Miracle-dz/UniFAR-FTUs huggingface dataset:
Intensity of Macrophage Infiltration in Glomeruli Predicts Response to Immunosuppressive Therapy in Patients with IgA Nephropathy

Visual Abstract Significance Statement The lack of a tool for predicting the response to immunosuppressive therapy in IgA nephropathy (IgAN) limits patient-specific risk stratification and early treatment decisions. To derive and validate the models for predicting response to immunosuppressive therapy in IgAN that can be applied at the time of kidney biopsy, the authors conducted a prospective cohort study of 621 Chinese patients with IgAN. Patients had persistent proteinuria of ≥1 g/d, despite 3 months of optimized supportive care with renin-angiotensin system inhibitors, and received immunosuppressive therapy. The authors used immunohistochemistry to identify cellular infiltrates in biopsy specimens and digital image analysis to quantify them. The intensity of glomerular macrophage infiltration, alone or combined with clinical and histologic data, accurately predicted the response to immunosuppression and, thus, may help physicians identify patients with IgAN who will benefit from immunosuppression. Background The lack of a tool for predicting the response to immunosuppressive therapy in IgA nephropathy (IgAN) limits patient-specific risk stratification and early treatment decision making. Models for predicting response to immunosuppression in IgAN that can be applied at the time of kidney biopsy are needed. Methods This prospective cohort study involved 621 Chinese patients with IgAN who were at high risk for disease progression and had persistent proteinuria ≥1 g/d, despite 3 months of optimized supportive care with renin-angiotensin system inhibitors. Participants received immunosuppressive therapy for a median of 18 months. We used immunochemistry to identify macrophage and lymphocyte infiltrates in biopsy specimens and digital image analysis to quantify them. The outcome was response to immunosuppression, defined as complete or partial remission within 12 months of immunosuppression. Results Kidney infiltration of CD68+ and CD206+ macrophages increased in patients with IgAN. Having higher levels of glomerular CD206+ macrophage infiltration was associated with a 40-fold increased probability of response to immunosuppression in adjusted analysis compared with having lower levels. Patients with a higher intensity of glomerular CD68+ infiltrates had a 13-fold increase in probability of responding to immunosuppression. Intensity of glomerular CD206+ and CD68+ macrophage infiltration predicted the response to immunosuppression (area under the curve [AUC], 0.84; 95% CI, 0.81 to 0.88). The AUC increased to 0.87 (95% CI, 0.84 to 0.91) in a model combining the infiltration score of CD206+ and CD68+ infiltrates with the MEST-C score and clinical data at biopsy. Conclusions Intensity of glomerular macrophage infiltration predicted response to immunosuppressive therapy in patients with IgAN who were at high risk of progression, and may help physicians identify patients who will benefit from such treatment.
Investigation of an injectable gold nanoparticle extracellular matrix

Post-traumatic osteoarthritis (PTOA) is a progressive articular degenerative disease that degrades articular cartilage and stimulates apoptosis in chondrocyte cells. An injectable decellularized, extracellular matrix (ECM) scaffold, that might be able to combat the effects of PTOA, was developed where the ECM was conjugated with 20 nm gold nanoparticles (AuNP) and supplemented with curcumin and hyaluronic acid (HA). Porcine diaphragm ECM was decellularized and homogenized; AuNPs were conjugated using chemical crosslinking followed by mixing with curcumin and/or HA. Injection force testing and scanning electron microscopy with energy-dispersive X-ray spectroscopy were utilized to characterize the ECM scaffolds. In vitro testing with L929 murine fibroblasts, equine synovial fibroblasts, and Human Chondrocytes were used to determine biocompatibility, reactive oxygen species (ROS) reduction, and chondroprotective ability. The results demonstrated that conjugation of 20 nm AuNPs to the ECM was successful without significantly altering the physical properties as noted in the low injection force. In vitro work provided evidence of biocompatibility with a propensity to reduce intracellular ROS and an ability to mitigate apoptosis of chondrocyte cells stimulated with IL-1β, a known apoptosis inducing cytokine. It was concluded that an injectable AuNP-ECM may have the ability to mitigate inflammation and apoptosis.
Malian Thick Porridges (tô) of Pearl Millet Are Made Thinner in Urban Than Rural Areas and Decrease Satiety

Background: Changes in preparation, preference, and consumption of traditional staple foods between rural and urban areas in sub-Saharan Africa may be associated with the nutrition transition. Objective: Millet porridge thickness and postprandial hunger were investigated in Mali with the aim of understanding consumer preference and satiety properties. Methods: Rural and urban residents from 3 regions (N = 60) were surveyed regarding their porridge consumption frequency and thickness preference. Influence of millet porridge thickness on satiety was investigated. Ten participants consumed 4 porridges of different thicknesses (3 of millet and 1 thin porridge of rice) and rated their subjective hunger on 4 different days. Results: Thicker porridges were consumed more frequently in rural areas than in urban (P < .05). For the satiety study, thicker porridges induced higher satiety than thinner ones at 2 and 4 hours postconsumption (P < .05; Visual Analog Scale rating). A greater amount of flour, but not volume, was consumed for the thicker porridges (P < .05). Conclusions: Urban participants preferred and consumed porridges that are less satiating, potentially contributing to higher food consumption related to the nutrition transition in Africa.
Land use and land cover change and its impacts on dengue dynamics in China: A systematic review

Background Dengue is a prioritized public health concern in China. Because of the larger scale, more frequent and wider spatial distribution, the challenge for dengue prevention and control has increased in recent years. While land use and land cover (LULC) change was suggested to be associated with dengue, relevant research has been quite limited. The “Open Door” policy introduced in 1978 led to significant LULC change in China. This systematic review is the first to review the studies on the impacts of LULC change on dengue dynamics in China. This review aims at identifying the research evidence, research gaps and provide insights for future research. Methods A systematic literature review was conducted following the PRISMA protocol. The combinations of search terms on LULC, dengue and its vectors were searched in the databases PubMed, Web of Science, and Baidu Scholar. Research conducted on China published from 1978 to December 2019 and written in English or Chinese was selected for further screening. References listed in articles meeting the inclusion criteria were also reviewed and included if again inclusion criteria were met to minimize the probability of missing relevant research. Results 28 studies published between 1978 and 2017 were included for the full review. Guangdong Province and southern Taiwan were the major regional foci in the literature. The majority of the reviewed studies observed associations between LULC change factors and dengue incidence and distribution. Conflictive evidence was shown in the studies about the impacts of green space and blue space on dengue in China. Transportation infrastructure and urbanization were repeatedly suggested to be positively associated with dengue incidence and spread. The majority of the studies reviewed considered meteorological and sociodemographic factors when they analyzed the effects of LULC change on dengue. Primary and secondary remote sensing (RS) data were the primary source for LULC variables. In 21 of 28 studies, a geographic information system (GIS) was used to process data of environmental variables and dengue cases and to perform spatial analysis of dengue. Conclusions The effects of LULC change on the dynamics of dengue in China varied in different periods and regions. The application of RS and GIS enriches the means and dimensions to explore the relations between LULC change and dengue. Further comprehensive regional research is necessary to assess the influence of LULC change on local dengue transmission to provide practical advice for dengue prevention and control.
Bayesian consensus clustering for multivariate longitudinal data

In clinical and epidemiological studies, there is a growing interest in studying the heterogeneity among patients based on longitudinal characteristics to identify subtypes of the study population. Compared to clustering a single longitudinal marker, simultaneously clustering multiple longitudinal markers allow additional information to be incorporated into the clustering process, which reveals co‐existing longitudinal patterns and generates deeper biological insight. In the current study, we propose a Bayesian consensus clustering (BCC) model for multivariate longitudinal data. Instead of arriving at a single overall clustering, the proposed model allows each marker to follow marker‐specific local clustering and these local clusterings are aggregated to find a global (consensus) clustering. To estimate the posterior distribution of model parameters, a Gibbs sampling algorithm is proposed. We apply our proposed model to the primary biliary cirrhosis study to identify patient subtypes that may be associated with their prognosis. We also perform simulation studies to compare the clustering performance between the proposed model and existing models under several scenarios. The results demonstrate that the proposed BCC model serves as a useful tool for clustering multivariate longitudinal data.
Effectiveness and safety of pyrotinib‐based therapy in patients with HER2‐positive metastatic breast cancer: A real‐world retrospective study

The previous studies had demonstrated the promising effectiveness and acceptable safety of pyrotinib in patients with HER2‐positive metastatic breast cancer. We aimed to investigate the real‐world data of pyrotinib in complex clinical practice and complement the findings of clinical trials. Two hundred and eighteen patients were included for effectiveness analysis. A total of 62.0% had received two or more lines of systematic therapy, and 95.4% had been exposed to prior anti‐HER2 therapy, with 95.4% receiving trastuzumab, 5.0% receiving pertuzumab, and 40.8% receiving lapatinib. The median progression‐free survival (PFS) was 9.3 months and the objective response rate (ORR) was 44.0%. Patients treated with pyrotinib‐based therapy as first, second, or later line had a median PFS of 15.0, 10.3, and 6.8 months, respectively. Patients treated with pyrotinib and trastuzumab received significant benefit in terms of median PFS compared with pyrotinib alone (10.7 (9.1–12.3) vs. 8.8 (8.1–9.5), p = 0.016). Patients pretreated with lapatinib had a median PFS of 6.9 months. The median PFS time was 7.0 months in patients with brain metastasis. Multivariate Cox regression analyses showed that lines of pyrotinib‐based therapy (1 vs. 2 vs. ≥3), prior treatment with lapatinib, and combination treatments with trastuzumab proved to be independent predictors of PFS. Two hundred and forty‐eight patients were included in the safety analysis, and the results showed that the toxicity of pyrotinib was tolerable, with the most common grade 3/4 adverse event being diarrhea (19.8%). Pyrotinib‐based therapy demonstrated promising efficacy and tolerable toxicity in first‐, second‐, and later‐line treatments and in lapatinib‐treated patients. The combination of pyrotinib and trastuzumab showed advantages in PFS, even for patients resisting trastuzumab. Pyrotinib‐based therapy could be the preferred choice for brain metastasis patients, especially when combined with brain radiotherapy.
Acceptance of SARS-CoV-2 vaccines by liver transplant recipients and candidates

Abstract Guidelines recommend vaccination against SARS-CoV-2 in transplant recipients, candidates, and their household contacts. However, little is known about the acceptance of COVID-19 vaccines in these groups. In March 2021, we surveyed 826 liver transplant recipients, candidates, and their household contacts to determine acceptance rates and factors influencing the acceptance of the COVID-19 vaccine; 341 patients (40%) and 237 household contacts (28%) returned the questionnaire. Ninety percent of patients returning the survey reported they were willing to receive the vaccine within the next 6 months or had already started vaccination. Only 2% of patients and 4% of household contacts reported refusing the vaccine, and 8% of patients and 9% of household contacts wanted to postpone vaccination because of concerns about side effects. Having received the influenza vaccine in the last 2 seasons was the strongest indicator of acceptance to receive the SARS-CoV-2 vaccine within 6 months (odds ratio 5.11; 95% confidence interval 2.43–10.74; p < 0.001). Thirty-two percent of responding patients reported fear of side effects as a reason for having refused vaccination before. Although the acceptance of the SARS-CoV-2 vaccine was particularly high among German liver transplant recipients, candidates, and household contacts in this survey, transplant physicians are encouraged to discuss safety concerns with patients who have refused the seasonal influenza vaccine in the past.
Asthma Phenotypes and COVID-19 Risk: A Population-based Observational Study

Rationale Studies have suggested some patients with asthma are at risk of severe coronavirus disease (COVID-19), but they have had limited data on asthma phenotype and have not considered if risks are specific to COVID-19. Objectives To determine the effect of asthma phenotype on three levels of COVID-19 outcomes. Compare hospitalization rates with influenza and pneumonia. Methods Electronic medical records were used to identify patients with asthma and match them to the general population. Patient-level data were linked to Public Health England severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test data, hospital, and mortality data. Asthma was phenotyped by medication, exacerbation history, and type 2 inflammation. The risk of each outcome, adjusted for major risk factors, was measured using Cox regression. Measurements and Main Results A total of 434,348 patients with asthma and 748,327 matched patients were included. All patients with asthma had a significantly increased risk of a General Practice diagnosis of COVID-19. Asthma with regular inhaled corticosteroid (ICS) use (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.01–1.61), intermittent ICS plus add-on asthma medication use (HR, 2.00; 95% CI, 1.43–2.79), regular ICS plus add-on use (HR, 1.63; 95% CI, 1.37–1.94), or with frequent exacerbations (HR, 1.82; 95% CI, 1.34–2.47) was significantly associated with hospitalization. These phenotypes were significantly associated with influenza and pneumonia hospitalizations. Only patients with regular ICS plus add-on asthma therapy (HR, 1.70; 95% CI, 1.27–2.26) or frequent exacerbations (HR, 1.66; 95% CI, 1.03–2.68) had a significantly higher risk of ICU admission or death. Atopy and blood eosinophil count were not associated with severe COVID-19 outcomes. Conclusions More severe asthma was associated with more severe COVID-19 outcomes, but type 2 inflammation was not. The risk of COVID-19 hospitalization appeared to be similar to the risk with influenza or pneumonia.
RefPlantNLR is a comprehensive collection of experimentally validated plant disease resistance proteins from the NLR family

Reference datasets are critical in computational biology. They help define canonical biological features and are essential for benchmarking studies. Here, we describe a comprehensive reference dataset of experimentally validated plant nucleotide-binding leucine-rich repeat (NLR) immune receptors. RefPlantNLR consists of 481 NLRs from 31 genera belonging to 11 orders of flowering plants. This reference dataset has several applications. We used RefPlantNLR to determine the canonical features of functionally validated plant NLRs and to benchmark 5 NLR annotation tools. This revealed that although NLR annotation tools tend to retrieve the majority of NLRs, they frequently produce domain architectures that are inconsistent with the RefPlantNLR annotation. Guided by this analysis, we developed a new pipeline, NLRtracker, which extracts and annotates NLRs from protein or transcript files based on the core features found in the RefPlantNLR dataset. The RefPlantNLR dataset should also prove useful for guiding comparative analyses of NLRs across the wide spectrum of plant diversity and identifying understudied taxa. We hope that the RefPlantNLR resource will contribute to moving the field beyond a uniform view of NLR structure and function.
Effectiveness of BNT162b2 Vaccine against Delta Variant in Adolescents

To the Editor: The B.1. 617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as the dominant strain circulating in many regions worldwide. The BNT162b2 mRNA vaccine against coronavirus disease 2019 (Covid-19) was found to be effective in preventing infection with the delta variant in a recent observational study,1 but other reports have suggested reduced vaccine effectiveness against this variant.2,3 On May 10, 2021, the U.S. Food and Drug Administration approved the emergency use of BNT162b2 in adolescents 12 years of age or older on the basis of a clinical trial that had been conducted before the delta variant had become prevalent in the United States.4 Additional evidence was needed regarding the effectiveness of the BNT162b2 vaccine among adolescents, particularly against the delta variant. We sought to estimate the vaccine effectiveness of BNT162b2 against the delta variant among vaccinated adolescents for whom an unvaccinated match was found. We used data from Clalit Health Services, the largest health care organization in Israel, to conduct an observational cohort study involving adolescents between the ages of 12 and 18 years who had no prior SARS-CoV-2 infection noted in their electronic medical record and who had been vaccinated between June 8 and September 14, 2021. According to the sequencing of samples obtained from infected persons that was performed by the Israeli Ministry of Health during this period, the delta variant was responsible for more than 95% of new infections in the general population in Israel. We used the same methods that were used in our previous studies of vaccine effectiveness, which were conducted in the same health care organization using the same database.5 (See the Methods section in the Supplementary Appendix, available with the full text of this letter at NEJM.org.) Vaccine effectiveness was defined as 1 minus the risk ratio, which was estimated over several follow-up periods for documented SARS-CoV-2 infection and symptomatic Covid-19. More severe outcomes related to Covid-19 are rare in this age group. Of 184,905 vaccinated adolescents, 130,464 met the eligibility requirements, and 94,354 of these vaccine recipients were successfully matched with 94,354 unvaccinated controls (Fig. S1 and the Methods section in the Supplementary Appendix). The eligible population was similar to the matched population with respect to several demographic and clinical characteristics (Tables
Mortality from leukemia, cancer and heart disease among U.S. nuclear power plant workers, 1957–2011

Abstract Background The aim of the Million Person Study of Low-Dose Health Effects (MPS) is to examine the level of radiation risk for chronic exposures received gradually over time and not acutely as was the case for the Japanese atomic bomb survivors. Nuclear power plant (NPP) workers comprise nearly 15 percent of the MPS. Leukemia, selected cancers, Parkinson’s disease, ischemic heart disease (IHD) and other causes of death are evaluated. Methods and material The U.S. Nuclear Regulatory Commission’s Radiation Exposure Information and Reporting System (REIRS) and the Landauer, Inc. dosimetry databases identified 135,193 NPP workers first monitored 1957–1984. Annual personal dose equivalents [Hp(10)] were available for each worker. Radiation records from all places of employment were sought. Vital status was determined through 2011. Mean absorbed doses to red bone marrow (RBM), esophagus, lung, colon, brain and heart were estimated by adjusting the recorded Hp(10) for each worker by scaling factors, accounting for exposure geometry and energy of the incident gamma radiation. Standardized mortality ratios (SMR) were calculated. Radiation risks were estimated using Cox proportional hazards models. Results Nearly 50% of workers were employed for more than 20 years. The mean duration of follow-up was 30.2 y. Overall, 29,124 total deaths occurred, 296 from leukemia other than chronic lymphocytic leukemia (CLL), 3382 from lung cancer, 140 from Parkinson’s disease and 5410 from IHD. The mean dose to RBM was 37.9 mGy (maximum 1.0 Gy; percent >100 mGy was 9.2%), 43.2 mGy to lung, 43.7 mGy to colon, 33.2 mGy to brain, and 43.9 mGy to heart. The SMRs (95% CI) were 1.06 (0.94; 1.19) for leukemia other than CLL, 1.10 (1.07; 1.14) for lung cancer, 0.90 (0.76; 1.06) for Parkinson’s disease, and 0.80 (0.78; 0.82) for IHD. The excess relative risk (ERR) per 100 mGy for leukemia other than CLL was 0.15 (90% CI −0.001; 0.31). For all solid cancers the ERR per 100 mGy (95% CI) was 0.01 (–0.03; 0.05), for lung cancer −0.04 (–0.11; 0.02), for Parkinson’s disease 0.24 (–0.02; 0.50), and for IHD −0.01 (–0.06; 0.04). Conclusion Prolonged exposure to radiation increased the risk of leukemia other than CLL among NPP workers. There was little evidence for a radiation association for all solid cancers, lung cancer or ischemic heart disease. Increased precision will be forthcoming as the different cohorts within the MPS are combined, such as industrial radiographers and medical radiation workers who were assembled and evaluated in like manner.