Miracle-dz/UniFAR-FTUs huggingface dataset:
Detecting aberrant DNA methylation in Illumina DNA methylation arrays: a toolbox and recommendations for its use

ABSTRACT In this study, our goal was to determine probe-specific thresholds for identifying aberrant, or outlying, DNA methylation and to provide guidance on the relative merits of using continuous or outlier methylation data. To construct a reference database, we downloaded Illumina Human 450K array data for more than 2,000 normal samples, characterized the distribution of DNA methylation and derived probe-specific thresholds for identifying aberrations. We made the decision to restrict our reference database to solid normal tissue and morphologically normal tissue found adjacent to solid tumours, excluding blood which has very distinctive patterns of DNA methylation. Next, we explored the utility of our outlier thresholds in several analyses that are commonly performed on DNA methylation data. Outliers are as effective as the full continuous dataset for simple tasks, like distinguishing tumour tissue from normal, but becomes less useful as the complexity of the problem increases. We developed an R package called OutlierMeth containing our thresholds, as well as functions for applying them to data.
Prognostic Effect of Liver Resection in Extended Cholecystectomy for T2 Gallbladder Cancer Revisited

Objective: This study aimed to evaluate the effect of liver resection on the prognosis of T2 gallbladder cancer (GBC). Background: Although extended cholecystectomy [lymph node dissection (LND) + liver resection] is recommended for T2 GBC, recent studies have shown that liver resection does not improve survival outcomes relative to LND alone. Methods: Patients with pT2 GBC who underwent extended cholecystectomy as an initial procedure and did not reoperation after cholecystectomy at 3 tertiary referral hospitals between January 2010 and December 2020 were analyzed. Extended cholecystectomy was defined as either LND with liver resection (LND+L group) or LND only (LND group). We conducted 2:1 propensity score matching to compare the survival outcomes of the groups. Results: Of the 197 patients enrolled, 100 patients from the LND+L group and 50 from the LND group were successfully matched. The LND+L group experienced greater estimated blood loss (P<0.001) and a longer postoperative hospital stay (P=0.047). There was no significant difference in the 5-year disease-free survival (DFS) of the 2 groups (82.7% vs 77.9%, respectively, P=0.376). A subgroup analysis showed that the 5-year DFS was similar in the 2 groups in both T substages (T2a: 77.8% vs 81.8%, respectively, P=0.988; T2b: 88.1% vs 71.5%, respectively, P=0.196). In a multivariable analysis, lymph node metastasis [hazard ratio (HR) 4.80, P=0.006] and perineural invasion (HR 2.61, P=0.047) were independent risk factors for DFS; liver resection was not a prognostic factor (HR 0.68, P=0.381). Conclusions: Extended cholecystectomy including LND without liver resection may be a reasonable treatment option for selected T2 GBC patients.
Immunosuppression in HIV-positive kidney transplant recipients

Purpose of study The purpose of this review is to provide the current state of immunosuppression therapy in kidney transplant recipients (KTR) with HIV and to discuss practical dilemmas to better understand and manage these patients. Recent findings Certain studies find higher rates of rejection, which raises the need to critically assess the approach to immunosuppression management in HIV-positive KTR. Induction immunosuppression is guided by transplant center-level preference rather than by the individual patient characteristics. Earlier recommendations expressed concerns about the use of induction immunosuppression, especially utilizing lymphocyte-depleting agents; however, updated guidelines based on newer data recommend that induction can be used in HIV-positive KTR, and the choice of agent be made according to immunological risk. Likewise, most studies point out success with using first-line maintenance immunosuppression including tacrolimus, mycophenolate, and steroids. In selected patients, belatacept appears to be a promising alternative to calcineurin inhibitors with some well established advantages. Early discontinuation of steroids in this population carries a high risk of rejection and should be avoided. Summary Immunosuppression management in HIV-positive KTR is complex and challenging, mainly because of the difficulty of maintaining a proper balance between rejection and infection. Interpretation and understanding of the current data towards a personalized approach of immunosuppression could improve management in HIV-positive KTR.
Differential diagnosis of lymphocytosis in routine laboratory practice: Contribution of lymphocyte parameters using the Sysmex‐XN9000 haematology analyzer

This study investigates the potential contribution of structural and dispersion parameters, as well as alarms provided by Sysmex XN9000 haematology analyzer. The objective was to assess the need for a microscopic examination in the context of lymphocytosis. It also aims to contribute in differentiating rapidly lymphoproliferative disorders such as chronic lymphocytic leukaemia (CLL), non‐chronic lymphocytic leukaemia (NON‐CLL) and non‐infectious reactive lymphocytosis (REAC).
Validity and reliability of an Emotional Thermometer tool: an exploratory cross-sectional study

Introduction There are a few screening tools to detect psychological symptoms among people with multiple chronic conditions (MCCs) in China. Aim The aim of this study was to examine the validity and reliability of a translated version of the Emotional Thermometer (ET) tool. Materials and methods This cross-sectional study consisted of two phases: (1) translation and content validity testing; and (2) assessment of psychometric properties, including internal consistency, test-retest reliability, and construct validity. For the first phase, the authors used a forward-backward translation approach for the Chinese version of the instrument and tested its content validity with a panel of six experts. For the second phase, the data, including the ET tool and demographic characteristics were collected in a convenience sample of 197 Chinese people with MCCs recruited from a university hospital. The first 50 participants participated in the two-week retest. Results The Chinese version of the ET tool had satisfactory psychometric properties; content validity index (0.83), internal consistency (0.92), and ICC (0.93 to 0.98 [p < 0.01]). Principal component analysis showed that there was only one component with an eigenvalue greater than 1 (value = 3.80), with 76.67% of the variance responding. All items loaded significantly onto this factor and demonstrated strong loadings of > 0.70. Conclusion The Chinese-version of the ET tool is psychometrically sound. It has the potential to be used as a screening tool for psychological symptoms in Chinese people with MCCs. Impact statement Findings from testing the Chinese translation of the Emotional Thermometer indicate this could be a convenient and useful screening tool to detect psychological symptoms in patients with multiple chronic conditions.
Method for selecting the parameters of support vector machines

A minmax method for selecting the parameters of SVM is presented. According to the geometric meanings of the parameters and its influences to generalization performance, and the relations between the number of support vectors and leave-one-out method, the method uses the ration of support vectors to training samples is applied to estimate the generalization performance, and updates the kennel parameter (s) and penalty factor respectively. Its feasibility and efficiency are proved theoretically and experimentally.
Human oral lectin ZG16B acts as a cell wall polysaccharide probe to decode host–microbe interactions with oral commensals

Significance There is an unmet need for strategies that uncover the roles of human lectins in modulating host–microbe interactions in complex physiological environments such as the mouth. We have developed a microbial glycan analysis probe (mGAP) from a predominant oral cavity lectin zymogen granule protein 16B (ZG16B) and applied the probe to interrogate the interactions of ZG16B. ZG16B binds to commensal bacteria including Streptococcus vestibularis through cell surface glycoconjugates and regulates its growth. ZG16B also recruits the salivary mucin MUC7 and induces the aggregation of S. vestibularis. Our findings suggest that ZG16B assists in maintaining homeostasis in the oral microbiome by capturing selective commensal bacteria and preventing overgrowth by a mucin-assisted clearance mechanism.
Semi-Technical Cryogenic Molecular Sieve Bed for the Tritium Extraction System of the Test Blanket Module for ITER

The tritium extraction from the ITER Helium Cooled Pebble Bed (HCPB) Test Blanket Module purge gas is proposed to be performed in a two steps process: trapping water in a cryogenic Cold Trap, and adsorption of hydrogen isotopes (H2, HT, T2) as well as impurities (N2, O2) in a Cryogenic Molecular Sieve Bed (CMSB) at 77K. A CMSB in a semi-technical scale (one-sixth of the flow rate of the ITER-HCPB) was design and constructed at the Forschungszentrum Karlsruhe. The full capacity of CMSB filled with 20 kg of MS-5A was calculated based on adsorption isotherm data to be 9.4 mol of H2 at partial pressure 120 Pa. The breakthrough tests at flow rates up to 2 Nm3h-1 of He with 110 Pa of H2 conformed with good agreement the adsorption capacity of the CMSB. The mass-transfer zone was found to be relatively narrow (12.5 % of the MS Bed height) allowing to scale up the CMSB to ITER flow rates.
Comparison of the immunogenicity of nasal‐spray rVSV vector, adenovirus vector, and inactivated COVID‐19‐based vaccines in rodent models

Intranasal (i.n.) vaccines can induce mucosal and systemic immunity against respiratory pathogens. Previously, we demonstrated that the recombinant vesicular stomatitis virus (rVSV)‐based COVID‐19 vaccine rVSV‐SARS‐CoV‐2, with poor immunogenicity via the intramuscular route (i.m.), is more suitable for i.n. administration in mice and nonhuman primates. Here, we found that the rVSV‐SARS‐CoV‐2 Beta variant was more immunogenic than the wild‐type strain and other variants of concern (VOCs) in golden Syrian hamsters. Furthermore, the immune responses elicited by rVSV‐based vaccine candidates via the i.n. route were significantly higher than those of two licensed vaccines: the inactivated vaccine KCONVAC delivered via the i.m. route and the adenovirus‐based Vaxzevria delivered i.n. or i.m. We next assessed the booster efficacy of rVSV following two i.m. doses of KCONVAC. Twenty‐eight days after receiving two i.m. doses of KCONVAC, hamsters were boosted with a third dose of KCONVAC (i.m.), Vaxzevria (i.m. or i.n.), or rVSVs (i.n.). Consistent with other heterologous booster studies, Vaxzevria and rVSV elicited significantly higher humoral immunity than the homogenous KCONVAC. In summary, our results confirmed that two i.n. doses of rVSV‐Beta elicited significantly higher humoral immune responses than commercial inactivated and adeno‐based COVID vaccines in hamsters. As a heterologous booster dose, rVSV‐Beta induced potent, persistent, and broad‐spectrum humoral and mucosal neutralizing responses against all VOCs, highlighting its potential to be developed into a nasal‐spray vaccine.
Agreement between ultrasound protocols for the estimation of body fat percentage: Comparison to a four‐compartment model

The purpose of this study was to examine the agreement between body fat percentage (%Fat) estimates derived from a standardized ultrasound protocol (%FatIASMS), a commonly used skinfold (SKF)‐site‐based ultrasound protocol (%FatJP), and a criterion four‐compartment (4C) model (%Fat4C). For the ultrasound protocols, all measurement sites were marked, measured and analyzed by the same evaluator. Subcutaneous adipose tissue (SAT) thickness was measured manually at the region where the muscle fascia was parallel to the skin and the average value per measurement site was used to calculate body density and subsequently %Fat. A repeated‐measures analysis of variance with a priori planned contrasts was used to compare %Fat values between the 4C criterion and both ultrasound methods. Small nonsignificant mean differences were observed between %FatIASMS (18.82 ± 14.21%Fat, effect size [ES] = 0.25, p = 0.178), %FatJP (18.23 ± 13.32%Fat, ES = 0.32, p = 0.050) and the %Fat4C criterion (21.70 ± 7.57%Fat); however, %FatIASMS did not yield a smaller mean difference than the %FatJP (p = 0.287). Additionally, %FatIASMS (r = 0.90, p < 0.001, standard error of the estimate [SEE] = 3.29%) and %FatJP (r = 0.88, p < 0.001, SEE = 3.60%) were strongly correlated with the 4C criterion, however, %FatIASMS did not yield better agreement than %FatJP (p = 0.257). Despite slightly underestimating %Fat, both ultrasound techniques demonstrated Good—Very Good agreement with the 4C criterion, with comparable mean differences, correlations, and SEE. The International Association of Sciences in Medicine and Sports (IASMS) standardized protocol using manual calculations of SAT was comparable to the SKF‐site‐based ultrasound protocol when compared to the 4C criterion. These results indicate that the IASMS (with manually measured SAT) and SKF‐site‐based ultrasound protocols may be of practical use to clinicians.
Neuropsychological Function in Traumatic Brain Injury and the Influence of Chronic Pain

Cognitive dysfunction, pain, and psychological morbidity all present unique challenges to those living with traumatic brain injury (TBI). In this study we examined (a) the impact of pain across domains of attention, memory, and executive function, and (b) the relationships between pain and depression, anxiety, and post-traumatic stress disorder (PTSD) in persons with chronic TBI. Our sample included 86 participants with a TBI and chronic pain (n = 26), patients with TBI and no chronic pain (n = 23), and a pain-free control group without TBI (n = 37). Participants visited the laboratory and completed a comprehensive battery of neuropsychological tests as part of a structured interview. Multivariate analysis of covariance using education as a covariate, failed to detect a significant group difference for neuropsychological composite scores of attention, memory, and executive function (p = .165). A follow-up analysis using multiple one-way analysis of variance (ANOVA) was conducted for individual measures of executive function. Post-hoc testing indicated that those in both TBI groups preformed significantly worse on measures of semantic fluency when compared to controls (p < 0.001, ηρ2 = .16). Additionally, multiple ANOVAs indicated that those with TBI and pain scored significantly worse across all psychological assessments (p < .001). We also found significant associations between measures of pain and most psychological symptoms. A follow-up stepwise linear regression among those in the TBI pain group indicated that post concussive complaints, pain severity, and neuropathic pain symptoms differentially contributed to symptoms of depression, anxiety, and PTSD. These findings suggest deficits in verbal fluency among those living with chronic TBI, with results also reinforcing the multidimensional nature of pain and its psychological significance in this population.
AN OPTIMAL COMBINATION OF SEVERAL BINARY MARKERS BASED ON NEYMAN- PEARSON LEMMA: WITH AN APPLICATION TO IMMUNOHISTOCHEMICAL MARKERS FOR THE DIAGNOSIS OF CLASSICAL HODGKIN LYMPHOMA

Combining the results of different binary diagnostic markers to reach maximum area under the receiver operating characteristic (ROC) curve is the aim of the present study. To this end, the Neyman-Pearson lemma is utilized to combine the results of several binary diagnostic markers to obtain an optimum decision rule. The applied procedure has two advantages: (1) no distributional assumptions are considered for diagnostic markers, and (2) the derived rules are optimal in the sense that their ROC curves are maximized at each point. As an application, eleven different subsets of six diagnostic markers of classical Hodgkin lymphoma (CD15, CD20, CD30, CD3, Pax-5 and LCA) are applied. Four best subsets are then selected based on the area under the ROC curve (AUC) and their optimal decision rules are derived at 0.05 error rate.
Childhood Sexual Trauma and Subjective Cognitive Decline: An Assessment of Racial/Ethnic and Sexual Orientation Disparities

Prior studies examining the association between childhood sexual abuse (CSA) and subjective cognitive decline (SCD) are limited. The aim of this study was to examine the racial/ethnic and sexual orientation disparities in the association between CSA and SCD. Using data from the 2019 Behavioral Risk Factor Surveillance System Survey, crude and multivariable logistic regression models were used to determine the association between CSA and SCD adjusting for sociodemographic characteristics, diabetes, hypertension, and depression. There were statistically significant differences in CSA status by age, gender, income, education, employment, and health status (depression). Black and Hispanic/Latine respondents had a stronger relationship between CSA and SCD compared to White populations. Also, sexual minority populations had a stronger relationship between CSA and SCD compared to heterosexual populations. Health disparities exist in the association between CSA and SCD. Trauma-informed interventions should be implemented among affected populations.
Dimer-assisted mechanism of (un)saturated fatty acid decarboxylation for alkene production

Significance Drop-in biohydrocarbons have the potential to directly replace fossil-based products due to their chemical and physical similarity, and are fully compatible with the existing petroleum processing, distribution, and components infrastructure. Herein, we report the structure and function of a cytochrome P450, a terminal (poly-unsaturated) olefin-producing decarboxylase, which enables the use of unsaturated fatty acids as feedstocks for alkene production. The enzyme exploits a distinct molecular mechanism for substrate binding and chemoselectivity comparing to the CYP-decarboxylases characterized thus far. The broad spectrum of substrates metabolized, and less-restrictive reaction conditions represent an advance toward the development of biological routes for the production of sustainable hydrocarbons, which is an urgent need for the mitigation of climate change and reduction of the dependence on petrochemicals.
Radiomic and clinical data integration using machine learning predict the efficacy of anti-PD-1 antibodies-based combinational treatment in advanced breast cancer: a multicentered study

Background Immune checkpoint inhibitors (ICIs)-based therapy, is regarded as one of the major breakthroughs in cancer treatment. However, it is challenging to accurately identify patients who may benefit from ICIs. Current biomarkers for predicting the efficacy of ICIs require pathological slides, and their accuracy is limited. Here we aim to develop a radiomics model that could accurately predict response of ICIs for patients with advanced breast cancer (ABC). Methods Pretreatment contrast-enhanced CT (CECT) image and clinicopathological features of 240 patients with ABC who underwent ICIs-based treatment in three academic hospitals from February 2018 to January 2022 were assigned into a training cohort and an independent validation cohort. For radiomic features extraction, CECT images of patients 1 month prior to ICIs-based therapies were first delineated with regions of interest. Data dimension reduction, feature selection and radiomics model construction were carried out with multilayer perceptron. Combined the radiomics signatures with independent clinicopathological characteristics, the model was integrated by multivariable logistic regression analysis. Results Among the 240 patients, 171 from Sun Yat-sen Memorial Hospital and Sun Yat-sen University Cancer Center were evaluated as a training cohort, while other 69 from Sun Yat-sen University Cancer Center and the First Affiliated Hospital of Sun Yat-sen University were the validation cohort. The area under the curve (AUC) of radiomics model was 0.994 (95% CI: 0.988 to 1.000) in the training and 0.920 (95% CI: 0.824 to 1.000) in the validation set, respectively, which were significantly better than the performance of clinical model (0.672 for training and 0.634 for validation set). The integrated clinical-radiomics model showed increased but not statistical different predictive ability in both the training (AUC=0.997, 95% CI: 0.993 to 1.000) and validation set (AUC=0.961, 95% CI: 0.885 to 1.000) compared with the radiomics model. Furthermore, the radiomics model could divide patients under ICIs-therapies into high-risk and low-risk group with significantly different progression-free survival both in training (HR=2.705, 95% CI: 1.888 to 3.876, p<0.001) and validation set (HR=2.625, 95% CI: 1.506 to 4.574, p=0.001), respectively. Subgroup analyses showed that the radiomics model was not influenced by programmed death-ligand 1 status, tumor metastatic burden or molecular subtype. Conclusions This radiomics model provided an innovative and accurate way that could stratify patients with ABC who may benefit more from ICIs-based therapies.
TRI-SCORE: a single-centre validation study

Abstract OBJECTIVES The TRI-SCORE is a recently published risk score for predicting in-hospital mortality in patients undergoing isolated tricuspid valve surgery (ITVS). The aim of this study is to externally validate the ability of the TRI-SCORE in predicting in-hospital and long-term mortality following ITVS. METHODS A retrospective review of our institutional database was carried out to identify all patients undergoing isolated tricuspid valve repair or replacement from March 1997 to March 2021. The TRI-SCORE was calculated for all patients. Discrimination of the TRI-SCORE was assessed using receiver operating characteristic curves. Accuracy of the models was tested calculating the Brier score. Finally, a COX regression was employed to evaluate the relationship between the TRI-SCORE value and long-term mortality. RESULTS A total of 176 patients were identified and the median TRI-SCORE was 3 (1–5). The cut-off value identified for increased risk of isolated ITVS was 5. Regarding in-hospital outcomes, the TRI-SCORE showed high discrimination (area under the curve 0.82), and high accuracy (Brier score 0.054). This score showed also very good performance in predicting long-term mortality (at 10 years, hazard ratio: 1.47, 95% confidence interval [1.31–1.66], P < 0.001), with high discrimination (area under the curve >0.80 at 1–5 and 10 years) and high accuracy values (Brier score 0.179). CONCLUSIONS This external validation confirms the good performance of the TRI-SCORE in predicting in-hospital mortality. Moreover, the score showed also very good performance in predicting the long-term mortality.