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The Valuable Prognostic Impact of Regional Lymph Node Removed on Outcomes for IIIA N0 NSCLC Patients

J Cancer. 2023 Jul 9;14(11):2093-2108. doi: 10.7150/jca.86495. eCollection 2023.

ABSTRACT

Background: Regional lymph nodes (RLNs) removed combined with surgery is a standard option for patients at stage I to IIIA NSCLC. The objective of the study is to clarify the effect of removing different number of RLNs on survival outcomes for patients at stage IIIA N0 NSCLC. Methods: Patients at stage IIIA N0 NSCLC from 2004 to 2015 were identified from Surveillance, Epidemiology, and End Results (SEER) database. Prior propensity score method (PSM), survival time was compared among different number (0, 1-3 and ≥4) of RLNs removed groups. After PSM, lung cancer-specific survival (LCSS) and overall survival (OS) were compared. Kaplan-Meier analysis and Cox regression analyses were used to clarify the impact of the factors on the prognosis with hazard ratio (HR) and 95% confidence interval (CI). Results: A total of 11,583 patients at stage IIIA N0 NSCLC were included. Prior PSM, survival indicators including 1-year mortality rate, 5-year mortality rate, median survival time (MDST) and mean survival time (MST) from good to bad were all: ≥4, 1-3 and none RLNs removed group. After PSM, Kaplan-Meier survival analyses and univariate Cox regression analyses on OS and LCSS revealed a statistically significance on survival curve (P<0.001) between each two of the three groups (none, 1-3 and ≥4 RLNs removed group). Multivariable Cox regression analyses on OS and LCSS showed an independent association of RLNs removed with higher OS (HR, 0.275; 95% CI, 0.259-0.291; P<0.001) and LCSS (HR, 0.239; 95% CI, 0.224-0.256; P<0.001) compared with none RLN removed and no statistical difference with OS (HR, 1.118; 95% CI, 0.983-1.271; P=0.088) and LCSS (HR, 1.107; 95% CI, 0.954-1.284; P=0.179) between 1-3 RLNs removed and ≥4 RLNs removed. Conclusions: Removing RLNs was beneficial to survival outcomes of patients at stage IIIA N0 NSCLC. Compared with 1-3 RLNs removed, ≥4 RLNs removed could bring a better survival time but not an independent prognostic factor (P>0.05).

PMID:37497411 | PMC:PMC10367914 | DOI:10.7150/jca.86495

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CAVIN2/SDPR Functioned as a Tumor Suppressor in Lung Adenocarcinoma from Systematic Analysis of Caveolae-Related Genes and Experimental Validation

J Cancer. 2023 Jul 3;14(11):2001-2014. doi: 10.7150/jca.84567. eCollection 2023.

ABSTRACT

Background: Caveolae-Related Genes include caveolins and cavins, which are the main component of the fossa and, play important roles in a variety of physiological and pathological processes. Although increasing evidence indicated that caveolins (CAVs) and cavins (CAVINs) are involved in carcinogenesis and progression, their clinical significance and biological function in lung cancer are still limited. Methods: We investigated the expression of CAVs and CAVINs at transcriptional levels using Oncomine and Gene Expression Profiling Interactive Analysis. The protein and mRNA expression levels of CAVs and CAVINs were determined by the human protein atlas website and our surgically resected samples, respectively. The clinical value of prognostic prediction based on the expression of CAVs and CAVINs was also assessed. cBioPortal, GeneMANIA and STRING were used to analyze the molecular characteristics of CAVs and CAVINs in lung adenocarcinoma (LUAD) comprehensively. Finally, we investigated the effect of CAVIN2/SDPR (serum deprivation protein response) on LUAD cells with biological experiments in vitro. Results: The expression of CAV1/2 and CAVIN1/2/3 were significantly downregulated in LUAD and lung squamous cell carcinoma (LUSC). The patients with high expression of CAV1, CAV2, CAV3, CAVIN1 and CAVIN2/SDPR were tightly correlated with a better prognosis in LUAD, while no statistical significances in LUSC. Further, our results found that CAVIN2/SDPR can be identified as a prognostic biomarker independent of other CAVINs in patients with LUAD. Mechanically, the overexpression of CAVIN2/SDPR inhibited cell proliferation and migration owing to the cell apoptosis induction and cell cycle arrest at S phase in LUAD cells. Conclusions: CAVIN2/SDPR functioned as a tumor suppressor, and was able to serve as prognostic biomarkers in precision medicine of LUAD. Mechanically, overexpression of CAVIN2/SDPR inhibited cell proliferation by inducing cell apoptosis and S phase arrest in LUAD cells.

PMID:37497407 | PMC:PMC10367915 | DOI:10.7150/jca.84567

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Modeling vaccination coverage during the 2022 central Ohio measles outbreak: a cross-sectional study

Lancet Reg Health Am. 2023 Jun 27;23:100533. doi: 10.1016/j.lana.2023.100533. eCollection 2023 Jul.

ABSTRACT

BACKGROUND: Of the eight large (>50 cases) US postelimination outbreaks, the first and last occurred in Ohio. Ohio’s vaccination registry is incomplete. Community-level immunity gaps threaten more than two decades of measles elimination in the US. We developed a statistical model, VaxEstim, to rapidly estimate the early-phase vaccination coverage and immunity gap in the exposed population during the 2022 Central Ohio outbreak.

METHODS: We used reconstructed daily incidence (from publicly available data) and assumptions about the distribution of the serial interval, or the time between symptom onset in successive measles cases, to estimate the effective reproduction number (i.e., the average number of secondary infections caused by an infected individual in a partially immune population). We estimated early-phase measles vaccination coverage by comparing the effective reproduction number to the basic reproduction number (i.e., the average number of secondary infections caused by an infected individual in a fully susceptible population) while accounting for vaccine effectiveness. Finally, we estimated the early-phase immunity gap as the difference between the estimated critical vaccination threshold and vaccination coverage.

FINDINGS: VaxEstim estimated the early-phase vaccination coverage as 53% (95% credible interval, 21%-77%), the critical vaccination threshold as 93%, and the immunity gap as 42% (95% credible interval, 18%-74%).

INTERPRETATION: This study estimates a significant immunity gap in the exposed population during the early phase of the 2022 Central Ohio measles outbreak, suggesting a robust public health response is needed to identify the susceptible community and develop community-specific strategies to close the immunity gap.

FUNDING: This work was supported in part by the National Institute of General Medical Sciences, National Institutes of Health; the UK Medical Research Council (MRC); the Foreign, Commonwealth and Development Office; the National Institute for Health Research (NIHR) Health Protection Research Unit in Modelling Methodology; Imperial College London, and the London School of Hygiene & Tropical Medicine, Community Jameel; the EDCTP2 programme, supported by the EU; and the Sergei Brin Foundation.

PMID:37497395 | PMC:PMC10366459 | DOI:10.1016/j.lana.2023.100533

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Predictors of nonunion for transverse femoral shaft fractures treated with intramedullary nailing: a SIGN database study

OTA Int. 2023 Jul 25;6(3):e281. doi: 10.1097/OI9.0000000000000281. eCollection 2023 Sep.

ABSTRACT

INTRODUCTION: Nonunion is a common postfracture complication resulting in decreased quality of life for patients in resource-limited settings. This study aims to determine how age, sex, injury mechanism, and surgical intervention affect the rate of nonunion in transverse femur fractures treated with a SIGN intramedullary nail (IMN).

METHODS: A retrospective study was conducted using the SIGN online surgical database. All patients older than 16 years with simple transverse (<30 degrees), open or closed, femur fractures treated using a SIGN IMN between 2007 and 2021 were included. Our primary outcome of nonunion was measured with the modified Radiographic Union Scale for Tibial fractures (mRUST); scores ≤9 of 16 defined nonunion. The secondary outcome was squat depth. Outcomes were evaluated at follow-up appointments between 240 and 365 days postoperatively. Univariate and multivariate analysis were used for statistical comparison.

RESULTS: Inclusion criteria were met for 182 patients. The overall radiographic union rate was 61.0%, and a high proportion (84.4%) of patients could squat with their hips at or below the level of their knees. Older age, retrograde approach, and fracture distraction were associated with nonunion, but sex, injury mechanism, and other surgical variables were not.

CONCLUSION: Poor reduction with fracture distraction was associated with a higher rate of nonunion. Loss of follow-up may have contributed to our overall union rate; however, we observed high rates of functional healing using the SIGN IMN.

LEVEL OF EVIDENCE: IV.

PMID:37497387 | PMC:PMC10368386 | DOI:10.1097/OI9.0000000000000281

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The Validity and Reliability of Automatic Tooth Segmentation Generated Using Artificial Intelligence

ScientificWorldJournal. 2023 Jul 18;2023:5933003. doi: 10.1155/2023/5933003. eCollection 2023.

ABSTRACT

This study aimed at evaluating the precision of the segmented tooth model (STM) that was produced by the artificial intelligence (AI) program (CephX®) with an intraoral scan (IOS) and insignia outcomes. Methods. 10 patients with Cl I malocclusion (mild-to-moderate crowding) who underwent nonextraction orthodontic therapy with the Insignia™ system had IOS and CBCT scans taken before treatment. AI was used to produce a total of 280 STMs; each tooth will be measured from three aspects (apexo-occlusal, mesiodistal, and labiolingual) for DICOM and STL formats. Also, root volume measurements for each tooth generated by using the CephX® software and Insignia™ system were compared. The software used for these measurements was the OnDemand3D program used for the multiplanar reconstruction for DICOM format and Geomagic® Control X™ used for STL format. Statistics. An intraclass correlation (ICC) analysis was used to check the agreement between the volume measurement of the segmented teeth generated by using the CephX® and Insignia™ system. Also, it was used to check the agreement between the STL (IOS), STL (CephX®), and DICOM tooth models. In addition, it was used to determine the intraexaminer repeatability by remeasuring five randomly selected individuals two weeks after the initial measurement. After confirmation of the data normality using the Shapiro-Wilk test, the right and left tooth models and the differences between the DICOM, CephX® (STL), and IOS (STL) tooth models were compared using a paired t-test. The STL (IOS), STL (CephX®), and DICOM tooth models were compared utilizing the ANOVA test. p < 0.05 was set as the statistical significance level. Result. Overall data showed good agreement with ICC. The measurements of the various tooth types on the right and left sides did not differ significantly. Also, there was no significant difference between the three groups. Conclusions. The automatic AI approach (CephX®) may be advised in the clinical practice for patients with mild crowding and no teeth restorations due to its speed and effectiveness.

PMID:37497386 | PMC:PMC10368498 | DOI:10.1155/2023/5933003

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Healthcare utilization, costs, and epidemiology of Huntington’s disease in Israel

Clin Park Relat Disord. 2023 Jun 28;9:100208. doi: 10.1016/j.prdoa.2023.100208. eCollection 2023.

ABSTRACT

INTRODUCTION: Data on Huntington’s disease (HD) epidemiology, treatment patterns, and economic burden in Israel are scarce.

METHODS: Annual prevalence and incidence of HD (ICD-9-CM 333.4) were assessed in the Israel-based Maccabi Healthcare Services (MHS) database 2016-2018. Adherence (medication possession rate [MPR], proportion of disease covered) were assessed for adult people with HD (PwHD) 2013-2018. Healthcare resources utilization (HCRU) and costs related to inpatient and outpatient visits and all medications in 2018 were assessed for PwHD, who were randomly matched to MHS members without HD (1:3) by birth-year and sex.

RESULTS: Overall, 164 patients had at least one HD diagnosis. Annual prevalence and incidence were 4.45 and 0.24/100,000, respectively. A total of 67.0% of adult patients (n = 106) were taking tetrabenazine (median MPR and proportion of disease covered, 74.3% and 30.2%, respectively), 65.1% benzodiazepines (75.8% and 32.3%), and 11.3% amantadine (79.2% and 6.0%). Over a 1-year follow-up, PwHD (n = 81) had significantly more neurologist, psychiatrist, physiotherapist, and speech therapist visits (P < 0.05 for each) and more hospitalization days (P < 0.0001) compared with matched controls (n = 243). Total healthcare and medication costs per patient (US dollars) were significantly higher for PwHD than controls ($7,343 vs. $3,625; P < 0.001).

DISCUSSION/CONCLUSION: PwHD have greater annual HCRU and medical costs than MHS members without HD in Israel. Among those who have taken medications, adherence was lower than 80% (both MPR and proportion of disease covered), which may translate into suboptimal symptom relief and quality of life.

PMID:37497383 | PMC:PMC10366633 | DOI:10.1016/j.prdoa.2023.100208

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Evaluating the impact of including non-randomised studies of interventions in meta-analysis of randomised controlled trials: a protocol for a meta-epidemiological study

BMJ Open. 2023 Jul 26;13(7):e073232. doi: 10.1136/bmjopen-2023-073232.

ABSTRACT

INTRODUCTION: Although interest in including non-randomised studies of interventions (NRSIs) in meta-analysis of randomised controlled trials (RCTs) is growing, estimates of effectiveness obtained from NRSIs are vulnerable to greater bias than RCTs. The objectives of this study are to: (1) explore how NRSIs can be integrated into a meta-analysis of RCTs; (2) assess concordance of the evidence from non-randomised and randomised trials and explore factors associated with agreement; and (3) investigate the impact on estimates of pooled bodies of evidence when NRSIs are included.

METHODS AND ANALYSIS: We will conduct a systematic survey of 210 systematic reviews that include both RCTs and NRSIs, published from 2017 to 2022. We will randomly select reviews, stratified in a 1:1 ratio by Core vs non-Core clinical journals, as defined by the National Library of Medicine. Teams of paired reviewers will independently determine eligibility and abstract data using standardised, pilot-tested forms. The concordance of the evidence will be assessed by exploring agreement in the relative effect reported by NRSIs and RCT addressing the same clinical question, defined as similarity of the population, intervention/exposure, control and outcomes. We will conduct univariable and multivariable logistic regression analyses to examine the association of prespecified study characteristics with agreement in the estimates between NRSIs and RCTs. We will calculate the ratio of the relative effect estimate from NRSIs over that from RCTs, along with the corresponding 95% CI. We will use a bias-corrected meta-analysis model to investigate the influence on pooled estimates when NRSIs are included in the evidence synthesis.

ETHICS AND DISSEMINATION: Ethics approval is not required. The findings of this study will be disseminated through peer-reviewed publications, conference presentations and condensed summaries for clinicians, health policymakers and guideline developers regarding the design, conduct, analysis, and interpretation of meta-analysis that integrate RCTs and NRSIs.

PMID:37495391 | DOI:10.1136/bmjopen-2023-073232

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Implications of rapid population growth on survey design and HIV estimates in the Rakai Community Cohort Study (RCCS), Uganda

BMJ Open. 2023 Jul 26;13(7):e071108. doi: 10.1136/bmjopen-2022-071108.

ABSTRACT

OBJECTIVE: Since rapid population growth challenges longitudinal population-based HIV cohorts in Africa to maintain coverage of their target populations, this study evaluated whether the exclusion of some residents due to growing population size biases key HIV metrics like prevalence and population-level viremia.

DESIGN, SETTING AND PARTICIPANTS: Data were obtained from the Rakai Community Cohort Study (RCCS) in south central Uganda, an open population-based cohort which began excluding some residents of newly constructed household structures within its surveillance boundaries in 2008. The study includes adults aged 15-49 years who were censused from 2019 to 2020.

MEASURES: We fit ensemble machine learning models to RCCS census and survey data to predict HIV seroprevalence and viremia (prevalence of those with viral load >1000 copies/mL) in the excluded population and evaluated whether their inclusion would change overall estimates.

RESULTS: Of the 24 729 census-eligible residents, 2920 (12%) residents were excluded from the RCCS because they were living in new households. The predicted seroprevalence for these excluded residents was 10.8% (95% CI: 9.6% to 11.8%)-somewhat lower than 11.7% (95% CI: 11.2% to 12.3%) in the observed sample. Predicted seroprevalence for younger excluded residents aged 15-24 years was 4.9% (95% CI: 3.6% to 6.1%)-significantly higher than that in the observed sample for the same age group (2.6% (95% CI: 2.2% to 3.1%)), while predicted seroprevalence for older excluded residents aged 25-49 years was 15.0% (95% CI: 13.3% to 16.4%)-significantly lower than their counterparts in the observed sample (17.2% (95% CI: 16.4% to 18.1%)). Over all ages, the predicted prevalence of viremia in excluded residents (3.7% (95% CI: 3.0% to 4.5%)) was significantly higher than that in the observed sample (1.7% (95% CI: 1.5% to 1.9%)), resulting in a higher overall population-level viremia estimate of 2.1% (95% CI: 1.8% to 2.4%).

CONCLUSIONS: Exclusion of residents in new households may modestly bias HIV viremia estimates and some age-specific seroprevalence estimates in the RCCS. Overall, HIV seroprevalence estimates were not significantly affected.

PMID:37495389 | DOI:10.1136/bmjopen-2022-071108

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Representation of Motion Direction in Visual Area MT Accounts for High Sensitivity to Centripetal Motion, Aligning with Efficient Coding of Retinal Motion Statistics

J Neurosci. 2023 Jul 26:JN-RM-0451-23. doi: 10.1523/JNEUROSCI.0451-23.2023. Online ahead of print.

ABSTRACT

The overrepresentation of centrifugal motion in the middle temporal visual area (area MT) has long been thought to provide an efficient coding strategy for optic flow processing. However, this overrepresentation compromises the detection of approaching objects, which is essential for survival. In the present study, we revisited this long-held notion by reanalyzing motion selectivity in area MT of three macaque monkeys (2 males, 1 female) using random-dot stimuli instead of spot stimuli. We found no differences in the number of neurons tuned to centrifugal versus centripetal motion; however, centrifugally tuned neurons showed stronger tuning than centripetally tuned neurons. This was attributed to the heightened suppression of responses in centrifugal neurons to centripetal motion compared to that of centripetal neurons to centrifugal motion. Our modeling implies that this intensified suppression accounts for superior detection performance for weak centripetal motion stimuli. Moreover, through Fisher information analysis, we establish that the population sensitivity to motion direction in peripheral vision corresponds well with retinal motion statistics during forward locomotion. While these results challenge established concepts, considering the interplay of logarithmic Gaussian receptive fields and spot stimuli can shed light on the previously documented overrepresentation of centrifugal motion. Significantly, our findings reconcile a previously found discrepancy between MT activity and human behavior, highlighting the proficiency of peripheral MT neurons in encoding motion direction efficiently.Significance StatementThe efficient coding hypothesis states that sensory neurons are tuned to specific, frequently experienced stimuli. Whereas previous work has found that neurons in the middle temporal (MT) area favor centrifugal motion, which results from forward locomotion, we show here that there is no such bias. Moreover, we found that the response of centrifugal neurons for centripetal motion was more suppressed than that of centripetal neurons for centrifugal motion. Combined with modeling, this provides a solution to a previously known discrepancy between reported centrifugal bias in MT and better detection of centripetal motion by human observers. Additionally, we show that population sensitivity in peripheral MT neurons conforms to an efficient code of retinal motion statistics during forward locomotion.

PMID:37495384 | DOI:10.1523/JNEUROSCI.0451-23.2023

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The effects of chromosome polymorphism on the clinical outcomes of in vitro fertilization/embryo transfer-assisted reproduction

J Matern Fetal Neonatal Med. 2023 Dec;36(2):2238863. doi: 10.1080/14767058.2023.2238863.

ABSTRACT

OBJECTIVE: To investigate the effects of chromosome polymorphism on the clinical outcomes of in vitro fertilization/embryo transfer (IVF/ET)-assisted reproductive technology.

METHODS: The case data of 2740 patients treated between January 2018 and January 2019 were retrospectively analyzed. The patients were organized into two groups: a case group and a control group. In the case group (n = 81), one or both parents were characterized by chromosomal polymorphism; in the control group (n = 2659), both parents had normal chromosome karyotyping. The primary outcomes included clinical pregnancy rate (clinical pregnancy rate of fresh transfer cycles = number of clinical pregnancy cycles/number of fresh embryo transfer cycles × 100%) and live birth rate (live birth rate per fresh transfer cycles = number of live births/numbers of fresh embryo transfer cycles × 100%). The propensity score matching (PSM) method was used for statistical analysis.

RESULTS: After PSM 1:2 matching for the patients in the two groups, 72 patients were successfully matched. The clinical pregnancy rate and live birth rate in the case group were lower than in the control group before PSM (clinical pregnancy rate: 33.30% case group vs. 46.60% control group, p = .020; live birth rate: 30.90% case group vs. 47.90% control group, p = .03). The differences were statistically significant (p < .05). The live birth rate in the case group was also significantly lower than in the control group after PSM (34.98% case group vs. 74.52% control group; p = .028). The correlation coefficient between clinical pregnancy and grouping (i.e. if there was a characteristic chromosome polymorphism) was -.045 (p = .02), while the correlation coefficient between live birth and grouping was -.046.

CONCLUSION: Chromosome polymorphism is weakly negatively correlated with live birth in IVF/ET-assisted reproduction and can significantly reduce the live birth rate of patients.

PMID:37495374 | DOI:10.1080/14767058.2023.2238863