Explore the vast range of titles available.

This study aimed to examine and compare the associations between different multimorbidity measures and mortality among older Chinese adults. Using the Chinese Longitudinal Healthy Longevity Survey 2002–2018, data on fourteen chronic conditions from 13,144 participants aged ≥65 years were collected. Multimorbidity measures included condition counts, multimorbidity patterns (examined by exploratory factor analysis), and multimorbidity trajectories (examined by a group-based trajectory model). Mortality risk associated with different multimorbidity measures was each analyzed using Cox regression. C-statistic, the Integrated Discrimination Improvement (IDI), and the Net Reclassification Index (NRI) were used to compare the performance of different multimorbidity measures. Participants with multimorbidity, regardless of measurements, had a higher risk of death compared with people without multimorbidity. Compared with the mortality prediction model using age and sex, C-statistics showed added discrimination (over 0.77, all P < .05) for models with multimorbidity measures. Multimorbidity trajectory showed integrated discrimination and net reclassification improvement for mortality prediction compared to condition count (IDI = 0.042, NRI = 0.033) and multimorbidity pattern (IDI = 0.041, NRI = 0.069). Adding multimorbidity measures significantly improved the performance of a mortality prediction model using age and sex as predictors. Trajectory-based measures of multimorbidity performed better than count- and pattern-based measures for mortality prediction.

Background This study aimed to evaluate the association of three multimorbidity indicators with mortality risk among senior adults, and compare their predictive performance on mortality risk. Methods This prospective cohort study was conducted using data from the Yuexiu Ageing and Health Cohort, a dynamic cohort established since January 2016. Annual health examination is conducted for the senior adults aged ≥ 65 years in the jurisdiction. Following exclusions for insufficient follow-up (< 6 months) and missing data, 162,958 participants were included. Mortality data up to 31 December 2023 were obtained from the National Death Registry of China. Information on eleven system diseases was extracted; three multimorbidity indicators (condition count, multimorbidity patterns, and multimorbidity index) were created. Hazard ratio (HR) with 95% confidence intervals (CI) was calculated using Cox proportional hazard model after adjustment for confounders. The C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were used to compare the performance of multimorbidity indicators. Results Fifteen thousand five hundred twenty-five deaths were identified during a median of 4.79 years of follow-up. Compared with participants with no multimorbidity, those with multimorbidity had a 1.56-fold risk of all-cause mortality. Every one condition count increment was associated with a 17% increased risk of all-cause mortality. Three multimorbidity patterns labeled as Patterns I, II, and III were extracted and were significantly associated with the increased mortality risk, with HR being 1.97, 1.41, and 1.44 for Patterns I, II, and III respectively. Every 1-unit increment of multimorbidity index was associated with an 18% increased mortality risk. The multimorbidity index demonstrated a slightly better discriminative ability compared to the condition count (IDI: 0.003, NRI: 0.0046) and multimorbidity pattern (IDI: 0.007, NRI: 0.0055). Conclusions Three multimorbidity indicators were all associated with the increased mortality risk in community-dwelling older Chinese. The multimorbidity index is considered an optimal indicator for predicting mortality risk in community-dwelling older adults. The condition count is also suggested due to its simplicity and superior predictive performance.

Differential white blood cell counts are frequently used in diagnosis, patient stratification, and treatment selection to optimize therapy responses. Referral laboratories are often used but challenged with use of different hematology platforms, variable blood shipping times and storage conditions, and the different sensitivities of specific cell types. To extend the scientific literature and knowledge on the temporal commutability of blood samples between hematology analyzers, we performed a comparative ex-vivo study using four of the most utilized commercial platforms, focusing on the assessment of eosinophils given its importance in asthma management. Whole blood from healthy volunteers with and without atopy (n = 6+6) and participants with eosinophilic asthma (n = 6) were stored under different conditions (at 4, 20, 30, and 37°C, with or without agitation) and analyzed at different time points (3, 6, 24, 48 and 72h post-sampling) in parallel on the Abbott CELL-DYN Sapphire, Beckman Coulter DxH900, Siemens ADVIA 2120i and Sysmex XN-1000V. In the same blood samples, eosinophil-derived neurotoxin (EDN), eosinophil activation and death markers were analyzed. All platforms gave comparable measurements of cell differentials on fresh blood within the same day of sampling. However, by 24 hours, significant temporal and temperature-dependent differences were observed, most markedly for eosinophils. None of the platforms performed perfectly across all temperatures tested during the 72 hours, showing that handling conditions should be optimized depending on the cell type of interest and the hematology analyzer. Neither disease status (healthy vs. asthma) nor agitation of the sample affected the cell quantification result or EDN release. The eosinophil activation markers measured by flow cytometry increased with time, were influenced by temperature, and were higher in those with asthma versus healthy participants. In conclusion, hematology analyzer, time window from sampling until analysis, and temperature conditions must be considered when analyzing blood cell differentials, particularly for eosinophils, via central labs to obtain counts comparable to the values obtained in freshly sampled blood.

Clonal expansion in aged normal tissues has been implicated in the development of cancer. However, the chronology and risk dependence of the expansion are poorly understood. Here we intensively sequence 682 micro-scale oesophageal samples and show, in physiologically normal oesophageal epithelia, the progressive age-related expansion of clones that carry mutations in driver genes (predominantly NOTCH1 ), which is substantially accelerated by alcohol consumption and by smoking. Driver-mutated clones emerge multifocally from early childhood and increase their number and size with ageing, and ultimately replace almost the entire oesophageal epithelium in the extremely elderly. Compared with mutations in oesophageal cancer, there is a marked overrepresentation of NOTCH1 and PPM1D mutations in physiologically normal oesophageal epithelia; these mutations can be acquired before late adolescence (as early as early infancy) and significantly increase in number with heavy smoking and drinking. The remodelling of the oesophageal epithelium by driver-mutated clones is an inevitable consequence of normal ageing, which—depending on lifestyle risks—may affect cancer development. In physiologically normal epithelia, age-related expansion of clones that carry mutations in NOTCH1 and other driver genes is accelerated by risk factors for developing oesophageal squamous cell carcinoma, such as alcohol consumption or smoking.

Introduction Male infertility is a widespread disease with an etiology that is not always clear. A number of studies have reported a decrease in sperm production in the last forty years. Although the reasons are still undefined, the change in environmental conditions and the higher exposure to endocrine-disrupting chemicals (EDCs), namely bisphenol A, phthalates, polychlorinated biphenyls, polybrominated diphenyl esters, dichlorodiphenyl-dichloroethylene, pesticides, and herbicides, organophosphates, and heavy metals, starting from prenatal life may represent a possible factor justifying the temporal decline in sperm count. Aim The aim of this study is to provide a comprehensive description of the effects of the exposure to EDCs on testicular development, spermatogenesis, the prevalence of malformations of the male genital tract (cryptorchidism, testicular dysgenesis, and hypospadias), testicular tumor, and the mechanisms of testicular EDC-mediated damage. Narrative review Animal studies confirm the deleterious impact of EDCs on the male reproductive apparatus. EDCs can compromise male fertility by binding to hormone receptors, dysregulating the expression of receptors, disrupting steroidogenesis and hormonal metabolism, and altering the epigenetic mechanisms. In humans, exposure to EDCs has been associated with poor semen quality, increased sperm DNA fragmentation, increased gonadotropin levels, a slightly increased risk of structural abnormalities of the genital apparatus, such as cryptorchidism and hypospadias, and development of testicular tumor. Finally, maternal exposure to EDCs seems to predispose to the risk of developing testicular tumors. Conclusion EDCs negatively impact the testicular function, as suggested by evidence in both experimental animals and humans. A prenatal and postnatal increase to EDC exposure compared to the past may likely represent one of the factors leading to the temporal decline in sperm counts.

Patients with systemic lupus erythematosus have substantial unmet medical need. Baricitinib is an oral selective Janus kinase (JAK)1 and JAK2 inhibitor that we hypothesised might have therapeutic benefit in patients with systemic lupus erythematosus. In this double-blind, multicentre, randomised, placebo-controlled, 24-week phase 2 study, patients were recruited from 78 centres in 11 countries. Eligible patients were aged 18 years or older, had a diagnosis of systemic lupus erythematosus, and had active disease involving skin or joints. We randomly assigned patients (1:1:1) to receive once-daily baricitinib 2 mg, baricitinib 4 mg, or placebo for 24 weeks. The primary endpoint was the proportion of patients achieving resolution of arthritis or rash at week 24, as defined by Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K). Efficacy and safety analyses included all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT02708095. Between March 24, 2016, and April 27, 2017, 314 patients were randomly assigned to receive placebo (n=105), baricitinib 2 mg (n=105), or baricitinib 4 mg (n=104). At week 24, resolution of SLEDAI-2K arthritis or rash was achieved by 70 (67%) of 104 patients receiving baricitinib 4 mg (odds ratio [OR] vs placebo 1·8, 95% CI 1·0–3·3; p=0·0414) and 61 (58%) of 105 patients receiving baricitinib 2 mg (OR 1·3, 0·7–2·3; p=0·39). Adverse events were reported in 68 (65%) patients in the placebo group, 75 (71%) patients in the baricitinib 2 mg group, and 76 (73%) patients in the baricitinib 4 mg group. Serious adverse events were reported in ten (10%) patients receiving baricitinib 4 mg, 11 (10%) receiving baricitinib 2 mg, and five (5%) receiving placebo; no deaths were reported. Serious infections were reported in six (6%) patients with baricitinib 4 mg, two (2%) with baricitinib 2 mg, and one (1%) with placebo. The baricitinib 4 mg dose, but not the 2 mg dose, significantly improved the signs and symptoms of active systemic lupus erythematosus in patients who were not adequately controlled despite standard of care therapy, with a safety profile consistent with previous studies of baricitinib. This study provides the foundation for future phase 3 trials of JAK1/2 inhibition with baricitinib as a new potential oral therapy for systemic lupus erythematosus. Eli Lilly and Company.

We study a sparse negative binomial regression (NBR) for count data by showing the non-asymptotic advantages of using the elastic-net estimator. Two types of oracle inequalities are derived for the NBR’s elastic-net estimates by using the Compatibility Factor Condition and the Stabil Condition. The second type of oracle inequality is for the random design and can be extended to many ℓ1 + ℓ2 regularized M-estimations, with the corresponding empirical process having stochastic Lipschitz properties. We derive the concentration inequality for the suprema empirical processes for the weighted sum of negative binomial variables to show some high-probability events. We apply the method by showing the sign consistency, provided that the nonzero components in the true sparse vector are larger than a proper choice of the weakest signal detection threshold. In the second application, we show the grouping effect inequality with high probability. Third, under some assumptions for a design matrix, we can recover the true variable set with a high probability if the weakest signal detection threshold is large than the turning parameter up to a known constant. Lastly, we briefly discuss the de-biased elastic-net estimator, and numerical studies are given to support the proposal.

The objective of this study was to evaluate the relationship between the platelet-to-lymphocyte ratio (PLR) and systemic lupus erythematosus (SLE). Additionally, the study aimed to establish an association between PLR and SLE disease activity, specifically lupus nephritis (LN). We conducted a comprehensive search across Medline, Embase, and Cochrane databases to identify relevant articles. Subsequently, we performed meta-analyses to compare PLR between SLE patients and controls, as well as active and inactive SLE cases, along with LN and non-LN groups. Furthermore, a meta-analysis was conducted on correlation coefficients between PLR and various parameters in SLE patients, including the SLE Disease Activity Index (SLEDAI), C3, C4, anti-dsDNA, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). In total, fifteen studies comprising 1,522 SLE patients and 1,424 controls were eligible for inclusion. The meta-analysis demonstrated a significant elevation of PLR in the SLE group compared to the control group (Standardized Mean Difference [SMD] = 0.604, 95% Confidence Interval [CI] = 0.299-0.909, p < 0.001). Upon stratification by ethnicity, an elevated PLR was observed in the SLE group among both Asian and Arab populations. Subgroup analysis based on sample size revealed consistently higher PLR in both small (n < 200) and large sample (n ≥ 200) SLE groups. Moreover, when considering disease activity, there was a noteworthy trend of increased PLR in the active disease group compared to the inactive group (SMD = 0.553, 95% CI = 0.000-1.106, p = 0.050). However, the meta-analysis did not demonstrate a significant distinction in PLR between the LN and non-LN groups. Notably, a positive association was established between PLR and SLEDAI (correlation coefficient = 0.325, 95% CI = 0.176-0.459, p < 0.001). Furthermore, PLR exhibited positive correlations with ESR, CRP, proteinuria, C3, and anti-dsDNA antibody levels. The outcomes of this meta-analysis underscored the elevated PLR in SLE patients, suggesting its potential as a biomarker for gauging systemic inflammation in SLE. Additionally, PLR exhibited correlations with SLEDAI, as well as with key indicators such as ESR, CRP, proteinuria, C3, and anti-dsDNA antibody levels.

Haematological parameters are valuable indicators of fish health status. This study is aimed to provide baseline data of the blood profile of two teleost fish species living in different environments and with divergent feeding behaviour, namely the flathead grey mullet Mugil cephalus Linnaeus, 1758, a marine herbivorous fish, and the goldfish Carassius auratus (Linnaeus, 1758), a freshwater omnivorous fish. Using an automated system coupled with flow cytometry and light microscopy, significant variations were found between M. cephalus and C. auratus blood parameters, except for haemoglobin concentration   (Hgb). A significant increase in red blood cell count (RBC) and haematocrit (Hct) levels, associated with reduced mean corpuscular volume (MCV), was revealed in mullets in respect to goldfish. These data may be attributable to differences in fish species, or to their divergent physiological activeness as high RBC values are associated with fast movement and high activity with streamlined bodies, or to environmental factors such as water salinity, an increase in which may lead to erythropoiesis as an adaptive process in seawater fish. Additionally, lower values of white blood cell count (WBC) and thrombocyte count (TC) were recorded in mullets with respect to goldfish, and these changes may be due to divergent feeding habits of the two fish species, or to their different environments since increased salinity may inversely affect WBC. Overall, findings from this study provide a better understanding of the influences of divergent environmental conditions and feeding habits on fish blood parameters. The combined use of an automatic haematological count with flow cytometry was demonstrated to be effective for an early assessment of blood parameters in different fish species.

A two-year (2015 and 2016) grazing study was established to compare ewe and lamb performance when grazed on a perennial ryegrass only sward compared to more diverse sward types. In that study four sward types were investigated: a perennial ryegrass (Lolium perenne) only sward receiving 163 kg nitrogen per hectare per year (N/ha/yr) (PRG); a perennial ryegrass and white clover (Trifolium repens) sward receiving 90 kg N/ha/yr (PRGWC); a six species sward (two grasses (perennial ryegrass and timothy (Phleum pratense)), two legumes (white and red clover (Trifolium pratense)) and two herbs (ribwort plantain (Plantago lanceolata) and chicory (Cichorium intybus)) receiving 90 kg N/ha/yr (6S); and a nine species sward containing cocksfoot (Dactylis glomerata), greater birdsfoot trefoil (Lotus pedunculatus) and yarrow (Achillea millefolium) in addition to the six species listed above, receiving 90 kg N/ha/yr (9S). Each sward type was managed as a separate farmlet and stocked with 30 twin-rearing ewes at a stocking rate of 12.5 ewes/ha under rotational grazing management from turnout post-lambing until housing. Lamb live weight was recorded fortnightly and lambs were drafted for slaughter at 45 kg. Ewe live weight and body condition score (BCS) were recorded on five occasions annually. Lamb faecal egg count (FEC) was recorded fortnightly and lambs were treated with anthelmintics when mean lamb FEC per sward type was above 400 eggs per gram. Ewes grazing the 6S and 9S swards had heavier (P < 0.01) live weights and BCS throughout the study than the ewes grazing the PRG sward. Lambs grazing the 6S sward were heavier than lambs grazing all other sward types of 14 weeks old (P < 0.05). Lambs grazing the PRG sward required more days to reach slaughter weight than lambs grazing all other sward types (P < 0.001). Lambs grazing the 6S and 9S swards required fewer anthelmintic treatments than lambs grazing the PRG or PRGWC swards. In conclusion, grazing multispecies swards improved ewe and lamb performance and reduced the requirement for chemical anthelmintics.