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Nevin Manimala Statistics

Vascular Endothelial Growth Factor and Ischemic Stroke Risk: A Mendelian Randomization Study

Neurol Ther. 2024 Apr 15. doi: 10.1007/s40120-024-00601-0. Online ahead of print.

ABSTRACT

INTRODUCTION: Previous studies have reported controversial relationships between circulating vascular endothelial growth factors (VEGF) and ischemic stroke (IS). This study aims to demonstrate the causal effect between VEGF and IS using Mendelian randomization (MR).

METHODS: Summary statistics data from two large-scale genome-wide association studies (GWAS) for 16,112 patients with measured VEGF levels and 40,585 patients with IS were downloaded from public databases and included in this study. A published calculator was adopted for MR power calculation. The primary outcome was any ischemic stroke, and the secondary outcomes were large-artery stroke, cardioembolic stroke, and small-vessel stroke. We used the inverse variance-weighted (IVW) method for primary analysis, supplemented by MR-Egger regression and the weighted median method.

RESULTS: Nine SNPs were included to represent serum VEGF levels. The IVW method revealed no strong causal association between VEGF and any ischemic stroke (odds ratio [OR] 1.01, 95% CI 0.99-1.04, p = 0.39), cardioembolic stroke (OR 1.04, 95% CI 0.97-1.12, p = 0.28), large-artery stroke (OR 1.02, 95% CI 0.95-1.09, p = 0.62), and small-vessel stroke (OR 0.98, 95% CI 0.91-1.04, p = 0.46). These findings remained robust in sensitivity analyses. MR-Egger regression suggested no horizontal pleiotropy.

CONCLUSIONS: This Mendelian randomization study found no relationship between genetically predisposed serum VEGF levels and risks of IS or its subtypes.

PMID:38619804 | DOI:10.1007/s40120-024-00601-0

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Prediction of Prospective Mutational Landscape of SARS-CoV-2 Spike ssRNA and Evolutionary Basis of Its Host Interaction

Mol Biotechnol. 2024 Apr 15. doi: 10.1007/s12033-024-01146-1. Online ahead of print.

ABSTRACT

Booster doses are crucial against severe COVID-19, as rapid virus mutations and variant emergence prolong the pandemic crisis. The virus’s quick evolution, short generation-time, and adaptive changes impact virulence and evolvability, helping predictions about variant of concerns’ (VOCs’) landscapes. Here, in this study, we used a new computational algorithm, to predict the mutational pattern in SARS-CoV-2 ssRNA, proteomics, structural identification, mutation stability, and functional correlation, as well as immune escape mechanisms. Interestingly, the sequence diversity of SARS Coronavirus-2 has demonstrated a predominance of G- > A and C- > U substitutions. The best validation statistics are explored here in seven homologous models of the expected mutant SARS-CoV-2 spike ssRNA and employed for hACE2 and IgG interactions. The interactome profile of SARS-CoV-2 spike with hACE2 and IgG revealed a strong correlation between phylogeny and divergence time. The systematic adaptation of SARS-CoV-2 spike ssRNA influences infectivity and immune escape. Data suggest higher propensity of Adenine rich sequence promotes MHC system avoidance, preferred by A-rich codons. Phylogenetic data revealed the evolution of SARS-CoV-2 lineages’ epidemiology. Our findings may unveil processes governing the genesis of immune-resistant variants, prompting a critical reassessment of the coronavirus mutation rate and exploration of hypotheses beyond mechanical aspects.

PMID:38619800 | DOI:10.1007/s12033-024-01146-1

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The Relationship Between Chromosomal Polymorphism and Male Reproductive Abnormalities

Reprod Sci. 2024 Apr 15. doi: 10.1007/s43032-024-01530-x. Online ahead of print.

ABSTRACT

This study aims to investigate the association between chromosomal polymorphisms and abnormalities in male reproductive health. Within the period from January 2018 to December 2022, a cohort of 10,827 males seeking fertility services at our reproductive center was selected for inclusion in this study. Peripheral blood chromosomal karyotype analysis was conducted for each participant to identify carriers of chromosomal polymorphisms, who were subsequently categorized into a polymorphism group. Additionally, a control group was constituted by randomly selecting 1,630 patients exhibiting normal chromosomal karyotypes. The study conducted statistical analyses to compare clinical outcomes between the two groups, focusing on infertility, history of spontaneous miscarriage in partners, anomalies in reproductive development, fetal abnormalities, and sperm quality metrics. (1) Among the cohort of 10,827 males, chromosomal polymorphisms were identified in 1,622 participants, yielding a detection rate of 14.98%. This rate is significantly elevated in comparison to the baseline prevalence of 1.77% observed in the general population. (2) The predominant variant among these polymorphisms was related to the Y chromosome, accounting for 1,082 cases (66.71% of the polymorphic findings), corresponding to a detection rate of 9.99%. This is markedly higher than the approximate 0.09% prevalence noted within a normative demographic. (3) Statistical analysis revealed significant disparities between the chromosomal polymorphism group and the control group in several clinical outcomes. Notably, the rates of spontaneous abortion (18.06% vs. 1.35%), fetal anomalies (1.97% vs. 0.25%), and poor sperm quality (41.74% vs. 7.18%) were markedly higher in the polymorphism group. Additionally, incidences of testicular dysgenesis (2.28% vs. 0.92%) and hypogonadism in partners (0.62% vs. 0.37%) also demonstrated significant differences, underscoring the potential reproductive implications of chromosomal polymorphisms. The study establishes a significant link between chromosomal polymorphisms and critical reproductive outcomes, including male infertility, spontaneous miscarriages in partners, fetal anomalies, and reduced sperm quality. These findings highlight the clinical relevance of chromosomal polymorphisms in reproductive health assessments and suggest the necessity for their consideration in the diagnostic and therapeutic strategies for male reproductive disorders.

PMID:38619795 | DOI:10.1007/s43032-024-01530-x

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Impaired cerebral autoregulation detected in early prevasospasm period is associated with unfavorable outcome after spontaneous subarachnoid hemorrhage: an observational prospective pilot study

Ultrasound J. 2024 Apr 15;16(1):24. doi: 10.1186/s13089-024-00371-8.

ABSTRACT

BACKGROUND: Subarachnoid hemorrhage (SAH) patients with cerebral autoregulation (CA) impairment at an early post-SAH period are at high risk of unfavorable outcomes due to delayed cerebral ischemia (DCI) or other complications. Limited evidence exists for an association between early-stage CA impairments and SAH patient outcomes. The objective of this prospective study was to explore associations between CA impairments detected in early post-SAH snapshot examinations and patient outcomes.

METHODS: The pilot observational study included 29 SAH patients whose CA status was estimated 2-3 days after spontaneous aneurysm rupture and a control group of 15 healthy volunteers for comparison. Inflatable leg recovery boots (reboots.com, Germany) were used for the safe controlled generation of arterial blood pressure (ABP) changes necessary for reliable CA examination. At least 5 inflation‒deflation cycles of leg recovery boots with a 2-3 min period were used during examinations. CA status was assessed according to the delay time (∆TCBFV) measured between ABP(t) and cerebral blood flow velocity (CBFV(t)) signals during artificially induced ABP changes at boot deflation cycle. CBFV was measured in middle cerebral artery by using transcranial Doppler device.

RESULTS: Statistically significant differences in ∆TCBFV were found between SAH patients with unfavorable outcomes (∆TCBFV = 1.37 ± 1.23 s) and those with favorable outcomes (∆TCBFV = 2.86 ± 0.99 s) (p < 0.001). Early assessment of baroreflex sensitivity (BRS) during the deflation cycle showed statistically significant differences between the DCI and non-DCI patient groups (p = 0.039).

CONCLUSIONS: A relatively small delay of ∆TCBFV <1.6 s between CBFV(t) and ABP(t) waves could be an early warning sign associated with unfavorable outcomes in SAH patients. The BRS during boot deflation can be used as a biomarker for the prediction of DCI.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06028906. Registered 31 August 2023 – Retrospectively registered, https://www.

CLINICALTRIALS: gov/study/NCT06028906 .

PMID:38619783 | DOI:10.1186/s13089-024-00371-8

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Factors affecting the need for ureteral catheterization in symptomatic pregnancy hydronephrosis

Int Urol Nephrol. 2024 Apr 15. doi: 10.1007/s11255-024-04052-2. Online ahead of print.

ABSTRACT

PURPOSE: In our study, considering the clinical parameters we aimed to determine the most appropriate treatment approach for symptomatic gestational hydronephrosis and conditions requiring DJS insertion.

METHODS: Our study was a retrospective cross-sectional study and 137 patients were included. The patients were divided into two groups: those with conservative follow-up and those with DJS. Demographic and clinical data, the degree of HUN detected in urinary ultrasonography and the anteroposterior diameter of the renal pelvis were evaluated. Factors affecting the need for DJS between groups were investigated. Also, it was aimed to determine the cut-off value for the HUN degree and renal pelvis AP diameter in patients with DJS.

RESULTS: The presence of urinary system stones was statistically significantly higher in the group with DJS than in the group without DJS (p = 0.014). HUN degrees and AP diameter were statistically significantly higher in the DJS group (p < 0.001, p < 0.001, respectively). HUN degree and renal pelvis AP diameter were the two most important predictors for DJS insertion (p = 0.005, p = 0.015, respectively). The AP diameter cut-off value for DJS installation was determined as 20.5 mm.

CONCLUSION: Although there are conservative and surgical treatment options for symptomatic hydronephrosis of pregnancy, the factors at the decision point between these options are still a matter of debate. In our study, we concluded that the most important determinants at this decision point are the HUN degree and renal pelvis AP diameter. We think that the cut-off values we have determined for these markers will guide clinicians in deciding on treatment.

PMID:38619779 | DOI:10.1007/s11255-024-04052-2

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Comparative analysis of bevacizumab and LITT for treating radiation necrosis in previously radiated CNS neoplasms: a systematic review and meta-analysis

J Neurooncol. 2024 Apr 15. doi: 10.1007/s11060-024-04650-1. Online ahead of print.

ABSTRACT

PURPOSE: Radiation necrosis (RN) is a local inflammatory reaction that arises in response to radiation injury and may cause significant morbidity. This study aims to evaluate and compare the efficacy of bevacizumab and laser interstitial thermal therapy (LITT) in treating RN in patients with previously radiated central nervous system (CNS) neoplasms.

METHODS: PubMed, Cochrane, Scopus, and EMBASE databases were screened. Studies of patients with radiation necrosis from primary or secondary brain tumors were included. Indirect meta-analysis with random-effect modeling was performed to compare clinical and radiological outcomes.

RESULTS: Twenty-four studies were included with 210 patients in the bevacizumab group and 337 patients in the LITT group. Bevacizumab demonstrated symptomatic improvement/stability in 87.7% of cases, radiological improvement/stability in 86.2%, and steroid wean-off in 45%. LITT exhibited symptomatic improvement/stability in 71.2%, radiological improvement/stability in 64.7%, and steroid wean-off in 62.4%. Comparative analysis revealed statistically significant differences favoring bevacizumab in symptomatic improvement/stability (p = 0.02), while no significant differences were observed in radiological improvement/stability (p = 0.27) or steroid wean-off (p = 0.90). The rates of adverse reactions were 11.2% for bevacizumab and 14.9% for LITT (p = 0.66), with the majority being grade 2 or lower (72.2% for bevacizumab and 62.5% for LITT).

CONCLUSION: Both bevacizumab and LITT exhibited favorable clinical and radiological outcomes in managing RN. Bevacizumab was found to be associated with better symptomatic control compared to LITT. Patient-, diagnosis- and lesion-related factors should be considered when choosing the ideal treatment modality for RN to enhance overall patient outcomes.

PMID:38619777 | DOI:10.1007/s11060-024-04650-1

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Real-World Treatment Patterns and Healthcare Resource Use for Ulcerative Colitis and Crohn’s Disease in Italy

Adv Ther. 2024 Apr 15. doi: 10.1007/s12325-024-02840-x. Online ahead of print.

ABSTRACT

INTRODUCTION: Real-world data are used to inform decision-makers and optimise therapeutic management for patients with ulcerative colitis (UC) and Crohn’s disease (CD). We analysed data on the epidemiology (by using proxies of prevalence and incidence), patient characteristics, treatment patterns and associated healthcare direct costs for the management of patients with UC and patients with CD in Italy.

METHODS: This retrospective observational study used administrative databases from eight Local Health Units geographically distributed across Italy. Adult patients with a hospitalisation and/or an exemption for UC or CD were included. Study outcomes were summarised descriptively, and limited statistical tests were performed.

RESULTS: At baseline, 9255 adults with UC and 4747 adults with CD were included. Mean (standard deviation) age at inclusion was 54.0 (18.4)/48.6 (18.1) years, for UC/CD. The estimated average incidence of UC and CD for the period 2013-2020 was 36.5 and 18.7 per 100,000, respectively. The most frequently prescribed drug category for patients with UC/CD was conventional treatment [mesalazine and topical corticosteroids (67.4%/61.1%), immunomodulators and systemic corticosteroids (43.2%/47.7%)], followed by biologic treatments (2.1%/5.1%). The mean annual total direct cost per patient was 7678 euro (€), for UC and €6925 for CD.

CONCLUSION: This analysis, carried-out in an Italian clinical setting, may help to optimise therapy for patients with UC and CD and provide relevant clinical practice data to inform decision-makers.

PMID:38619721 | DOI:10.1007/s12325-024-02840-x

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Simultaneous Co-surgeon Deep Inferior Epigastric Perforator (DIEP) Flap Breast Reconstructions: Feasibility and Clinical Outcomes

Ann Surg Oncol. 2024 Apr 15. doi: 10.1245/s10434-024-15266-0. Online ahead of print.

ABSTRACT

BACKGROUND: A co-surgeon model is known to be favorable in microvascular breast reconstruction, but simultaneous co-surgeon deep inferior epigastric perforator (DIEP) flap cases have not been well-studied. The authors hypothesize that performing two simultaneous co-surgeon bilateral DIEP flap reconstructions results in non-inferior clinical outcomes and may improve patient access to care.

METHODS: A single-institution, retrospective cohort study was performed utilizing record review to identify all cases of co-surgeon free-flap breast reconstructions over a 38-month period. Patients who underwent simultaneous bilateral DIEP flap breast reconstructions with the same two co-surgeons were identified. The control group consisted of subjects who underwent non-simultaneous reconstruction by the same co-surgeons within the same, preceding, or following month of those in the study group. Primary outcome variables were 90-day postoperative complications, while secondary outcomes were operating time, ischemia time, and length of stay. Descriptive statistics, univariate and multivariable regression analyses were performed.

RESULTS: Overall, 137 subjects were identified and 64 met the inclusion criteria (n = 28 study, n = 36 control). There were no statistically significant differences between groups in body mass index, radiation, trainee experience, flap perforator number, immediate/delayed reconstruction, or length of stay. There were also no statistically significant differences in complications, including flap loss, anastomosis revision, take-back to the operating room, or re-admission. Operative time was longer in the simultaneous DIEP group (540.5 vs. 443.5 min, p < 0.01), but ischemia time was shorter in the simultaneous group (64.0 vs. 80.5 min, p < 0.01).

CONCLUSIONS: A simultaneous co-surgeon approach to bilateral DIEP flap reconstruction may improve access to care and does not result in a higher complication rate compared with non-simultaneous bilateral DIEP flaps.

PMID:38619709 | DOI:10.1245/s10434-024-15266-0

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From leaf to multiscale models of photosynthesis: applications and challenges for crop improvement

Photosynth Res. 2024 Apr 15. doi: 10.1007/s11120-024-01083-9. Online ahead of print.

ABSTRACT

To keep up with the growth of human population and to circumvent deleterious effects of global climate change, it is essential to enhance crop yield to achieve higher production. Here we review mathematical models of oxygenic photosynthesis that are extensively used, and discuss in depth a subset that accounts for diverse approaches providing solutions to our objective. These include models (1) to study different ways to enhance photosynthesis, such as fine-tuning antenna size, photoprotection and electron transport; (2) to bioengineer carbon metabolism; and (3) to evaluate the interactions between the process of photosynthesis and the seasonal crop dynamics, or those that have included statistical whole-genome prediction methods to quantify the impact of photosynthesis traits on the improvement of crop yield. We conclude by emphasizing that the results obtained in these studies clearly demonstrate that mathematical modelling is a key tool to examine different approaches to improve photosynthesis for better productivity, while effective multiscale crop models, especially those that also include remote sensing data, are indispensable to verify different strategies to obtain maximized crop yields.

PMID:38619700 | DOI:10.1007/s11120-024-01083-9

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Association Between Iodine Status and Prevalence of Hypothyroidism, Autoimmune Thyroiditis, and Thyroid Nodule: a Cross-Sectional Study in Shandong Province, China

Biol Trace Elem Res. 2024 Apr 15. doi: 10.1007/s12011-024-04179-4. Online ahead of print.

ABSTRACT

In this study, the aim was to investigate the correlation between varying levels of urinary iodine concentration (UIC) in adults and the occurrence of thyroid diseases, with the additional objective of determining the optimal iodine status level for adults. A cross-sectional study was conducted on adults from six areas with different drinking water iodine concentrations (WIC) without eating iodized salt in Heze and Jining counties, Shandong Province, China. A total of 1336 adults were included in this study, and drinking water samples, blood samples, urine samples, thyroid ultrasound, and a questionnaire were collected. UIC, free triiodothyronine (FT3), free thyroid hormone (FT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) were detected. There were no significant differences in the detection rates of hypothyroidism and thyroid autoimmunity (TAI) among the different median UIC groups (UIC < 100 μg/L, 100-199 μg/L, 200-299 μg/L, ≥ 300 μg/L). However, the detection rates of hypothyroidism were higher in the UIC < 100 μg/L group (16.67%) and the UIC ≥ 300 μg/L group (16.51%) compared to the other groups. The detection rate of TAI increased as UIC levels increased. The detection rate of thyroid nodule (TN) in the UIC < 100 μg/L group was significantly higher than that in the UIC 200-299 μg/L UIC group (χ2 = 10.814, P = 0.001). After adjusting confounding factors, it was found that low UIC (< 100 μg/L) was a risk factor for TN (OR 1.83, 95% CI [1.04-3.22]). Meanwhile, there no statistical difference between UIC 200 and 299 μg/L and UIC 100 and199 μg/L for OR of hypothyroidism, TAI, and TN. This study identified associations between different UIC levels and the prevalence of thyroid disorders, with low UIC (< 100 μg/L) posing a risk for TN, and the detection rate of TN and hypothyroidism was the lowest in UIC (200-299 μg/L) group. Therefore, the acceptable UIC range of ‘adequate’ iodine intake among adults can be widened from 100-199 µg/L to 100-299 µg/L.

PMID:38619679 | DOI:10.1007/s12011-024-04179-4