigorous increase in Tregs. This leads to profound changes in posttransplant B cell homeostasis, including decreased B cell activating factors, increased transitional and regulatory B cells, and decreased germinal center B cells. To identify the cells responsible for PTCy-induced B cell tolerance, we selectively depleted Treg populations that were graft or HSC derived using DEREG mice. Deletion of either Treg population without PTCy resulted in critical B cytopenia. PTCy rescued B lymphopoiesis from graft-derived Treg deletion. In contrast, the negative effect of HSC-derived Treg deletion could not be overcome by PTCy, indicating that HSC-derived Tregs are essential for maintaining favorable B lymphopoiesis following PTCy. These findings define the mechanisms by which PTCy restores homeostasis of the B cell lineage and reestablishes immune tolerance.
Lymph Node Follicle‐Targeting STING Agonist Nanoshells Enable Single‐Shot M2e Vaccination for Broad and Durable Influenza Protection

The highly conserved matrix protein 2 ectodomain (M2e) of influenza viruses presents a compelling vaccine antigen candidate for stemming the pandemic threat of the mutation‐prone pathogen, yet the low immunogenicity of the diminutive M2e peptide renders vaccine development challenging. A highly potent M2e nanoshell vaccine that confers broad and durable influenza protectivity under a single vaccination is shown. Prepared via asymmetric ionic stabilization for nanoscopic curvature formation, polymeric nanoshells co‐encapsulating high densities of M2e peptides and stimulator of interferon genes (STING) agonists are prepared. Robust and long‐lasting protectivity against heterotypic influenza viruses is achieved with a single administration of the M2e nanoshells in mice. Mechanistically, molecular adjuvancy by the STING agonist and nanoshell‐mediated prolongation of M2e antigen exposure in the lymph node follicles synergistically contribute to the heightened anti‐M2e humoral responses. STING agonist‐triggered T cell helper functions and extended residence of M2e peptides in the follicular dendritic cell network provide a favorable microenvironment that induces Th1‐biased antibody production against the diminutive antigen. These findings highlight a versatile nanoparticulate design that leverages innate immune pathways for enhancing the immunogenicity of weak immunogens. The single‐shot nanovaccine further provides a translationally viable platform for pandemic preparedness.