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Nevin Manimala Statistics

Increased Serum Neurofilament Light and Thin Ganglion Cell-Inner Plexiform Layer Are Additive Risk Factors for Disease Activity in Early Multiple Sclerosis

Neurol Neuroimmunol Neuroinflamm. 2021 Aug 4;8(5):e1051. doi: 10.1212/NXI.0000000000001051. Print 2021 Sep.

ABSTRACT

OBJECTIVE: To investigate the association of combined serum neurofilament light chain (sNfL) and retinal optical coherence tomography (OCT) measurements with future disease activity in patients with early multiple sclerosis (MS).

METHODS: We analyzed sNfL by single molecule array technology and performed OCT measurements in a prospective cohort of 78 patients with clinically isolated syndrome and early relapsing-remitting MS with a median (interquartile range) follow-up of 23.9 (23.3-24.7) months. Patients were grouped into those with abnormal or normal sNfL levels, defined as sNfL ≥/<80th percentile of age-corrected reference values. Likewise, patients were grouped by a median split into those with thin or thick ganglion cell and inner plexiform layer (GCIP), peripapillary retinal nerve fiber layer, and inner nuclear layer in nonoptic neuritis eyes. Outcome parameters were violation of no evidence of disease activity (NEDA-3) criteria or its components.

RESULTS: Patients with abnormal baseline sNfL had a higher risk of violating NEDA-3 (hazard ratio [HR] 2.28, 95% CI 1.27-4.09, p = 0.006) and developing a new brain lesion (HR 2.47, 95% CI 1.30-4.69, p = 0.006), but not for a new relapse (HR 2.21, 95% CI 0.97-5.03, p = 0.058). Patients with both abnormal sNfL and thin GCIP had an even higher risk for NEDA-3 violation (HR 3.61, 95% CI 1.77-7.36, p = 4.2e-4), new brain lesion (HR 3.19, 95% CI 1.51-6.76, p = 0.002), and new relapse (HR 5.38, 95% CI 1.61-17.98, p = 0.006) than patients with abnormal sNfL alone.

CONCLUSIONS: In patients with early MS, the presence of both abnormal sNfL and thin GCIP is a stronger risk factor for future disease activity than the presence of each parameter alone.

PMID:34348969 | DOI:10.1212/NXI.0000000000001051

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Nevin Manimala Statistics

Medical encounters at community-based physical activity events (parkrun) in the UK

Br J Sports Med. 2021 Aug 4:bjsports-2021-104256. doi: 10.1136/bjsports-2021-104256. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the incidence, clinical correlates and exposure risk of medical encounters during community-based physical activity events in the UK.

METHODS: An analysis of medical data from weekly, community-based physical activity events (parkrun) at 702 UK locations over a 6-year period (29 476 294 participations between 2014 and 2019) was conducted in order to define the incidence and clinical correlates of serious life-threatening, non-life-threatening and fatal medical encounters.

RESULTS: 84 serious life-threatening encounters (overall incidence rate=0.26/100 000 participations) occurred including 18 fatalities (0.056/100 000 participations). Statistical modelling revealed that the probabilities of serious life-threatening encounters were exceptionally low, however, male sex, increasing age, slower personal best parkrun time and less prior running engagement/experience (average number of runs per year and number of years as a parkrun participant) were associated with increased probability of serious life-threatening encounters. These were largely accounted for by cardiac arrest (48/84, 57%) and acute coronary syndromes (20/84, 24%). Non-life-threatening medical encounters were mainly attributed to tripping or falling, with a reported incidence of 39.2/100 000 participations.

CONCLUSIONS: Serious life-threatening and fatal medical encounters associated with parkrun participation are extremely rare. In the context of a global public health crisis due to inactivity, this finding underscores the safety and corollary public health value of community running/walking events as a strategy to promote physical activity.

PMID:34348921 | DOI:10.1136/bjsports-2021-104256

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Bilateral salpingo-oophorectomy and breast cancer risk for BRCA1 and BRCA2 mutation carriers: Assessing the evidence

Cancer Prev Res (Phila). 2021 Aug 4:canprevres.0141.2021. doi: 10.1158/1940-6207.CAPR-21-0141. Online ahead of print.

ABSTRACT

Without preventive interventions, women with germline pathogenic variants in BRCA1 or BRCA2 have high lifetime risks for breast cancer (BC) and tubo-ovarian cancer. The increased risk for BC starts at a considerably younger age than that for tubo-ovarian cancer. Risk-reducing bilateral salpingo-oophorectomy (rrBSO) is effective in reducing tubo-ovarian cancer risk for BRCA1 and BRCA2 mutation carriers, but whether it reduces BC risk is less clear. All studies of rrBSO and BC risk are observational in nature, and subject to various forms of bias and confounding, thus limiting conclusions that can be drawn about causation. Early studies supported a statistically significant protective association for rrBSO on BC risk, which is reflected by several international guidelines that recommend consideration of pre-menopausal rrBSO for BC risk reduction. However, these historical studies were hampered by the presence of several important biases, including immortal person-time bias, confounding by indication, informative censoring, and confounding by other risk factors, which may have led to over-estimation of any protective benefit. Contemporary studies, specifically designed to reduce some of these biases, have yielded contradictory results. Taken together, there is no clear and consistent evidence for a role of pre-menopausal rrBSO in reducing BC risk in BRCA1 or BRCA2 mutation carriers.

PMID:34348913 | DOI:10.1158/1940-6207.CAPR-21-0141

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Nevin Manimala Statistics

Repurposing RNA sequencing for discovery of RNA modifications in clinical cohorts

Sci Adv. 2021 Aug 4;7(32):eabd2605. doi: 10.1126/sciadv.abd2605. Print 2021 Aug.

ABSTRACT

The study of RNA modifications in large clinical cohorts can reveal relationships between the epitranscriptome and human diseases, although this is especially challenging. We developed ModTect (https://github.com/ktan8/ModTect), a statistical framework to identify RNA modifications de novo by standard RNA-sequencing with deletion and mis-incorporation signals. We show that ModTect can identify both known (N 1-methyladenosine) and previously unknown types of mRNA modifications (N 2,N 2-dimethylguanosine) at nucleotide-resolution. Applying ModTect to 11,371 patient samples and 934 cell lines across 33 cancer types, we show that the epitranscriptome was dysregulated in patients across multiple cancer types and was additionally associated with cancer progression and survival outcomes. Some types of RNA modification were also more disrupted than others in patients with cancer. Moreover, RNA modifications contribute to multiple types of RNA-DNA sequence differences, which unexpectedly escape detection by Sanger sequencing. ModTect can thus be used to discover associations between RNA modifications and clinical outcomes in patient cohorts.

PMID:34348892 | DOI:10.1126/sciadv.abd2605

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Nevin Manimala Statistics

The physics of cement cohesion

Sci Adv. 2021 Aug 4;7(32):eabg5882. doi: 10.1126/sciadv.abg5882. Print 2021 Aug.

ABSTRACT

Cement is the most produced material in the world. A major player in greenhouse gas emissions, it is the main binding agent in concrete, providing a cohesive strength that rapidly increases during setting. Understanding how such cohesion emerges is a major obstacle to advances in cement science and technology. Here, we combine computational statistical mechanics and theory to demonstrate how cement cohesion arises from the organization of interlocked ions and water, progressively confined in nanoslits between charged surfaces of calcium-silicate-hydrates. Because of the water/ions interlocking, dielectric screening is drastically reduced and ionic correlations are proven notably stronger than previously thought, dictating the evolution of nanoscale interactions during cement hydration. By developing a quantitative analytical prediction of cement cohesion based on Coulombic forces, we reconcile a fundamental understanding of cement hydration with the fully atomistic description of the solid cement paste and open new paths for scientific design of construction materials.

PMID:34348896 | DOI:10.1126/sciadv.abg5882

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Nevin Manimala Statistics

Incidence and risk factors of cancer in individuals with cystic fibrosis in the UK; a case-control study

J Cyst Fibros. 2021 Aug 1:S1569-1993(21)01302-3. doi: 10.1016/j.jcf.2021.07.004. Online ahead of print.

ABSTRACT

To assess cancer incidence in the UK cystic fibrosis (CF) population and determine the associated risk factors, we undertook a nested case-control study of patients with CF, registered with the UK CF Registry. Each case with a first reported cancer between 1999 and 2017 was matched with up to 4 controls: by age (±2-years) and year of cancer diagnosis. Conditional logistic regressions were adjusted for sex, lung function (FEV1%), CF related diabetes (CFRD), F508del status, transplant status, DIOS, gastro-oesophageal reflux disease, meconium ileus, Pseudomonas aeruginosa infection, pancreatic insufficiency, proton pump inhibitor (PPI) use, IV antibiotic days and BMI. Results: From 12,886 registered patients, 146 (1.1%) cases of malignancy were identified with 14.3% of cases occurring post solid organ transplant. Site of primary cancer was available for 98 patients: 22% were gastro-intestinal in origin (77% lower, 23% upper GI), 13% skin, 13% breast and 11% lymphomas/leukaemia. In univariable analysis, transplantation increased the odds of reporting any cancer by 2.46 times (95%CI: 1.3-4.6). CFRD also increased the odds of reporting any cancer (OR 2.35; CI: 1.37-4.0) and PPI use (OR 2.0; CI 1.28-3.19). In the multivariable models significant associations with CFRD and transplant remained, while PA infection, PPI use and being overweight showed increased, but statistically insignificant risks. The incidence of GI cancer was strongly associated with CFRD (OR=4.04; 1.47-11.1). Conclusions: We observed a high incidence of lower GI cancers in our cohort which was significantly affected by the presence of CFRD. Screening for gastrointestinal cancers could benefit patients at higher risk.

PMID:34348871 | DOI:10.1016/j.jcf.2021.07.004

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Nevin Manimala Statistics

COVID-19 Vaccine Perception in South Korea: A Web-Crawling Approach

JMIR Public Health Surveill. 2021 Aug 4. doi: 10.2196/31409. Online ahead of print.

ABSTRACT

BACKGROUND: The US Center for Disease Control and Prevention and the World Health Organization emphasized vaccination against the Coronavirus disease 2019 (COVID-19) because physical distancing proved inadequate to mitigate death, illness, and massive economic loss.

OBJECTIVE: This study aimed to investigate Korean citizens’ perceptions of vaccines by examining their views on COVID-19 vaccines, their positive and negative perceptions of each vaccine, and ways to enhance policies to increase vaccine acceptance.

METHODS: This cross-sectional study analyzed posts on NAVER and Instagram to examine Korean citizens’ perception of COVID-19 vaccines. The keywords searched were “vaccine,” “AstraZeneca,” and “Pfizer.” In total 8,100 posts in NAVER and 5,291 posts in Instagram were sampled through web crawling. Morphology analysis was performed, overlapping or meaningless words were removed, sentiment analysis was implemented, and three public health professionals reviewed the results.

RESULTS: : The findings revealed a negative perception of COVID-19 vaccines; of the words crawled, the proportion of negative words for AstraZeneca was 71.0% and for Pfizer was 56.3%. Moreover, 70.5% considered Pfizer safe, while 30.4% thought AstraZeneca safe. Among words crawled with “vaccine,” “good” ranked first, with a frequency of 312 (13.4%). Meanwhile, “side effect” ranked highest, with a frequency of 163 (18.4%) for “AstraZeneca,” but 0.6%. for “Pfizer.” With “vaccine,” positive words were more frequently used, whereas with “AstraZeneca” and “Pfizer” negative words were prevalent.

CONCLUSIONS: There is a negative perception of AstraZeneca and Pfizer vaccines in Korea, with one in four people refusing vaccination. To address this, accurate information needs to be shared about vaccines including AstraZeneca, and the experiences of those vaccinated. Furthermore, government communication about risk management is required to increase the AstraZeneca vaccination rate for herd immunity before the vaccine expires.

PMID:34348890 | DOI:10.2196/31409

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Nevin Manimala Statistics

Olfactory dysfunction in LATY136F knock-in mice

Auris Nasus Larynx. 2021 Aug 1:S0385-8146(21)00201-7. doi: 10.1016/j.anl.2021.07.009. Online ahead of print.

ABSTRACT

OBJECTIVE: This study examined olfactory dysfunction in LATY136F knock-in mice and its pathogenic mechanism.

METHODS: The olfactory function of LATY136F knock-in mice was assessed by a behavioral test using cycloheximide solution, which has been used as a mice repellant because of its peculiar smell and unpleasant taste. The tests were administered to each group of LATY136F knock-in mice and WT mice at 8, 12, 16, 20, and 24 weeks of age. After the behavioral tests to evaluate olfactory function, the mice were sacrificed for evaluations by immunohistochemistry.

RESULTS: Behavioral tests to evaluate olfactory function showed that the LATY136F knock-in mice had a statistically significant level of olfactory dysfunction (P < 0.05). Histological analysis showed that the thickness of the olfactory epithelium in these mice was thinner than that in the age-matched wild type mice. There was no IgG4-RD like lesion in the olfactory epithelium of LATY136F knock-in mice. Olfactory marker protein and growth-associated protein 43 expressions in the olfactory epithelium of the LATY136F knock-in mice were markedly lesser than those in the wild type mice (P < 0.05).

CONCLUSION: The present study demonstrated that olfactory disturbances occurred in LATY136F knock-in mice. Furthermore, the mechanism was suggested to be reduced regeneration of the olfactory epithelium.

PMID:34348847 | DOI:10.1016/j.anl.2021.07.009

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Review of Variables Associated With Positive Surgical Margins Using Scout Reflector Localizations for Breast Conservation Therapy

Clin Breast Cancer. 2021 Jul 13:S1526-8209(21)00180-4. doi: 10.1016/j.clbc.2021.07.003. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate factors contributing to positive surgical margins associated with reflector guidance for patients undergoing breast conserving therapy for malignancy.

MATERIALS AND METHODS: A retrospective IRB-approved review of our institutional database was performed for malignant breast lesions preoperatively localized from January 1, 2018 to December 31, 2020. The following data was recorded using electronic medical records: lesion type and grade, lesion location, reflector and wire placement modality, use of intraoperative ultrasound, margin status, patient age, family history, BMI, and final pathology. Statistical analysis was performed with univariate summary statistics and logistic regression. P < .05 was significant.

RESULTS: A total of 606 image-guided pre-surgical localizations were performed for lumpectomies of breast malignancies. A total of 352 of 606 (58%) wire localizations and 254 of 606 (42%) SCOUT reflector localizations were performed. Sixty out of 352 (17%) of wire-localized patients had positive surgical margins, whereas forty-eight out of 254 (19%) of reflector-localized patients had positive surgical margins. (OR = 1.12, P value: .59). For reflector guided cases, the use of intraoperative ultrasound (IOUS) was associated with decreased positive margin status (OR = 0 .28, 95% CI = [0.14, 0.58]) while in situ disease was associated with increased positive margin status (OR = 1.99, 95% CI = [1.05, 3.75]). No association between modality used for localization (mammography vs. ultrasound) and positive margin status was observed (OR = 0.63, 95% CI = [0.33, 1.19]). No association between positive margins and age, family history, tumor location and BMI was observed.

CONCLUSION: For reflector guided surgeries, the use of IOUS was associated with decreased positive margins, by contrast the presence of ductal carcinoma in situ was associated with increased positive margins. There was no statistically significant difference in surgical outcomes for reflector-guided localization compared to wire localizations of the breast.

PMID:34348869 | DOI:10.1016/j.clbc.2021.07.003

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Ultra-processed food intake and all-cause mortality: DRECE cohort study

Public Health Nutr. 2021 Aug 5:1-28. doi: 10.1017/S1368980021003256. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the association between ultra-processed food intake and all-cause mortality in a representative sample of Spanish population.

DESIGN: Prospective cohort design in which follow-up lasted from baseline (1991) to mortality date or December 31st, 2017, whichever was first. Dietary information was collected using a validated frequency questionnaire and categorized following the NOVA classification according to the extent of food processing. The association between consumption of ultra-processed food and mortality was analysed using Cox models. Isocaloric substitution models were constructed to compare the health effects of the NOVA groups.

SETTING: Cohort from the DRECE study, representative of the Spanish population.

PARTICIPANTS: 4679 subjects between 5 and 59 years old.

RESULTS: Average consumption of ultra-processed food was 370.8 grams/day (24.4% of energy intake). After a median follow-up of 27 years, 450 deaths occurred. Those who consumed the highest amount of ultra-processed foods had higher risk of mortality. For every 10% of the energy intake from ultra-processed foods consumption, an increase of 15% in the hazard of all-cause mortality was observed (HR, 1.15; 95%CI, 1.03-1.27; p-value= 0.012). Substitution of ultra-processed foods with minimally processed foods was significantly associated with a decreased risk of mortality.

CONCLUSIONS: An increase in ultra-processed foods consumption was associated with higher risk of all-cause mortality in a representative sample of the Spanish population. Moreover, the theoretical substitution of ultra-processed food with unprocessed or minimally processed foods leads to a decrease in mortality. These results support the need to promote diets based on unprocessed or minimally processed foods.

PMID:34348832 | DOI:10.1017/S1368980021003256