Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical application value of metagenomic second-generation sequencing technology in hematologic diseases with and without transplantation

Introduction Hematological patients are at risk of infections. It is unknown whether the pathogenic microbial spectrum differs between HSCT and non-HSCT patients, and whether metagenomic next-generation sequencing (mNGS) of peripheral blood can be used as a substitute test specimen such as alveolar lavage. Methods A retrospective study was conducted to evaluate the clinical application value of mNGS in hematological patients with and without HSCT. Results Viruses were prevalent pathogens in both non-HSCT (44%) and HSCT (45%) patients, chiefly human cytomegalovirus and Epstein–Barr virus. In non-HSCT patients, Gram-negative bacilli accounted for 33% (predominantly Klebsiella pneumonia), and Gram-positive cocci accounted for 7% (predominantly Enterococcus faecium) of pathogens. However, in HSCT patients, Gram-negative bacilli accounted for 13% (predominantly Stenotrophomonas maltophilia), and Gram-positive cocci accounted for 24% (predominantly Streptococcus pneumonia) of pathogens. Mucor was the most common fungu s in two groups. The positive rate of pathogens by mNGS was 85.82%, higher than conventional detection (20.47%, P < 0.05). Mixed infection accounted for 67.00%, among which the mixed infection of bacteria and virus (25.99%) was the most common. 78 cases had pulmonary infection, the positive rate of traditional laboratory tests was 42.31% (33/78), and of mNGS in peripheral blood was 73.08% (57/78), showing a statistical difference (P = 0.000). The non-HSCT patients had a higher frequency of Klebsiella pneumonia (OR=0.777, 95% CI, 0.697-0.866, P = 0.01) and Torque teno virus (OR=0.883, 95% CI, 0.820-0.950, P = 0.031) infections than HSCT patients, while the rates of Streptococcus pneumonia (OR=12.828, 95% CI, 1.378-119.367, P = 0.016), Candida pseudosmooth (OR=1.100, 95% CI, 0.987-1.225, P = 0.016), human betaherpesvirus 6B (OR=6.345, 95% CI, 1.105-36.437, P = 0.039) and human polyomavirus 1 (OR=1.100, 95% CI, 0.987-1.225, P = 0.016) infections were lower. Leishmania could be detected by mNGS. Conclusion mNGS of peripheral blood can be used as a substitute test method for hematological patients with pulmonary infection, the detection rate of mixed infections by mNGS was high, and mNGS has high clinical recognition rate and sensitivity in pathogen detection, and provides a basis for guiding the anti-infective treatment in hematological diseases with symptoms such as fever.
Algorithmic barriers to representing conditional independence

We define a represention of conditional independence in terms of products of probability kernels, and ask when such representations are computable. We pursue this question in the context of exchangeable sequences and arrays of random variables, which arise in statistical contexts. Exchangeable sequences are conditionally i.i. d. by de Finetti's theorem. Known results about the computability of de Finetti's theorem imply that these conditional independences are computable. The conditional independences underlying exchangeable arrays are characterized by the Aldous-Hoover theorem. In the special case of adjacency matrices of undirected graphs, i.e., symmetric binary arrays, this representation theorem expresses the conditional independences in terms of graphons. We prove that there exist exchangeable random graphs that can be computably sampled but whose corresponding graphons are not computable as functions or even as $L^{1}$ equivalence classes. We also give results on the approximability of graphons in certain special cases.
Metformin is associated with improved clinical outcomes in patients with melanoma: a retrospective, multi-institutional study

Background Pre-clinical studies have shown that metformin reduces intratumoral hypoxia, improves T-cell function, and increases sensitivity to PD-1 blockade, and metformin exposure has been associated with improved clinical outcomes in various types of cancer. However, the impact of this drug in diabetic melanoma patients has not yet been fully elucidated. Methods We reviewed 4,790 diabetic patients with stage I-IV cutaneous melanoma treated at the UPMC-Hillman Cancer Center and Memorial Sloan Kettering Cancer Center between 1996-2020. The primary endpoints included recurrence rates, progression free survival (PFS), and overall survival (OS) with and without metformin exposure. Tabulated variables included BRAF mutational status, immunotherapy (IMT) by type, and incidence of brain metastases. Results The five-year incidence of recurrence in stage I/II patients was significantly reduced with metformin exposure (32.3% vs 47.7%, p=0.012). The five-year recurrence rate for stage III patients was also significantly reduced (58.3% vs 77.3%, p=0.013) in the metformin cohort. OS was numerically increased in nearly all stages exposed to metformin, though this did not reach statistical significance. The incidence of brain metastases was significantly lower in the metformin cohort (8.9% vs 14.6%, p=0.039). Conclusion This is the first study to demonstrate significantly improved clinical outcomes in diabetic melanoma patients exposed to metformin. Overall, these results provide further rationale for ongoing clinical trials studying the potential augmentation of checkpoint blockade with metformin in advanced melanoma.
Diabetes and Metabolic Disorders: Their Impact on Cardiovascular Events in Liver Transplant Patients

Cardiovascular diseases are currently one of the most important causes of morbidity and mortality in liver transplant patients over the long term. Therefore, evaluating prognostic factors for cardiovascular events (CVEs) in this population is essential for taking preventive measures. The aim of this study was to identify the impact of diabetes and other metabolic disorders on CVEs in liver transplant patients. Three hundred fifty-six liver transplant recipients who survived at least 6 months after surgery were enrolled. Patients were followed for a median time of 118 months (12–250 months). All cardiovascular events were carefully recorded and detailed in the patients' charts. Demographic data, diabetes, hypertension, dyslipidemia, weight changes, and a diagnosis of metabolic syndrome both before and after transplantation were noted to assess their possible relationship with CVE. The presence of a diagnosis of metabolic-associated fatty liver disease (MAFLD) was also evaluated. Immunosuppressive therapy was included in the analysis. Diabetes mellitus (DM), especially when present before transplantation, was strongly associated with CVEs (hazard risk HR 3.10; 95% confidence interval CI: 1.60–6.03). Metabolic syndrome was found to be associated with CVEs in univariate analysis (HR 3.24; 95% CI: 1.36–7.8), while pretransplantation and de novo MAFLD were not. Immunosuppressive therapy had no influence on predisposing transplanted patients to CVEs during follow-up. Further prospective studies may be useful in investigating the risk factors for CVEs after liver transplantation and improving the long-term survival of transplant patients.
Systematic review and theoretical comparison of children’s outcomes in post-separation living arrangements

The purpose of the systematic review was to synthesize the literature on children’s outcomes across different living arrangements (nuclear families, shared physical custody [SPC], lone physical custody [LPC]) by extracting and structuring relevant theoretical hypotheses (selection, instability, fewer resources, and stressful mobility) and comparing the empirical findings against these hypotheses. Following the PRISMA guidelines, the review included 39 studies conducted between January 2010-December 2022 and compared the living arrangements across five domains of children’s outcomes: emotional, behavioral, relational, physical, and educational. The results showed that children’s outcomes were the best in nuclear families but in 75% of the studies children in SPC arrangements had equal outcomes. Children in LPC tended to report the worst outcomes. When compared with the different theoretical hypotheses, the results were the most consistent with fewer resources hypothesis which suggests that children especially in LPC families have fewer relational and economic resources whereas children in SPC families are better able to maintain resources from both parents.
Comparative chloroplast genome analysis of Sambucus L. (Viburnaceae): inference for phylogenetic relationships among the closely related Sambucus adnata Wall. ex DC Sambucus javanica Blume

Sambucus L. is found in the family Viburnaceae (syn. Adoxaceae) and encompasses approximately 29 accepted species. The complex morphology of these species has caused continued confusion concerning their nomenclature, classification, and identification. Despite previous attempts to resolve taxonomic complexities in the Sambucus genus, there are still unclear phylogenetic relationships among several species. In this study, the newly obtained plastome of Sambucus williamsii Hance. as well as the populations of Sambucus canadensis L. , Sambucus javanica Blume, and Sambucus adnata Wall. ex DC were sequenced, and their sizes, structural similarity, gene order, gene number, and guanine–cytosine (GC) contents were analyzed. The phylogenetic analyses were conducted using the whole chloroplast genomes and protein-coding genes (PCGs). The findings revealed that the chloroplast genomes of Sambucus species exhibited typical quadripartite double-stranded DNA molecules. Their lengths ranged from 158,012 base pairs (bp) (S. javanica) to 158,716 bp (S. canadensis L). Each genome comprised a pair of inverted repeats (IRs), which separated the large single-copy (LSC) and small single-copy (SSC) regions. In addition, the plastomes contained 132 genes, encompassing 87 protein-coding, 37 tRNA, and four rRNA genes. In the simple sequence repeat (SSR) analysis, A/T mononucleotides had the highest proportion, with the most repetitive sequences observed in S. williamsii. The comparative genome analyses showed high similarities in structure, order, and gene contents. The hypervariable regions in the studied chloroplast genomes were trnT-GGU, trnF-GAA, psaJ, trnL-UAG, ndhF, and ndhE, which may be used as candidate barcodes for species discrimination in Sambucus genus. Phylogenetic analyses supported the monophyly of Sambucus and revealed the separation of S. javanica and S. adnata populations. Sambucus chinensis Lindl. was nested within S. javanica in the same clade, collaborating their conspecific treatment. These outcomes indicate that the chloroplast genome of Sambucus plants is a valuable genetic resource for resolving taxonomic discrepancies at the lower taxonomic levels and can be applied in molecular evolutionary studies.
Economic losses associated with respiratory and helminth infections in domestic pigs in Lira district, Northern Uganda

This study sought to quantify direct economic losses due to respiratory and gastrointestinal (GI) helminth infections in domestic pigs in Uganda. In a longitudinal study design with repeated measures, farm visits were made at 2 month intervals from October 2018 to September 2019. Weaner and grower pigs (n = 288) aged 2–6 months from 94 farms were sampled. The pigs were monitored for growth and screened for exposure to four important respiratory pathogens: porcine circovirus type 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSv), Mycoplasma hyopneumoniae (M. hyo), Actinobacillus pleuropneumoniae (App) using ELISA tests. Farm management practices were recorded and used to generate management level scores. Treatment expenses incurred were recorded throughout the study. A mixed effects model was fitted to quantify effects of respiratory and helminth infections on average daily weight gains (ADGs), with farm and pig as random effects. Analysis of variance (ANOVA) was used to determine differences in mean treatment costs by farm management standard. Financial losses were estimated from average carcass dressing percentage, ADG reductions during fattening (200 days). Results showed a grower pig in a given farm exposed to PRRSv and Ascaris spp. had significantly lower ADG by 17.10 gr/day and 16.80 grams/day respectively, compared to a similar unexposed pig (p < 0.05). Mean treatment costs per pig declined significantly with increase in management standard scores (MSS), from USD 1.13 per pig in MSS 1 (poor management) farms to USD 0.95 for MSS 3 (better management) farms (p < 0.05). We show that monetary losses due to PRRSv and Ascaris spp. infection amounted to USD 6.6 ± 2.7 and 6.50 ± 3.2 (Mean ± SEM) per pig, respectively during 200 days of fattening. This study strengthens evidence that improving management practices to reduce infections mitigates economic losses. To guide interventions, further studies are required to unravel the full extent of indirect economic losses.
Lower limb joint loading in patients with unilateral hip osteoarthritis during bipedal stance and the effect of total hip replacement

Osteoarthritis of the hip is a common condition that affects older adults. Total hip replacement is the end-stage treatment to relief pain and improve joint function. Little is known about the mechanical load distribution during the activity of bipedal stance, which is an important daily activity for older adults who need to rest more frequently. This study investigated the distribution of the hip and knee joint moments during bipedal stance in patients with unilateral hip osteoarthritis and how the distribution changed 1 year after total hip replacement. Kinematic and kinetic data from bipedal stance were recorded. External hip and knee adduction moments were calculated and load distribution over both limbs was calculated using the symmetry angle. Preoperatively, the non-affected limb carried 10% more body weight than the affected limb when standing on two legs. Moreover, the mean external hip and knee adduction moments of the non-affected limb were increased compared to the affected limb. At follow-up no significant differences were observed between the patients’ limbs. Preoperative and postoperative changes in hip adduction moment were mainly explained by the combination of the vertical ground reaction force and the hip adduction angle. Stance width also explained changes in the hip and knee adduction moments of the affected leg. Furthermore, as with walking, bipedal standing also showed an asymmetric mechanical load distribution in patients with unilateral hip osteoarthritis. Overall, the findings suggest the need for preventive therapy concepts that focus not only on walking but also on optimizing stance towards a balanced load distribution of both legs.
Case report: Irinotecan-induced interstitial lung disease in an advanced colorectal cancer patient resurfacing decades after allogeneic bone marrow transplantation for aplastic anemia; a case report and narrative review of literature

Two mechanisms of drug-induced interstitial lung disease (DILD) have been reported: 1) direct injury of lung epithelial cells and/or endothelial cells in lung capillaries by the drug and/or its metabolites and 2) hypersensitivity reactions. In both mechanisms, immune reactions such as cytokine and T cell activation are involved in DILD. While past and present lung diseases and accumulative lung damage due to smoking and radiation are risk factors for DILD, the association between the immune status of the host and DILD is not well known. Herein, we report a case of advanced colorectal cancer with a history of allogeneic bone marrow transplantation for aplastic anemia more than 30 years prior, in which DILD occurred early after irinotecan-containing chemotherapy. Bone marrow transplantation might be a potential risk factor for DILD.
Iodine deficiency and real-life supplementation ineffectiveness in Polish pregnant women and its impact on thyroid metabolism

Introduction Iodine is a pivotal component of thyroid hormones, and its deficiency leads to negative pregnancy outcomes. Therefore, during gestation, additional iodine supplementation is recommended. Objectives By evaluating a group of women from western Poland, the study updated on iodine status during pregnancy and the effectiveness of iodine supplementation in relation to the maternal and neonatal thyroid function. Patients and methods A total of 91 women were recruited before the delivery between 2019 and 2021. During the medical interview, the patients declared their dietary supplements intake. Thyroid parameters (TSH, ft3, ft4, a-TPO, a-Tg, and TRAb) were measured in the serum of mothers and in the cord blood of newborns after birth. Urinary iodine concentration (UIC) and urine/creatinine (UIC/crea) ratio were assessed in single urine samples using a validated high-performance liquid chromatography with ultraviolet detection (HPLC-UV). Neonatal TSH screening from dried blood spot was analyzed. Results Pregnant women showed a median (interquartile range) UIC of 106 (69–156) µg/liter and UIC/crea ratio of 104 (62–221) µg/g, whereas approximately 20% had UIC/crea below 50 µg/g, indicating iodine deficiency. The iodine supplementation ratio was 68%. No significant differences in UIC, UIC/crea and thyroid parameters were found between iodine supplemented and non-supplemented groups; however, the highest ioduria was detected when iodine was supplemented in addition to levothyroxine in comparison with both substances administered separately. Patients with UIC/crea within 150–249 µg/g demonstrated the lowest TSH and a-TPO levels. Screening TSH was above 5 mIU/liter in 6% of children. Conclusions Despite the national salt iodization and the recommendation to supplement iodine during gestation, the status of the abovementioned microelement and real-life intake revealed the ineffectiveness of the current iodine-deficiency prophylaxis model in pregnancy.
Excessively increased thalamocortical connectivity and poor initial antiseizure medication response in epilepsy patients

Objectives The network mechanism underlying the initial response to antiseizure medication in epilepsy has not been revealed yet. Given the central role of the thalamus in the brain network, we conducted a case-control study to investigate the association between thalamic connectivity and medication response. Methods We recruited 39 patients with newly diagnosed and medication-naïve epilepsy of genetic or unknown etiology, including 26 with a good response (GR group) and 13 with a poor response (PR group), and 26 matched healthy participants (control group). We measured the gray matter density (GMD) and the amplitude of low-frequency fluctuation (ALFF) of bilateral thalami. We then set each thalamus as the seed region of interest (ROI) to calculate voxel-wise functional connectivity (FC) and assessed ROI-wise effective connectivity (EC) between the thalamus and targeted regions. Results We found no significant difference between groups in the GMD or ALFF of bilateral thalami. However, we observed that the FC values of several circuits connecting the left thalamus and the cortical areas, including the bilateral Rolandic operculum, the left insula, the left postcentral gyrus, the left supramarginal gyrus, and the left superior temporal gyrus, differed among groups (False Discovery Rate correction, P < 0.05), with a higher value in the PR group than in the GR group and/or the control group (Bonferroni correction, P < 0.05). Similarly, both the outflow and the inflow EC in each thalamocortical circuit were higher in the PR group than in the GR group and the control group, although these differences did not remain statistically significant after applying the Bonferroni correction (P < 0.05). The FC showed a positive correlation with the corresponding outflow and inflow ECs for each circuit. Conclusion Our finding suggested that patients with stronger thalamocortical connectivity, potentially driven by both thalamic outflowing and inflowing information, may be more likely to respond poorly to initial antiseizure medication.
Potential use of angiotensin receptor blockers in skin pathologies

Renin-angiotensin system (RAS) components such as angiotensin II, angiotensin receptors (AT1R and AT2R), and angiotensin-converting enzyme (ACE) are expressed in different cell types of the skin. Through AT1R, angiotensin II increases proinflammatory cytokines contributing to fibrosis, angiogenesis, proliferation, and migration of immune cells to the skin. In contrast, AT2R suppresses the effects mentioned above. Many studies show that angiotensin receptor blockers (ARBs) and angiotensin-converting enzymes (ACEi) reduce the proinflammatory cytokines and fibrogenic factors including transforming growth factor β (TGF-β), Connective tissue growth factor (CTGF), and IL-6. This review article provides a detailed research study on the implications of ARBs in wound healing, hypertrophic scar, and keloids. We further discuss the therapeutic potentials of ARBs in autoimmune and autoinflammatory skin diseases and cancer, given their anti-fibrotic and anti-inflammatory effects.
Cardiometabolic risk factors and social jetlag in university professors

Chronic stress leads to circadian disruption, with variability in sleep time and duration. This scenario increases the prevalence and incidence of cardiometabolic abnormalities. Social jetlag (SJL), a proxy of circadian disruption, has been associated with increased vulnerability to the development of metabolic syndrome, obesity, and type 2 diabetes. This research aimed to evaluate how variables associated with cardiometabolic risk are related to SJL and poor sleep among university professors. From 2018 to 2019, full-time university professors (n=103) with a mean age of 44±5.4 years were assessed for sleep quality, chronotype, SJL, metabolic components, sociodemographic characteristics, and physical evaluation. Sleep quality and weekday sleep duration were associated with stress (r=0.44 and r=-0.34) and anxiety (r=0.40), respectively. Mean sleep duration (n=65) was 7.0±1.1 h and all professors with poor sleep (41.2%; n=28) worked 40 h/week. Professors who slept less were significantly (r=-0.25) older, and teaching time (years) was positively correlated with blood glucose (r=0.42). Mean SJL was 59.8 ±4.5 min (n=68) and 48.5% of these professors had values ≤1 h and 51.4% ≥1 h. SJL and blood glucose concentration were associated (r=0.35), which reinforced that challenges to the circadian system reverberate on metabolism. In this study, professors at the Federal University of Rio Grande do Norte had cardiometabolic risks related to anxiety, stress, and sleep quality.