Evaluation of Log Odds of Positive Lymph Nodes in Predicting the Survival of Neoadjuvant Therapy Patients with Non-Small Cell Lung Cancer After Surgery: A SEER Cohort-Based Study

Background log odds of positive lymph nodes (LODDS) is a novel lymph node (LN) descriptor, demonstrating promising prognostic value in many tumors. However, there was limited information on LODDS in non-small cell lung cancer (NSCLC) patients, especially those receiving neoadjuvant therapy followed by lung surgery. Methods A total of 2,059 NSCLC patients who received neoadjuvant therapy and surgery were identified in the Surveillance, Epidemiology, and End Results (SEER) database. We used the X-tile software to calculate the cut-off value of LODDS. Kaplan-Meier survival analysis and receiver operating characteristics (ROC) curve were used to compare the predictive value of the American Joint Committee on Cancer (AJCC) N staging descriptor and LODDS. Univariate and multivariate Cox regression and inverse probability of treatment weighting (IPTW) analyses were conducted to construct the model predicting the prognosis. Results LODDS showed better differentiating ability in survival analysis than N staging descriptor (Log-rank test, P<0.0001 vs. P=0.031). The ROC curve demonstrated that the AUC of LODDS was significantly higher than the N staging descriptor in 1-year, 3-year, and 5-year survival analyses (All P<0.05). Univariate and multivariate Cox regression analysis showed that the LODDS was an independent risk factor for NSCLC patients receiving neoadjuvant therapy followed by surgery, both before and after IPTW (all P<0.001). A clinicopathological model with LODDS, age, gender, T, and radiotherapy could better predict the prognosis. Conclusions Compared with the AJCC N staging descriptor, LODDS exhibits better predictive ability for NSCLC patients receiving neoadjuvant therapy followed by surgery. A multivariate clinicopathological model with LODDS included demonstrates sound performance in predicting the prognosis.

Assessment of bidirectional relationships between 98 genera of the human gut microbiota and amyotrophic lateral sclerosis: a 2-sample Mendelian randomization study

Background Growing evidence suggests a mutual interaction between gut microbiome alterations and ALS pathogenesis. However, previous studies were susceptible to potential confounding factors and reverse causation bias, likely leading to inconsistent and biased results. Objectives To decipher the potentially mutual relationship between gut microbiota and ALS, we used a bidirectional two-sample MR approach to examine the associations between the gut microbiome and ALS. Results Using the inverse variance-weighted method, OTU10032 unclassified Enterobacteriaceae species-level OTU and unclassified Acidaminococcaceae were associated with a higher risk of ALS (per relative abundance: OR, 1.04; 95% CI, 1.01–1.07; P = 0.011 and OR, 1.02; 95% CI, 1.01–1.04; P = 0.009, respectively). Importantly, Gamma-Glu-Phe was showed potential deleterious effects on the risk of ALS (genetically predicted per a 1-standard deviation increase in the level of Gamma-Glu-Phe: OR, 1.96; 95% CI, 1.50–2.55; P = 0.012). Sensitivity analysis of the two candidate genera and metabolites using the MR-Egger and weighted-median methods produced similar estimates, and no horizontal pleiotropy or outliers were observed. Intriguingly, genetically predicted ALS was associated with an increase in the relative abundance of OTU4607_Sutterella (per 1-unit higher log odds: β, 2.23; 95% CI, 1.27–3.18; P = 0.020) and Lactobacillales_ORDER (per 1-unit higher log odds: β, 0.51; 95% CI, 0.09–0.94; P = 0.019). Conclusions Our findings provide novel evidence supporting the bidirectional relationship between the gut microbiota and ALS. These results may contribute to designing microbiome- and microbiome-dependent metabolite interventions in future ALS clinical trials.

Correlation between Reduced FEF25-75% and a Positive Methacholine Challenge Test in Adults with Nonobstructive Baseline Spirometry

Rationale. FEF25-75% is routinely reported on spirometry and is thought to be a marker of small airway obstruction. It is reduced in children with asthma, but its significance in adults and especially those without asthma diagnosis remains unclear. Objective. To clarify whether in adults with a nonobstructive spirometry a reduced FEF25-75% is associated with a positive methacholine challenge test (MCT). Methods. Data was collected for all the patients who had a MCT done between April 2014 and January 2020 but had nonobstructive baseline spirometry. Logistic regression was utilized to estimate the log odds of a positive methacholine test as a function of FEF25-75% and also for age, gender, BMI, FEV1, and FEV1/FVC. Results. Out of 496 patients, 187 (38%) had a positive MCT. Baseline characteristics in two groups were similar except that patients with positive MCT were younger ( 32 ± 11.57 vs. 38 ± 13.25 years, respectively, p < 0.001 ). Mean FEF25-75% was lower in MCT positive ( 3.12 ± 0.99 L/s) vs. MCT negative ( 3.39 ± 0.97 L/s) patients, p = 0.003 . Logistic regression results suggest that MCT outcome is inversely related to FEF25-75%, age, and gender. Specifically, as FEF25-75% percentage of predicted value increases, the log odds of a positive MCT decrease ( odds ratio OR = 0.90 , 95% confidence intervals CI = 0.84 ‐ 0.96 , p = 0.002 ). Also, as age increases, the log odds of a positive MCT decrease ( OR = 0.95 , 95 % CI = 0.94 ‐ 0.97 , p < 0.001 ). Conclusions. Reduced FEF25-75% in adults with nonobstructive spirometry can predict a positive response to MCT in younger patients. However, this relationship becomes weaker with increasing age.

Probability of pregnancy before ninety days postpartum in water buffaloes

This study aimed to determine the effect of parity and season of calving on the probability of water buffalo cows becoming pregnant before 90 days postpartum. A retrospective analysis of reproductive records of 1,465 water buffaloes with 3,181 pregnancies was carried out. Buffaloes were grouped according to parity in one, two, or three and more calvings. Season of calving was created with the following values: long photoperiod (March-August) and short photoperiod (September-February) and predicted probabilities from the mixed-effects logistic regression model were calculated, and a generalized linear mixed model was fitted with random intercepts to calculate the log odds of becoming pregnant ≤90 days postpartum. The probability of pregnancy ≤90 days postpartum was 0.3645, and this was lower in primiparous (0.2717) in comparison with two-calved (0.3863) and three or more calving buffaloes (0.5166). Probability of pregnancy ≤90 days postpartum increased 1.77 odds by each increase in parity. The probability of becoming pregnant ≤90 days postpartum was higher in water buffaloes calving during the short photoperiod season (0.4239 vs. 0.2474, P>0.000), and water buffaloes calving during the long photoperiod season only had 0.2645 odds to become pregnant than those calving during the short photoperiod season. The negative effect of long photoperiod was observed indifferently of parity. In conclusion, primiparity and the long photoperiod affect water buffalo cow's reproductive performance, decreasing pregnancy probability during the first 90 days postpartum.

Expanding the phenotypic spectrum of mutations in LRP2: a novel candidate gene of non-syndromic familial comitant strabismus

Background Comitant strabismus (CS) is a heterogeneous disorder that is a major contributing factor to unilateral childhood-onset visual impairment. Studies have confirmed that genetic factors play an important role in the development of CS. The aim of this study was to identify the genetic cause of non-syndromic familial CS. Methods Fourteen unrelated CS families were recruited for the study. Twelve affected and 2 unaffected individuals from a large four-generation family (CS08) were selected to perform whole genome-wide linkage analysis. Parallel whole-exome sequencing (WES) was conducted in the same family (9 patients and 1 unaffected member) and 31 additional CS cases from 13 other unrelated families. Sanger sequencing was used to determine whether any of the remaining variants co-segregated with the disease phenotype in the corresponding family. Results Based on linkage analysis, CS in family CS08 mapped to a novel region of 34.17 centimorgan (cM) on chromosome 2q22.3-2q32.1 between markers D2S151 and D2S364, with a maximum log odds (LOD) score of 3.54 (theta = 0) at D2S142. Parallel WES identified a heterozygous variant, LRP2 c.335 A > G (p.Q112R), located in such a linkage interval that completely co-segregated with the disease in the family. Furthermore, another novel heterozygous variant (c.7274A > G, p.D2425G) in LRP2 that co-segregated was detected in 2 additional affected individuals from another unrelated family by WES. Both variants are predicted to be damaging by PolyPhen-2, SIFT and MutationTaster, and were absent in 100 ethnically matched normal controls. Conclusion LRP2 is a novel candidate genetic cause of non-syndromic familial CS.

Additive Bayesian network analysis of the relationship between bovine respiratory disease and management practices in dairy heifer calves at pre-weaning stage

Background Nursery farms that accept nursing and growing pre-weaned heifer calves from private dairy farms must work to prevent bovine respiratory disease (BRD). Knowledge of the BRD-associated risk factors related to calf management and calves’ condition will help to develop appropriate neonatal management practices at original farms and to identify calves at higher risk for BRD at nursery farms. In this study, the relationship between BRD and calf management practices (colostrum feeding, dam parity, serum total protein concentration at introduction (TP), body weight at introduction, introduction season, and daily average growth) was investigated using observational data from pre-weaned dairy calves introduced into a nursery farm in Hokkaido, Japan between 2014 and 2018 (n = 3185). Using additive Bayesian network (ABN) analysis, which is a multivariate statistical modelling approach, the direct and indirect associations between these factors were assessed. Results Colostrum feeding contributed to an increase in TP (correlation 1.02 [95 % CI, 0.94;1.10]), which was negatively associated with BRD directly (log odds ratio − 0.38 [− 0.46;−0.31]) and indirectly through increasing daily growth (correlation 0.12 [0.09;0.16]). Calves of multiparous dams had higher body weight at introduction (correlation 0.82 [0.74;0.89]), which indirectly reduced BRD risk through the increasing daily growth (correlation 0.17 [0.14;0.21]). Calves introduced during winter had the highest risk for BRD (log odds ratio 0.29 [0.15;0.44]), while those introduced in summer had the lowest risk (log odds ratio − 0.91 [− 1.06;−0.75]). The introduction season was also associated with BRD indirectly through dam parity, body weight at introduction, and daily growth. Conclusions The following calf management practices are recommended for preventing BRD in pre-weaned calves at nursery farms: (1) encouraging colostrum feeding to neonatal calves at their original farms; and (2) identifying calves with higher BRD risk, i.e., those without feeding colostrum, born to primiparous cattle, with low body weight at introduction, and/or introduced in winter, and paying intensive attention to the calves for rapid detection of BRD. ABN analysis applied enabled us to understand the complex inter-relationships between BRD incidence and the risk factors, which will help to reduce BRD incidence and to rear healthy calves at nursery farms.

The log odds of positive neck lymph nodes is a superior lymph node predictor for overall survival in head and neck cancer: a population-based analysis in Germany

Background This population-based study investigated the influence of different lymph node (LN) classifications on overall survival (OS) in head and neck cancer (HNC). Methods 401 patients (median age: 57 years; 47% stage IV) of the Thuringian cancer registries with diagnosis of a primary HNC receiving a neck dissection (ND) in 2009 and 2010 were included. OS was assessed in relation to total number of LN removed, number of positive LN, LN ratio, and log odds of positive LN (LODDS). Results Mean number of LODDS was 0–0.96 ± 0.57. When limiting the multivariate analysis to TNM stage, only the UICC staging (stage IV: HR 9.218; 95% CI 2.721–31.224; p < 0.001) and LODDS > – 1.0 (HR 2.120; 95% CI 1.129–3.982; p = 0.019) were independently associated with lower OS. Conclusion LODDS was an independent and superior predictor for OS in HNC in a population-based setting with representative real-life data.

Downstream funding success of early career researchers for resubmitted versus new applications: A matched cohort

Background Early career researchers face a hypercompetitive funding environment. To help identify effective intervention strategies for early career researchers, we examined whether first-time NIH R01 applicants who resubmitted their original, unfunded R01 application were more successful at obtaining any R01 funding within 3 and 5 years than original, unfunded applicants who submitted new NIH applications, and we examined whether underrepresented minority (URM) applicants differentially benefited from resubmission. Our observational study is consistent with an NIH working group’s recommendations to develop interventions to encourage resubmission. Methods and findings First-time applicants with US medical school academic faculty appointments who submitted an unfunded R01 application between 2000–2014 yielded 4,789 discussed and 7,019 not discussed applications. We then created comparable groups of first-time R01 applicants (resubmitted original R01 application or submitted new NIH applications) using optimal full matching that included applicant and application characteristics. Primary and subgroup analyses used generalized mixed models with obtaining any NIH R01 funding within 3 and 5 years as the two outcomes. A gamma sensitivity analysis was performed. URM applicants represented 11% and 12% of discussed and not discussed applications, respectively. First-time R01 applicants resubmitting their original, unfunded R01 application were more successful obtaining R01 funding within 3 and 5 years than applicants submitting new applications—for both discussed and not discussed applications: discussed within 3 years (OR 4.17 [95 CI 3.53, 4.93]) and 5 years (3.33 [2.82–3.92]); and not discussed within 3 years (2.81 [2.52, 3.13]) and 5 years (2.47 [2.22–2.74]). URM applicants additionally benefited within 5 years for not discussed applications. Conclusions Encouraging early career researchers applying as faculty at a school of medicine to resubmit R01 applications is a promising potential modifiable factor and intervention strategy. First-time R01 applicants who resubmitted their original, unfunded R01 application had log-odds of obtaining downstream R01 funding within 3 and 5 years 2–4 times higher than applicants who did not resubmit their original application and submitted new NIH applications instead. Findings held for both discussed and not discussed applications.