Author: Nevin Manimala

Neuro Oncol. 2023 Jan 7:noad002. doi: 10.1093/neuonc/noad002. Online ahead of print.

ABSTRACT

Durable objective response rate (ORR) remains a meaningful endpoint in recurrent cancer; however, the target ORR for single arm recurrent glioblastoma trials has not been based on historic information or tied to patient outcomes. The current study reviewed 68 treatment arms comprising 4,793 patients in past trials in recurrent glioblastoma in order to judiciously define target ORRs for use in recurrent glioblastoma trials. ORR was estimated at 6.1%[95% CI 4.23; 8.76%] for cytotoxic chemotherapies (ORR=7.59% for CCNU, 7.57% for TMZ, 0.64% for CPT-11, and 5.32% for other agents), 3.37% for biologic agents, 7.97% for (select) immunotherapies, and 26.8% for anti-angiogenic agents. ORRs were significantly correlated with median overall survival (mOS) across chemotherapy (R2=0.4078,P<0.0001), biologics (R2=0.4003,P=0.0003), and immunotherapy trials (R2=0.8994,P<0.0001), but not anti-angiogenic agents (R2=0, P=0.8937). Pooling data from chemotherapy, biologics, and immunotherapy trials, a meta-analysis indicated a strong correlation between ORR and mOS (R2=0.3900, P<0.0001; mOS[weeks]=1.4xORR+24.8). Assuming an ineffective cytotoxic (control) therapy has ORR=7.6%, the average ORR for lomustine and temozolomide trials, a sample size of ≥40 patients with target ORR>25% is needed to demonstrate statistical significance compared to control with a high level of confidence (P<0.01) and adequate power (>80%). Given this historic data and potential biases in patient selection, we recommend that well-controlled, single-arm phase II studies in recurrent glioblastoma should have a target ORR >25% (which translates to a median OS of approximately 15 months) and a sample size of ≥40 patients, in order to convincingly demonstrate antitumor activity. Crucially, this response needs to have sufficient durability, which was not addressed in the current study.

PMID:36617262 | DOI:10.1093/neuonc/noad002

J Anim Sci. 2023 Jan 7:skad008. doi: 10.1093/jas/skad008. Online ahead of print.

ABSTRACT

Reducing age at first calving has been a challenge in beef herds. There is anecdotal evidence that herd owners choose to calve heifers older because of the perceived consequences of calving heifers at 24 mo of age compare to 36 mo on performance traits in beef herds. The objective of this study was to estimate the association of calving heifers at younger ages on subsequent performance traits, calving interval, longevity, cow weight, dystocia and progeny weaning weight for parities 1 to 5. Available to the study after data edits were 219,818 calving interval records, 219,818 longevity records, 118,504 cow live-weight records, 230,998 dystocia records and 230,998 weaning weight records. Linear mixed models were used to quantify performance of each trait in age at first calving (AFC) groups for each parity. As parity increased, there was a favorable reduction in calving interval and dystocia (P<0.001), while the likelihood of cows surviving reduced (P<0.001). Both cow live-weight and progeny weaning weight increased as parity increased. Age at first calving only had a significant association with dystocia within parity one (P<0.001), where older heifers at first calving subsequently had lower risk of calving. Calving interval for parity 1 cows was observed to be longer by 6 days in cows that calved for the first time at 33 to 36 months compared to cows calved for the first time at 22 to 24 months (P<0.001). No statistical difference was observed for longevity between cows with an AFC of 22 to 24 mo compared to cows with an AFC of 33 to 36 mo (P>0.05). Cows that calved at a younger age did wean lighter calves for their first 3 lactations (P<0.01) but had no association with weaning weight for parity 4 and 5 cows (P>0.05). Cows with a lower AFC were lighter for parity 1, 2, 3 and 4 (P<0.001); at parity 5, AFC had no association with cow live-weight (P>0.05). The performance of mature cows for calving interval, longevity, calving difficulty, cow live-weight and weaning weight was not impacted by AFC. In conclusion, calving cows for the first time at younger ages does pose risks and associated performance loss but this risk and loss should be minimized by good management.

PMID:36617256 | DOI:10.1093/jas/skad008

Arch Clin Neuropsychol. 2023 Jan 6:acac110. doi: 10.1093/arclin/acac110. Online ahead of print.

ABSTRACT

OBJECTIVE: It is essential to interpret performance validity tests (PVTs) that are well-established and have strong psychometrics. This study evaluated the Child and Adolescent Memory Profile (ChAMP) Validity Indicator (VI) using a pediatric sample with traumatic brain injury (TBI).

METHOD: A cross-sectional sample of N = 110 youth (mean age = 15.1 years, standard deviation [SD] = 2.4 range = 8-18) on average 32.7 weeks (SD = 40.9) post TBI (71.8% mild/concussion; 3.6% complicated mild; 24.6% moderate-to-severe) were administered the ChAMP and two stand-alone PVTs. Criterion for valid performance was scores above cutoffs on both PVTs; criterion for invalid performance was scores below cutoffs on both PVTs. Classification statistics were used to evaluate the existing ChAMP VI and establish a new VI cutoff score if needed.

RESULTS: There were no significant differences in demographics or time since injury between those deemed valid (n = 96) or invalid (n = 14), but all ChAMP scores were significantly lower in those deemed invalid. The original ChAMP VI cutoff score was highly specific (no false positives) but also highly insensitive (sensitivity [SN] = .07, specificity [SP] = 1.0). Based on area under the curve (AUC) analysis (0.94), a new cutoff score was established using the sum of scaled scores (VI-SS). A ChAMP VI-SS score of 32 or lower achieved strong SN (86%) and SP (92%). Using a 15% base rate, positive predictive value was 64% and negative predictive value was 97%.

CONCLUSIONS: The originally proposed ChAMP VI has insufficient SN in pediatric TBI. However, this study yields a promising new ChAMP VI-SS, with classification metrics that exceed any other current embedded PVT in pediatrics.

PMID:36617240 | DOI:10.1093/arclin/acac110

Mol Biol Evol. 2023 Jan 7:msad001. doi: 10.1093/molbev/msad001. Online ahead of print.

ABSTRACT

Adaptive introgression (AI) facilitates local adaptation in a wide range of species. Many state-of-the-art methods detect AI with ad-hoc approaches that identify summary statistic outliers or intersect scans for positive selection with scans for introgressed genomic regions. Although widely used, approaches intersecting outliers are vulnerable to a high false-negative rate as the power of different methods varies, especially for complex introgression events. Moreover, population genetic processes unrelated to AI, such as background selection or heterosis, may create similar genomic signals to AI, compromising the reliability of methods that rely on neutral null distributions. In recent years, machine learning (ML) methods have been increasingly applied to population genetic questions. Here, we present a ML-based method called MaLAdapt for identifying AI loci from genome-wide sequencing data. Using an Extra-Trees Classifier algorithm, our method combines information from a large number of biologically meaningful summary statistics to capture a powerful composite signature of AI across the genome. In contrast to existing methods, MaLAdapt is especially well-powered to detect AI with mild beneficial effects, including selection on standing archaic variation, and is robust to non-AI selective sweeps, heterosis from deleterious mutations, and demographic misspecification. Further, MaLAdapt outperforms existing methods for detecting AI based on the analysis of simulated data and on a validation of empirical signals through visual inspection of haplotype patterns. We apply MaLAdapt to the 1000 Genomes Project human genomic data, and discover novel AI candidate regions in non-African populations, including genes that are enriched in functionally important biological pathways regulating metabolism and immune responses.

PMID:36617238 | DOI:10.1093/molbev/msad001

Dis Esophagus. 2023 Jan 6:doac100. doi: 10.1093/dote/doac100. Online ahead of print.

ABSTRACT

It is unknown whether Ivor Lewis (IL) or McKeown (McK) esophagectomy is preferred in patients with potentially curable esophageal or gastro-esophageal junction (GEJ) cancer. Patients with mid- and distal esophageal and GEJ cancer without distant metastases who underwent IL or McK esophagectomy in the Netherlands between 2015 and 2017, were selected from the Netherlands Cancer Registry. Patients were propensity score matched for sex, age, American Society of Anesthesiologist classification, comorbidity, tumor type, tumor location, clinical stage, neoadjuvant treatment and year of diagnosis. The primary outcome was a 3-year relative survival (RS). Secondary outcome parameters were number of lymph nodes examined, number of positive lymph nodes, radical resection rate, tumor regression grade, post-operative complications and mortality. A total of 1627 patients who underwent IL (n = 1094) or McK (n = 533) esophagectomy were included. Patient and tumor characteristics were balanced after propensity score matching, leaving 658 patients to be compared. The 3-year RS was 54% after IL and 50% after McK esophagectomy, P = 0.140. The median number of lymph nodes examined, median number of positive lymph nodes, radical resection rate and tumor regression grade were comparable between both groups. Recurrent laryngeal nerve palsy (2 vs. 5%, P = 0.006) occurred less frequently after IL esophagectomy. No differences were observed in post-operative anastomotic leakage rate, pulmonary complication rate and mortality rates. There was no statistically significant difference in the 3-year RS between IL and McK esophagectomy. Based on these results, both IL and McK esophagectomy can be performed in patients with mid to distal esophageal and GEJ cancer.

PMID:36617230 | DOI:10.1093/dote/doac100

J Burn Care Res. 2023 Jan 6:irad002. doi: 10.1093/jbcr/irad002. Online ahead of print.

ABSTRACT

A history of malignancy is associated with worse outcomes in cardiac disease and trauma. Our objective was to determine if a past medical history or comorbid condition of cancer portends an increased morbidity or mortality in burns or skin-sloughing disorders at our institution. Patients were identified using our Institutional Burn Center registry and linked to the clinical and administrative data. All patients admitted between January 1, 2014 and June 30, 2021 were eligible for inclusion. Demographics, length of stay, comorbid conditions and mortality were evaluated. Statistical analysis was performed with Kruskal-Wallis, chi-square, and Fisher’s exact tests. Seven thousand three hundred seventy-two patients were admitted during this time period. Three hundred eighty-six patients had a history of cancer (5%). Patients with a history of cancer were older (56 versus 44 years, p<0.0001). They had a significantly longer length of stay (16 versus 10 days, p<0.0001). They also had larger burns and higher hospital costs ($147,021 versus $83,788, p<0.0001), were more likely to be male and more likely to have a skin-sloughing disorder. A history of cancer was not associated with increased odds of burn mortality. Thus, a history of cancer is associated with increased lengths of stay and costs in patients admitted for burn injury or skin-sloughing disorders, but not associated with increased mortality. Further study is warranted to investigate and mitigate what aspects of their care could be adjusted to improve outcomes.

PMID:36617221 | DOI:10.1093/jbcr/irad002

Int J Fertil Steril. 2023 Jan 1;17(1):75-79. doi: 10.22074/ijfs.2022.548477.1259.

ABSTRACT

BACKGROUND: Nowadays, using medicinal properties is a good alternative for infertility treatment to use them is increasing in the world. The aim of this study was to determine the effects of Herbal oral capsules included palm pollen extract (DPP) and Nigella Sativa extract (NS) on sex hormones in adult infertile men.

MATERIALS AND METHODS: In this a single-blind, placebo-controlled clinical trial study, a total of 62 infertile men between 22 and 42 years of age were randomly selected and tested for sex hormones and prolactin. Thirty people in the case group received two 500 mg/kg capsules on a daily basis containing an herbal composition of palm pollen extract (350 mg) and black seed powder extract (250 mg) and the 20 in the control group received a placebo in the morning and at night for 3 months. The herbal composition capsules were manufactured by the Golbadistan Company. At the end of the three -month period, blood and semen tests were performed before and after the intervention in the case group that was compared with the control group. Hormonal assays were performed by Immunoradiometric Assay (IRMA) method. The data entered SPSS statistical software and the level of significance was set at P≤0.05.

RESULTS: The spermiogram test results showed significant changes in the sperm count, progressive motility and rapid progressivity of the case group at the end of a quarterly period after consuming plant composition except for morphology (P=0.001, P=0.001, P=0.02, P=0.23). In addition, in the case group, the concentration of testosterone, follicle stimulating hormone (FSH), luteinizing hormone (LH) was significantly increased compared to the control group (P=0.000, P=0.004, P=0.012).

CONCLUSION: It seems that taking one 500 mg/kg capsule of DPP and NS extract can significantly increase sperm parameters and testosterone (registration number: IRCT2015020120895N1).

PMID:36617207 | DOI:10.22074/ijfs.2022.548477.1259

Int J Fertil Steril. 2023 Jan 1;17(1):7-11. doi: 10.22074/ijfs.2022.542410.1219.

ABSTRACT

Toxoplasma gondii is found as an intracellular protozoan parasite in the Apicomplexa phylum that can be transmitted to the fetus and causes miscarriage, infection, and asymptomatic neonatal disease. In the present study, we characterized the seroprevalence rate of anti-Toxoplasma gondii antibodies in a population of Iranian women with a recent a spontaneous abortion. We examined our national and international databases including Irandoc, Magiran, SID, Medlib, Scopus, PubMed, and the Science Direct. The search strategy was carried out by using keywords and MeSH terms. The statistical analysis was performed by STATA 14.2. By using the random effects model and the fixed effects model the statistical analysis was performed while the heterogeneity was ≥75 and ≤50%, respectively. We used the chi-squared test and I2 index to calculate heterogeneity among studies, and for evaluating publication bias, Funnel plots and Egger tests were used. The seroprevalence positive rate of IgG among women who had experienced abortion was observed 32% [95% confidence interval (CI): 20-45%] based on the random-effects model. The seroprevalence positive rate of IgM based on the fixed-effect model and positive IgG rate based on the random-effect model was evaluated 4% (95% CI: 3-6%) and 32% (9% CI: 3-42%) among women immediately after an abortion, respectively. According to the finding of our study, toxoplasmosis can be one of the most significant causes of abortion.

PMID:36617196 | DOI:10.22074/ijfs.2022.542410.1219

Brief Bioinform. 2023 Jan 6:bbac607. doi: 10.1093/bib/bbac607. Online ahead of print.

ABSTRACT

Differential abundance analysis (DAA) is one central statistical task in microbiome data analysis. A robust and powerful DAA tool can help identify highly confident microbial candidates for further biological validation. Current microbiome studies frequently generate correlated samples from different microbiome sampling schemes such as spatial and temporal sampling. In the past decade, a number of DAA tools for correlated microbiome data (DAA-c) have been proposed. Disturbingly, different DAA-c tools could sometimes produce quite discordant results. To recommend the best practice to the field, we performed the first comprehensive evaluation of existing DAA-c tools using real data-based simulations. Overall, the linear model-based methods LinDA, MaAsLin2 and LDM are more robust than methods based on generalized linear models. The LinDA method is the only method that maintains reasonable performance in the presence of strong compositional effects.

PMID:36617187 | DOI:10.1093/bib/bbac607

J AOAC Int. 2023 Jan 6:qsad006. doi: 10.1093/jaoacint/qsad006. Online ahead of print.

ABSTRACT

BACKGROUND: Given the recent detection of TTX in bivalve molluscs but the absence of a full collaborative validation study for TTX determination in a large number of shellfish samples, interlaboratory assessment of method performance was required to better understand current capabilities for accurate and reproducible TTX quantitation using chemical and immunoassay methods.

OBJECTIVE: The aim was to conduct a collaborative study with multiple laboratories, using results to assess method performance and acceptability of different TTX testing methods.

METHODS: Homogenous and stable mussel and oyster materials were assessed by participants using a range of published and in-house detection methods to determine mean TTX concentrations. Data was used to calculate recoveries, repeatability and reproducibility, together with participant acceptability z-scores.

RESULTS: Method performance characteristics were good, showing excellent sensitivity, recovery and repeatability. Acceptable reproducibility was evidenced by HorRat values for all LC-MS/MS and ELISA methods being less than the 2.0 limit of acceptability. Method differences between the LC-MS/MS participants did not result in statistically-different results. Method performance characteristics compared well with previously-published single-laboratory validated methods and no statistical difference was found in results returned by ELISA in comparison with LC-MS/MS.

CONCLUSIONS: The results from this study demonstrate that current LC-MS/MS methods and the ELISA are on the whole capable of sensitive, accurate and reproducible TTX quantitation in shellfish. Further work is recommended to expand the number of laboratories testing ELISA and to standardise an LC-MS/MS protocol to further improve interlaboratory precision.

HIGHLIGHTS: Multiple mass spectrometric methods and a commercial ELISA have been successfully assessed through collaborative study, demonstrating excellent performance.

PMID:36617186 | DOI:10.1093/jaoacint/qsad006