A Semi-Quantitative Approach to Deriving a Model Structure for the Uptake of Organic Chemicals by Vegetation

An expert elicitation exercise was undertaken to determine those components and processes that are most important for modeling plant uptake of organic chemicals. The state of our knowledge of these processes was also assessed. This semi-quantitative analysis allowed the construction of an idealized model with seven compartments; soil bulk, soil water, roots, stem, leaves, fruit, and air. Three main areas were identified further research: 1) the uptake of organic chemicals by fruit; 2) the internal transfer of organic chemicals between plant structures (e.g., stem and leaves); and 3) the transfer via the soil–air–plant pathway. Until new data becomes available to quantify these processes, it is proposed that an equilibrium partitioning approach is used between plant components other than fruit or that models consist of both an edible and inedible compartment.     

Seasonal variation of admission severity and outcomes in ischemic stroke – a consecutive hospital-based stroke registry

Different morbidities and mortalities of ischemic stroke may occur among seasons. For detecting the seasonal variations of severity after stroke onset and prognosis, we employed a retrospective analysis on a prospective regional hospital-based stroke registry and included a total of 1039 consecutive patients with onset date from January 2014 to December 2015. Patients were divided into four groups according to the onset seasons. Baseline characteristics, stroke subtypes, admission National Institute of Health Stroke Scale (NIHSS) score and modified Rankin Scale (mRS) score in 90 d were recorded and compared. Ordinal logistic regression was used to evaluate the association of seasons and severity or outcomes. Higher proportion of cardiac embolisms appeared in spring and winter (p < 0.001). The median admission NIHSS score was 5 in spring, 3 in summer, 4 in fall and 4 in winter (p = 0.036). After 90 d from onset, 40.5% of patients in spring suffered poor outcome (mRS 3–6), while 24.6% in summer, 33.9% in fall and 40.1% in winter (p < 0.001). After adjusted for age, sex, stroke subtypes and other covariates, patients in spring and winter had 1.76 times (95%CI 1.14–2.70, p = 0.010) and 1.53 times (95%CI 1.08–2.18, p = 0.017) the risk of suffering higher severity category than patients in summer, respectively. Compared with summer group, risk of worse outcomes at 90 d increased to 2.30 times in spring (95%CI 1.53–3.45, p < 0.001), 1.57 times in fall (95%CI 1.14–2.16, p = 0.006) and 2.09 times in winter (95%CI 1.50–2.91, p < 0.001), respectively. In conclusion, onset seasons were associated with severity and outcomes in ischemic stroke, and patients admitted in spring and winter had more severity and worse outcomes than patients in summer.     

Mitogenome evidence shows two radiation events and dispersals of matrilineal ancestry from northern coastal China to the Americas and Japan

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Estimation and interpretation of incidence rate difference for recurrent events when the estimation model is misspecified

Recurrent events data are common in experimental and observational studies. It is often of interest to estimate the effect of an intervention on the incidence rate of the recurrent events. The incidence rate difference is a useful measure of intervention effect. A weighted least squares estimator of the incidence rate difference for recurrent events was recently proposed for an additive rate model in which both the baseline incidence rate and the covariate effects were constant over time. In this article, we relax this model assumption and examine the properties of the estimator under the additive and multiplicative rate models assumption in which the baseline incidence rate and covariate effects may vary over time. We show analytically and numerically that the estimator gives an appropriate summary measure of the time‐varying covariate effects. In particular, when the underlying covariate effects are additive and time‐varying, the estimator consistently estimates the weighted average of the covariate effects over time. When the underlying covariate effects are multiplicative and time‐varying, and if there is only one binary covariate indicating the intervention status, the estimator consistently estimates the weighted average of the underlying incidence rate difference between the intervention and control groups over time. We illustrate the method with data from a randomized vaccine trial.     

Clinical characteristics and outcomes of immune checkpoint inhibitor-induced diabetes mellitus

ObjectiveTo better understand immune checkpoint inhibitor (ICI)-induced diabetes mellitus (DM) in cancer patients.Design and methodWe present a case of ICI-induced diabetic ketoacidosis (DKA) and conduct a systematic review of the PubMed and Web of Science databases up to September 2021 to identify all published cases of ICI-induced diabetes.ResultsIn addition to our case, a total of 171 published cases were identified during the literature search. Summary and statistical analyzes were conducted for all 172 cases. The median onset time from ICI initiation to DM diagnosis was 12 weeks (range: 0–122). DKA was present in 67.4% (116/172) of the cases, and low C-peptide levels were detected in 91.8% (123/134), indicating an acute onset of diabetes. Patients with positive glutamic acid decarboxylase antibodies (GADA) had an earlier onset of ICI-induced diabetes (median time 7 weeks vs. 16 weeks for GADA-negative patients, p < 0.001) and a higher frequency of DKA development (82.8 vs. 62.1%, p = 0.006). All but two patients developed insulin-dependent diabetes permanently. Immunotherapy rechallenge was reported in 53 cases after glycemia was well controlled.ConclusionICI-induced DM is a serious adverse event that often presents with life-threatening ketoacidosis. GADA positivity is related to an earlier onset of ICI-induced diabetes and a higher frequency of DKA development. Close monitoring of glucose levels is needed in patients receiving ICI treatment. ICI-induced DM is usually insulin-dependent since damage to β cells is irreversible. On the premise of well-controlled glycemia, immunotherapy rechallenge is feasible.     

Evolutionary histories of soil fungi are reflected in their large‐scale biogeography

Although fungal communities are known to vary along latitudinal gradients, mechanisms underlying this pattern are not well‐understood. We used high‐throughput sequencing to examine the large‐scale distributions of soil fungi and their relation to evolutionary history. We tested the Tropical Conservatism Hypothesis, which predicts that ancestral fungal groups should be more restricted to tropical latitudes and conditions than would more recently derived groups. We found support for this hypothesis in that older phyla preferred significantly lower latitudes and warmer, wetter conditions than did younger phyla. Moreover, preferences for higher latitudes and lower precipitation levels were significantly phylogenetically conserved among the six younger phyla, possibly because the older phyla possess a zoospore stage that is vulnerable to drought, whereas the younger phyla retain protective cell walls throughout their life cycle. Our study provides novel evidence that the Tropical Conservatism Hypothesis applies to microbes as well as plants and animals.     

Neoadjuvant PD-1 blockade plus chemotherapy versus chemotherapy alone in locally advanced stage II-III gastric cancer: A single-centre retrospective study

BackgroundPD-1 blockade has been shown to have promising efficacy and acceptable safety profiles in advanced and metastatic gastric cancer; however, the efficacy and safety of neoadjuvant PD-1 blockade-based immunotherapy plus chemotherapy in locally advanced gastric cancer (LAGC) remain uncertain.MethodsWe performed a retrospective review of patients with LAGC who received neoadjuvant treatment followed by D2 radical resection at the Affiliated Hospital of Qingdao University from 2019 to 2021. The primary aim was to investigate the difference in pathological response rates between neoadjuvant PD-1 immunotherapy plus chemotherapy and neoadjuvant chemotherapy alone. Multivariable models for pathological complete response (pCR) were constructed to investigate the factors that facilitate pCR. Trial registration: QYFYWZLL27406.ResultsA total of 77 patients were included in the analysis, among whom 34 (44.2%) received neoadjuvant PD-1 blockade immunotherapy plus chemotherapy. A higher pCR rate was observed in the neoadjuvant PD-1 blockade immunotherapy plus chemotherapy group (8 of 34, 23.5% vs. 2 of 43, 4.7%, P=0.019). Multivariate logistic regression analysis of pCR revealed neoadjuvant PD-1 blockade plus chemotherapy regimen promoted pCR (OR 12.95, P=0.016). Regarding safety, 76.5% (26 of 34) of patients in the PD-1 blockade plus chemotherapy group and 76.7% (33 of 43) of patients in the chemotherapy group experienced treatment-related adverse events (TRAEs), and grade 3 or worse adverse events were 29.4% (10 of 34) and 34.9% (15 of 43), respectively.ConclusionNeoadjuvant PD-1 blockade plus chemotherapy induced a higher pCR rate than neoadjuvant chemotherapy, and the combined therapy was tolerable in LAGC patients.