Nevin Manimala

JAMA Netw Open. 2023 May 1;6(5):e2316060. doi: 10.1001/jamanetworkopen.2023.16060.

ABSTRACT

IMPORTANCE: Rates of pediatric hospitalizations following an injury while riding an all-terrain vehicle (ATV) are increasing. Few studies have compared the rates of severe injuries among children, adolescents, and adults.

OBJECTIVES: To investigate whether younger ATV riders are at risk for more severe ATV-related injuries.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was conducted using administrative data from hospitals in 9 provinces in Canada. Participants included patients admitted to hospitals with ATV-related injuries between 2002 and 2019. Statistical analysis was performed from June 2020 to September 2021.

EXPOSURES: The primary exposure was age younger than 16 years. Comparison groups were youths aged 16 to 20 years and adults aged 21 years and older.

MAIN OUTCOMES AND MEASURES: The main outcomes of interest were death, spinal cord injury, and an Injury Severity Score (ISS) greater than 25. Secondary outcomes were less severe injuries, including head injuries, crush type injuries, and fractures.

RESULTS: Among 52 745 patients with complete data, 15% were youths younger than 16 years, 13% were youths aged 16 to 20 years, 82% were male, and 47% lived in rural areas. After adjusting for covariates, the odds of dying were higher among youths aged 16 to 20 years (adjusted odds ratio [aOR], 1.64; 95% CI, 1.04-2.60) compared with those younger than 16 years. Youths aged 16 to 20 years also had higher odds of spinal cord injury (aOR, 2.72; 95% CI, 1.80-4.20) and an injury severity score greater than 25 (aOR, 1.63; 95% CI, 1.36-1.96) compared with youths 16 years of age or less. Sex-specific analyses revealed these associations were greater for male youths aged 16 to 20 years (spinal cord injury: aOR, 3.81; 95% CI, 1.38-11.10, and dying in a hospital: aOR, 4.37; 95% CI, 1.19-21.02) than female youths aged 16 to 20 years.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of patients hospitalized for ATV injuries in Canada, youths aged 16 to 20 years and adults aged 21 years and older were at an increased risk of death and severe injuries compared with youths younger than 16 years. The increased risk of death and severe injuries was most evident among male patients.

PMID:37256619 | DOI:10.1001/jamanetworkopen.2023.16060

JAMA Dermatol. 2023 May 31. doi: 10.1001/jamadermatol.2023.1338. Online ahead of print.

ABSTRACT

IMPORTANCE: Biosimilars have the potential to reduce costs for the management of moderate-to-severe psoriasis compared with originators. However, the extrapolation of evidence enables the approval of a biosimilar for use in indications held by the originator without directly being studied in clinical trials. Thus, biosimilars can be approved for psoriasis based on extrapolated evidence from other diseases. The availability of evidence for the effectiveness and safety of biosimilars for the treatment of psoriasis is therefore unclear.

OBJECTIVE: To compare the efficacy/effectiveness and safety of biosimilars with originator biologics for the treatment of patients with psoriasis.

EVIDENCE REVIEW: MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov, and The European Union Clinical Trials Register were searched in August 2022. Eligible studies were appraised using the Cochrane Risk of Bias 2 and ROBINS-I tools. All analyses were conducted from September 2022 to November 2022.

FINDINGS: Fourteen trials (10 adalimumab, 2 etanercept, 1 infliximab, and 1 ustekinumab) and 3 cohort studies (1 adalimumab, 1 etanercept, 1 infliximab and etanercept) were included. Twelve trials compared biosimilars with originators in originator-naive patients (starters), and 11 trials compared switching from originator to biosimilar (switchers) with continuous originator treatments. There was no clinically or statistically significant difference in rates of achieving 75% improvement in Psoriasis Area and Severity Index scores and risks of adverse events (AEs) at week 16 and week 52 between the comparators. Two cohort studies showed no difference in effectiveness and safety outcomes between originators and biosimilars, whereas 1 study reported more AEs in patients who switched to biosimilars of adalimumab at 12 months. Three trials showed low risk of bias, whereas 11 trials had moderate risk of bias. All cohort studies had moderate to high risk of bias.

CONCLUSIONS AND RELEVANCE: In this systematic review, there was no clinically or statistically significant difference in the efficacy and safety between biosimilars and originators for the treatment of patients with psoriasis. Most of the available evidence was based on randomized clinical trials, although high-quality real-world evidence was lacking. Future studies are needed to examine the long-term effectiveness and safety of biosimilars for the treatment of patients with psoriasis.

PMID:37256582 | DOI:10.1001/jamadermatol.2023.1338

Zoolog Sci. 2023 Jun;40(3):175-188. doi: 10.2108/zs220093.

ABSTRACT

The cheilostome bryozoan Cauloramphus magnus is common in the rocky intertidal habitat from southeastern Alaska to northern Japan. We examined its phylogeography by analyzing 576 bp of the mitochondrial COI (cox1) gene sequenced for 298 colonies from 16 localities in northern Japan. A maximum-likelihood phylogeny detected three main clades (A, B, C). Clades A and B occurred throughout the study area but differed in frequency, haplotype diversity, and haplotype distribution; each resolved into three divergent subclades (AI-III, BI-III). Clade A shared none among 15 haplotypes between the Pacific and Sea of Japan sides of Hokkaido. In contrast, Clade B (29 haplotypes) was thrice as common as Clade A among samples, with haplotype B28 common on both sides. Divergent Clade C (nine haplotypes) was detected only at Rumoi. K2P divergences of 12.3-28.3% among Clades A-C suggest these are distinct biological species, a conclusion supported by different inferred evolutionary histories. A bPTP species delimitation analysis indicated nine phylogenetic species among the sequences included in our phylogeny (AI-III, BI-III, C, and one specimen each from Alaska and the Commander Islands), with K2P divergences of 3.9-6.5% among subclades in A or B. Statistical and principal components analyses suggested weak morphological differentiation between Clades A + B and C, although overlapping ranges of measurements preclude identification to clade; these three clades are morphologically cryptic. For taxonomy, we suggest retaining the name C. magnus for lineages within this species complex across its range, followed by a clade designation, if known.

PMID:37256564 | DOI:10.2108/zs220093

Phys Chem Chem Phys. 2023 May 31. doi: 10.1039/d3cp01404e. Online ahead of print.

ABSTRACT

This study comprehensively investigates the efficiency of the formulation of tetraethoxysilane (TEOS) and 3-aminopropyltriethoxysilane (APTES) copolymer in sol-gel syntheses as part of a multivariate experiment. A methodology-based response surface was used to estimate the influence of independent variables such as polymerization time and temperature, as well as the ratio of TEOS and APTES components on the surface charge response function and product yield, and in order to predict the best response values. Analysis of variance showed that when assessing the value of the zeta potential, the polymerization temperature and the ratio of components are statistically significant factors, but on the other hand, when assessing the yield of the finished product, only the ratio of components is significant. The combination of various options for temperature, time and ratio of components allows one to obtain a zeta potential in the range from +61.2 mV to -48.8 mV and a product yield of up to 4.7 g. Evaluation of the data with TGA-DTA, FTIR-ATR, and ELS methods showed an unexpected result, according to which the highest degree of polymerization and the highest surface charge were inherent in an amino-deficient system. Thus, the smaller the amino component in the system (the APTES-TEOS molar ratio is 0.25), the more efficient the polycondensation is over the absorption area of the Si-O-Si band, and the higher the zeta potential.

PMID:37256559 | DOI:10.1039/d3cp01404e

Int J Clin Oncol. 2023 May 31. doi: 10.1007/s10147-023-02356-4. Online ahead of print.

ABSTRACT

BACKGROUND: Advances in whole-slide image capture and computer image analyses using deep learning technologies have enabled the development of computer-assisted diagnostics in pathology. Herein, we built a deep learning algorithm to detect lymph node (LN) metastasis on whole-slide images of LNs retrieved from patients with gastric adenocarcinoma and evaluated its performance in clinical settings.

METHODS: We randomly selected 18 patients with gastric adenocarcinoma who underwent surgery with curative intent and were positive for LN metastasis at Chiba University Hospital. A ResNet-152-based assistance system was established to detect LN metastases and to outline regions that are highly probable for metastasis in LN images. Reference standards comprising 70 LN images from two different institutions were reviewed by six pathologists with or without algorithm assistance, and their diagnostic performances were compared between the two settings.

RESULTS: No statistically significant differences were observed between these two settings regarding sensitivity, review time, or confidence levels in classifying macrometastases, isolated tumor cells, and metastasis-negative. Meanwhile, the sensitivity for detecting micrometastases significantly improved with algorithm assistance, although the review time was significantly longer than that without assistance. Analysis of the algorithm’s sensitivity in detecting metastasis in the reference standard indicated an area under the curve of 0.869, whereas that for the detection of micrometastases was 0.785.

CONCLUSIONS: A wide variety of histological types in gastric adenocarcinoma could account for these relatively low performances; however, this level of algorithm performance could suffice to help pathologists improve diagnostic accuracy.

PMID:37256523 | DOI:10.1007/s10147-023-02356-4

Alzheimers Dement. 2023 May 31. doi: 10.1002/alz.13160. Online ahead of print.

ABSTRACT

OBJECTIVE: The Longitudinal Early-Onset Alzheimer’s Disease Study (LEADS) seeks to provide comprehensive understanding of early-onset Alzheimer’s disease (EOAD; onset <65 years), with the current study profiling baseline clinical, cognitive, biomarker, and genetic characteristics of the cohort nearing the data-collection mid-point.

METHODS: Data from 371 LEADS participants were compared based on diagnostic group classification (cognitively normal [n = 89], amyloid-positive EOAD [n = 212], and amyloid-negative early-onset non-Alzheimer’s disease [EOnonAD; n = 70]).

RESULTS: Cognitive performance was worse for EOAD than other groups, and EOAD participants were apolipoprotein E (APOE) ε4 homozygotes at higher rates. An amnestic presentation was common among impaired participants (81%), with several clinical phenotypes present. LEADS participants generally consented at high rates to optional trial procedures.

CONCLUSIONS: We present the most comprehensive baseline characterization of sporadic EOAD in the United States to date. EOAD presents with widespread cognitive impairment within and across clinical phenotypes, with differences in APOE ε4 allele carrier status appearing to be relevant.

HIGHLIGHTS: Findings represent the most comprehensive baseline characterization of sporadic early-onset Alzheimer’s disease (EOAD) to date. Cognitive impairment was widespread for EOAD participants and more severe than other groups. EOAD participants were homozygous apolipoprotein E (APOE) ε4 carriers at higher rates than the EOnonAD group. Amnestic presentation predominated in EOAD and EOnonAD participants, but other clinical phenotypes were present.

PMID:37256497 | DOI:10.1002/alz.13160

Appl Biochem Biotechnol. 2023 May 31. doi: 10.1007/s12010-023-04573-z. Online ahead of print.

ABSTRACT

Gentamicin (GM) is an aminoglycoside antibiotic used to treat bacterial infections. Nephrotoxicity refers to the impairments of the kidneys caused by the use of GM and can result in decreased kidney function and in severe cases, kidney failure. Aronia melanocarpa extract (AME), also known as the black chokeberry, has been used for its protective effects on the kidneys. AME concentration of 3.38 mg/kg (max antioxidant activity in vitro) was used to determine its effectiveness against induced nephropathy during 30 days. GM treatment caused significant hypoalbuminemia and high values of globulins, creatinine, and urea compared to the control group. GM application lead to hemolysis occurrence, echinocytosis, and platelets aggregation. Significantly high values of segmented neutrophils and low values of non-segmented neutrophils were recorded in the blood of rats treated with chokeberry extract (AME). In the pre-treatment (AME + GM), severe hypochromic anemia and a significant improvement in hematological parameters, as well as a reduction of anemia in the post-treatment (GM + AME), were noted. Post-treatment AME also significantly regulates urea and creatinine values. Statistically significantly low hemoglobin values were found in all groups treated with AME. Current study suggests that compounds in the AME have a moderate beneficial effect against renal injury and anti-inflammatory properties that may help protect the kidneys from injury caused by GM.

PMID:37256488 | DOI:10.1007/s12010-023-04573-z

Jpn J Radiol. 2023 May 31. doi: 10.1007/s11604-023-01452-9. Online ahead of print.

ABSTRACT

PURPOSE: Neuromelanin-sensitive MRI (NM-MRI) has proven useful for diagnosing Parkinson’s disease (PD) by showing reduced signals in the substantia nigra (SN) and locus coeruleus (LC), but requires a long scan time. The aim of this study was to assess the image quality and diagnostic performance of NM-MRI with a shortened scan time using a denoising approach with deep learning-based reconstruction (dDLR).

MATERIALS AND METHODS: We enrolled 22 healthy volunteers, 22 non-PD patients and 22 patients with PD who underwent NM-MRI, and performed manual ROI-based analysis. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in ten healthy volunteers were compared among images with a number of excitations (NEX) of 1 (NEX1), NEX1 images with dDLR (NEX1 + dDLR) and 5-NEX images (NEX5). Acquisition times for NEX1 and NEX5 were 3 min 12 s and 15 min 58 s, respectively. Diagnostic performances using the contrast ratio (CR) of the SN (CR_SN) and LC (CR_LC) and those by visual assessment for differentiating PD from non-PD were also compared between NEX1 and NEX1 + dDLR.

RESULTS: Image quality analyses revealed that SNRs and CNRs of the SN and LC in NEX1 + dDLR were significantly higher than in NEX1, and comparable to those in NEX5. In diagnostic performance analysis, areas under the receiver operating characteristic curve (AUC) using CR_SN and CR_LC of NEX1 + dDLR were 0.87 and 0.75, respectively, which had no significant difference with those of NEX1. Visual assessment showed improvement of diagnostic performance by applying dDLR.

CONCLUSION: Image quality for NEX1 + dDLR was comparable to that of NEX5. dDLR has the potential to reduce scan time of NM-MRI without degrading image quality. Both 1-NEX NM-MRI with and without dDLR showed high AUCs for diagnosing PD by CR. The results of visual assessment suggest advantages of dDLR. Further tuning of dDLR would be expected to provide clinical merits in diagnosing PD.

PMID:37256470 | DOI:10.1007/s11604-023-01452-9

Trop Anim Health Prod. 2023 May 31;55(3):230. doi: 10.1007/s11250-023-03600-9.

ABSTRACT

The early attainment of puberty in heifers is essential for the profitability of the cow-calf farm. This study aimed to evaluate the impact of juvenile average daily gain (ADG) and sire’s expected progeny difference (EPD) on puberty of crossbred beef heifers. Sixty Angus × Nellore heifers early weaned (age = 102 ± 4.3 d; initial BW = 103 ± 4.7 kg) were used in a 2 × 2 factorial arrangement. The factor 1 was the sire’s EPD for scrotal circumference, in which heifers born from sires with positive EPD were considered precocious (P), and heifers born from sires with negative EPD were considered non-precocious (NP). The factor 2 was the high (HG; ADG = 0.9 kg; ad libitum) and medium ADG (MG; ADG = 0.7 kg) from 3^rd to 7^th month of age (1^st phase). After 1^st phase until puberty, all heifers were fed ad libitum (2^nd phase). Statistical analysis was performed by SAS. There was an interaction between factors for DMI in the 1^st phase (P = 0.02), which PHG heifers had higher DMI than NPHG. There was no effect on puberty rate, BW, age and BCS at puberty comparing HG vs. MG. However, favorable sires’ EPD for scrotal circumference induced a higher proportion of puberty (P 87% vs. NP 59%) at 15 months of age. Thus, the ADG in juvenile age did not affect puberty rate, but sires with positive EPD increased puberty rate of Angus × Nellore heifers in heifers fed a high gain diet.

PMID:37256457 | DOI:10.1007/s11250-023-03600-9

Nat Prod Res. 2023 May 31:1-9. doi: 10.1080/14786419.2023.2217705. Online ahead of print.

ABSTRACT

Hepatocellular carcinoma is the most common primary malignant tumor of the liver, and its incidence is increasing worldwide. There is a need to develop new therapeutic strategies to treat the disease. In this study, we synthesised the oxime derivative of thymoquinone and investigated cytotoxicity, genotoxicity, and apoptosis in hepatocellular cancer cells. The synthesised thymoquinone-oxime structure was confirmed by NMR. After incubating the hepatocellular cancer cell line for 24 h, the cytotoxicity ATP by luminometric, intracellular reactive oxygen species, and intracellular calcium by fluorometric. The mitochondrial membrane potential was determined by flow cytometry. DNA damage by alkaline single-cell gel electrophoresis, and apoptosis damage by acridine orange/ethidium bromide double dye method. Concentrations of thymoquinone-oxime statistically increased cytotoxicity, intracellular reactive oxygen species, intracellular calcium, apoptosis, and DNA damage in a concentration-dependent manner. Mitochondrial membrane potential and glutathione levels are also decreased. These findings show that thymoquinone-oxime has an anti-tumor effect on hepatocellular carcinoma cells.

PMID:37254835 | DOI:10.1080/14786419.2023.2217705