bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prenatal cannabinoid exposure and early language development
Authors: Talavera-Barber Maria M. , Morehead Evlyn , Ziegler Katherine , Hockett Christine , Elliott Amy J. 
Published: November 2023

IntroductionThe effect of prenatal cannabis exposure (PCE) on childhood neurodevelopment remains poorly understood. There is a paucity of studies describing the neurodevelopment impact of PCE in infancy. The Mullen Scale of Early Learning (MSEL) is a cognitive screening tool that can be used from birth to 68 months and includes language and motor domains. Here we aim to explore the association between PCE during pregnancy and neurodevelopmental outcomes at 12 months of age.MethodsParticipants were pregnant persons/infant pairs enrolled in The Safe Passage Study, a large prospective cohort study. Inclusion criteria included data available on PCE with associated MSEL scores at 12 months of age. Exposed participants were defined as early exposure (1st trimester only) or late exposure (2nd or 3rd trimester) and were randomly matched with unexposed participants. Multiple linear regression models were performed to test associations between prenatal cannabis exposure and the five Mullen subscales: gross motor, fine motor, expressive language, receptive language, and visual reception.ResultsSixty-nine exposed and 138 randomly matched unexposed infants were included in the analyses. Mothers of children with PCE were younger with the mean age 23.7 years for early exposure (n = 51) and 22.8 years for late exposure (n = 18). Maternal characteristics with prenatal cannabis use include a high-school education, American Indian or Alaska Native descent, lower socioeconomic status and co-use of tobacco. There were no gestational age or sex difference among the groups. Expressive (95% CI: 2.54–12.76; p = 0.0036,) and receptive language scores (95% CI: 0.39–8.72; p = 0.0322) were significantly increased between late-exposed infants compared to unexposed infants following adjustment for covariates. Gross motor scores (95% CI: 1.75–13; p = 0.0105) were also significantly increased for early-exposed infants with no difference in visual reception scores.ConclusionPreclinical studies have shown abnormal brain connectivity in offspring exposed to cannabis affecting emotional regulation, hyperactivity, and language development. Results from this study link PCE to altered early language development within the first year of life. Exposed infants demonstrated increased expressive and receptive language scores at 12 months of age, which can translate to better performance in school. However, further research is needed to determine the implications of these results later in childhood.
Optimal timing of surgery for prenatally diagnosed choledochal cysts
Authors: Ho In Geol , Ihn Kyong , Jeon Ho Jong , Lee Dong Eun , Han Seok Joo 
Published: November 2023

ObjectiveCholedochal cysts are increasingly being diagnosed antenatally. The appropriate time of surgical treatment has the greatest impact on the prognosis of choledochal cyst treatment. The purpose of this study was to compare the clinical outcomes of prenatally diagnosed choledochal cysts in infants according to the surgical treatment timing.MethodsWe retrospectively reviewed the medical records of infants who underwent surgery for choledochal cysts with antenatal diagnoses. We investigated each patient's demographic information, type of choledochal cyst, serum liver enzyme levels, and surgical outcomes according to the surgical intervention timing.ResultsBetween May 2006 and December 2020, 93 infants underwent surgery to treat choledochal cysts; among them, 68 had antenatally suspected choledochal cysts. Of the 68 patients, 21 developed symptoms directly after birth. While 38 patients remained asymptomatic, 9 developed symptoms before operation. To compare surgical outcomes, asymptomatic patients were divided into early (13 cases) and late (25 cases) operation groups based on an age benchmark of 30 days. The early surgical group experienced longer times to resume a full diet (6.0 ± 1.6 vs. 4.5 ± 0.7, p &lt; 0.001) and longer postoperative hospital stays (11 ± 3.9 vs. 7.5 ± 0.8, p &lt; 0.001). Surgical complications occurred in two patients in the early operation group. Minimally invasive surgery was performed in 12 patients in the late operation group. In both groups, postoperative liver function recovered at 6 months, with no significant difference.ConclusionThe results of this study showed longer hospital stays, increased diet durations, and postoperative complications in early surgery patients. However, liver function recovery was not different between the early and late operation groups. Thus, asymptomatic patients should be closely monitored, and we recommend that definitive surgical intervention be postponed until 4 months of age or until weight reaches 7 kg.
Hypertrophic cardiomyopathy is characterized by alterations of the mitochondrial calcium uniporter complex proteins: insights from patients with aortic valve stenosis versus hypertrophic obstructive cardiomyopathy
Authors: Paar Vera , Haslinger Michael , Krombholz-Reindl Philipp , Pittner Stefan , Neuner Matthias , Jirak Peter , Kolbitsch Tobias , Minnich Bernd , Schrödl Falk , Kaser-Eichberger Alexandra , Kopp Kristen , Koller Andreas , Steinwender Clemens , Lichtenauer Michael , Monticelli Fabio C. , Seitelberger Rainald , Hoppe Uta C. , Dinges Christian , Motloch Lukas J. 
Published: November 2023

Introduction: Hypertrophies of the cardiac septum are caused either by aortic valve stenosis (AVS) or by congenital hypertrophic obstructive cardiomyopathy (HOCM). As they induce cardiac remodeling, these cardiac pathologies may promote an arrhythmogenic substrate with associated malignant ventricular arrhythmias and may lead to heart failure. While altered calcium (Ca2+) handling seems to be a key player in the pathogenesis, the role of mitochondrial calcium handling was not investigated in these patients to date.Methods: To investigate this issue, cardiac septal samples were collected from patients undergoing myectomy during cardiac surgery for excessive septal hypertrophy and/or aortic valve replacement, caused by AVS and HOCM. Septal specimens were matched with cardiac tissue obtained from post-mortem controls without cardiac diseases (Ctrl).Results and discussion: Patient characteristics and most of the echocardiographic parameters did not differ between AVS and HOCM. Most notably, the interventricular septum thickness, diastolic (IVSd), was the greatest in HOCM patients. Histological and molecular analyses showed a trend towards higher fibrotic burden in both pathologies, when compared to Ctrl. Most notably, the mitochondrial Ca2+ uniporter (MCU) complex associated proteins were altered in both pathologies of left ventricular hypertrophy (LVH). On the one hand, the expression pattern of the MCU complex subunits MCU and MICU1 were shown to be markedly increased, especially in AVS. On the other hand, PRMT-1, UCP-2, and UCP-3 declined with hypertrophy. These conditions were associated with an increase in the expression patterns of the Ca2+ uptaking ion channel SERCA2a in AVS (p = 0.0013), though not in HOCM, compared to healthy tissue. Our data obtained from human specimen from AVS or HOCM indicates major alterations in the expression of the mitochondrial calcium uniporter complex and associated proteins. Thus, in cardiac septal hypertrophies, besides modifications of cytosolic calcium handling, impaired mitochondrial uptake might be a key player in disease progression.
Enhancing phase I dose-finding trials design through dynamic borrowing information and handling late-onset toxicity
Authors: Yang Wenyun , He Ruyue , Sun Yuehan , Yan Fangrong , Wang Fei 
Published: November 2023

Introduction: In recent years, there has been a growing trend among regulatory agencies to consider the use of historical controls in clinical trials as a means of improving the efficiency of trial design. In this paper, to enhance the statistical operating characteristic of Phase I dose-finding trials, we propose a novel model-assisted design method named “MEM-Keyboard”.Methods: The proposed design is based on the multisource exchangeability models (MEMs) that allows for dynamic borrowing of information from multiple supplemental data sources, including historical trial data, to inform the dose-escalation process. Furthermore, with the frequent occurrence of delayed toxicity in novel anti-cancer drugs, we extended our proposed method to handle late-onset toxicity by incorporating historical data. This extended method is referred to as “MEM-TITE-Keyboard” and aims to improve the efficiency of early clinical trials.Results: Simulation studies have indicated that the proposed methods can improve the probability of correctly selecting the maximum tolerated dose (MTD) with an acceptable level of risk, compared to designs that do not account for information borrowing and late-onset toxicity.Discussion: The MEM-Keyboard and MEM-TITE-Keyboard, easy to implement in practice, provide a useful tool for identifying MTD and accelerating drug development.
Dose-response association of metformin use and risk of age-related macular degeneration among patients with type 2 diabetes mellitus: a population-based study
Authors: Huang Kuang-Hua , Chang Ya-Lan , Lee Chiachi Bonnie , Gau Shuo-Yan , Tsai Tung-Han , Chung Ning-Jen , Lee Chien-Ying 
Published: November 2023

Background: Recent studies have demonstrated that patients with type 2 diabetes mellitus (T2DM) who receive metformin have a decreased risk of developing age-related macular degeneration (AMD). However, other studies have also suggested that metformin may increase the risk of AMD development. Therefore, this study investigated the association between treatment with metformin and the risk of AMD in patients with T2DM by using Taiwan’ National Health Insurance Research Database.Methods: Patients who received a diagnosis of new-onset T2DM between 2002 and 2013 were enrolled in this study. The patients were divided into patients treated and not treated with metformin to evaluate the risk of AMD after 5 years of follow-up. The logistic regression was used to estimate the risk of AMD associated with the intensity of treatment with metformin.Result: A total of 7 517 patients (103.16 patients per 10,000 people) developed AMD in 5 years after DM diagnosis. After adjusting for the relevant variables, patients with T2DM treated with &lt;5 defined daily dose (DDD)/month of metformin had a lower risk of AMD (odds ratios [OR]: 0.93; 95% confidence interval [CI]: 0.88 0.99). Patients treated with &gt;25 DDD/month of metformin had a higher risk of AMD (OR: 1.39; 95% CI: 1.08-1.78).Conclusion: Metformin use may be associated with a risk of AMD among patients with T2DM in a dose-dependent association manner, with the greater benefit at lower DDD/month. However, higher DDD/month exhibited an increased risk of AMD.
Comparing efficacy of first-line treatment of metastatic castration resistant prostate cancer: a network meta-analysis of randomized controlled trials
Authors: Liu Yang , Deng Xianzhong , Wen Zhi , Huang Jing , Wang Chongjian , Chen Caixia , Bao Erhao , Wang Jiahao , Yang Xuesong 
Published: November 2023

Background: Metastatic castration-resistant prostate cancer (mCRPC) presents significant treatment selection challenges due to limited therapeutic options. This study aimed to comprehensively assess the efficacy of multiple treatment regimens for mCRPC through a network meta-analysis (NMA) of randomized controlled trials (RCTs).Methods: A systematically comprehensive search for randomized controlled trials (RCTs) was performed in Pubmed, Cochrane Library, Embase, and Web of Science databases. The network meta-analysis was employed to compare the overall survival (OS), progression-free survival (PFS), and radiographic progression-free survival (rPFS) among different interventions at specific time points. This study was prospectively registered with PROSPERO (CRD42023422823).Results: A total of 29 RCTs, involving 12,706 patients and investigating 16 interventions, were included in the analysis. Chempretarget ((capivasertib or cabozantinib) + docetaxel + prednisone)) and PARP (Olaparib or rucaparib) inhibitors emerged as interventions that significantly improved survival outcomes compared to first-line treatment in mCRPC patients. Chempretarget demonstrated superior overall survival starting from the 12th month, while PARP inhibitors showed a clear advantage in progression-free survival within the 3–18 months range. Notably, chempre ((Docetaxel or Cabazitaxel) + prednisone) exhibited favorable performance in radiographic progression-free survival during the 3–18 month period.Conclusion: Our findings underscore the efficacy of chempretarget, PARP inhibitors, and chempre in enhancing survival outcomes for mCRPC patients. Further head-to-head comparisons are warranted to validate these results. These findings carry important implications for treatment decision-making in mCRPC and may guide the development of more effective therapeutic strategies.
Efficacy and safety of tocilizumab and baricitinib among patients hospitalized for COVID-19: a systematic review and meta-analysis
Authors: Zhang Jin , Fan Xiongxiong , Zhang Xiaoyu , Jiang Fengli , Wu Yiping , Yang Beibei , Li Xinghuan , Liu Dong 
Published: November 2023

Introduction: Tocilizumab and baricitinib are recommended treatment options for COVID-19 patients with hyperinflammatory response; however, there is a lack of systematic review directly evaluating their efficacy and safety.Objective: This review was conducted to evaluate the efficacy and safety of tocilizumab and baricitinib in the treatment of hospitalized patients with COVID-19.Methods: Relevant databases were searched for studies that compared the effect or safety of baricitinib or tocilizumab in hospitalized patients with COVID-19. The mortality was the main outcome. The hospital length of stay or adverse drug reactions were taken into consideration as secondary endpoints. The analyses were performed in Revman 5.3 or Stata 16.0. The protocol and analysis plan were pre-registered in PROSPERO, with the registration number CRD42023408219.Results: In total, 10 studies with 2,517 patients were included. The overall pooled data demonstrated that, there was no statistically significant difference in the 28-day mortality rate and the hospital length of stay between the tocilizumab and baricitinib (OR = 1.10, 95% CI = 0.80–1.51, p = 0.57; OR = −0.68, 95% CI = −2.24–0.87, p = 0.39). The adverse reactions including secondary infection rate, thrombotic and bleeding events, and acute liver injury of tocilizumab were significantly higher than that of baricitinib. (OR = 1.49, 95% CI = 1.18–1.88, p &lt; 0.001,OR = 1.52, 95% CI = 1.11–2.08, p = 0.009; OR = 1.52, 95% CI = 1.11–2.08, p = 0.009; OR = 2.24, 95% CI = 1.49–3.35, p &lt; 0.001).Conclusion: In patients hospitalized with COVID-19, no discernible difference in therapeutic efficacy was observed between tocilizumab and baricitinib; however, the group treated with baricitinib demonstrated a significantly lower incidence of adverse effects.
Relation of leg phase angle from bioelectrical impedance analysis with voluntary and evoked contractile properties of the plantar flexors
Authors: Hirata Kosuke , Yamada Yosuke , Iida Natsuki , Kanda Akihiro , Shoji Mikio , Yoshida Tsukasa , Akagi Ryota 
Published: November 2023

Introduction: Bioelectrical impedance analysis (BIA) can noninvasively and quickly assess electrical properties of the body, such as the phase angle. Phase angle is regarded as the quantity and/or quality of skeletal muscle and is associated with exercise performance, such as jump height and walking speed. Although the phase angle derived from BIA is assumed to be a useful way to assess muscle function, the relationship between the phase angle and neuromuscular properties has not been fully investigated. The purpose of this study was to investigate the association of phase angle with voluntary and evoked contractile properties in 60 adults (age, 21–83 years; 30 females and 30 males).Methods: The phase angle of the right leg at 50 kHz was evaluated using BIA. The twitch contractile properties (peak twitch torque [PTtwitch], rate of twitch torque development [RTDtwitch], and time-to-PTtwitch [TPTtwitch]) of the plantar flexors were measured using tibial nerve electrical stimulation. Maximal voluntary isometric contractions (MVICs) were performed to measure the maximal muscle strength and explosive muscle strength, from which the peak MVIC torque (PTMVIC) and rate of torque development (RTD) over a time interval of 0–200 ms were assessed, respectively. The root mean square (RMS) values of electromyographic (EMG) activity during the PTMVIC and RTD measurements (EMG-RMSMVIC and EMG-RMSRTD, respectively) were calculated. The RTD and EMG-RMSRTD were normalized using PTMVIC and EMG-RMSMVIC, respectively.Results and discussion: Phase angle significantly correlated with twitch contractile properties (|r| ≥ 0.444, p &lt; 0.001), PTMVIC (r = 0.532, p &lt; 0.001), and RTD (r = 0.514, p &lt; 0.001), but not with normalized RTD (r = 0.242, p = 0.065) or normalized EMG-RMSRTD (r = −0.055, p = 0.676). When comparing measurement variables between the low- and high-phase angle groups while controlling for sex and age effects, the high-phase angle group showed greater PTtwitch, RTDtwitch, PTMVIC, and RTD (p &lt; 0.001) and shorter TPTtwitch (p &lt; 0.001) but not normalized RTD (p = 0.184) or normalized EMG-RMSRTD (p = 0.317). These results suggest that the leg phase angle can be an indicator of voluntary and evoked muscle contractile properties but not the neuromuscular activity of the plantar flexors, irrespective of sex and age.
Forest stand spectrum reconstruction using spectrum spatial feature gathering and multilayer perceptron
Authors: Wang Fan , Song Linghan , Liu Xiaojie , Zhong Shuangwen , Wang Jiawei , Zhang Yao , Wu Yun 
Published: November 2023

IntroductionThree-dimensional spectral distributions of forest stands can provide spatial information on the physiological and biochemical status of forests, which is vital for forest management. However, three-dimensional spectral studies of forest stands are limited.MethodsIn this study, LiDAR and multispectral data were collected from Masson pine stands in southern Fujian Province, China, and a method was proposed for inverting forest spectra using point clouds as a unit. First, multispectral values were mapped to a point cloud, and the isolated forest algorithm combined with K-means clustering was applied to characterize fusion data. Second, five deep learning algorithms were selected for semantic segmentation, and the overall accuracy (oAcc) and mean intersection ratio (mIoU) were used to evaluate the performance of various algorithms on the fusion data set. Third, the semantic segmentation model was used to reconfigure the class 3D spectral distribution, and the model inversion outcomes were evaluated by the peaks and valleys of the curve of the predicted values and distribution gaps.ResultsThe results show that the correlations between spectral attributes and between spatial attributes were both greater than 0.98, while the correlation between spectral and spatial attributes was 0.43. The most applicable method was PointMLP, highest oAcc was 0.84, highest mIoU was 0.75, peak interval of the prediction curve tended to be consistent with the true values, and maximum difference between the predicted value and the true value of the point cloud spectrum was 0.83.DiscussionExperimental data suggested that combining spatial fusion and semantic segmentation effectively inverts three-dimensional spectral information for forest stands. The model could meet the accuracy requirements of local spectral inversion, and the NIR values of stands in different regions were correlated with the vertical height of the canopy and the distance from the tree apex in the region. These findings improve our understanding of the precise three-dimensional spectral distribution of forests, providing a basis for near-earth remote sensing of forests and the estimation of forest stand health.
Compost application boosts soil restoration in highly disturbed hillslope vineyard
Authors: Lucchetta Marco , Romano Alessandro , Alzate Zuluaga Monica Yorlady , Fornasier Flavio , Monterisi Sonia , Pii Youry , Marcuzzo Patrick , Lovat Lorenzo , Gaiotti Federica 
Published: November 2023

A field trial was carried out to investigate the effects of compost application on a young Cabernet sauvignon vineyard located in a hilly area in the North-East of Italy and subjected to land terracing before plantation. The use of a compost based on manure, pruning residues and pomace at a rate of 65 t ha-1 was compared to the mineral fertilization regime recommended for the vineyards in the area (NPK: 80, 50, 200 kg ha-1). A multi-factorial approach that considered soil chemical properties, microbial community structure and function, vine nutritional and vegetative indexes, yield and quality parameters was applied in the attempt of depict interrelated effects of compost on all these factors. Results of this study show that the application of compost for three consequent years greatly increased soil organic matter content and improved the mineral nutrient availability in the soil. Soil biological fertility showed a slow but significant response to compost addition as from the second year of treatment microbial growth and enzyme activity were increased compared to those of the inorganic fertilization, with special regard to enzymes involved in P cycle. A shift in the soil microbial community structure was also observed in compost-treated soil, with higher presence of copiotrophic bacteria, indicators of soil quality, and phosphorus solubilizing bacteria. A decrease of pathogenic fungal strains was also observed. Organic fertilization increased plant nutrient uptake and vegetative growth compared to those observed in chemically fertilized vines. A trend toward increased yield and improvements for some grape quality parameters such as acidity and pH were observed in the first year of production. These results provide evidence that compost can boost soil fertility restoration in vineyard disturbed by land terracing, allowing for agronomic performances comparable or even improved than those of chemically fertilized vines.