Miracle-dz/UniFAR-FTUs huggingface dataset:
Preliminary evaluation of the diagnostic performance of Roche Elecsys® active vitamin B12 versus total vitamin B12 for vitamin B12 deficiency screening

Introduction The prevalence of vitamin B12 deficiency is high in at-risk populations with sometimes irreversible consequences. Beside total B12 (TVB12), active B12 (AVB12) is a promising first-line marker. Only Abbott AVB12 assays were largely evaluated and generally demonstrated benefit in clinical practice. More recently developed Roche AVB12 still requires some investigations. Objectives Our study aimed to evaluate the Roche Elecsys® AVB12 immunoassay performance versus Roche Elecsys® TVB12 competition assay. Design and Methods: We included 175 patients at Rouen University Hospital who had a TVB12 value <300 pmol/L. We evaluated performance of AVB12 by comparing the results with TVB12 and MMA values in case of disagreement. Results Positive correlation was found between the AVB12 and TVB12. We found a disagreement between TVB12 and AVB12 in 18.8% of cases. Among 33 cases of disagreement, 76% had normal AVB12 but low TVB12, whereas 24% had low AVB12 and normal TVB12. Thirty-one MMA determinations were performed: 71% showed agreement between MMA and AVB12, versus 29% between MMA and TVB12. TVB12 reported a sensitivity (Se) at 66.7%, specificity (Sp) at 20%, positive predictive value (PPV) at 16.7% and negative predictive value (NPV) at 71.4% for the prediction of MMA elevation. We determined an optimized cut-off value of 45.5 pmol/L for AVB12, which reported a Se 66.7%, Sp 60%, PPV 30.7%, and NPV 88.9%. Conclusions Our results provide preliminary evidence that Roche AVB12 may offer better discrimination than Roche TVB12 in the diagnosis of vitamin B12 deficiency. Further more detailed evaluation is warranted.
Unsupervised home spirometry is not equivalent to supervised clinic spirometry in children and young people with cystic fibrosis: Results from the CLIMB‐CF study

Handheld spirometry allows monitoring of lung function at home, of particular importance during the COVID‐19 pandemic. Pediatric studies are unclear on whether values are interchangeable with traditional, clinic‐based spirometry. We aimed to assess differences between contemporaneous, home (unsupervised) and clinic (supervised) spirometry and the variability of the former. The accuracy of the commercially available spirometer used in the study was also tested.
Sanguinarine induces apoptosis in osteosarcoma by attenuating the binding of STAT3 to the single‐stranded DNA‐binding protein 1 (SSBP1) promoter region

Osteosarcoma, a primary malignant bone tumour prevalent among adolescents and young adults, remains a considerable challenge despite protracted progress made in enhancing patient survival rates over the last 40 years. Consequently, the development of novel therapeutic approaches for osteosarcoma is imperative. Sanguinarine (SNG), a compound with demonstrated potent anticancer properties against various malignancies, presents a promising avenue for exploration. Nevertheless, the intricate molecular mechanisms underpinning SNG's actions in osteosarcoma remain elusive, necessitating further elucidation.
Enterobacterales draft genome sequences: 15 historical (1998–2004) and 30 contemporary (2015–2016) clinical isolates from Pakistan

ABSTRACT The continued emergence and spread of antimicrobial resistance among pathogenic bacteria are ever-growing threats to health and economy. Here, we report the draft genomes for 45 Enterobacterales clinical isolates, including historical and contemporary drug-resistant organisms, obtained in Pakistan between 1998 and 2016: 5 Serratia, 3 Salmonella, 3 Enterobacter, and 34 Klebsiella.
Effect of IGF1 and FSH on the function of granulosa cells from prehierarchal follicles in chickens

Abstract Insulin-like growth factor 1 (IGF1) is an essential regulator of mammalian follicle development and synergizes with follicle-stimulating hormone (FSH) to amplify its effects. In avian preovulatory follicles, IGF1 increases the expression of genes involved in steroidogenesis and progesterone and inhibin A production. The role of IGF1 in prehierarchal follicles has not been well studied in chickens. The aim of this study was to investigate the role of IGF1 in granulosa cells from prehierarchal follicles and to determine whether IGF1 and FSH synergize to promote follicle development. Granulosa cells of 3–5 and 6–8 mm prehierarchal follicles were cultured with IGF1 (0, 10, 100 ng/mL) in the presence or absence of FSH (0, 10 ng/mL). Cell proliferation, expression of genes important in follicle development (FSHR, IGF1R, AMH, STAR, CYP11A1, INHA, and INHBA), and progesterone production were evaluated following treatment. IGF1 treatment alone significantly increased STAR, CYP11A1, and INHBA mRNA expression and cell proliferation in granulosa cells of 6–8 mm follicles. IGF1 and FSH synergized to increase STAR mRNA expression in 6–8 mm follicles. IGF1 and FSH co-treatment were necessary to increase INHA mRNA expression in 6–8 mm follicles. Although IGF1 significantly increased the expression of genes involved in steroidogenesis, progesterone production in granulosa cells of 6–8 mm follicles was not affected. IGF1 did not affect AMH mRNA expression, although FSH significantly decreased AMH expression in granulosa cells of 3–5 mm follicles. These results suggest that IGF1 may act with FSH to promote follicle selection at the prehierarchal follicle stage. Summary Sentence Insulin-like growth factor 1 and follicle-stimulating hormone treatment of cultured granulosa cells from prehierarchal follicles promote expression of follicle development markers including STAR, CYP11A1, INHA, and INHBA. Graphical Abstract
ebony underpins Batesian mimicry in melanic stoneflies

The evolution of Batesian mimicry – whereby harmless species avoid predation through their resemblance to harmful species – has long intrigued biologists. In rare cases, Batesian mimicry is linked to intraspecific colour variation, in which only some individuals within a population resemble a noxious ‘model’. Here, we assess intraspecific colour variation within a widespread New Zealand stonefly, wherein highly melanized individuals of Zelandoperla closely resemble a chemically defended aposematic stonefly, Austroperla cyrene. We assess convergence in the colour pattern of these two species, compare their relative palatability to predators, and use genome‐wide association mapping to assess the genetic basis of this resemblance. Our analysis reveals that melanized Zelandoperla overlap significantly with Austroperla in colour space but are significantly more palatable to predators, implying that they are indeed Batesian mimics. Analysis of 194,773 genome‐wide SNPs reveals an outlier locus (ebony) strongly differentiating melanic versus non‐melanic Zelandoperla. Genotyping of 338 specimens from a single Zelandoperla population indicates that ebony explains nearly 70% of the observed variance in melanism. As ebony has a well‐documented role in insect melanin biosynthesis, our findings indicate this locus has a conserved function across deeply divergent hexapod lineages. Distributional records suggest a link between the occurrence of melanic Zelandoperla and the forested ecosystems where the model Austroperla is abundant, suggesting the potential for adaptive shifts in this system underpinned by environmental change.
The Relationship between Changes in Serum Element Concentrations and Pathological Condition and Disease Status in Japanese Multiple Myeloma Patients: A Pilot Study and Literature Review

Background: Multiple myeloma (MM) is a rare cancer, and information on its pathological condition and serum element levels is lacking. In this pilot study, we examined serum element concentrations in Japanese patients with MM by a comprehensive multi-element analysis. Methods: This is a case-control study of 12 Japanese patients diagnosed with MM at the Nagoya City University Hospital between 2008 and 2013. Blood samples were taken, at the initial diagnosis and at relapse. The serum concentrations of 12 elements were analyzed by inductively coupled plasma mass spectrometry and compared between MM patients and non-MM volunteers. We also analyzed the correlation between serum element concentrations and laboratory values related to disease status and tumor volume of MM. Results: We found that serum chromium (Cr), copper (Cu), molybdenum (Mo), and barium (Ba) concentrations were significantly increased in MM patients. Ba was significantly increased in MM patients, suggesting an association with bone lesions. There was no consistent trend between these elements and existing indices related to MM tumor volume and disease status. Conclusions: Although this is a pilot study, serum Cr, Cu, Mo, and Ba concentrations were found to be significantly elevated in MM patients. Further studies with large sample sizes are needed, since the changes in serum concentrations of these elements may reflect the pathological condition of MM.
Tyrosine kinase alterations in colorectal cancer with emphasis on the distinct clinicopathological characteristics

Tyrosine kinase (TK) alterations, such as anaplastic lymphoma kinase (ALK) fusion, neurotrophic tyrosine receptor kinase (NTRK) fusion, c‐ros oncogene 1 (ROS1) fusion and mesenchymal–epithelial transition factor (MET) exon 14 skipping, have been reported in colorectal cancers (CRC). We have previously reported CRCs with NTRK fusion among our cohort. However, their clinicopathological features have not been fully elucidated.
A topological analysis on patches of optical flow

The research of optical flow is vitally important topic in computer vision. In this paper we research a topological analysis of space of optical flow locally. We use the methods of computing topology to the spaces of 4 × 4 and 6 × 6 high contrast optical flow patches. We experimentally prove that in both cases there exist subspaces of the spaces of all high contrast optical flow patches that is topologically equivalent to a circle, which states that some results on the topological analysis of natural images and range images can be extended to the scope of image motion. c ©2016 All rights reserved.
Histological findings of thyroid cancer after lenvatinib therapy

Lenvatinib is a multikinase inhibitor used for treating unresectable or metastatic cancers, including thyroid cancer. As total thyroidectomy followed by radioactive iodine therapy is a commonly recommended initial treatment for thyroid cancer, histological findings of the thyroid after lenvatinib therapy remain unclear. Therefore, the aim of this study was to analyse in‐vivo changes in patients who underwent thyroidectomy after lenvatinib therapy.
Assessment of Intratumoural and Stromal Infiltrating Lymphocytes in the Various Subtypes of Breast Carcinoma Patients who have Received Neoadjuvant Chemotherapy

Background: Breast cancer comprises a highly heterogeneous subset of tumours that respond well to Neoadjuvant Chemotherapy (NAC). Tumour Infiltrating Lymphocytes (TIL) act as a means to an end by shedding light on the treatment response as well as predictive factors to the clinicopathological features for the same. Therefore, this article attempts to shift the attention to the relevance of TIL in the aforementioned aspects by bringing to notice the contrasting traits displayed by them in the different immunohistochemical subtypes of breast carcinoma. Materials and methods: 75 triple-negative breast cancer (TNBC) patients, 25 human epidermal growth factor receptor (HER2BC) positive patients and 77 hormone receptor (HRBC) positive breast cancer patients were included in this study who received NAC before surgical excision of the tumour which was then stained using routine Haematoxylin and Eosin techniques. Standardised guidelines were used to evaluate TIL in the stroma and the tumour. Results: In TNBC, a significant association between Intratumoural (IT) TIL (p=0.0288) and Intrastromal (IS) TIL (p=0.0250) with pathological complete response (pCR). IS TIL and age at operation (p=0.0494) showed significant values but no correlation was found with IT TIL. In HER2BC, IS TIL revealed a significant association with the tumour response(p=0.0229). A strong association was found between IT TIL and the age of menopause(p=0.0441). In HRBC, no significant associations were found between IT and IS TIL scores and the clinicopathological features. Conclusion: The predictive factors of TIL and complete response post-neoadjuvant chemotherapy can be a strong indicative factor for immunohistochemical markers. It also helps throw light on further studies which can be carried out to determine the clinicopathological features and TIL correlation in the various subtypes of breast carcinoma.
Categorification of Gromov-Hausdorff Distance and Interleaving of Functors

One of the central notions to emerge from the study of persistent homology is that of interleaving distance. Here we present a general study of this topic. We define interleaving of categories and of functors with common codomain. In order to define interleaving distance in this setting we are led to categorical generalizations of Hausdorff distance, Gromov-Hausdorff distance, and the space of metric spaces. We obtain comparisons with previous notions of interleaving via the study of future equivalences. As an application we recover a definition of shift equivalences of discrete dynamical systems.
RAD51 as a biomarker for homologous recombination deficiency in high‐grade serous ovarian carcinoma: robustness and interobserver variability of the RAD51 test

The RAD51 test is emerging as a promising biomarker for the assessment of functional homologous recombination deficiency (HRD). Yet, the robustness and reproducibility of the immunofluorescence‐based RAD51 test, in different academic laboratories, have not been systematically investigated. Therefore, we tested the performance of the RAD51 assay in formalin‐fixed paraffin‐embedded (FFPE) high‐grade serous ovarian carcinoma (HGSOC) samples in four European laboratories. Here, we confirm that subtle differences in staining procedures result in low variability of RAD51 and γH2AX scores. However, substantial variability in RAD51 scoring was observed in some samples, likely due to complicating technical and biological features, such as high RAD51 signal‐to‐noise ratio and RAD51 heterogeneity. These results support the need to identify and perform additional quality control steps and/or automating image analysis. Altogether, resolving technical issues should be a priority, as identifying tumours with functional HRD is urgently needed to guide the individual treatment of HGSOC patients. Follow‐up studies are needed to define the key tissue quality requirements to assess HRD by RAD51 in FFPE tumour samples, as this test could help in guiding the individual treatment of HGSOC patients.
A Versatile Adaptive Dose-Finding Design Based on Multiple Endpoints

ABSTRACT In drug development, assessment of the dose–response relationship gives essential insight into which doses are efficacious, yet safe. These relationships are often estimated by parametric, nonlinear models. A hurdle for trials that aim to estimate these models, is that the optimal study design depends on the unknown model parameters. A solution is to use adaptive designs. Ideally, such procedures evaluate a safety and an efficacy endpoint to get the best understanding of the therapeutic window. Many such designs have already been proposed. However, the outcomes are typically required to be of a specific type and the correlation between them has to be modeled explicitly. We propose a more general and simpler approach. Separate models can be specified for each endpoint, without restrictions on the type of model or outcome. The dependence between the outcomes is considered, without having to specify its structure. A new penalty function is introduced to balance the need for optimal precision and safe dose assignments. The method is illustrated by an example study in depression. Simulation results indicate that the adaptive design is more efficient than a fixed design. Use of the penalty function decreases estimation efficiency, but increases dose assignment to favorable doses. Supplementary materials for this article are available online.
Vitamin E supplementation in the treatment on nonalcoholic fatty liver disease (NAFLD): Evidence from an umbrella review of meta‐analysis on randomized controlled trials

We conducted this umbrella review of meta‐analysis on randomized controlled trials to clarify the effects of vitamin E administration on alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma‐glutamyl transferase (GGT), degrees of steatosis and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD).
The transcription factor SPL13 mediates strigolactone suppression of shoot branching by inhibiting cytokinin synthesis in Solanum lycopersicum

Abstract Plant architecture imposes a large impact on crop yield. IDEAL PLANT ARCHITECTURE 1 (IPA1), which encodes a SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factor, is a target of molecular design for improving grain yield. However, the roles of SPL transcription factors in regulating tomato (Solanum lycopersicum) plant architecture are unclear. Here, we show that the expression of SPL13 is down-regulated in the lateral buds of strigolactone (SL)-deficient ccd mutants and is induced by GR24 (a synthetic analog of SL). Knockout of SPL13 by CRISPR/Cas9 resulted in higher levels of cytokinins (CKs) and transcripts of the CK synthesis gene ISOPENTENYL TRANSFERASES 1 (IPT1) in the stem nodes, and more growth of lateral buds. GR24 suppresses CK synthesis and lateral bud growth in ccd mutants, but is not effective in spl13 mutants. On the other hand, silencing of the IPT1 gene inhibited bud growth of spl13 mutants. Interestingly, SL levels in root extracts and exudates are significantly increased in spl13 mutants. Molecular studies indicated that SPL13 directly represses the transcription of IPT1 and the SL synthesis genes CAROTENOID CLEAVAGE DIOXYGENASE 7 (CCD7) and MORE AXILLARY GROWTH 1 (MAX1). The results demonstrate that SPL13 acts downstream of SL to suppress lateral bud growth by inhibiting CK synthesis in tomato. Tuning the expression of SPL13 is a potential approach for decreasing the number of lateral shoots in tomato.
Network pharmacology and molecular docking analyses of the potential target proteins and molecular mechanisms underlying the anti-arrhythmic effects of Sophora Flavescens

The objective was to investigate the potential cardiac arrhythmia-related target proteins and molecular mechanisms underlying the anti-arrhythmic effects of Sophora flavescens using network pharmacology and molecular docking. The bioactive ingredients and related target proteins of S flavescens obtained from the Traditional Chinese medicine systems pharmacology data platform, and gene names for target proteins were obtained from the UniProt database. Arrhythmia-related genes were identified by screening GeneCards and Online Mendelian inheritance in man databases. A Venn diagram was used to identify the key arrhythmia-related genes that are potentially targeted by the bioactive ingredients of S flavescens. Furthermore, CytoScape 3.7. 2 software was used to construct an “ingredient-target” network diagram and the “drug-ingredient-target-disease” network diagram. We performed gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis in the Metascape database and performed the docking analysis using CB-Dock software. We identified 45 main bioactive ingredients, from S flavescens and 66 arrhythmia-related target proteins. Gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment analysis showed that these targets were related to the chemical carcinogenesis-receptor activation signaling pathway, lipid and atherosclerosis signaling pathway, and fluid shear stress and atherosclerosis signaling pathway. Molecular docking showed that the target protein had good binding power with the main active components of the compound of S flavescens. Our study demonstrated the synergistic effects of multiple bioactive components of S flavescens on multiple arrhythmia-related target proteins and identified potential therapeutic mechanisms underlying the anti-arrhythmic effects of S flavescens, providing new clinical ideas for arrhythmia treatment.
Hepatic steatosis and nonalcoholic fatty liver disease are common and associated with cardiometabolic risk in a primary prevention cohort of people with HIV

Background: Hepatic steatosis, including nonalcoholic fatty liver disease (NAFLD), is common among people with HIV (PWH). We present baseline steatosis prevalence and cardiometabolic characteristics among REPRIEVE substudy participants. Methods: REPRIEVE is an international, primary cardiovascular disease prevention, randomized, controlled trial of pitavastatin calcium vs. placebo among 7769 PWH ages 40–75 years on antiretroviral therapy (ART) and with low-to-moderate cardiovascular risk. A subset of participants underwent noncontrast computed tomography, with hepatic steatosis defined as mean hepatic attenuation less than 40 HU or liver/spleen ratio less than 1.0, and NAFLD defined as steatosis in the absence of frequent alcohol use or viral hepatitis. Results: Of 687 evaluable persons, median age was 51 years, BMI 27 kg/m2, CD4+ T-cell count 607 cells/μl; 17% natal female sex, 36% Black, 24% Hispanic, and 98% HIV-1 RNA less than 400 copies/ml. Hepatic steatosis prevalence was 22% (149/687), and NAFLD 21% (96/466). Steatosis/NAFLD prevalence was higher in men and with older age, non-Black race, and higher BMI and waist circumference. Both were associated with BMI greater than 30 kg/m2, metabolic syndrome components, higher atherosclerotic cardiovascular disease (ASCVD) risk score, HOMA-IR, LpPLA-2 and hs-CRP, and lower high-density lipoprotein cholesterol. Of HIV-specific/ART-specific characteristics, only history of an AIDS-defining illness was more common among persons with steatosis/NAFLD. After adjusting for age, sex and race/ethnicity, BMI greater than 30 kg/m2, HOMA-IR greater than 2.0, Metabolic syndrome and each of its components were associated with NAFLD prevalence. Conclusion: In this cohort with controlled HIV and low-to-moderate cardiovascular risk, hepatic steatosis and NAFLD were common and associated with clinically relevant metabolic and inflammatory disturbances but not current HIV-related or ART-related factors.
Phase Property of Envelope-Tracking EEG Response Is Preserved in Patients with Disorders of Consciousness

Abstract When listening to speech, the low-frequency cortical response below 10 Hz can track the speech envelope. Previous studies have demonstrated that the phase lag between speech envelope and cortical response can reflect the mechanism by which the envelope-tracking response is generated. Here, we analyze whether the mechanism to generate the envelope-tracking response is modulated by the level of consciousness, by studying how the stimulus-response phase lag is modulated by the disorder of consciousness (DoC). It is observed that DoC patients in general show less reliable neural tracking of speech. Nevertheless, the stimulus-response phase lag changes linearly with frequency between 3.5 and 8 Hz, for DoC patients who show reliable cortical tracking to speech, regardless of the consciousness state. The mean phase lag is also consistent across these DoC patients. These results suggest that the envelope-tracking response to speech can be generated by an automatic process that is barely modulated by the consciousness state.