Nevin Manimala

J Nutr. 2021 Oct 2:nxab348. doi: 10.1093/jn/nxab348. Online ahead of print.

ABSTRACT

BACKGROUND: Observational studies have suggested that better protein nutritional status may contribute to prevention of frailty.

OBJECTIVE: To examine this hypothesis using a Mendelian randomization (MR) analysis.

METHODS: We conducted a two-sample MR study using GWAS summary statistics data of the UK Biobank. We applied genetically predicted serum albumin as a primary exposure measure and serum total protein as a secondary exposure measure. The outcome measure was the Rockwood frailty index (FI) based on 49 deficits from 356,432 individuals (53.3% of them were women, with a mean [SD] age of 56.7 [8.0] years. The association between serum protein measures and FI was mainly analyzed by the inverse variance weighted method.

RESULTS: A genetically predicted serum albumin level was not statistically significantly associated with FI in the full sample. However, in women, we observed a preventive association between genetically predicted serum albumin and FI (beta = -0.172 per g/L; 95% confidence interval = -0.336 to -0.007; P = 0.041). In the full sample, genetically predicted serum total protein was inversely associated with FI (beta = -0.153 per g/L; 95% confidence interval = -0.251 to -0.056; P = 0.002). In both women and men, higher serum total protein was significantly inversely associated with FI; regression coefficients were -0.148 per g/L (95% confidence interval = -0.287 to -0.009; P = 0.037) for women, -0.154 per g/L (95% confidence interval = -0.290 to -0.018; P = 0.027) for men.

CONCLUSIONS: The present MR study implies that better protein nutritional status modestly contributes to reducing the risk of frailty.

PMID:34601600 | DOI:10.1093/jn/nxab348

J Clin Endocrinol Metab. 2021 Oct 3:dgab713. doi: 10.1210/clinem/dgab713. Online ahead of print.

ABSTRACT

CONTEXT: The causal role of endogenous estradiol in cancers other than breast and endometrial cancer remains unclear.

OBJECTIVE: To assess the causal associations of endogenous 17β-estradiol (E2), the most potent estrogen, with cancer risk in women through Mendelian randomization.

METHODS: As primary genetic instrument, we used a genetic variant in the CYP19A1 gene that is strongly associated with serum E2 levels. Summary statistics genetic data for the association of the E2 variant with breast, endometrial, and ovarian cancer were obtained from large-scale consortia. We additionally estimated the associations of the E2 variant with any and 20 site-specific cancers in 198 825 women of European descent in UK Biobank. Odds ratios (OR) of cancer per 0.01 unit increase in log-transformed serum E2 levels in pmol/L were estimated using the Wald ratio.

RESULTS: Genetic predisposition to higher serum E2 levels was associated with increased risk of estrogen receptor positive breast cancer (OR 1.02; 95% confidence interval [CI] 1.01-1.03; P=2.5×10 -3), endometrial cancer overall (OR 1.09; 95% CI 1.06-1.11; P=7.3×10 -13), and endometrial cancer of the endometrioid histology subtype (OR 1.10; 95% CI 1.07-1.13; P=2.1×10 -11). There were suggestive associations with breast cancer overall (OR 1.01; 95% CI 1.00-1.02; P=0.02), ovarian cancer of the endometrioid subtype (OR 1.05; 95% CI 1.01-1.10; P=0.02), and stomach cancer (OR 1.12; 95% CI 1.00-1.26; P=0.05), but no significant association with other cancers.

CONCLUSION: This study supports a role of E2 in the development of estrogen receptor positive breast cancer and endometrioid endometrial cancer, but found no strong association with other cancers in women.

PMID:34601599 | DOI:10.1210/clinem/dgab713

Bioinformatics. 2021 Oct 2:btab690. doi: 10.1093/bioinformatics/btab690. Online ahead of print.

ABSTRACT

MOTIVATION: Tea is a cross pollinated woody perennial plant, which is why, application of conventional breeding is limited for its genetic improvement. However, lack of the genome-wide high-density SNP markers and genome-wide haplotype information has greatly hampered the utilization of tea genetic resources towards fast-track tea breeding programs. To address this challenge, we have generated a first-generation haplotype map of tea (Tea HapMap-1). Out-crossing and highly heterozygous nature of tea plants, make them more complicated for DNA level variant discovery.

RESULTS: In the present study, whole genome re-sequencing data of 369 tea genotypes were used to generate 2,334,564 biallelic SNPs and 1,447,985 InDels. Around 2928.04 million paired-end reads were generated with an average mapping depth of ∼0.31X per accession. Identified polymorphic sites in this study will be useful in mapping the genomic regions responsible for important traits of tea. These resources lay the foundation for future research to understand the genetic diversity within tea germplasm and utilize genes that determine tea quality. This will further facilitate the understanding of tea genome evolution and tea metabolite pathways thus, offers an effective germplasm utilization for breeding the tea varieties.

PMID:34601584 | DOI:10.1093/bioinformatics/btab690

Theriogenology. 2021 Sep 25;176:94-103. doi: 10.1016/j.theriogenology.2021.09.025. Online ahead of print.

ABSTRACT

Antifreeze proteins (AFPs) are synthesized by diverse non-mammalian species, allowing them to survive in severely cold environments. Since the 1990s, the scientific literature reports their use for low-temperature preservation of germplasm. The aim of this systematic review was to compile available scientific evidence regarding the use of AFP for low-temperature preservation of several reproductive specimens. Internet databases were consulted using the terms: “antifreeze protein” OR “AFP” OR “antifreeze glycoprotein” OR “AFGP” OR “ice-binding protein” OR “IBP” OR “thermal hysteresis protein” AND “cryopreservation”. From 56 articles, 87 experiments testing AFPs in low-temperature preservation of gametes, embryos or reproductive tissues/cells were fully analyzed and outcomes were annotated. A positive outcome was considered as a statistically significant improvement on any parameter evaluated after low-temperature preservation with AFP, whereas a negative outcome included worsening of any evaluated parameter, in comparison to untreated groups or groups treated with a lower concentration of AFP. The findings indicated that research on the use of AFP as a cryoprotectant for reproductive specimens has increased markedly over the past decade. Some experiments reported both positive and negative results, which depended, on AFP concentration in the preservation media. Variation in the outcomes associated with species was also observed. Among the 66 experiments conducted in mammals, 77.3% resulted in positive, and 28.8% in negative outcomes after the use of AFP. In fishes, positive and negative outcomes were observed in 71.4% and 33.3% of 21 experiments, respectively. Most positive outcomes included preserving cell post-warming survival. The beneficial effect of AFP supports its use in cryobiological approaches used in human and veterinary medicines and animal protein industry. Moreover, combination of different AFP types, or AFP with antioxidants, or even the use of AFP-biosimilar, comprise some promising approaches to be further explored in cryopreservation.

PMID:34600433 | DOI:10.1016/j.theriogenology.2021.09.025

Am J Otolaryngol. 2021 Sep 8;43(1):103200. doi: 10.1016/j.amjoto.2021.103200. Online ahead of print.

ABSTRACT

PURPOSE: Managing hearing health in older adults has become a public health imperative, and cochlear implantation is now the standard of care for aural rehabilitation when hearing aids no longer provide sufficient benefit. The aim of our study was to compare speech performance in cochlear implant patients ≥80 years of age (Very Elderly) to a younger elderly cohort between ages 65-79 years (Less Elderly).

MATERIALS AND METHODS: Data were collected from 53 patients ≥80 years of age and 92 patients age 65-79 years who underwent cochlear implantation by the senior author between April 1, 2017 and May 12, 2020. The primary outcome measure compared preoperative AzBio Quiet scores to 6-month post-activation AzBio Quiet results for both cohorts.

RESULTS: Very Elderly patients progressed from an average AzBio Quiet score of 22% preoperatively to a score of 45% in the implanted ear at 6-months post-activation (p < 0.001) while the Less Elderly progressed from an average score of 27% preoperatively to 60% at 6-months (p < 0.001). Improvements in speech intelligibility were statistically significant within each of these cohorts (p < 0.001). Comparative statistics using independent samples t-test and evaluation of effect size using the Hedges’ g statistic demonstrated a significant difference for average improvement of AzBio in quiet scores between groups with a medium effect size (p = 0.03, g = 0.35). However, when the very oldest patients (90+ years) were removed, the statistical difference between groups disappeared (p = 0.09).

CONCLUSIONS: When assessing CI performance, those over age 65 are typically compared to younger patients; however, this manuscript further stratifies audiometric outcomes for older CI recipients in a single-surgeon, high-volume practice. Our data indicates that for speech intelligibility, patients between age 65-79 perform similarly to CI recipients 80-90 years of age and should not be dismissed as potential cochlear implant candidates.

PMID:34600410 | DOI:10.1016/j.amjoto.2021.103200

Lung Cancer. 2021 Sep 20;161:163-170. doi: 10.1016/j.lungcan.2021.09.011. Online ahead of print.

ABSTRACT

OBJECTIVES: Programmed death-ligand 1 (PD-L1) expression is a predictive biomarker of response to immunotherapies targeting programmed death-1/PD-L1 in advanced-stage lung adenocarcinoma. The aim of this study was to investigate the associations between PD-L1 expression and clinicopathological features, prognosis, and driver oncogene alterations in patients with lung adenocarcinoma.

MATERIALS AND METHODS: We evaluated PD-L1 expression in 1,005 surgically resected lung adenocarcinoma specimens, by immunohistochemistry using the 22C3 antibody. PD-L1 positivity was defined based on the proportion of stained tumor cells (TPS) on tissue microarrays: <1% (negative), 1-49% (weakly positive), and ≥ 50% (strongly positive). Correlations between PD-L1 expression and clinicopathological features, prognosis, and driver oncogene (EGFR, KRAS, ALK, ROS1, and RET) alterations in lung adenocarcinoma were analyzed.

RESULTS: PD-L1 expression was negative in 726 (72%) of 1,005 tumors, weakly positive in 161 (16%), and strongly positive in 118 (12%). Male sex, smoking, elevated serum carcinoembryonic antigen levels, advanced pathological stages, high-grade tumors, predominantly solid tumors, tumors with lymphatic permeation or vascular or pleural invasion, tumors without EGFR mutations, and tumors with KRAS mutations were more common in patients with PD-L1-positive tumors (TPS ≥ 1%) than in those with PD-L1-negative tumors (TPS < 1%). PD-L1 positivity was not associated with ALK, ROS1, or RET fusion status. Although PD-L1 positivity was associated with poor overall survival and poor relapse-free survival in all patients, this was not statistically significant after adjusting for prognostic factors in the multivariate analysis. In the subgroup analysis according to driver oncogene alterations, PD-L1 positivity was associated with poor relapse-free survival only in patients with EGFR-mutated tumors.

CONCLUSION: Surgically resected lung adenocarcinomas with increased PD-L1 expression were biologically aggressive tumors that frequently occurred in male smokers. PD-L1 expression and its prognostic significance differed according to driver oncogene alterations.

PMID:34600407 | DOI:10.1016/j.lungcan.2021.09.011

Phys Med. 2021 Sep 29;90:108-114. doi: 10.1016/j.ejmp.2021.09.010. Online ahead of print.

ABSTRACT

PURPOSE: Dosiomics allows to parameterize regions of interest (ROIs) and to produce quantitative dose features encoding the spatial and statistical distribution of radiotherapy dose. The stability of dosiomics features extraction on dose cube pixel spacing variation has been investigated in this study.

MATERIAL AND METHODS: Based on 17 clinical delivered dose distributions (P_n), dataset has been generated considering all the possible combinations of four dose grid resolutions and two calculation algorithms. Each dose voxel cube has been post-processed considering 4 different dose cube pixel spacing values: 1x1x1, 2x2x2, 3x3x3 mm³ and the one equal to the planning CT. Dosiomics features extraction has been performed from four different ROIs. The stability of each extracted dosiomic feature has been analyzed in terms of coefficient of variation (CV) intraclass correlation coefficient (ICC).

RESULTS: The highest CV mean values were observed for PTV ROI and for the grey level size zone matrix features family. On the other hand, the lowest CV mean values have been found for RING ROI for the grey level co-occurrence matrix features family. P₃ showed the highest percentage of CV >1 (1.14%) followed by P₁₅ (0.41%), P₁ (0.29%) and P13 (0.19%). ICC analysis leads to identify features with an ICC >0.95 that could be considered stable to use in dosiomic studies when different dose cube pixel spacing are considered, especially the features in common among the seventeen plans.

CONCLUSION: Considering the observed variability, dosiomic studies should always provide a report not only on grid resolution and algorithm dose calculation, but also on dose cube pixel spacing.

PMID:34600351 | DOI:10.1016/j.ejmp.2021.09.010

Arch Oral Biol. 2021 Sep 25;131:105272. doi: 10.1016/j.archoralbio.2021.105272. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to characterize Neolithic human maxillary molars from archeological remains at the Jiaojia site, Shandong, China, and compare their ultrastructural features with sex and age-matched modern locals.

DESIGN: Maxillary first (n = 86) and second (n = 80) molars in 5000-year-old individuals (n = 50) from the Jiaojia site were scanned by cone-beam computed tomography (CBCT). Sex and age-matched control groups were assigned from oral surgical patients at Shandong University. Images were analyzed for crown size, root length, root morphology, canal inter-orifice distances, mesiobuccal canal morphology, and second mesiobuccal (MB2) canal prevalence and location. Neolithic and modern values were compared statistically using Chi-squared and Mann-Whitney test at p < .05.

RESULTS: Crown and root size were smaller, and canal inter-orifice distances were shorter in Neolithic maxillary molars than their modern counterparts. For mesiobuccal roots, Weine’s Type I single canals were the most prevalent in Neolithic and modern first and second molars. MB2 canal prevalence were not significantly different (p > .05) in Neolithic (53.3%) or modern (60.5%) first molars, and Neolithic (11.3%) or modern (21.3%) second molars. But, MB2 prevalence was significantly higher for modern than ancient male first (p = .032) and second (p = .005) molars. Additionally, MB2 were located more mesially and closer to MB1 in Neolithic than modern molars.

CONCLUSIONS: Maxillary molar root and canal morphology of ancient 5000-year-old remains at the Jiaojia site resemble that of local patients. A trend towards larger tooth size, and more dispersed MB2 canals over this short evolutionary period warrants additional investigation.

PMID:34600333 | DOI:10.1016/j.archoralbio.2021.105272

Epilepsy Behav. 2021 Sep 29;124:108339. doi: 10.1016/j.yebeh.2021.108339. Online ahead of print.

ABSTRACT

INTRODUCTION: Idiopathic/genetic generalized epilepsy (GGE) accounts for 15-20% of all epilepsy cases. Neuropsychiatric comorbidities and disorders, such as attention-deficit hyperactivity disorder (ADHD), academic failure, and poor social competence, are present at a higher rate in patients with epilepsy compared with the general population. In this study, we aimed to determine the frequency of neuropsychiatric comorbidities in GGE subgroups, and to reveal the risk factors in the patient group with neuropsychiatric comorbidities.

MATERIAL AND METHOD: This hospital-based, cross-sectional study follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Patients with seizure-controlled GGE were invited to a semi-structured interview at the hospital. Variables [photosensitivity, valproic acid (VPA) resistance, timing of the neuropsychiatric comorbidities Attention deficit and hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and low academic performance), seizure control, and timing of the antiepileptic treatment] were statistically analyzed and evaluated in terms of their association with GGE subgroups [Generalized tonic-clonic seizures alone (EGTGS), juvenile myoclonic epilepsy (JME), and juvenile absence epilepsy (JAE)], RESULTS: Total 101 patients with GGE were included in the study and the mean age was 13.94 ± 1.66 years. A total of 12.9% (n = 13) of the patients had EGTGS, 49.5% (n = 50) had JME, and 37.6% (n = 38) had JAE. VPA resistance, photosensitivity, and the presence of neuropsychiatric symptoms before the starting of epilepsy were found to be risk factors in the GGE group with neuropsychiatric comorbidities compared with the group without neuropsychiatric comorbidities (p < 0.001). The subgroups of GGE did not show any relationship with psychiatric disorders, including ADHD, ODD, and low academic performance (neuropsychiatric comorbidities) (p > 0.005). No correlation was found between seizure control and decline in neuropsychiatric symptoms (p > 0.05).

CONCLUSION: In this study, the onset of psychiatric symptoms prior to the onset of epilepsy, photosensitivity, and VPA resistance were the most important factors affecting neuropsychiatric comorbidities. The JME, JAE, and EGTCS subgroups, early initiation of antiepileptic treatment, and seizure control were found to have no effect on poor psychosocial outcome and neuropsychiatric comorbidities.

PMID:34600282 | DOI:10.1016/j.yebeh.2021.108339

Child Abuse Negl. 2021 Sep 29;122:105344. doi: 10.1016/j.chiabu.2021.105344. Online ahead of print.

ABSTRACT

BACKGROUND: Child maltreatment is prevalent in the United States and carries long-term consequences. Parental substance use may have associations with child maltreatment. It is unclear whether co-occurring parental substance use aggravates childhood psychiatric outcomes related to suspected maltreatment.

OBJECTIVE: To compare psychiatric and healthcare utilization outcomes in children with suspected abuse reports, with and without documented parental substance use.

PARTICIPANTS AND SETTING: Retrospective cohort study (n = 2831) of children with suspected abuse/neglect (SANC) reports filed in the electronic health record between January 1, 2000 and January 1, 2016. Children who had SANC reports referencing parental substance use (n = 458) were compared with those who had SANC reports that did not reference substance use (n = 2346).

METHODS: Outcome data included ICD-10 coded medical and psychiatric diagnoses and healthcare utilization.

RESULTS: Compared to children who had a SANC report filed without parental substance use, children with parental substance use in a SANC showed significantly lower age-adjusted odds of anxiety disorder, mood disorder and externalizing disorder, and higher odds of a substance use disorder diagnosis. They were also less likely to present to an emergency department visit for any reason in the year prior to the report.

CONCLUSIONS: Children with exposure to parental substance use in a household where parental abuse or neglect was suspected had lower odds of adverse psychiatric outcomes as compared to children with suspected report of abuse or neglect unrelated to parental substance use. The present findings highlight the complex interplay of psychosocial factors associated with outcomes of childhood maltreatment.

PMID:34600277 | DOI:10.1016/j.chiabu.2021.105344