Miracle-dz/UniFAR-FTUs huggingface dataset:
Inflated Gamma Interferon Response with QuantiFERON-TB Gold Plus Using the Automated Liaison XL Analyzer: a Testing Algorithm To Mitigate False-Positive Results in Low-Incidence Settings

The Liaison XL chemiluminescence immunoassay (CLIA) analyzer allows total automation of gamma interferon (IFN-γ) measurement for the QuantiFERON-TB Gold Plus assay (QFT-Plus) that is used to diagnose Mycobacterium tuberculosis infection. To evaluate CLIA accuracy, plasma samples from 278 patients undergoing QFT-Plus testing were first tested with an enzyme-linked immunosorbent assay (ELISA; 150 negatives and 128 positives) and subsequently with the CLIA. ABSTRACT The Liaison XL chemiluminescence immunoassay (CLIA) analyzer allows total automation of gamma interferon (IFN-γ) measurement for the QuantiFERON-TB Gold Plus assay (QFT-Plus) that is used to diagnose Mycobacterium tuberculosis infection. To evaluate CLIA accuracy, plasma samples from 278 patients undergoing QFT-Plus testing were first tested with an enzyme-linked immunosorbent assay (ELISA; 150 negatives and 128 positives) and subsequently with the CLIA. Three strategies to mitigate false-positive CLIA results were investigated in 220 samples with borderline-negative ELISA results (TB1 and/or TB2, 0.1 to 0.34 IU/mL). The Bland-Altman plot of difference versus average of the two IFN-γ measurements in the Nil and antigen (TB1 and TB2) tubes showed higher IFN-γ measurements across the range of values with the CLIA than with the ELISA. Bias was 0.21 IU/mL (standard deviation, 0.61; 95% confidence interval [CI], −1.0 to 1.41). Linear regression of difference versus average had a slope of 0.08 (95% CI, 0.05 to 0.10), which was significantly nonzero (P < 0.0001). The CLIA had positive and negative percent agreement levels with the ELISA of 91.7% (121/132) and 95.2% (139/146), respectively. In borderline-negative samples tested with ELISA, CLIA was positive in 42.7% (94/220). CLIA with a standard curve resulted in 36.4% (80/220) positivity. Retesting CLIA false positives (TB1 or TB2 range, 0 to ≤1.3 IU/mL) with ELISA reduced false positives by 84.3% (59/70). Retesting with CLIA reduced the false-positive rate by 10.4% (8/77). Implementing the Liaison CLIA for QFT-Plus in low-incidence settings risks falsely elevating conversion rates and overburdening clinics and overtreating patients. Confirming borderline positives with ELISA is a viable strategy to mitigate false-positive CLIA results.
Diagnostic and therapeutic approaches for elderly asthma patients: the importance of multidisciplinary and multidimensional management

ABSTRACT Introduction Asthma is commonly considered a disease of younger ages; however, it is not infrequent to pose a diagnosis of the disease in older individuals. Although current recommendations do not distinguish between young and old asthmatics in terms of diagnostic and therapeutic approaches, asthma in the elderly may present with peculiar features that contribute to complicate its management. Areas covered The current review focuses on the challenges that arise when approaching an older individual with suspected asthma. Age-associated changes of the lung may complicate the diagnostic approach. Measurement of the forced expiratory volume in the first 6 s (FEV6) in an easier and faster alternative to FVC estimation, and residual volume should always be assessed. Older individuals are often affected by concomitant diseases, both age- and drug-related, that need to be considered when approaching elderly asthmatics, since they can affect the efficacy of the treatment as well as the control of the disease. Expert opinion The potential drug to drug interaction should be routinely investigated, and documented in medical records. The effect of aging on the response to pharmacological therapy in older asthmatics should be explored. Therefore, the need of a multidisciplinary and multidimensional approach to the elderly asthmatics is strongly encouraged.
Staphylococcus aureus bloodstream infection in a Chinese tertiary-care hospital: A single-center retrospective study

Department of Critical Care Medicine, Taizhou Municipal Hospital, Taizhou, Zhejiang 318000, China; Department of Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China; Department of Critical Care Medicine, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, Taizhou, Zhejiang 318050, China; Department of Critical Care Medicine, Anji County People’s Hospital, Huzhou, Zhejiang 313300, China; Department of Neurointensive Care Unit, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China; Department of Critical Care Medicine, The First People’s Hospital of Huzhou, Huzhou, Zhejiang 313000, China; Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
Influência da Gordura do Braço sobre Medida Indireta da Pressão Sanguínea: Uma Abordagem Estatística e de Machine Learning

Resumo Fundamento A mensuração indireta da pressão sanguínea (PS) é sabidamente influenciada por diversos fatores como técnica, observador e equipamento, mas a influência da composição do braço ainda não foi investigada. Objetivo Identificar a influência da gordura do braço sobre a medida indireta da pressão sanguínea, utilizando modelos de inferência estatística e machine learning. Métodos Estudo transversal, com 489 adultos jovens saudáveis de 18 a 29 anos de idade. Foram medidos comprimento (COB), circunferência do braço (CB) e índice de gordura do braço (IGB). A PS foi mensurada em ambos os braços, simultaneamente. Os dados foram processados utilizando-se Python 3.0 e pacotes específicos para análise descritiva, regressão e clusterização. Um nível de significância de 5% foi adotado para todos os cálculos. Resultados A PS e as medidas antropométricas foram diferentes entre os hemicorpos. A pressão sanguínea sistólica (PAS), COB, e IGB foram maiores no braço direito (BD), enquanto CB foi similar em comparação ao braço esquerdo. COB e CB apresentaram correlação positiva com a PAS. Conforme o modelo de regressão, para determinado valor de CB e COB, a leitura da PAS poderá ter uma redução média de 1,80 mmHg no BD, e 1,62 mmHg no braço esquerdo, a cada 10% de aumento na IGB. A clusterização corroborou os resultados da regressão. Conclusão Foi encontrada uma influência significativa do IGB sobre a leitura da PS. A PAS teve correlação positiva com COB e CB, e correlação negativa com IGB, o que sugere a necessidade de mais investigações sobre a relação da PS com as frações de gordura e músculo do braço.
American Society of Hematology 2023 guidelines for management of venous thromboembolism: thrombophilia testing

Background Hereditary and acquired thrombophilia are risk factors for venous thromboembolism (VTE). Whether testing helps guide management decisions is controversial. Objective These evidence-based guidelines from the American Society of Hematology (ASH) intend to support decision making about thrombophilia testing. Methods ASH formed a multidisciplinary guideline panel covering clinical and methodological expertise and minimizing bias from conflicts of interest. The McMaster University GRADE Centre provided logistical support, performed systematic reviews, and created evidence profiles and evidence-to-decision tables. The Grading of Recommendations Assessment, Development, and Evaluation approach (GRADE) was used. Recommendations were subject to public comment. Results The panel agreed on 23 recommendations regarding thrombophilia testing and associated management. Nearly all recommendations are based on very low certainty in the evidence due to modeling assumptions. Conclusions The panel issued a strong recommendation against testing the general population before starting combined oral contraceptives (COCs) and conditional recommendations for thrombophilia testing in the following scenarios: (a) patients with VTE associated with nonsurgical major transient or hormonal risk factors; (b) patients with cerebral or splanchnic venous thrombosis, in settings where anticoagulation would otherwise be discontinued; (c) individuals with a family history of antithrombin, protein C, or protein S deficiency when considering thromboprophylaxis for minor provoking risk factors and for guidance to avoid COCs/hormone replacement therapy; (d) pregnant women with a family history of high-risk thrombophilia types; and (e) patients with cancer at low or intermediate risk of thrombosis and with a family history of VTE. For all other questions, the panel provided conditional recommendations against testing for thrombophilia.
WebQUAST: online evaluation of genome assemblies

Abstract Selecting proper genome assembly is key for downstream analysis in genomics studies. However, the availability of many genome assembly tools and the huge variety of their running parameters challenge this task. The existing online evaluation tools are limited to specific taxa or provide just a one-sided view on the assembly quality. We present WebQUAST, a web server for multifaceted quality assessment and comparison of genome assemblies based on the state-of-the-art QUAST tool. The server is freely available at https://www.ccb. uni-saarland.de/quast/. WebQUAST can handle an unlimited number of genome assemblies and evaluate them against a user-provided or pre-loaded reference genome or in a completely reference-free fashion. We demonstrate key WebQUAST features in three common evaluation scenarios: assembly of an unknown species, a model organism, and a close variant of it.
Near-infrared imaging for automated tsetse pupae sex sorting in support of the sterile insect technique

Tsetse flies are the cyclical vectors of African trypanosomes and one of several methods to manage this vector is the sterile insect technique (SIT). The ability to determine the sex of tsetse pupae with the objective to separate the sexes before adult emergence has been a major goal for decades for tsetse management programmes with an SIT component. Tsetse females develop faster and pharate females inside the pupae melanise 1–2 days before males. This earlier melanisation can be detected by infrared cameras through the pupal shell, and the newly developed Near InfraRed Pupae Sex Sorter (NIRPSS) takes advantage of this. The melanisation process is not homogeneous for all fly organs and the pupa needs to be examined ventrally, dorsally and laterally to ensure accurate classification by an image analysis algorithm. When the pupae are maturing at a constant temperature of 24 °C and sorted at the appropriate age, 24 days post-larviposition for Glossina palpalis gambiensis, the sorting machine can efficiently separate the sexes. The recovered male pupae can then be sterilised for field releases of males, while the rest of the pupae can be used to maintain the laboratory colony. The sorting process with the new NIRPSS had no negative impact on adult emergence and flight ability. A mean male recovery of 62.82 ± 3.61% was enough to provide sterile males to an operational SIT programme, while mean contamination with females (4.69 ± 3.02%) was low enough to have no impact on the maintenance of a laboratory colony.
Antipsychotics and obsessive–compulsive disorder/obsessive–compulsive symptoms: A pharmacovigilance study of the FDA adverse event reporting system

Antipsychotics have conflicting data with respect to obsessive–compulsive disorder/symptoms (OCD/OCS), with some reporting causality and some reporting treatment benefits. This pharmacovigilance study aimed to investigate reporting of OCD/OCS in association with the use of antipsychotics in comparison to one another, as well as treatment failure using data derived from the FDA Adverse Event Reporting System (FAERS).
Changes of placental three-dimensional power Doppler ultrasonography in third trimester among hypertensive disorders complicating pregnancy

Hypertensive disorders complicating pregnancy (HDCP) represent a systemic condition specific to pregnant women. Three-dimensional (3D) power Doppler ultrasonography is a technique that utilizes erythrocyte density, scattered intensity, or energy distribution in the bloodstream for imaging purposes. This study aimed to compare the changes in 3D power Doppler ultrasonography parameters in late pregnancy between patients with HDCP and those without HDCP, and to evaluate the predictive value of these parameters for pregnancy outcomes in patients with HDCP. The study included 160 pregnant women diagnosed with HDCP and 100 pregnant women without HDCP, who served as the control group. 3D power Doppler ultrasonography was performed, and the values of the vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were measured. In the HDCP group, the VI, FI, and VFI were all lower than those observed in patients without HDCP. In HDCP patients with positive outcomes, these three parameters were higher than those recorded in patients with negative outcomes. The area under the predicted curve (AUC) for VI, FI, VFI, and the combination of these three parameters were 0.69, 0.63, 0.66, and 0.75, respectively. The parameters of 3D power Doppler ultrasonography can reflect the perfusion status of the placenta and predict the outcome of pregnancy in patients with HDCP. By monitoring these relevant hemodynamic parameters, valuable information can be provided for the clinical diagnosis, objective evaluation, and treatment of HDCP.
Improved mini-Tn7 Delivery Plasmids for Fluorescent Labeling of Stenotrophomonas maltophilia

The bacterium S. maltophilia is an important opportunistic nosocomial pathogen that can cause bacteremia and pneumonia in immunocompromised patients with a high rate of mortality. It is now considered as a clinically relevant and notorious pathogen in cystic fibrosis patients but has also been isolated from lung specimen of healthy donors. ABSTRACT Fluorescently labeled bacterial cells have become indispensable for many aspects of microbiological research, including studies on biofilm formation as an important virulence factor of various opportunistic bacteria of environmental origin such as Stenotrophomonas maltophilia. Using a Tn7-based genomic integration system, we report the construction of improved mini-Tn7 delivery plasmids for labeling of S. maltophilia with sfGFP, mCherry, tdTomato and mKate2 by expressing their codon-optimized genes from a strong, constitutive promoter and an optimized ribosomal binding site. Transposition of the mini-Tn7 transposons into single neutral sites located on average 25 nucleotides downstream of the 3′-end of the conserved glmS gene of different S. maltophilia wild-type strains did not have any adverse effects on the fitness of their fluorescently labeled derivatives. This was demonstrated by comparative analyses of growth, resistance profiles against 18 antibiotics of different classes, the ability to form biofilms on abiotic and biotic surfaces, also independent of the fluorescent protein expressed, and virulence in Galleria mellonella. It is also shown that the mini-Tn7 elements remained stably integrated in the genome of S. maltophilia over a prolonged period of time in the absence of antibiotic selection pressure. Overall, we provide evidence that the new improved mini-Tn7 delivery plasmids are valuable tools for generating fluorescently labeled S. maltophilia strains that are indistinguishable in their properties from their parental wild-type strains. IMPORTANCE The bacterium S. maltophilia is an important opportunistic nosocomial pathogen that can cause bacteremia and pneumonia in immunocompromised patients with a high rate of mortality. It is now considered as a clinically relevant and notorious pathogen in cystic fibrosis patients but has also been isolated from lung specimen of healthy donors. The high intrinsic resistance to a wide range of antibiotics complicates treatment and most likely contributes to the increasing incidence of S. maltophilia infections worldwide. One important virulence-related trait of S. maltophilia is the ability to form biofilms on any surface, which may result in the development of increased transient phenotypic resistance to antimicrobials. The significance of our work is to provide a mini-Tn7-based labeling system for S. maltophilia to study the mechanisms of biofilm formation or host-pathogen interactions with live bacteria under non-destructive conditions.
Metabolic Adaptation to Tyrosine Kinase Inhibition in Leukemia Stem Cells.

Tyrosine kinase inhibitors (TKI) are very effective in treating chronic myelogenous leukemia (CML), but primitive, quiescent leukemia stem cells persist as a barrier to cure. We performed a comprehensive evaluation of metabolic adaptation to TKI treatment and its role in CML hematopoietic stem and progenitor cell persistence. Using a CML mouse model, we found that glycolysis, glutaminolysis, TCA cycle and oxidative phosphorylation (OXPHOS) were initially inhibited by TKI treatment in CML committed progenitors but were restored with continued treatment, reflecting both selection and metabolic reprogramming of specific subpopulations. TKI treatment selectively enriched primitive CML stem cells with reduced metabolic gene expression. Persistent CML stem cells also showed metabolic adaptation to TKI treatment through altered substrate utilization and maintenance of mitochondrial respiration. Evaluation of transcription factors underlying these changes identified increased HIF-1 protein levels and activity in TKI-treated stem cells. Treatment with a HIF-1 inhibitor depleted murine and human CML stem cells in combination with TKI treatment. HIF-1 inhibition increased mitochondrial activity and ROS levels, and reduced quiescence, increased cycling, and reduced self-renewal and regenerating potential of dormant CML stem cells. We therefore identify HIF-1-mediated inhibition of OXPHOS and ROS and maintenance of CML stem cell dormancy and repopulating potential as a key mechanism of CML stem cell adaptation to TKI treatment. Our results identify a key metabolic dependency in CML stem cells persisting after TKI treatment that can be targeted to enhance their elimination.
THE PLANT GROWTH CORRECTION FACTOR. I. THE HYPOTHETICAL AND PHILOSOPHICAL BASIS

There are two possible reasons why regeneration ability in plant tissue culture (PTC) differs from study to study. In life, not all beings are born equal. In PTC, too, not all explants have the same regeneration capacity. A plethora of factors influence the organogenic outcome of an explant in PTC, but differences in production, yield and organogenic output are all measured by one factor, and one factor alone: the size of the explant. In this ground-breaking paper, we put forward a radical notion that would attempt to allow for the direct comparison of organogenic potential of PTCs of the same cultivar or species conducted in different studies or laboratories. The prototype concept, the growth correction factor or GCF, has been tested on a model species, apple (Malus sp.). _____________________________________________________________________________________________________________
Delivery of PEGylated liposomal doxorubicin by bispecific antibodies improves treatment in models of high-risk childhood leukemia

High-risk childhood leukemia has a poor prognosis because of treatment failure and toxic side effects of therapy. Drug encapsulation into liposomal nanocarriers has shown clinical success at improving biodistribution and tolerability of chemotherapy. However, enhancements in drug efficacy have been limited because of a lack of selectivity of the liposomal formulations for the cancer cells. Here, we report on the generation of bispecific antibodies (BsAbs) with dual binding to a leukemic cell receptor, such as CD19, CD20, CD22, or CD38, and methoxy polyethylene glycol (PEG) for the targeted delivery of PEGylated liposomal drugs to leukemia cells. This liposome targeting system follows a “mix-and-match” principle where BsAbs were selected on the specific receptors expressed on leukemia cells. BsAbs improved the targeting and cytotoxic activity of a clinically approved and low-toxic PEGylated liposomal formulation of doxorubicin (Caelyx) toward leukemia cell lines and patient-derived samples that are immunophenotypically heterogeneous and representative of high-risk subtypes of childhood leukemia. BsAb-assisted improvements in leukemia cell targeting and cytotoxic potency of Caelyx correlated with receptor expression and were minimally detrimental in vitro and in vivo toward expansion and functionality of normal peripheral blood mononuclear cells and hematopoietic progenitors. Targeted delivery of Caelyx using BsAbs further enhanced leukemia suppression while reducing drug accumulation in the heart and kidneys and extended overall survival in patient-derived xenograft models of high-risk childhood leukemia. Our methodology using BsAbs therefore represents an attractive targeting platform to potentiate the therapeutic efficacy and safety of liposomal drugs for improved treatment of high-risk leukemia. Description Targeting PEGylated liposomal doxorubicin delivery with bispecific antibodies improves treatment in models of high-risk childhood leukemia. Targeting leukemia treatment Caelyx, a PEGylated liposomal formulation of doxorubicin, has shown promise as a therapy for cancer. However, efficacy has been limited because of issues of tolerability and specificity of delivery to tumor cells. To address this, Moles et al. generated bispecific antibodies (BsAbs) that bound to PEG on the Caelyx product and to the leukemic cell markers CD19, CD20, CD22, or CD38. Targeted delivery of Caelyx with the BsAbs improved activity of Caelyx against leukemia cells with minimal evidence of toxicity toward normal immune cells. Beyond the direct implications for treating childhood leukemia, the results of this study suggest that BsAb-mediated targeting may overcome similar delivery barriers for other drugs. —CM
Hemorrhoids as a risk factor for colorectal adenomas on colonoscopy

Abstract Background and study aims Colorectal premalignant polyps and hemorrhoids are important findings in colonoscopy; however, the association between them is unclear. Therefore, we investigated the association between the presence and severity of hemorrhoids and the detection of precancerous colorectal polyps on colonoscopy. Patients and methods This retrospective, single-center, cross-sectional study enrolled patients who underwent colonoscopy at Toyoshima Endoscopy Clinic between May 2017 and October 2020. The association between hemorrhoids and other outcomes (patient age, sex, withdrawal time for colonoscopy, expert endoscopist, number of adenomas per colonoscopy, detection rates of adenoma, advanced neoplasia, clinically significant serrated polyp, and sessile serrated lesion) was assessed using a binomial logistic regression model. Results A total of 12,408 patients were enrolled in this study. Hemorrhoids were identified in 1,863 patients. Univariable analysis showed that patients with hemorrhoids were older (61.0 vs. 52.5 years, P < 0.001), had a higher number of adenomas per colonoscopy (1.16 vs. 0.756, P < 0.001) than those without hemorrhoids. Multivariable analyses also demonstrated that hemorrhoids were associated with a higher number of adenomas per colonoscopy (odds ratio [OR]: 1.061; P = 0.002), regardless of patient age, sex, and expert endoscopist. Among patients with hemorrhoids, severe hemorrhoids with a mucosal elevation ≥ 10 mm were associated with a higher number of adenomas per colonoscopy than mild hemorrhoids (OR: 1.112, P = 0.044), regardless of patient age, sex, and expert endoscopist. Conclusions Hemorrhoids, especially severe ones, are associated with a high number of adenomas. Complete colonoscopy should be performed in patients with hemorrhoids.