Nevin Manimala

Thorac Cancer. 2022 Nov 21. doi: 10.1111/1759-7714.14730. Online ahead of print.

ABSTRACT

OBJECTIVES: This study investigated whether radiomic features extracted from radial-probe endobronchial ultrasound (radial EBUS) images can assist in decision-making for subsequent clinical management in cases with indeterminate pathologic results.

METHODS: A total of 494 patients who underwent radial EBUS biopsy for lung nodules between January 2017 and December 2018 were allocated to our training set. For the validation set, 229 patients with radial EBUS biopsy results from January 2019 to April 2020 were used. A multivariate logistic regression analysis was used for feature selection and prediction modeling.

RESULTS: In the training set, 157 (67 benign and 90 malignant) of 212 patients pathologically diagnosed as indeterminate were analyzed. In the validation set, 213 patients were diagnosed as indeterminate, and 158 patients (63 benign and 95 malignant) were included in the analysis. The performance of the radiomics-added model, which considered satellite nodules, linear arc, shape, patency of vessels and bronchi, echogenicity, spiculation, C-reactive protein, and minimum histogram, was 0.929 for the training set and 0.877 for the validation set, whereas the performance of the model without radiomics was 0.910 and 0.891, respectively.

CONCLUSION: Although the next diagnostic step for indeterminate lung biopsy results remains controversial, integrating various factors, including radiomic features from radial EBUS, might facilitate decision-making for subsequent clinical management.

PMID:36408780 | DOI:10.1111/1759-7714.14730

Biometrics. 2022 Nov 21. doi: 10.1111/biom.13785. Online ahead of print.

ABSTRACT

I discuss the assumptions needed for identification of average treatment effects and local average treatment effects in instrumented difference-in-differences (IDID), and the possible trade-offs between assumptions of standard IV and those needed for the new proposal IDID, in one- and two-sample settings. I also discuss the interpretation of the estimands identified under monotonicity. I conclude by suggesting possible extensions to the estimation method, by outlining a strategy to use data-adaptive estimation of the nuisance parameters, based on recent developments.

PMID:36408762 | DOI:10.1111/biom.13785

Pharmacogenomics. 2022 Nov 21. doi: 10.2217/pgs-2022-0123. Online ahead of print.

ABSTRACT

Aim: To investigate the influence of CYP3A5 and IL-10 polymorphisms on tarcolimus metabolism and renal function for renal transplantation recipients at a stable period. Methods: CYP3A5 and IL-10 polymorphisms, together with other clinical factors, were collected for 149 renal transplantation patients at postoperative stable period. Statistics analysis was performed to explore key factors affecting tarcolimus metabolism. Results: CYP3A5 6986A >G and IL-10 -819C >T significantly impacted tacrolimus metabolism (p < 0.001). CYP3A5 6986A >G G allele and IL-10 -819C >T T allele were associated with poorer tacrolimus metabolic capability. Patients with various tacrolimus metabolism rates presented little difference in renal functions at stable period. Conclusion: Genotyping of CYP3A5 and IL-10 might benefit the precision dosage of tacrolimus for renal transplantation recipients.

PMID:36408735 | DOI:10.2217/pgs-2022-0123

Mol Oncol. 2022 Nov 21. doi: 10.1002/1878-0261.13345. Online ahead of print.

ABSTRACT

Epigenome-wide gene-gene (G×G) interactions associated with non-small cell lung cancer (NSCLC) survival may provide insights into molecular mechanisms and therapeutic targets. Hence, we proposed a three-step analytic strategy to identify significant and robust G×G interactions that are relevant to NSCLC survival. In the first step, among 49 billion pairs of DNA methylation probes, we identified 175,775 G×G interactions with P_Bonferroni ≤0.05 in the discovery phase of epigenomic analysis; among them, 15,534 were confirmed with P≤0.05 in the validation phase. In the second step, we further performed a functional validation for these G×G interactions at the gene expression level by way of a two-phase (discovery and validation) transcriptomic analysis, and confirmed 25 significant G×G interactions enriched in the 6p21.33 and 6p22.1 regions. In the third step, we identified two G×G interactions using the trans-omics analysis, which had significant (P≤0.05) epigenetic cis-regulation of transcription and robust G×G interactions at both the epigenetic and transcriptional levels. These interactions were cg14391855×cg23937960 (β_interaction =0.018, P=1.87×10^-12 ), which mapped to RELA×HLA-G (β_interaction =0.218, P=8.82×10^-11 ), and cg08872738×cg27077312 (β_interaction =-0.010, P=1.16×10^-11 ), which mapped to TUBA1B×TOMM40 (β_interaction =-0.250, P=3.83×10^-10 ). A trans-omics mediation analysis revealed that 20.3% of epigenetic effects on NSCLC survival were significantly (P=0.034) mediated through transcriptional expression. These statistically significant trans-omics G×G interactions can also discriminate patients with high risk of mortality. In summary, we identified two G×G interactions at both the epigenetic and transcriptional levels, and our findings may provide potential clues for precision treatment of NSCLC.

PMID:36408734 | DOI:10.1002/1878-0261.13345

J Clin Lab Anal. 2022 Nov 21:e24780. doi: 10.1002/jcla.24780. Online ahead of print.

ABSTRACT

BACKGROUND: IL-10 is thought to play an important role in preventing inflammatory bowel disease (IBD), although its efficacy is limited in IBD inflammation treatment. The purpose of this study is to investigate the association between SNP polymorphism in the promoter region of the IL-10 gene and Crohn’s disease (CD).

METHODS: In 86 children with CD disease and 142 healthy controls, polymorphisms of three SNPs (rs3790622, rs1800872, and rs1800896) in the IL-10 promoter region were successfully identified. The risk alleles, genotypes, and haplotypes were also analyzed in the CD patient group and the control group. 2 × 2 chi-square test was used to identify whether there is a statistically significant association between CD risk and SNP polymorphisms.

RESULTS: According to the chi-square test results, only the polymorphism of rs1800872 was associated with pediatric CD. T allele in rs1800872 showed a high risk for pediatric CD (Pearson χ² p = 0.030). TT genotype of rs1800872 was associated with a higher risk of CD in the pediatric population (OR 1.986, 95% CI 1.146-3.442, p = 0.020, TT vs. TG + GG). Finally, a risk haplotype GTT (rs3790622-rs1800872-rs1800896) in IL-10 was found (OR 1.570, 95% CI 1.054-2.341, p = 0.028).

CONCLUSIONS: Our data suggested that T allele, TT genotype, and haplotype GTT in rs1800872 were associated with the susceptibility to pediatric CD in China.

PMID:36408729 | DOI:10.1002/jcla.24780

Br J Educ Psychol. 2022 Nov 21. doi: 10.1111/bjep.12558. Online ahead of print.

ABSTRACT

BACKGROUND: COVID-19 has resulted in some educators and allied health practitioners transitioning to online delivery of literacy instruction. As far as we are aware, no studies have investigated online delivery of comprehensive literacy instruction for children with Down syndrome.

AIMS: In this pilot study, we explore the efficacy of online delivery of ABRACADABRA (a free literacy web application) for children with Down syndrome, alongside supplementary parent-led shared book reading, during the COVID-19 pandemic.

SAMPLE: Six children with Down syndrome, aged 8-12 years, participated in this within-participants design study.

METHODS: Participants acted as their own controls with outcome variables measured at three timepoints: baseline, pre-instruction and post-instruction. Children participated in 16-18 hrs of one-to-one literacy instruction online over a 6-week instruction phase, along with twice weekly parent-led shared book reading activities.

RESULTS: Outcomes from standardized assessments revealed statistically significant improvements in word- and passage-level reading accuracy skills over the instruction phase (pre-instruction to post-instruction) compared with the no-instruction control phase (baseline to pre-instruction). Improvements in reading comprehension skills were inconsistent across assessment measures and statistical analyses.

CONCLUSION: Children with Down syndrome can benefit from comprehensive literacy instruction delivered via telepractice. Our study provides critical initial evidence of successful service delivery during a global pandemic and beyond.

PMID:36408697 | DOI:10.1111/bjep.12558

Geriatr Gerontol Int. 2022 Nov 21. doi: 10.1111/ggi.14508. Online ahead of print.

ABSTRACT

AIM: To examine the relationship between the number of present and functional teeth at baseline and future incidence of loss of independence.

METHODS: Participants were community-dwelling older individuals who participated in a comprehensive geriatric health examination conducted in Kusatsu town, Japan, between 2009 and 2015. The primary endpoint was the incidence of loss of independence among participants, defined as the first certification of long-term care insurance in Japan. The numbers of present and functional teeth at baseline were determined via an oral examination. Demographics, clinical variables (e.g., history of chronic diseases and psychosocial factors), blood nutritional markers, physical functions, and perceived masticatory function were assessed.

RESULTS: This study included 1121 individuals, and 205 individuals suffered from loss of independence during the follow-up period. Kaplan-Meier estimates of loss of independence for participants with smaller numbers of present and functional teeth were significantly greater than for those with larger numbers of teeth. Cox proportional hazard analyses indicated that a smaller number of present teeth was not a significant risk factor after adjusting for demographic characteristics. However, the number of functional teeth was a significant risk factor after the adjustment (hazard ratio: 1.975 [1.168-3.340]). Additionally, higher hazard ratios were observed in other adjusted models, but they were not statistically significant.

CONCLUSIONS: The number of functional teeth may be more closely related to the future incidence of loss of independence than the number of present teeth. This novel finding suggests that prosthodontic rehabilitation for tooth loss possibly prevents the future incidence of this life-event. Geriatr Gerontol Int 2022; ••: ••-••.

PMID:36408675 | DOI:10.1111/ggi.14508

J Dairy Res. 2022 Nov 21:1-4. doi: 10.1017/S0022029922000723. Online ahead of print.

ABSTRACT

The aim of the research reported in this Research Communication was to apply the 5-point body condition scoring (BCS) system to dairy buffaloes and subjectively validate it by assessing the intra- and inter-assessor agreement. For this purpose, the BCS system developed for dairy cows was applied to buffaloes. A total of 230 Nili Ravi buffaloes of varying parity, lactation stages and pregnancy status were enrolled from the Buffalo Research Institute, Pattoki, Pakistan. Four observers independently assigned BCS values to each enrolled buffalo in two phases, as follows: (1) during phase I, the assessors were trained for BCS assessment using a BCS chart developed by Elanco Animal Health Ltd.; and (2) during phase II, the assessors were trained using live buffaloes for BCS assessment. Kappa statistics (kw) were used to determine the intra- and inter-assessor agreement. The results revealed that the exact overall inter- and intra-assessor agreement was moderate (kw = 0.48-0.55) and increased to substantial levels after training on live animals (kw = 0.63-0.87). Furthermore, the intra- and inter-assessor exact agreement was higher (kw = 0.57-0.58) for buffaloes tied to the mangers compared to the buffaloes standing in the loafing area (kw = 0.50). The inter-assessor agreements within 0.25 and 0.5 points were almost perfect (kw = 0.97-1.0). The current results suggested that the 5-point BCS system (using a scale from 1 to 5 with 0.25 increments) had substantial agreement for assessment and repeatability when applied to buffaloes.

PMID:36408674 | DOI:10.1017/S0022029922000723

Cancer. 2022 Nov 21. doi: 10.1002/cncr.34507. Online ahead of print.

ABSTRACT

BACKGROUND: Antibody-drug conjugates (ADCs) have complex molecular structures and have been tested in numerous clinical trials. Therefore, understanding the mechanisms of their toxicity when applied in medical practice is of high importance.

METHODS: In a systematic review and meta-analysis of data gathered from different scientific databases (PubMed, Embase, Cochrane, and Web of Science) between January 1, 2000, and June 7, 2022, the authors applied a random-effects model with logit transformation and evaluated the heterogeneity between studies using I² statistics. The primary outcome was the incidence and 95% confidence interval (CI) for all-grade and grade ≥3 treatment-related adverse events and differences between different drugs, molecular structures, and cancer types.

RESULTS: In total, 2511 records were identified that included 169 clinical trials involving 22,492 patients. The overall incidence of treatment-related adverse events was 91.2% (95% CI, 90.7%-91.7%; I² = 95.9%) for all-grade adverse events and 46.1% (95% CI, 45.2%-47.0%; I² = 96.3%) for grade ≥3 adverse events. The most common all-grade adverse events were lymphopenia (53.0%; 95% CI, 48.7%-57.3%), nausea (44.1%; 95% CI, 43.2%-44.9%), neutropenia (43.7%; 95% CI, 42.6%-44.9%), blurred vision (40.5%; 95% CI, 37.4%-43.6%), and peripheral neuropathy (39.6%; 95% CI, 38.2%-41.1%); and the most common grade ≥3 adverse events were neutropenia (31.2%; 95% CI, 30.2%-32.3%), hypoesthesia (23.3%; 95% CI, 10.6%-35.9%), thrombocytopenia (22.6%; 95% CI, 21.3%-23.9%), febrile neutropenia (21.2%; 95% CI, 19.3%-23.1%), and lymphopenia (21.0%; 95% CI, 18.2%-23.7%).

CONCLUSIONS: Different ADCs appear to affect various treatment-related adverse events and provide comprehensive data on treatment-related adverse events for ADCs. The current results provide an important reference for clinicians and patients on how to care for toxicities from ADCs in clinical practice.

LAY SUMMARY: Unique anticancer drugs called antibody-drug conjugates (ADCs) have made significant progress in oncology in recent years because of their great success, and they are rapidly being used in the clinic as well as in hundreds of ongoing trials exploring their further use. The occurrence of serious side effects (adverse events) related to the receipt of ADCs was studied using data from 169 clinical trials involving 22,492 patients to determine the treatment-related causes of higher toxicity and adverse events in patients who receive ADCs, because these data are crucial for informing physicians how to safely treat patients using ADCs. The results indicate that different ADCs appear to affect various adverse events related to their use, providing comprehensive data on these ADCs that provide an important reference for clinicians and patients on how to care for toxicities from ADCs in clinical practice.

PMID:36408673 | DOI:10.1002/cncr.34507

Colorectal Dis. 2022 Nov 21. doi: 10.1111/codi.16424. Online ahead of print.

ABSTRACT

INTRODUCTION: Empty pelvis syndrome is a source of considerable morbidity following a total pelvic exenteration. None of the available methods have been universally successful in mitigating this problem. We aimed to evaluate the safety and efficacy of the obstetric Bakri balloon in preventing empty pelvis syndrome.

METHODS: Combined prospective and retrospective study of all total pelvic exenterations for rectal cancers from a single institution was performed between October 2013 to May 2022. Bakri balloon was used since December 2019 in all patients that provided consent. Empty pelvis syndrome within 90 days was the primary end point, and included bowel obstruction, pelvic collection, and entero-perineal fistula. Comparison with the patients that did not have a Bakri balloon was performed.

RESULTS: Seventy-five patients with Bakri balloon were compared with 96 patients without the balloon placed after pelvic exenterations. No patient experienced an untoward complication from balloon deployment. The incidence of empty pelvis syndrome was 13.3% and 22.9% in the Bakri and no Bakri cohort, respectively (p-0.110). Every component of empty pelvis syndrome was proportionally lower without statistical significance. The number needed to treat to prevent EPS using the Bakri balloon was ten based on point estimates.

CONCLUSIONS: The use of Bakri balloon was safe without serious adverse events. The incidence of EPS after TPE was not statistically different with the use of Bakri Balloon despite a 9.6% reduction. A larger comparative study is needed to evaluate the efficacy of the balloon.

PMID:36408669 | DOI:10.1111/codi.16424