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Nevin Manimala Statistics

Investigation of optimal hernia repair techniques in patients with inflammatory bowel disease

Surg Endosc. 2023 Nov 15. doi: 10.1007/s00464-023-10537-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Multiple laparotomies, immunosuppressive therapy, wound infection, and malnutrition are risk factors for incisional hernia development, which places inflammatory bowel disease (IBD) patients at high risk. With advances in minimally invasive techniques, this study assesses incisional hernia repair techniques and complications in the IBD population.

METHODS: A single-center, retrospective review of adults with IBD who underwent incisional hernia repair from 2008 to 2022. Complications relative to operative approach and mesh placement location were assessed using descriptive and univariate statistics.

RESULTS: Eighty-eight IBD patients underwent incisional hernia repair. Fifty-two (59.1%) were on immunomodulators and 30 (34.1%) were repaired primarily. Thirty-five (39.7%) hernias recurred, of whom 19 (33%) had mesh placed. Three (30%) occurred in onlay repairs and 16 (33%) occurred in underlay repairs. Subdivision of underlay repairs into intraperitoneal, preperitoneal and retrorectus mesh placement revealed recurrence rates of 35.1%, 50%, and 14.3%, respectively. Patients with open repair were more likely to have intraoperative bowel injury (28.6% vs 9.7%, p = 0.041) and develop postoperative seromas/abscesses (12.5% vs 0%, p = 0.001) and wound complications (17.9% vs 0%, p = 0.012) compared to laparoscopic. Seromas/abscesses developed more frequently in onlay repairs compared to underlay (40% vs 2.13%, p = 0.001). Twelve (13.6%) patients presented with postoperative small bowel obstruction (SBO), 7 (58.3%) of whom had mesh placed, and 6 (85.7%) were underlay. All SBO after underlay repair had intraperitoneally placed mesh. When comparing surgeons, hernias were more likely to recur performed by colorectal surgeons compared to hernia surgeons (63.3% vs 21.3%, p < 0.001).

CONCLUSION: In IBD patients, minimally invasive approaches lead to fewer perioperative complications compared to open. Underlay mesh placement demonstrated decreased incidence of seroma/abscess formation compared to onlay. When sub-grouped, underlay placements were similar in terms of complications. Retrorectus placement, however, had fewer recurrences and no readmissions for SBO. This suggests a minimally invasive approach or placement of retrorectus mesh may provide the optimal repair in this patient population.

PMID:37968385 | DOI:10.1007/s00464-023-10537-5

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Heritability and developmental plasticity of growth in an oviparous lizard

Heredity (Edinb). 2023 Nov 15. doi: 10.1038/s41437-023-00660-3. Online ahead of print.

ABSTRACT

Selective processes act on phenotypic variation although the evolutionary potential of a trait relies on the underlying heritable variation. Developmental plasticity is an important source of phenotypic variation, but it can also promote changes in genetic variation, yet we have a limited understanding of how they are both impacted. Here, we quantified the influence of developmental temperature on growth in delicate skinks (Lampropholis delicata) and partitioned total phenotypic variance using an animal model fitted with a genomic relatedness matrix. We measured mass for 261 individuals (nhot = 125, ncold = 136) over 16 months (nobservations = 3002) and estimated heritability and maternal effects over time. Our results show that lizards reared in cold developmental temperatures had consistently higher mass across development compared to lizards that were reared in hot developmental temperatures. However, developmental temperature did not impact the rate of growth. On average, additive genetic variance, maternal effects and heritability were higher in the hot developmental temperature treatment; however, these differences were not statistically significant. Heritability increased with age, whereas maternal effects decreased upon hatching but increased again at a later age, which could be driven by social competition or intrinsic changes in the expression of variation as an individual’s growth. Our work suggests that the evolutionary potential of growth is complex, age-dependent and not overtly affected by extremes in natural nest temperatures.

PMID:37968348 | DOI:10.1038/s41437-023-00660-3

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Prediction of alternative pre-mRNA splicing outcomes

Sci Rep. 2023 Nov 15;13(1):20000. doi: 10.1038/s41598-023-47348-6.

ABSTRACT

To understand the biological impact of alternative pre-mRNA splicing, it is vital to know which exons are involved, what protein domains they encode, and how the translated isoforms differ. Therefore, we developed a computational pipeline (RiboSplitter) focused on functional effect prediction. It builds on event-based alternative splicing detection with additional filtering steps leading to more efficient statistical testing, and with detection of isoform-specific protein changes. A key methodological advance is reading frame prediction by translating exonic DNA in all possible frames, then finding a single open reading frame, or a single frame with matches to known proteins of the gene. This allowed unambiguous translation in 93.9% of alternative splicing events when tested on RNA-sequencing data of B cells from Sjögren’s syndrome patients. RiboSplitter does not depend on reference annotations and translates events even when one or both isoform(s) are novel (unannotated). RiboSplitter’s visualizations illustrate each event with translation outcomes, show event location within the gene, and align exons to protein domains.

PMID:37968320 | DOI:10.1038/s41598-023-47348-6

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Nevin Manimala Statistics

On effectively predicting autism spectrum disorder therapy using an ensemble of classifiers

Sci Rep. 2023 Nov 15;13(1):19957. doi: 10.1038/s41598-023-46379-3.

ABSTRACT

An ensemble of classifiers combines several single classifiers to deliver a final prediction or classification decision. An increasingly provoking question is whether such an ensemble can outperform the single best classifier. If so, what form of ensemble learning system (also known as multiple classifier learning systems) yields the most significant benefits in the size or diversity of the ensemble? In this paper, the ability of ensemble learning to predict and identify factors that influence or contribute to autism spectrum disorder therapy (ASDT) for intervention purposes is investigated. Given that most interventions are typically short-term in nature, henceforth, developing a robotic system that will provide the best outcome and measurement of ASDT therapy has never been so critical. In this paper, the performance of five single classifiers against several multiple classifier learning systems in exploring and predicting ASDT is investigated using a dataset of behavioural data and robot-enhanced therapy against standard human treatment based on 3000 sessions and 300 h, recorded from 61 autistic children. Experimental results show statistically significant differences in performance among the single classifiers for ASDT prediction with decision trees as the more accurate classifier. The results further show multiple classifier learning systems (MCLS) achieving better performance for ASDT prediction (especially those ensembles with three core classifiers). Additionally, the results show bagging and boosting ensemble learning as robust when predicting ASDT with multi-stage design as the most dominant architecture. It also appears that eye contact and social interaction are the most critical contributing factors to the ASDT problem among children.

PMID:37968315 | DOI:10.1038/s41598-023-46379-3

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Heavy metal toxicity arising from the industrial effluents repercussions on oxidative stress, liver enzymes and antioxidant activity in brain homogenates of Oreochromis niloticus

Sci Rep. 2023 Nov 15;13(1):19936. doi: 10.1038/s41598-023-47366-4.

ABSTRACT

Industrial effluents reaching to the aquatic ecosystem is one of the major causes of environmental pollution and exposure to industrial effluents containing harmful substances may be a serious threat to human health. Therefore, the present study aimed to determine the sub-lethal (1/5th of predetermined LC50) impact of industrial effluents from Sundar Industrial Estate on Oreochromis niloticus with proper negative control. The physicochemical analysis of industrial effluents showed enormous loads of inorganic pollutants and exhibited high mean levels of heavy metals, Mn, Fe, Pb, Ni, Cr, Hg, As, Zn and Fe with statistically significant differences at p < 0.05. Highest level of Mn and Fe was detected in effluent’s samples as 147.36 ± 80.91 mg/L and 90.52 ± 32.08 mg/L, respectively. Exposure led to increase in serum biochemical parameters alanine aminotransferase + 25%, aspartate aminotransferase + 20% and alkaline phosphatase + 7% over control although superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione significantly increased as 3.42, 2.44, 4.8 and 8 folds, respectively in metabolically active tissue brain which indicated stress caused by industrial effluents. The results concluded that industrial effluent has potent oxidative stress inducers on one hand whereas histoarchitectural and physiological toxicity causing contaminants on the other. This condition may adversely affect the health of aquatic organisms, the fish and ultimately the human beings.

PMID:37968305 | DOI:10.1038/s41598-023-47366-4

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Evaluation of retinal vascularization in retinopathy of prematurity regressed after intravitreal ranibizumab monotherapy or without treatment based on fluorescein angiography

Sci Rep. 2023 Nov 15;13(1):19946. doi: 10.1038/s41598-023-47212-7.

ABSTRACT

To investigate the fluorescein angiography (FA) findings and compare the extent of retinal vascularization in retinopathy of prematurity (ROP), recovered after intravitreal ranibizumab (IVR) monotherapy and those regressed spontaneously. Infants with a history of ROP who underwent FA between April 2018 and November 2021 were retrospectively included. The patients were divided into two groups based on whether they had received IVR (IVR group) or had ROP that regressed spontaneously without treatment (untreated group). The differences between the two groups in zone II ROP were also compared, to equalize the subgroups as much as possible in terms of disease severity. FA findings were recorded. The extent of vascularization was measured by the ratio of the distance from the center of the disk to the border of the vascularized zone (DB) and the distance from the center of the disk to the center of the fovea (DF). The width of the persistent avascular retina (PAR) was counted by disc diameters (DD). One hundred and ten eyes of 55 infants were included in the IVR group and 76 eyes of 38 babies in the untreated group. The ratio of abnormal shape of vessels was significantly higher in the IVR group than in the untreated group (50.9% vs. 35.5%; P = 0.038), while the linear choroidal filling pattern, tortuosity of vessels over the posterior pole, dye leakage, anomalous branching of vessels, circumferential vessels, arteriovenous shunt, abnormal capillary bed, and macular abnormalities were similarly. There was a smaller temporal DB/DF ratio (4.48 vs. 4.63; P = 0.003) and greater PAR (2.63 vs. 1.76; P < 0.001) in the IVR group compared to the untreated group. In zone II ROP, the progression of retinal vascularization was significantly larger in the IVR group than that in the untreated group (P = 0.003), while no statistical differences were observed in FA features, the DB/DF ratio, and PAR between the two subgroups. The residual vascular abnormalities and PAR may be common results of ROP regression. The DB/DF ratio of 4.0 temporally and 3.3 nasally could be used as the preliminary indicators for safe retinal vascularization in the completion of ROP regression.

PMID:37968276 | DOI:10.1038/s41598-023-47212-7

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Nevin Manimala Statistics

Evaluation of pragmatic oxygenation measurement as a proxy for Covid-19 severity

Nat Commun. 2023 Nov 15;14(1):7374. doi: 10.1038/s41467-023-42205-6.

ABSTRACT

Choosing optimal outcome measures maximizes statistical power, accelerates discovery and improves reliability in early-phase trials. We devised and evaluated a modification to a pragmatic measure of oxygenation function, the [Formula: see text] ratio. Because of the ceiling effect in oxyhaemoglobin saturation, [Formula: see text] ratio ceases to reflect pulmonary oxygenation function at high [Formula: see text] values. We found that the correlation of [Formula: see text] with the reference standard ([Formula: see text]/[Formula: see text] ratio) improves substantially when excluding [Formula: see text] and refer to this measure as [Formula: see text]. Using observational data from 39,765 hospitalised COVID-19 patients, we demonstrate that [Formula: see text] is predictive of mortality, and compare the sample sizes required for trials using four different outcome measures. We show that a significant difference in outcome could be detected with the smallest sample size using [Formula: see text]. We demonstrate that [Formula: see text] is an effective intermediate outcome measure in COVID-19. It is a non-invasive measurement, representative of disease severity and provides greater statistical power.

PMID:37968269 | DOI:10.1038/s41467-023-42205-6

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Left ventricle hypertrophy and re-modeling in children with essential hypertension: does the race matter?

Cardiol Young. 2023 Nov 16:1-8. doi: 10.1017/S1047951123003840. Online ahead of print.

ABSTRACT

BACKGROUND: This is the first study to report on the impact of race on differences in the prevalence of echocardiographic left ventricular hypertrophy and left ventricular adaptation at the time of diagnosis of essential hypertension in children.

METHODS: This cross-sectional, single-centre study included patients aged 3-18 years who had newly diagnosed essential hypertension. Echocardiography was used to assess left ventricular mass index and left ventricular relative wall thickness. An left ventricular mass index > the 95th percentile for age and gender, and an left ventricular relative wall thickness > 0.42, were used to diagnose left ventricular hypertrophy and concentric adaptation. Various echocardiographic parameters were compared between African Americans and Caucasians.

RESULTS: The study included 422 patients (289 African Americans and 133 Caucasians) diagnosed with essential hypertension at a median age of 14.6 (interquartile range; 12.1-16.3) years. Eighty-eight patients (20.9%) had left ventricular hypertrophy. There was no statistically significant difference in the prevalence of left ventricular hypertrophy between African Americans and Caucasians (22.5% versus 17.3%, p=0.22). The median left ventricular relative wall thickness was 0.35 (0.29-0.43), and 114 patients (27.0%) had an left ventricular relative wall thickness > 0.42. The presence of an left ventricular relative wall thickness > 0.42 was significantly higher among African Americans compared to Caucasians (30.1% versus 20.3%, p = 0.04). The African American race was a strong predictor for an left ventricular relative wall thickness > 0.42 (odds ratio 1.7, p = 0.04), but not for left ventricular mass index > the 95th percentile (p = 0.22). Overweight/obesity was a strong predictor for an left ventricular mass index > the 95th percentile.

CONCLUSIONS: There was no difference in the prevalence of left ventricular hypertrophy in children with essential hypertension of different races. Obesity, rather than being African American, is associated with left ventricular hypertrophy.

PMID:37968238 | DOI:10.1017/S1047951123003840

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Phase III randomized clinical studies to evaluate the immunogenicity, lot-to-lot consistency, and safety of ROTAVAC® liquid formulations (ROTAVAC 5C & 5D) and non-inferiority comparisons with licensed ROTAVAC® (frozen formulation) in healthy infants

Hum Vaccin Immunother. 2023 Dec 15;19(3):2278346. doi: 10.1080/21645515.2023.2278346. Epub 2023 Nov 15.

ABSTRACT

The WHO pre-qualified rotavirus vaccine, ROTAVAC®, is derived naturally from the neonatal 116E rotavirus strain, and stored at -20°C. As refrigerator storage is preferable, immunogenicity and safety of liquid formulations kept at 2-8°C, having excipients to stabilize the rotavirus, with or without buffers, were compared with ROTAVAC® in different clinical studies. Study-1, the pivotal trial for this entire product development work, was a randomized, single-blind trial with two operationally seamless phases: (i) an exploratory phase involving 675 infants in which two formulations, ROTAVAC 5C (LnHRV-1.5 mL and LnHRV-2.0 mL) containing buffer and excipients to stabilize the virus against gastric acidity and temperature, were compared with ROTAVAC®. As the immune response of ROTAVAC 5C (LnHRV-2.0 mL) was non-inferior to ROTAVAC®, it was selected for (ii) confirmatory phase, involving 1,302 infants randomized 1:1:1:1 to receive three lots of LnHRV-2.0 mL, or ROTAVAC®. Primary objectives were the evaluation of non-inferiority and lot-to-lot consistency. The secondary objectives were to assess the safety and interference with the concomitant pentavalent vaccine. As it was separately established that buffers are not required for ROTAVAC®, in Study-2, the safety and immunogenicity of ROTAVAC 5D® (with excipients) were compared with ROTAVAC® and lot-to-lot consistency was assessed in another study. All lots elicited consistent immune responses, did not interfere with UIP vaccines, and had reactogenicity similar to ROTAVAC®. ROTAVAC 5C and ROTAVAC 5D® were immunogenic and well tolerated as ROTAVAC®. ROTAVAC 5D® had comparable immunogenicity and safety profiles with ROTAVAC® and can be stored at 2-8°C, leading to WHO pre-qualification.Clinical Trials Registration: Clinical Trials Registry of India (CTRI): CTRI/2015/02/005577CTRI/2016/11/007481 and CTRI/2019/03/017934.

PMID:37968237 | DOI:10.1080/21645515.2023.2278346

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The association between parental age differences and perinatal outcomes

Hum Reprod. 2023 Nov 15:dead236. doi: 10.1093/humrep/dead236. Online ahead of print.

ABSTRACT

STUDY QUESTION: Are there significant associations existing between parental age differences and adverse perinatal outcomes?

SUMMARY ANSWER: Large differences in parental age are associated with adverse perinatal outcomes, particularly with older mothers paired with younger fathers.

WHAT IS KNOWN ALREADY: The association between advanced maternal age and perinatal outcomes is well-documented with women over 35 years showing an increased risk of several adverse outcomes. Other studies have identified potential associations between advanced paternal age and adverse perinatal outcomes.

STUDY DESIGN, SIZE, DURATION: A historical (retrospective) cohort analysis was performed utilizing a multivariable logistic regression model to evaluate the association between varying differences in parental age and adverse perinatal outcomes while controlling for demographic and health-related covariates. Data were compiled from the National Vital Statistics System for 20 613 704 births between 2012 and 2018.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Parental age differences, categorized into eleven 4-year intervals, were stratified by seven maternal age categories and evaluated for their associations with adverse perinatal outcomes. Main outcome measures included low birth weight, very low birth weight, preterm birth, very preterm birth, small size for gestational age, low 5-min appearance, pulse, grimace, activity, and respiration score, congenital defects, and chromosomal anomalies.

MAIN RESULTS AND THE ROLE OF CHANCE: Increased parental age differences, in either direction, were associated with significant risks for all adverse outcomes, aside from congenital defects, even when controlling for maternal age. Restricting maternal age to the reference range of 25-29 years, infants born to fathers aged 9-12 years younger (n = 3773) had 27% (odds ratio (OR) 1.27, 95% CI, 1.17-1.37) higher odds of having any adverse perinatal outcome. Infants born to fathers aged >16 years older (n = 98 555) had 14% (OR 1.14, 95% CI, 1.12-1.16) higher odds of having any adverse perinatal outcome.

LIMITATIONS, REASONS FOR CAUTION: Data extracted from US birth certificates may be compromised by errors in reporting or documentation. Information regarding the mother’s socioeconomic status was estimated using proxy variables and may be susceptible to uncontrolled factors. Use of a pre-compiled dataset may potentially exclude additional maternal comorbidities that could impact perinatal outcomes.

WIDER IMPLICATIONS OF FINDINGS: Older mothers paired with younger fathers demonstrated the highest risk, even when maternal age was below the threshold of 35 years. For the clinical setting, parental age differences should be considered alongside maternal and paternal age when assessing risks of adverse perinatal outcomes for potential parents. This is particularly relevant for older women with younger male partners as this may exacerbate the impact of advanced maternal age.

STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the NIH Research Fellowship T35 Training Grant. There are no competing interests.

TRIAL REGISTRATION NUMBER: N/A.

PMID:37968231 | DOI:10.1093/humrep/dead236