Miracle-dz/UniFAR-FTUs huggingface dataset:
Urinary potassium excretion and mortality risk in community-dwelling individuals with and without obesity

ABSTRACT Background Potassium intake has been shown to be inversely associated with blood pressure and premature mortality. Previous studies have suggested that the association between potassium intake and blood pressure is modified by obesity, but whether obesity similarly influences the association between potassium intake and mortality is unclear. Objectives We investigated whether potassium intake, reflected by 24-h urinary excretion, is associated with all-cause mortality, and explored potential effect modification by obesity. Methods We performed a prospective cohort study in community-dwelling individuals. The association between urinary potassium excretion and all-cause mortality was investigated by using multivariable Cox regression. We performed multiplicative interaction analysis and subgroup analyses according to BMI and waist circumference. Results In 8533 individuals (50% male), the mean age was 50 ± 13 y, mean urinary potassium excretion was 71 ± 21 mmol/24 h, median BMI (in kg/m2) was 25.6 (IQR: 23.1, 28.4) and mean waist circumference was 89 ± 13 cm. During median follow-up of 18.4 (IQR: 13.5, 18.8) y, 1663 participants died. Low urinary potassium excretion (first compared with third sex-specific quintile) was associated with an increased mortality risk (fully adjusted HR: 1.38; 95% CI: 1.18, 1.61), P < 0.001, irrespective of body dimensions (HR range for all body dimensions: 1.36–1.70, all P < 0.05). High urinary potassium excretion (fifth compared with third quintile) was associated with increased mortality risk in participants with obesity (BMI ≥30; HR: 1.52; CI: 1.00, 2.30), but not in participants without obesity (BMI: <25; HR: 0.89; 95% CI: 0.62, 1.26; P-interaction = 0.001). Conclusions Low potassium intake was associated with increased mortality risk in community-dwelling individuals. In individuals with obesity, high potassium intake was also associated with increased mortality risk.
Palliative Care in Breast Cancer During the COVID-19 Pandemic: A Scoping Review

Background: The COVID-19 pandemic has harmed the provision of palliative care (PC) services for women with breast cancer due to all the restrictions that came along with the virus. Objective: To map the available evidence on the situation of PC in breast cancer during the COVID-19 pandemic. Methods: A scoping review was carried out based on the methodology proposed by the Joanna Briggs Institute. The search was conducted in nine databases, one electronic repository, and one library, using controlled vocabularies. Results: Twenty-nine articles and seven documents were included. The majority (11.4% each) were published in the United Kingdom, Italy, and the United States, 38.9% addressed palliative radiotherapy (RT), and 47.2% consisted of recommendations. From the content analysis, five categories were obtained focused on the recommendations on changes in palliative treatment guidelines and the response of PC teams to the evolving crisis. Conclusions: The evidence pointed to the management of general PC, palliative RT, palliative chemotherapy, management of metastatic breast cancer, and use of technologies in palliative care. No recommendations were found to manage frequent symptoms in PC, indicating the need to develop primary studies that investigate these aspects in detail in this vulnerable group. Implications: The results contained in this document can provide professionals working in this field of care with a global view of how other teams have dealt with the pandemic, thereby identifying the best guidelines to apply in their reality, taking into account the clinical and social situation of each patient.
Plant Hormonomics: A Key Tool for Deep Physiological Phenotyping to Improve Crop Productivity

Abstract Agriculture is particularly vulnerable to climate change. To cope with the risks posed by climate-related stressors to agricultural production, global population growth, and changes in food preferences, it is imperative to develop new climate-smart crop varieties with increased yield and environmental resilience. Molecular genetics and genomic analyses have revealed that allelic variations in genes involved in phytohormone-mediated growth regulation have greatly improved productivity in major crops. Plant science has remarkably advanced our understanding of the molecular basis of various phytohormone-mediated events in plant life. These findings provide essential information for improving the productivity of crops growing in changing climates. In this review, we highlight the recent advances in plant hormonomics (multiple phytohormone profiling) and discuss its application to crop improvement. We present plant hormonomics as a key tool for deep physiological phenotyping, focusing on representative plant growth regulators associated with the improvement of crop productivity. Specifically, we review advanced methodologies in plant hormonomics, highlighting mass spectrometry- and nanosensor-based plant hormone profiling techniques. We also discuss the applications of plant hormonomics in crop improvement through breeding and agricultural management practices.
Clinical Evaluation of Surgery for Single‐Segment Lumbar Spinal Stenosis: A Systematic Review and Bayesian Network Meta‐Analysis

To compare the efficacy and safety of different surgical procedures for patients with single‐segment lumbar spinal stenosis (LSS), Bayesian network meta‐analysis (NMA) was conducted in this study. Randomized controlled trials (RCTs) which reported 2 years' results after surgery were searched from PubMed, Embase, and Cochrane Register of Controlled Trials up to February 2021. Eligible RCTs that contained at least two of the following surgical procedures, bilateral decompression via the unilateral approach (BDUL), decompression with conventional laminectomy (CL), decompression with fusion (DF), endoscopic decompression (ED), interspinous process devices only (IPDs), decompression with interlaminar stabilization (DILS), decompression with lumbar spinal process‐splitting laminectomy (LSPSL), and minimally invasive tubular decompression (MTD), would be included after screening based on the inclusion and exclusion criteria. The primary outcome was Oswestry Disability Index (ODI). Twenty eligible RCTs were included, with a total of 2201 patients enrolled. The NMA showed that the following surgical procedures ranked first (surface under the cumulative ranking) when compared with CL and DF: DILS for ODI (SUCRA 87.8%); LSPSL for back pain (95%); and MTD for leg pain (95.6%). MTD ranked among the top three surgical procedures for most outcomes. The quality of the synthesized evidence was low according to the Grading of Recommendations Assessment, Development, and Evaluation criteria. DILS, LSPSL, MTD, IPDs, and ED are the most effective procedures for patients with single‐segment LSS. Because of combining efficacy and safety, MTD may be the most promising routine surgical option for treating single‐segment LSS.
AENEAS: A Randomized Phase III Trial of Aumolertinib Versus Gefitinib as First-Line Therapy for Locally Advanced or MetastaticNon–Small-Cell Lung Cancer With EGFR Exon 19 Deletion or L858R Mutations

PURPOSE Aumolertinib (formerly almonertinib; HS-10296) is a novel third-generation epidermal growth factor receptor tyrosine kinase inhibitor approved in China. This double-blind phase III trial evaluated the efficacy and safety of aumolertinib compared with gefitinib as a first-line treatment for locally advanced or metastatic EGFR-mutated non–small-cell lung cancer (NSCLC; ClinicalTrials.gov identifier: NCT03849768). METHODS Patients at 53 sites in China were randomly assigned 1:1 to receive either aumolertinib (110 mg) or gefitinib (250 mg) once daily. The primary end point was progression-free survival (PFS) per investigator assessment. RESULTS A total of 429 patients who were naïve to treatment for locally advanced or metastatic NSCLC were enrolled. PFS was significantly longer with aumolertinib compared with gefitinib (hazard ratio, 0.46; 95% CI, 0.36 to 0.60; P < .0001). The median PFS with aumolertinib was 19.3 months (95% CI, 17.8 to 20.8) versus 9.9 months with gefitinib (95% CI, 8.3 to 12.6). Objective response rate and disease control rate were similar in the aumolertinib and gefitinib groups (objective response rate, 73.8% and 72.1%, respectively; disease control rate, 93.0% and 96.7%, respectively). The median duration of response was 18.1 months (95% CI, 15.2 to not applicable) with aumolertinib versus 8.3 months (95% CI, 6.9 to 11.1) with gefitinib. Adverse events of grade ≥ 3 severity (any cause) were observed in 36.4% and 35.8% of patients in the aumolertinib and gefitinib groups, respectively. Rash and diarrhea (any grade) were observed in 23.4% and 16.4% of patients who received aumolertinib compared with 41.4% and 35.8% of those who received gefitinib, respectively. CONCLUSION Aumolertinib is a well-tolerated third-generation epidermal growth factor receptor tyrosine kinase inhibitor that could serve as a treatment option for EGFR-mutant NSCLC in the first-line setting.
Soluble HLA peptidome of pleural effusions is a valuable source for tumor antigens

Background Soluble human leucocyte antigen (sHLA) molecules, released into the plasma, carry their original peptide cargo and provide insight into the protein synthesis and degradation schemes of their source cells and tissues. Other body fluids, such as pleural effusions, may also contain sHLA-peptide complexes, and can potentially serve as a source of tumor antigens since these fluids are drained from the tumor microenvironment. We explored this possibility by developing a methodology for purifying and analyzing large pleural effusion sHLA class I peptidomes of patients with malignancies or benign diseases. Methods Cleared pleural fluids, cell pellets present in the pleural effusions, and the primary tumor cells cultured from cancer patients’ effusions, were used for immunoaffinity purification of the HLA molecules. The recovered HLA peptides were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) and the resulting LC-MS/MS data were analyzed with the MaxQuant software tool. Selected tumor antigen peptides were tested for their immunogenicity potential with donor peripheral blood mononuclear cells (PBMCs) in an in vitro assay. Results Mass spectrometry analysis of the pleural effusions revealed 39,669 peptides attributable to 11,305 source proteins. The majority of peptides identified from the pleural effusions were defined as HLA ligands that fit the patients’ HLA consensus sequence motifs. The membranal and soluble HLA peptidomes of each individual patient correlated to each other. Additionally, soluble HLA peptidomes from the same patient, obtained at different visits to the clinic, were highly similar. Compared with benign effusions, the soluble HLA peptidomes of malignant pleural effusions were larger and included HLA peptides derived from known tumor-associated antigens, including cancer/testis antigens, lung-related proteins, and vascular endothelial growth factor pathway proteins. Selected tumor-associated antigens that were identified by the immunopeptidomics were able to successfully prime CD8+ T cells. Conclusions Pleural effusions contain sHLA-peptide complexes, and the pleural effusion HLA peptidome of patients with malignant tumors can serve as a rich source of biomarkers for tumor diagnosis and potential candidates for personalized immunotherapy.
Signaling pathways involved in NMDA‐induced suppression of M‐channels in corticotropin‐releasing hormone neurons in central amygdala

Glutamate N‐methyl‐d‐aspartate (NMDA) receptors (NMDARs) and Kv7/M channels are importantly involved in regulating neuronal activity involved in various physiological and pathological functions. Corticotropin‐releasing hormone (CRH)‐expressing neurons in the central nucleus of the amygdala (CeA) critically mediate autonomic response during stress. However, the interaction between NMDA receptors and Kv7/M channels in the CRHCeA neurons remains unclear. In this study, we identified rat CRHCeA neurons through the expression of an AAV viral vector‐mediated enhanced green fluorescent protein (eGFP) driven by the rat CRH promoter. M‐currents carried by Kv7/M channels were recorded using the whole‐cell patch‐clamp approach in eGFP‐tagged CRHCeA neurons in brain slices. Acute exposure to NMDA significantly reduced M‐currents recorded from the CRHCeA neurons. NMDA‐induced suppression of M‐currents was eliminated by chelating intracellular Ca2+, supplying phosphatidylinositol 4,5‐bisphosphate (PIP2) intracellularly, or blocking phosphoinositide3‐kinase (PI3K). In contrast, inhibiting protein kinase C (PKC) or calmodulin did not alter NMDA‐induced suppression of M‐currents. Sustained exposure of NMDA decreased Kv7.3 membrane protein levels and suppressed M‐currents, while the Kv7.2 expression levels remained unaltered. Pre‐treatment of brain slices with PKC inhibitors alleviated the decreases in Kv7.3 and reduction of M‐currents in CRHCeA neurons induced by NMDA. PKC inhibitors did not alter Kv7.2 and Kv7.3 membrane protein levels and M‐currents in CRHCeA neurons. These data suggest that transient activation of NMDARs suppresses M‐currents through the Ca2+‐dependent PI3K‐PIP2 signaling pathway. In contrast, sustained activation of NMDARs reduces Kv7.3 protein expression and suppresses M‐currents through a PKC‐dependent pathway.
Change in hyper-palatable food availability in the US food system over 30 years: 1988–2018

Abstract Objective: To quantify the change in availability of hyper-palatable foods (HPF) in the US foods system over 30 years (1988–2018). Design: Three datasets considered representative of the US food system were used in analyses to represent years 1988, 2001 and 2018. A standardised definition from Fazzino et al. (2019) that specifies combinations of nutrients was used to identify HPF. Setting: Analysis of food-item level data was conducted. Differences in the prevalence of HPF were characterised by Cochran’s Q and McNemar’s tests. Generalised linear mixed models with a fixed effect for time and random intercept for food item estimated change in the likelihood that a food was classified as hyper-palatable over time. Participants: No participant data were used. Results: The prevalence of HPF increased 20 % from 1988 to 2018 (from 49 % to 69 %; P < 0·0001). The most prominent difference was in the availability of HPF high in fat and Na, which evidenced a 17 % higher prevalence in 2018 compared with 1988 (P < 0·0001). Compared with 1988, the same food items were >2 times more likely to be hyper-palatable in 2001, and the same food items were >4 times more likely to be classified as hyper-palatable in 2018 compared with 1988 (P values < 0·0001). Conclusions: The availability of HPF in the US food system increased substantially over 30 years. Existing food products in the food system may have been reformulated over time to enhance their palatability.
Left amygdala structure mediates longitudinal associations between exposure to threat and long‐term psychiatric symptomatology in youth

Traumatic experiences during childhood can have profound effects on stress sensitive brain structures (e.g., amygdala and hippocampus) and the emergence of psychiatric symptoms. Recent theoretical and empirical work has delineated dimensions of trauma (i.e., threat and deprivation) as having distinct neural and behavioral effects, although there are few longitudinal examinations. A sample of 243 children and adolescents were followed for three time points, with each assessment approximately 1 year apart (ages 9–15 years at Time 1; 120 males). Participants or their caregiver reported on youths' threat exposure, perceived stress (Time 1), underwent a T1‐weighted structural high‐resolution MRI scan (Time 2), and documented their subsequent psychiatric symptoms later in development (Time 3). The primary findings indicate that left amygdala volume, in particular, mediated the longitudinal association between threat exposure and subsequent internalizing and externalizing symptomatology. Greater threat exposure related to reduced left amygdala volume, which in turn differentially predicted internalizing and externalizing symptoms. Decreased bilateral hippocampal volume was related to subsequently elevated internalizing symptoms. These findings suggest that the left amygdala is highly threat‐sensitive and that stress‐related alterations may partially explain elevated psychopathology in stress‐exposed adolescents. Uncovering potential subclinical and/or preclinical predictive biomarkers is essential to understanding the emergence, progression, and eventual targeted treatment of psychopathology following trauma exposure.
Clinical, Brain, and Multilevel Clustering in Early Psychosis and Affective Stages.

Importance Approaches are needed to stratify individuals in early psychosis stages beyond positive symptom severity to investigate specificity related to affective and normative variation and to validate solutions with premorbid, longitudinal, and genetic risk measures. Objective To use machine learning techniques to cluster, compare, and combine subgroup solutions using clinical and brain structural imaging data from early psychosis and depression stages. Design, Setting, and Participants A multisite, naturalistic, longitudinal cohort study (10 sites in 5 European countries; including major follow-up intervals at 9 and 18 months) with a referred patient sample of those with clinical high risk for psychosis (CHR-P), recent-onset psychosis (ROP), recent-onset depression (ROD), and healthy controls were recruited between February 1, 2014, to July 1, 2019. Data were analyzed between January 2020 and January 2022. Main Outcomes and Measures A nonnegative matrix factorization technique separately decomposed clinical (287 variables) and parcellated brain structural volume (204 gray, white, and cerebrospinal fluid regions) data across CHR-P, ROP, ROD, and healthy controls study groups. Stability criteria determined cluster number using nested cross-validation. Validation targets were compared across subgroup solutions (premorbid, longitudinal, and schizophrenia polygenic risk scores). Multiclass supervised machine learning produced a transferable solution to the validation sample. Results There were a total of 749 individuals in the discovery group and 610 individuals in the validation group. Individuals included those with CHR-P (n = 287), ROP (n = 323), ROD (n = 285), and healthy controls (n = 464), The mean (SD) age was 25.1 (5.9) years, and 702 (51.7%) were female. A clinical 4-dimensional solution separated individuals based on positive symptoms, negative symptoms, depression, and functioning, demonstrating associations with all validation targets. Brain clustering revealed a subgroup with distributed brain volume reductions associated with negative symptoms, reduced performance IQ, and increased schizophrenia polygenic risk scores. Multilevel results distinguished between normative and illness-related brain differences. Subgroup results were largely validated in the external sample. Conclusions and Relevance The results of this longitudinal cohort study provide stratifications beyond the expression of positive symptoms that cut across illness stages and diagnoses. Clinical results suggest the importance of negative symptoms, depression, and functioning. Brain results suggest substantial overlap across illness stages and normative variation, which may highlight a vulnerability signature independent from specific presentations. Premorbid, longitudinal, and genetic risk validation suggested clinical importance of the subgroups to preventive treatments.
Hoxb5 reprogrammes murine multipotent blood progenitors into haematopoietic stem cell‐like cells

The expression of transcription factor Hoxb5 specifically marks the functional haematopoietic stem cells (HSC) in mice. However, our recent work demonstrated that ectopic expression of Hoxb5 exerted little effect on HSC but could convert B‐cell progenitors into functional T cells in vivo. Thus, cell type‐ and development stage‐specific roles of Hoxb5 in haematopoietic hierarchy await more extensive exploration. In this study, we aim to investigate the effect of Hoxb5 expression in multipotent blood progenitor cells.
Assessment technologies of rail systems’ structural adequacy — A review from mechanical engineering perspectives

The structural adequacy challenges of railroad track structures have received considerable attention globally. Track defects and failures due to weak strength and buckling effect account for one-third of all railroad accidents. The current paper provides a comprehensive study of the recent work on the structural adequacy/bearing capacity of rail systems from mechanical engineering perspectives; existing techniques for track stiffness/modulus evaluations, including standstill and continuous methods. Further, this paper demonstrates the current techniques for track stiffness/modulus evaluation. Prevailing track modulus techniques, while accurate but time-taking, effortful, requires a track closure and provides only single-point information. Also, this review provides a suggestion on the non-destructive and non-invasive technologies for example Ground-penetrating radar (GPR) and evaluation of the substructures of tracks as they have great potential for image subsurface features.
Adjusting for collider bias in genetic association studies using instrumental variable methods

Genome‐wide association studies have provided many genetic markers that can be used as instrumental variables to adjust for confounding in epidemiological studies. Recently, the principle has been applied to other forms of bias in observational studies, especially collider bias that arises when conditioning or stratifying on a variable that is associated with the outcome of interest. An important case is in studies of disease progression and survival. Here, we clarify the links between the genetic instrumental variable methods proposed for this problem and the established methods of Mendelian randomisation developed to account for confounding. We highlight the critical importance of weak instrument bias in this context and describe a corrected weighted least‐squares procedure as a simple approach to reduce this bias. We illustrate the range of available methods on two data examples. The first, waist–hip ratio adjusted for body‐mass index, entails statistical adjustment for a quantitative trait. The second, smoking cessation, is a stratified analysis conditional on having initiated smoking. In both cases, we find little effect of collider bias on the primary association results, but this may propagate into more substantial effects on further analyses such as polygenic risk scoring and Mendelian randomisation.