Miracle-dz/UniFAR-FTUs huggingface dataset:
Limited Dose-Dependent Effects of Vedolizumab on Various Leukocyte Subsets

OBJECTIVES: The anti-α4β7 integrin antibody vedolizumab (VDZ) is successfully used for the treatment of inflammatory bowel diseases. However, only a subgroup of patients respond to therapy. VDZ is administered at a fixed dose, leading to a wide range of serum concentrations in patients. Previous work from our group showed a dose-dependent preferential binding of VDZ to effector compared with regulatory CD4+ T cells. Therefore, we aimed to determine the dose-dependent binding profile of VDZ to other leukocyte subsets. METHODS: We characterized α4β7 integrin expression on CD8+ T cells, CD19+ B cells, CD14+ monocytes, natural killer cells, and eosinophils from patients with inflammatory bowel disease and healthy controls. We studied the binding of VDZ to these cells at different concentrations and investigated the functional consequences for dynamic adhesion and transmigration in vitro. RESULTS: The expression of α4β7 differed between the analyzed leukocyte subsets and was significantly higher on eosinophils from inflammatory bowel disease patients compared with controls. Almost all α4β7-expressing cells from these subsets were bound by VDZ at a concentration of 10 μg/mL. Dynamic cell adhesion was significantly impaired in all subsets, but there were no dose-dependent differences in the inhibition of adhesion. DISCUSSION: Our data suggest that α4β7-expressing CD8+ T cells, CD19+ B cells, CD14+ monocytes, natural killer cells, and eosinophils are a target of VDZ. However, there do not seem to be concentration-dependent differences, regarding the effects on these cells in the clinically relevant range. Thus, the reported exposure-efficacy characteristic of VDZ can probably mainly be attributed to CD4+ T-cell subsets.
Associated factors and short-term mortality of early versus late acute kidney injury following on-pump cardiac surgery

Abstract OBJECTIVES Acute kidney injury (AKI) is common following cardiac surgery. The aim was to investigate the characteristics of AKI that occurred within 48 h and during 48 h to 7 days after cardiac surgery. METHODS Patient data were extracted from Medical Information Mart for Intensive Care III database. AKI was defined according to the Kidney Disease Improving Global Outcomes guideline and divided into early (within 48 h) and late (during 48 h to 7 days) AKI. Multivariable logistic regression models were established to investigate risk factors for AKI. Cox proportional hazards model was used to analyse 90-day survival. RESULTS AKI occurred in 51.2% (2741/5356) patients within the first 7 days following cardiac surgery, with the peak occurrence at 36–48 h. The incidence of early and late AKI was 41.9% and 9.2%, respectively. Patients with late AKI were older and had more comorbidities compared to early AKI patients. Risk factors associated with early AKI included age, body mass index, congestive heart failure and diabetes. While late AKI was related to atrial fibrillation, estimated glomerular filtration rate, sepsis, norepinephrine, mechanical ventilation and packed red blood cell transfusion. In Cox proportional model, both late and early AKIs were independently associated with 90-day mortality, and patients with early AKI had better survival than those with late AKI. CONCLUSIONS AKI that occurred earlier was distinguishable from AKI that occurred later after cardiac surgery. Time frame should be taken into consideration.
Albumin-templated manganese carbonate nanoparticles for precise magnetic resonance imaging of acute myocardial infarction

Myocardial infarction (MI) is a major cause of death worldwide. Early and precise diagnosis of myocardial viability after MI is extremely important for effective treatment and prognosis evaluation. Herein, we developed the BSA-templated manganese carbonate (MnCO3@BSA) nanoparticles as an MR imaging contrast agent for accurate detection of the infarcted regions. The chemophysical features, targeting capability toward the infarct, and biocompatibility were evaluated. The nanoparticles showed superior chemical stability. In vitro study suggested that the MnCO3@BSA nanoparticles do not enter normal cardiomyocytes. MR imaging indicated that the MnCO3@BSA with a high longitudinal (r 1 ) relaxivity of 5.84 mM−1s−1 at physiological condition specifically accumulated into the infarcted regions of myocardial ischemia/reperfusion (I/R) mice. In addition, the MnCO3@BSA nanoparticles exhibited low cytotoxicity to cardiomyocytes, no damage to organs and good hemocompatibility. Thereby, the MnCO3@BSA nanoparticles manifested great potential as an extracellular contrast agent of MR imaging for sensitive and specific detection of the infarcted regions during acute myocardial I/R injury.
Facilitating connection to enhance college student well‐being: Evaluation of an experiential group program

Abstract This randomized controlled trial examined the impact of The Connection Project, an experiential, relationship‐focused intervention designed to improve school belongingness and decrease symptoms of depression and loneliness among new college students. Participants were 438 first‐year and transfer students (232 treatment, 206 waitlist‐control) at a medium‐sized, 4years, predominantly White public university in the Southeastern United States. At postintervention, the treatment group reported significant relative increases in school belonging and significant relative reductions in levels of loneliness and depressive symptoms in comparison to waitlist‐controls. Program effects were stronger for students from marginalized racial or ethnic backgrounds, students from lower socioeconomic status households, and transfer students. Results are interpreted as suggesting the utility of experiential, peer‐support prevention programming to promote college students' well‐being, particularly college students who hold identities that are traditionally disadvantaged in this context.
Population features of alleles and genotypes frequency distribution of polymorphic genetic markers of antipsychotic medications pharmacokinetics in the Kazakh population

The presented article is relevant, as the main goals of schizophrenia treatment are to achieve a response to psychopharmacotherapy, reduction and stabilization of psychopathological symptoms, qualitative remission, which in general implies the creation of a stable quality of life for the patient. The purpose of the study was to evaluate the population features of the frequency distribution of alleles and genotypes of polymorphic genetic variants of according to genome‐wide association studies analysis of pharmacokinetics‐associated antipsychotic medications, in an ethnically homogeneous Kazakh population. The research material was deoxyribonucleic acid (DNA) isolated from the peripheral blood of 1,800 conditionally healthy persons of Kazakh nationality. DNA isolation was carried out by the magnetic polyvinyl alcohol magnetic particle separation method. The analysis of the frequency distribution of the studied genotypes in the Kazakh population showed their compliance with the Hardy–Weinberg equilibrium for all studied polymorphisms (p > .05). The obtained results showed that CYP2C19 (rs4244285, rs4986893) polymorphisms occurs in Kazakhs significantly more often than European and a number of Asian populations, which significantly affects the decrease in effectiveness and increases the risk of side complications during therapy with antipsychotic medications in the Kazakh population.
Somatic Hypermutation and Framework Mutations of Variable Region Contribute to Anti-Zika Virus-Specific Monoclonal Antibody Binding and Function

ZIKV is a global health concern against which no vaccine or therapeutics are available. We characterized eight novel rabbit monoclonal antibodies recognizing ZIKV envelope and prM proteins and studied the relationship between somatic hypermutation of complementarity-determining regions, framework regions, mutations, antibody specificity, binding, and neutralizing activity. ABSTRACT Zika virus (ZIKV) is a global public health concern due to its ability to cause congenital Zika syndrome and lack of approved vaccine, therapeutic, or other control measures. We discovered eight novel rabbit monoclonal antibodies (MAbs) that bind to distinct ZIKV envelope protein epitopes. The majority of the MAbs were ZIKV specific and targeted the lateral ridge of the envelope (E) protein domain III, while the MAb with the highest neutralizing activity recognized a putative quaternary epitope spanning E protein domains I and III. One of the non-neutralizing MAbs specifically recognized ZIKV precursor membrane protein (prM). Somatic hypermutation of immunoglobulin variable regions increases antibody affinity maturation and triggers antibody class switching. Negative correlations were observed between the somatic hypermutation rate of the immunoglobulin heavy-chain variable region and antibody binding parameters such as equilibrium dissociation constant, dissociation constant, and half-maximal effective concentration value of MAb binding to ZIKV virus-like particles. Complementarity-determining regions recognize the antigen epitopes and are scaffolded by canonical framework regions. Reversion of framework region amino acids to the rabbit germ line sequence decreased anti-ZIKV MAb binding activity of some MAbs. Thus, antibody affinity maturation, including somatic hypermutation and framework region mutations, contributed to the binding and function of these anti-ZIKV MAbs. IMPORTANCE ZIKV is a global health concern against which no vaccine or therapeutics are available. We characterized eight novel rabbit monoclonal antibodies recognizing ZIKV envelope and prM proteins and studied the relationship between somatic hypermutation of complementarity-determining regions, framework regions, mutations, antibody specificity, binding, and neutralizing activity. The results contribute to understanding structural features and somatic mutation pathways by which potent Zika virus-neutralizing antibodies can evolve, including the role of antibody framework regions.
An improved joint non-negative matrix factorization for identifying surgical treatment timing of neonatal necrotizing enterocolitis

Neonatal necrotizing enterocolitis is a severe neonatal intestinal disease. Timely, the identification of surgical indications is essential for newborns to seek the best time for treatment and improve prognosis. This paper attempts to establish an algorithm model based on multimodal clinical data to determine the features of surgical indications and construct an auxiliary diagnosis model. The proposed algorithm adds hypergraph constraints on the two modal data based on Joint Non-negative Matrix Factorization, aiming to mine the higher-order correlations of the two data features. In addition, the adjacency matrix of the two kinds of data is used as a network regularization constraint to prevent overfitting. Orthogonal and L1-norm regulations were introduced to avoid feature redundancy and perform feature selection, respectively, and confirmed 14 clinical features. Finally, we used three classifiers, random forest, support vector machine, and logistic regression, to perform binary classification of patients requiring surgery. The results show that when the features selected by the proposed algorithm model are classified by random forest, the area under the ROC curve is 0.8, which has high prediction accuracy.
SVA Retrotransposons and a Low Copy Repeat in Humans and Great Apes: A Mobile Connection

Abstract Segmental duplications (SDs) constitute a considerable fraction of primate genomes. They contribute to genetic variation and provide raw material for evolution. Groups of SDs are characterized by the presence of shared core duplicons. One of these core duplicons, low copy repeat (lcr)16a, has been shown to be particularly active in the propagation of interspersed SDs in primates. The underlying mechanisms are, however, only partially understood. Alu short interspersed elements (SINEs) are frequently found at breakpoints and have been implicated in the expansion of SDs. Detailed analysis of lcr16a-containing SDs shows that the hominid-specific SVA (SINE-R-VNTR-Alu) retrotransposon is an integral component of the core duplicon in Asian and African great apes. In orang-utan, it provides breakpoints and contributes to both interchromosomal and intrachromosomal lcr16a mobility by inter-element recombination. Furthermore, the data suggest that in hominines (human, chimpanzee, gorilla) SVA recombination-mediated integration of a circular intermediate is the founding event of a lineage-specific lcr16a expansion. One of the hominine lcr16a copies displays large flanking direct repeats, a structural feature shared by other SDs in the human genome. Taken together, the results obtained extend the range of SVAs’ contribution to genome evolution from RNA-mediated transduction to DNA-based recombination. In addition, they provide further support for a role of circular intermediates in SD mobilization.
Central retinal artery occlusion and subsequent amaurosis fugax in the contralateral eye associated with the G20210A prothrombin gene (F2) variant: a case report

ABSTRACT Purpose Report the case of a patient with a history of central retinal artery occlusion in her right eye and amaurosis fugax associated with acute ischemic changes in her left eye related to a prothrombin G20210A gene variant, in which OCT-A was used as a diagnostic and therapeutic tool. Case presentation 55-year-old woman with a history of central retinal artery occlusion in her right eye and prothrombin gene G20210A (F2) variant diagnosis. She presented to our consultation with amaurosis fugax in her left eye. As medical history, she had an episode of bilateral posterior scleritis diagnosed asynchronously with the current episode. Vascular, autoimmune, and metabolic prothrombotic diseases were ruled out. OCT-A showed areas suggesting acute ischemia consistent with macular retinopathy in her left eye. Anticoagulant therapy with Apixaban was initiated, considering the risk for her vision. Control OCT-A showed perfusion improvement in the previous site of the occlusive vascular event. We also considered the extent of the inflammatory response due to posterior scleritis as a differential diagnosis. Nevertheless, it is less likely, considering the temporality between scleritis and the retinal-vascular episodes. Conclusions While the G20210A prothrombin gene (F2) variant is a rare cause of retinal artery occlusion, it is important to consider it a differential diagnosis. Good visual outcomes can be achieved with prompt initiation of antithrombotic treatment. In addition, OCT-A is useful for diagnosing ischemic retinal changes that cannot be observed with other diagnostic methods and monitoring them.
The efficacy of myo-inositol supplementation to reduce the incidence of gestational diabetes: a meta-analysis

Abstract Introduction Myo-inositol supplementation is used to reduce the incidence of gestational diabetes, but its efficacy is not well established. This meta-analysis aims to explore the influence of myo-inositol supplementation on the prevention of gestational diabetes. Methods This meta-analysis has been conducted up to March 2022 to identify randomized clinical trials comparing the efficacy of myo-inositol supplementation to prevent gestational diabetes. Several databases including PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systemically. Results We have included eight RCTs in this meta-analysis. Compared with control group in pregnant women, myo-inositol supplementation was found to significantly decrease the incidence of gestational diabetes (OR = 0.40; 95% CI = 0.19 to 0.84; p = .01), 2-h glucose OGTT (SMD = −0.22; 95% CI = −0.41 to −0.02; p = .03), HOMA-IR (SMD = −0.25; 95% CI = −0.42 to −0.08; p = .004) and preterm delivery (OR = 0.41; 95% CI = 0.23 to 0.73; p = .003), but demonstrated no obvious impact on gestational age at birth (SMD = 0.12; 95% CI = −0.05 to 0.29; p = .18) or birth weight (SMD = −0.04; 95% CI = −0.20 to 0.13; p = .68). Conclusions Myo-inositol supplementation is effective to reduce the incidence of gestational diabetes, 2-h glucose OGTT, HOMA-IR and preterm delivery, which suggested that myo-inositol supplementation should be recommended to prevent gestational diabetes.
Early plasma D-dimer as a predictor of acute intracranial atherosclerosis-related large vessel occlusion in acute ischemic stroke

Background Intracranial atherosclerosis-related large vessel occlusion (ICAS+LVO) poses an important technical challenge for endovascular thrombectomy (EVT). Purpose To evaluate the value of D-dimer in predicting ICAS+LVO alone and in combination with other clinical and imaging predictors. Material and Methods Consecutive patients who underwent EVT at our center between January 2018 and June 2021 were retrospectively reviewed. Patients were classified to the ICAS+LVO or ICAS–LVO group according to angiographic findings. Collateral gradings were evaluated based on computed tomography angiography and categorized as follows: score 0–1 unfavorable collaterals and score 2–3 favorable collaterals. Receiver operating characteristic curve was analyzed to evaluate the predictive value of D-dimer and the combination of other predictors for ICAS+LVO. Results A total of 374 patients were enrolled, among them, 107 (28.6%) had an ICAS+LVO, while ICAS–LVO was determined in 267 (71.4%) patients. Median D-dimer levels were lower (0.36 vs. 1.18 mg/L; P < 0.001) while the proportion of favorable collaterals was higher (85.0% vs. 22.5%; P < 0.001) in the ICAS+LVO group than the ICAS–LVO group. After multivariable analysis, D-dimer (adjusted odds ratio [OR]=0.32, 95% confidence interval [CI]=0.21–0.50; P < 0.001) and collaterals (adjusted OR=16.25, 95% CI=7.58–34.84; P < 0.001) remained independent predictors of ICAS+LVO. The area under the curve of D-dimer, collaterals, and combination for identification of ICAS+LVO was 0.82, 0.85, and 0.92, respectively. Conclusion Low early plasma D-dimer levels are a significant and independent predictor of ICAS+LVO, and predictive value strengthens when in a combined model using D-dimer and collateral grading.
The effects of dietary linoleic acid on reducing serum cholesterol and atherosclerosis development are nullified by a high-cholesterol diet in male and female apoE-deficient mice

Abstract Linoleic acid (LA) has a two-sided effect with regard to serum cholesterol-lowering and pro-inflammation, although whether this fatty acid reduces serum cholesterol and the development of atherosclerosis under high-cholesterol conditions has yet to be ascertained. In this study, we examine the effects of dietary LA on reducing serum cholesterol and atherosclerosis development under high-cholesterol conditions. Male and female apoE-deficient (ApoE-/-) mice were fed AIN-76-based diets containing 10% SFA and 0·04 % cholesterol, 10% LA and 0·04% low cholesterol (LALC), or 10% LA and 0·1% high cholesterol (LAHC) for 9 weeks. The results revealed significant reduction in serum cholesterol levels and aortic lesions with increasing levels of pro-inflammatory biomarkers (urinary isoprostane and aortic MCP-1 mRNA) in male and female LALC groups compared with those in the SFA groups (P < 0·05). Furthermore, whereas there were significant increases in the serum cholesterol levels and aortic lesions (P < 0·05), there was no difference in aortic MCP-1 mRNA levels in male and female LAHC groups compared with those in the LALC groups. A high-dietary intake of cholesterol eliminated the serum cholesterol-lowering activity of LA but had no significant effect on aortic inflammation in either male or female ApoE-/- mice. The inhibitory effect of LA on arteriosclerosis is cancelled by a high-cholesterol diet due to a direct increase in serum cholesterol levels. Accordingly, serum cholesterol levels might represent a more prominent pathogenic factor than aortic inflammation in promoting the development of atherosclerosis.
Relationships Between Psychopathy and DSM Personality Disorders in Men and Women

The current investigation asseses the relationship between DSM personality disorders (PDs) and PCL psychopathy in a community study: the Cambridge Study in Delinquent Development (CSDD). The children (Generation 3) of the original CSDD males (Generation 2) were assessed for PDs and psychopathy in early adulthood. Generation 3 consisted of both males (n = 291) and females (n = 260) and allowed for analyses separately for each gender. Cluster B PDs showed the strongest relationships with psychopathy, especially Borderline and Antisocial PD. Histrionic PD did not appear to have strong relationships with psychopathy, and there were no indications that histrionic PD overlaps with psychopathy in females as past research has hypothesized. There were however some other gender-specific relationships in the analyses, most notably between psychopathy and schizoid and schizotypal PDs for females, and between psychopathy and paranoid PD in males. Implications for the understanding of psychopathy in males and females are discussed.
Development of a network of carcinogenicity adverse outcome pathways and its employment as an evidence framework for safety assessment.

The traditional paradigm for safety assessment of chemicals for their carcinogenic potential to humans relies heavily on a battery of well-established genotoxicity tests, usually followed up by long term, high dose rodent studies. There are a variety of problems with this approach, not least that the rodent may not always be the best model to predict toxicity in humans. Consequently, new approach methodologies (NAMs) are being developed to replace or enhance predictions coming from the existing assays. However, a combination of the data arising from NAMs is likely to be required to improve upon the current paradigm and consequently a framework is needed to combine evidence in a meaningful way. Adverse outcome pathways (AOPs) represent an ideal construct on which to organise this evidence. In this work a data structure outlined previously was used to capture AOPs and evidence relating to carcinogenicity. Knowledge held within the predictive system Derek Nexus was extracted, built upon, and arranged into a coherent network containing 37 AOPs. 60 Assays and 351 in silico alerts were then associated with KEs in this network and it was brought to life by associating data and contextualising evidence and predictions for over 13,400 compounds. Initial investigations into using the network to view knowledge and reason between evidence in different ways were made. Organising knowledge and evidence in this way provides a flexible framework on which to carry out more consistent and meaningful carcinogenicity safety assessments in many different contexts.