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Nevin Manimala Statistics

Local ancestry at the MHC region is not a major contributor to disease heterogeneity in a multi-ethnic lupus cohort

Arthritis Rheumatol. 2023 Dec 10. doi: 10.1002/art.42766. Online ahead of print.

ABSTRACT

OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease resulting in debilitating clinical manifestations that vary in severity by race and ethnicity with a disproportionate burden in African American, Mestizo, and Asian populations compared to populations of European descent. Differences in global and local genetic ancestry may shed light on the underlying mechanisms contributing to these disparities, including increased prevalence of lupus nephritis, younger age of symptom onset, and presence of autoantibodies.

METHODS: A total of 1,139 SLE European, African American, and Mestizos patients were genotyped using the Affymetrix LAT1 World array. Global ancestry proportions were estimated using ADMIXTURE and local ancestry was estimated using RFMIXv2.0. We investigated associations between lupus nephritis, age of onset, and autoantibody status with both global and local ancestry proportions within the MHC region.

RESULTS: Our results showed small effect sizes that did not meet the threshold for statistical significance for global or local ancestry proportions in either African American or Mestizo SLE patients who presented with the clinical manifestations of interest compared to those who did not.

CONCLUSION: These findings suggest that local genetic ancestry within the MHC region is not a major contributor to these SLE manifestations among patients with SLE from admixed populations. This article is protected by copyright. All rights reserved.

PMID:38073021 | DOI:10.1002/art.42766

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Different Immunologic Profiles are Associated with Distinct Clinical Phenotypes in Longitudinally Followed Systemic Lupus Erythematosus Patients

Arthritis Rheumatol. 2023 Dec 10. doi: 10.1002/art.42776. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the immunologic profile associated with flares of systemic lupus erythematosus (SLE) and to investigate the clinical significance of any differences observed between patients during and following flare.

METHODS: Multi-parameter flow cytometry was used to examine 47 immune populations within the peripheral blood of 16 healthy controls, 25 clinically quiescent SLE patients and 46 SLE patients experiencing a flare, at baseline and at 6- and 12-month follow-up visits. Unsupervised clustering was used to identify subjects with similar immune profiles and to track changes over time. Parametric or non-parametric statistics were used, where appropriate, to assess the association of cellular phenotypes with clinical and laboratory parameters.

RESULTS: Five clusters of subjects were identified that variably contained active and quiescent SLE patients and that had distinct clinical phenotypes. Patients characterized by increased T peripheral helper, activated B, and age-associated B cells were the most likely to be flaring at baseline, as well as the most likely to remain active or flare over the subsequent year if they acquired or retained this phenotype at follow-up. In contrast, patients who had increased T helper cells in the absence of B cell changes, or who had increased Th 1 cells and innate immune populations, mostly became quiescent on follow-up. A significant proportion of SLE patients had depletion of many immune populations at flare and only showed increases in these populations post-flare.

CONCLUSION: Cellular phenotyping of SLE patients reveals several distinct immunologic profiles that may help to stratify patients with regard to prognosis and treatment.

PMID:38073017 | DOI:10.1002/art.42776

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Preliminary study of HPV integration status on the occurrence and development of vaginal intraepithelial neoplasia

J Obstet Gynaecol Res. 2023 Dec 10. doi: 10.1111/jog.15855. Online ahead of print.

ABSTRACT

AIM: The aim of this study was to investigate how the integration status of HPV in the vaginal epithelium affects the development of vaginal intraepithelial neoplasia (VaIN).

METHODS: Twenty-four vaginal tissues were collected before applying high-throughput viral integration detection (HIVID), medical records of them were documented, including age, thin-prep cytologic test (TCT) and HPV test results, colposcopic biopsy pathology, and other clinical data, such as history of total hysterectomy for cervical lesions, whether they were infected with HPV16/18 with a follow-up span of 2 years. We summarized the distribution of HPV integration on the host chromosome and HPV type, as well as the hotspot integration gene and its role in the development of VaIN.

RESULTS: In this study, 24 cases suffered from VaIN were involved. HPV integration was detected in 11 cases; furthermore, we discovered HPV 16 and 73, chromosome 1 and 2 possessed most HPV integration sites while EMBP1, CLO5A1, EHF, ELF5 as dominate hot spots. Taken clinical outcome into account, we found a significant difference between HPV integration occurrence and VaIN (p = 0.011).

CONCLUSION: (1) This study found a statistical difference between HPV integration and the occurrence of VaIN; (2) HPV integration may provide a new clinical predictor for VaIN and facilitate risk assessment and stratified management of high-risk patients.

PMID:38072997 | DOI:10.1111/jog.15855

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Effect of different types of Tai Chi exercise programs on the rate of change in bone mineral density in middle-aged adults at risk of osteoporosis: a randomized controlled trial

J Orthop Surg Res. 2023 Dec 11;18(1):949. doi: 10.1186/s13018-023-04324-0.

ABSTRACT

OBJECTIVE: To evaluate three Tai Chi (TC) exercise programs as intervention measures to compare their effects on improving rate of change in bone mineral density (BMD) in elderly individuals with osteoporosis (OP) and to propose the optimal exercise duration.

METHODS: A randomized controlled trial (RCT) was conducted to identify study participants based on inclusion and exclusion criteria. Due to subject attrition, the number of participants analyzed decreased from 60 to 49. These participants were divided into four groups: 24-style TC Chuan group (24TCCG) (n = 13, 7 males/6 females), TC Kung Fu Fan group (TCKFFG) (n = 12, 5 males/7 females), TC Softball group (TCSBG) (n = 11, 6 males/5 females), and a control group (CG) (n = 13, 6 males/7 females). Except for the control group, each group received different TC exercise programs four times a week for 60 min per session, lasting for 16 weeks. BMD was measured using dual-energy X-ray absorptiometry (DXA) at the L2-L4 lumbar vertebrae, Ward’s triangle, femoral neck, and greater trochanter. The rate of change of BMD was calculated using the formula.

RESULTS: Compared with CG, all three TC groups showed significant improvements in BMD changes (P < 0.05), but their effects on the improvement of femoral neck and greater tuberosity BMD change rates were similar (P > 0.05). In addition, compared to the other exercise regimens, 24TCCG demonstrated more significant improvements in BMD at the L2-L4 lumbar vertebrae region and exhibited a more pronounced improvement in Ward’s triangle BMD after only 8 weeks (P < 0.05). Short-term (≤ 4 weeks) TCKFFG was more effective than TCSBG in enhancing femoral neck BMD (P < 0.05). However, statistical significance was not found (P > 0.05) in all other cases.

CONCLUSION: These three TC exercise programs have similar positive effects on the BMD of the femoral neck and greater trochanter. However, compared with other exercise schemes, 24TCC showed a more significant improvement in BMD of the L2-L4 lumbar vertebrae region after just 8 weeks, as well as a more pronounced improvement in BMD of Ward’s triangle. In terms of improving femoral neck BMD, TCKFF was found to be more effective than TCSB in less than 4 weeks. This study provides evidence for the effectiveness of TC exercise in improving BMD and preventing OP in the middle-aged and elderly high-risk population.

PMID:38072989 | DOI:10.1186/s13018-023-04324-0

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Machine learning model for predicting immediate postoperative desaturation using spirometry signal data

Sci Rep. 2023 Dec 11;13(1):21881. doi: 10.1038/s41598-023-49062-9.

ABSTRACT

Postoperative desaturation is a common post-surgery pulmonary complication. The real-time prediction of postoperative desaturation can become a preventive measure, and real-time changes in spirometry data can provide valuable information on respiratory mechanics. However, there is a lack of related research, specifically on using spirometry signals as inputs to machine learning (ML) models. We developed an ML model and postoperative desaturation prediction index (DPI) by analyzing intraoperative spirometry signals in patients undergoing laparoscopic surgery. We analyzed spirometry data from patients who underwent laparoscopic, robot-assisted gynecologic, or urologic surgery, identifying postoperative desaturation as a peripheral arterial oxygen saturation level below 95%, despite facial oxygen mask usage. We fitted the ML model on two separate datasets collected during different periods. (Datasets A and B). Dataset A (Normal 133, Desaturation 74) was used for the entire experimental process, including ML model fitting, statistical analysis, and DPI determination. Dataset B (Normal 20, Desaturation 4) was only used for verify the ML model and DPI. Four feature categories-signal property, inter-/intra-position correlation, peak value/interval variability, and demographics-were incorporated into the ML models via filter and wrapper feature selection methods. In experiments, the ML model achieved an adequate predictive capacity for postoperative desaturation, and the performance of the DPI was unbiased.

PMID:38072984 | DOI:10.1038/s41598-023-49062-9

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Do we know enough about the effect of low-dose computed tomography screening for lung cancer on mortality to act? An updated systematic review, meta-analysis and network meta-analysis of randomised controlled trials 2017 to 2021

Diagn Progn Res. 2023 Dec 11;7(1):26. doi: 10.1186/s41512-023-00162-0.

ABSTRACT

BACKGROUND: For people at high risk of lung cancer, low-dose computed tomography (LDCT) is proposed as a method to reduce mortality.

METHODS: Our objective was to estimate the effect of LDCT lung cancer screening on mortality in high-risk populations. A systematic review of randomised controlled trials (RCTs) comparing LDCT screening programmes with usual care (no screening) or other imaging screening programme (such as chest X-ray (CXR)) was conducted. RCTs of CXR screening were additionally included in the network meta-analyses. Bibliographic sources including MEDLINE, Embase, Web of Science and the Cochrane Library were searched to January 2017, and then further extended to November 2021. All key review steps were done by two persons. Quality assessment used the Cochrane Risk of Bias tool. Meta-analyses were performed.

RESULTS: Nine RCTs, with up to 12.3 years of follow-up from randomisation, were included in the direct meta-analysis, which showed that LDCT screening was associated with a statistically significant decrease in lung cancer mortality (pooled relative risk (RR) 0.86, 95% confidence interval [CI] 0.77 to 0.96). There was a statistically non-significant decrease in all-cause mortality (pooled RR 0.98, 95% CI 0.95 to 1.01). The statistical heterogeneity for both outcomes was minimal. Network meta-analysis including the nine RCTs in the direct meta-analysis plus two further RCTs comparing CXR with usual care confirmed the size of the effect of LDCT on lung cancer mortality and that this was very similar irrespective of whether the comparator was usual care or CXR screening.

CONCLUSIONS: LDCT screening is effective in reducing lung cancer mortality in high-risk populations. The uncertainty of its effect on lung cancer mortality observed in 2018 has been much reduced with new trial results and updates to existing trials, emphasising the importance of updating systematic reviews. Although there are still a number of RCTs unreported or in progress, we predict that further evolution of summary mortality estimates is unlikely. The focus for debate now moves to resolving uncertainty about the cost-effectiveness of LDCT screening taking into account the balance between benefits and harms which occur in all screening programmes.

PMID:38072977 | DOI:10.1186/s41512-023-00162-0

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A 3D “sandwich” co-culture system with vascular niche supports mouse embryo development from E3.5 to E7.5 in vitro

Stem Cell Res Ther. 2023 Dec 10;14(1):349. doi: 10.1186/s13287-023-03583-2.

ABSTRACT

BACKGROUND: Various methods for ex utero culture systems have been explored. However, limitations remain regarding the in vitro culture platforms used before implanting mouse embryos and the normal development of mouse blastocysts in vitro. Furthermore, vascular niche support during mouse embryo development from embryonic day (E) 3.5 to E7.5 is unknown in vitro.

METHODS: This study established a three-dimensional (3D) “sandwich” vascular niche culture system with in vitro culture medium (IVCM) using human placenta perivascular stem cells (hPPSCs) and human umbilical vein endothelial cells (hUVECs) as supportive cells (which were seeded into the bottom layer of Matrigel) to test mouse embryos from E3.5 to E7.5 in vitro. The development rates and greatest diameters of mouse embryos from E3.5 to E7.5 were quantitatively determined using SPSS software statistics. Pluripotent markers and embryo transplantation were used to monitor mouse embryo quality and function in vivo.

RESULTS: Embryos in the IVCM + Cells (hPPSCs + hUVECs) group showed higher development rates and greater diameters at each stage than those in the IVCM group. Embryos in the IVCM + Cells group cultured to E5.5 morphologically resembled natural egg cylinders and expressed specific embryonic cell markers, including Oct4 and Nanog. These features were similar to those of embryos developed in vivo. After transplantation, the embryos were re-implanted in the internal uterus and continued to develop to a particular stage.

CONCLUSIONS: The 3D in vitro culture system enabled embryo development from E3.5 to E7.5, and the vascularization microenvironment constructed by Matrigel, hPPSCs, and hUVECs significantly promoted the development of implanted embryos. This system allowed us to further study the physical and molecular mechanisms of embryo implantation in vitro.

PMID:38072932 | DOI:10.1186/s13287-023-03583-2

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Correction to: Adverse effects of sodium‑glucose cotransporter‑2 inhibitors in patients with heart failure: a systematic review and meta‑analysis

Heart Fail Rev. 2023 Dec 11. doi: 10.1007/s10741-023-10378-3. Online ahead of print.

NO ABSTRACT

PMID:38072892 | DOI:10.1007/s10741-023-10378-3

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Analysis of maxillary asymmetry before and after treatment of functional posterior cross-bite: a retrospective study using 3D imaging system and deviation analysis

Prog Orthod. 2023 Dec 11;24(1):41. doi: 10.1186/s40510-023-00494-z.

ABSTRACT

BACKGROUND: Previous evidence would suggest that subjects affected by functional posterior cross-bite (FPXB) present an asymmetric morphology of the maxilla. However, no evidence is available concerning the morphology (symmetry/asymmetry) of the maxilla after treatment of FPXB. This study aimed to investigate the volumetric and morphological changes of the palate in FPXB subjects treated with maxillary expansion and to compare these data with an untreated control group. The study sample included 20 FPXB subjects (mean age 8.1 ± 0.9 years) who underwent maxillary expansion (MEG group) and 21 FPXB subjects (mean age 7.7 ± 1.2 years) as controls (CG group). Digital models were recorded at T0 (first observation) and T1 (12-18 months after first observation) and analyzed to assess palatal volume and symmetry. Deviation analysis and percentage matching calculation were also performed between original and mirrored palatal models for each patient. All data were statistically analyzed for intra-timing, inter-timing and inter-groups assessments.

RESULTS: At T0, the cross-bite side (CBS) was significantly smaller than non-cross-bite side (non-CBS) in both groups (p < 0.05). At T1, the CBS/non-CBS difference reduced significantly in the MEG group (p < 0.05) while slightly worsened in the CG, however without statistical significance (p > 0.05). The matching percentage of the palatal models improved significantly at T1 in the MEG group (T0 = 74.02% ± 9.8; T1 = 89.95% ± 7.12) (p < 0.05) while no significant differences were recorded in the CG (T0 = 76.36 ± 8.64; 72.18% ± 9.65) (p > 0.05).

LIMITATIONS: The small sample size and the retrospective design of the study represent two limitations that should be overcome with further clinical trials.

CONCLUSIONS: Subjects with FPXB present an asymmetric development of the maxillary vault that improves after reestablishment of normal occlusion following maxillary expansion.

PMID:38072875 | DOI:10.1186/s40510-023-00494-z

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Impact of family history of cancer on colorectal cancer screening: a propensity score-matched analysis from the Health Information National Trends Survey (HINTS)

J Egypt Natl Canc Inst. 2023 Dec 11;35(1):38. doi: 10.1186/s43046-023-00201-3.

ABSTRACT

BACKGROUND: Early detection of colon cancer leads to better survival outcomes. This can be achieved through colorectal cancer (CRC) screening. People with a family history of cancer (FHC) have increased risk of developing CRC. Increasing screening in this group will reduce CRC mortality. This study evaluated CRC screening in people with FHC.

METHODS: The study used data from the Health Information National Trends Survey (HINTS) 5, cycle 3. This is an annual cross-sectional survey with a nationally representative sample of American adults. The objective was to study the association between FHC and performing CRC screening. Propensity score matching was used to create a matched population with variables that constituted beliefs in cancer from the survey. Replication procedure, which is based on repeated sampling and allows for accurate computation of standard errors, was used for calculating statistical tests. Multivariable models were fitted in the matched population to assess the association between FHC and performing CRC screening.

RESULTS: People with FHC were 14% (OR = 1.14; 95% CI: 0.81-1.60) more likely to perform CRC screening than those without FHC, even though not statistically significant. Age in years (OR = 1.14; 95% CI: 1.12-5.27) had increased likelihood of performing CRC screening, while other races such as American Indians/Alaskan Natives (except African Americans) compared to Caucasians (OR = 0.49; 95% CI: 0.29-0.84) had significantly decreased likelihood of performing CRC screening.

CONCLUSION: FHC was not significantly associated with having a colorectal cancer screening test. Public health advocacy should be directed towards increasing awareness of CRC screening among people with FHC.

PMID:38072859 | DOI:10.1186/s43046-023-00201-3