bluuebunny/crossref_metadata_2025 huggingface dataset:
Integration of very small modular reactors and renewable energy resources in the microgrid
Authors: Raza Muhammad Kazim , Alghassab Mohammed , Altamimi Abdullah , Khan Zafar A. , Abbas Kazmi Syed Ali , Ali Majid , Diala Uchenna
Published: May 2024

Hybrid microgrids, integrating local energy resources, present a promising but challenging solution, especially in areas with limited or no access to the national grid. Reliable operation of off-grid energy systems necessitates sustainable energy sources, given the intermittent nature of renewables. While fossil fuel diesel generators mitigate risks, they increase carbon emissions. This study assesses the viability of integrating a very small modular renewable energy reactor into a microgrid for replacing conventional diesel generators, substantially curbing greenhouse gas emissions. A comprehensive analysis, including design and economic evaluation, was conducted for an off-grid community microgrid with an annual generation and load of 8.5 GWh and 7.8 GWh, respectively. The proposed microgrid configurations incorporate very small modular reactors, alongside solar, wind, and battery storage systems. MATLAB modeling and simulation across eight cases, accounting for seasonal variations, demonstrate the technical and economic feasibility of case 7. This configuration, integrating modular reactors, photovoltaics, wind turbines, and battery storage, satisfactorily meets load demands. Notably, it boasts a high internal rate of return up to ∼31% and a shorter payback period of around 4 years compared to alternative scenarios.
Research on the impact of digital economy on green total factor productivity: theoretical mechanism and multidimensional empirical analysis
Authors: Liu Wanwan , Naseem N. A. M. , Mazlan Nur Syazwani
Published: May 2024

The digital economy (DE) is emerging as a crucial driver of economic growth and an effective tool for alleviating resource and environmental pressures, thereby evolving into a significant force in facilitating green transformation. This study elaborates on the theoretical mechanism of the impact of DE on green total factor productivity (GTFP), and conducts multidimensional empirical tests using panel data from 284 cities in China. The main findings are as follows: (1) DE exerts significant positive direct, indirect, and spatial spillover effects on GTFP, signifying its growing role as a robust driver of GTFP. Notably, technological innovation emerges as a key mediator of DE’s impact on GTFP. (2) The impact of DE on GTFP exhibits a distinct pattern: initially pronounced, gradually diminishing, and then rebounding as DE progresses. (3) DE tends to exacerbate, rather than alleviate, the development divide and resource curse, especially in underdeveloped and resource-rich cities where its benefits are constrained. (4) Government behavior is pivotal in influencing DE’s impact on GTFP. Supportive policies and strict environmental regulations are critical in harnessing DE’s positive contributions to GTFP. This study lays a scientific foundation for leveraging the “green attributes” of DE and offers insights into bridging the developmental disparities among cities.
Identification, molecular evolution, codon bias, and expansion analysis of NLP transcription factor family in foxtail millet (Setaria italica L.) and closely related crops
Authors: Chen Huilong , Liu Fang , Chen Jing , Ji Kexin , Cui Yutong , Ge Weina , Wang Zhenyi
Published: May 2024

The NODULE-INCEPTION-like protein (NLP) family is a plant-specific transcription factor (TF) family involved in nitrate transport and assimilation in plants, which are essential for improving plant nitrogen use efficiency. Currently, the molecular nature and evolutionary trajectory of NLP genes in the C4 model crop foxtail millet are unknown. Therefore, we performed a comprehensive analysis of NLP and molecular evolution in foxtail millet by scanning the genomes of foxtail millet and representative species of the plant kingdom. We identified seven NLP genes in the foxtail millet genome, all of which are individually and separately distributed on different chromosomes. They were not structurally identical to each other and were mainly expressed on root tissues. We unearthed two key genes (Si5G004100.1 and Si6G248300.1) with a variety of excellent characteristics. Regarding its molecular evolution, we found that NLP genes in Gramineae mainly underwent dispersed duplication, but maize NLP genes were mainly generated via WGD events. Other factors such as base mutations and natural selection have combined to promote the evolution of NLP genes. Intriguingly, the family in plants showed a gradual expansion during evolution with more duplications than losses, contrary to most gene families. In conclusion, this study advances the use of NLP genetic resources and the understanding of molecular evolution in cereals.
Machine learning in the prediction of immunotherapy response and prognosis of melanoma: a systematic review and meta-analysis
Authors: Li Juan , Dan Kena , Ai Jun
Published: May 2024

Background

The emergence of immunotherapy has changed the treatment modality for melanoma and prolonged the survival of many patients. However, a handful of patients remain unresponsive to immunotherapy and effective tools for early identification of this patient population are still lacking. Researchers have developed machine learning algorithms for predicting immunotherapy response in melanoma, but their predictive accuracy has been inconsistent. Therefore, the present systematic review and meta-analysis was performed to comprehensively evaluate the predictive accuracy of machine learning in melanoma response to immunotherapy.

Methods

Relevant studies were searched in PubMed, Web of Sciences, Cochrane Library, and Embase from their inception to July 30, 2022. The risk of bias and applicability of the included studies were assessed using the Prediction Model Risk of Bias Assessment Tool (PROBAST). Meta-analysis was performed on R4.2.0.

Results

A total of 36 studies consisting of 30 cohort studies and 6 case-control studies were included. These studies were mainly published between 2019 and 2022 and encompassed 75 models. The outcome measures of this study were progression-free survival (PFS), overall survival (OS), and treatment response. The pooled c-index was 0.728 (95%CI: 0.629–0.828) for PFS in the training set, 0.760 (95%CI: 0.728–0.792) and 0.819 (95%CI: 0.757–0.880) for treatment response in the training and validation sets, respectively, and 0.746 (95%CI: 0.721–0.771) and 0.700 (95%CI: 0.677–0.724) for OS in the training and validation sets, respectively.

Conclusion

Machine learning has considerable predictive accuracy in melanoma immunotherapy response and prognosis, especially in the former. However, due to the lack of external validation and the scarcity of certain types of models, further studies are warranted.
Targeted proteomics-determined multi-biomarker profiles developed classifier for prognosis and immunotherapy responses of advanced cervical cancer
Authors: Li Jin , Zhang Xu , Yang Liuke , Zhu Youwei , Gao Rongrong , Zhang Tiancheng , Chen Xuwen , Fu Jun , He Gaoyang , Shi Huijuan , Peng Shenjie , Wu XiaoHua
Published: May 2024

Background

Cervical cancer (CC) poses a global health challenge, with a particularly poor prognosis in cases of recurrence, metastasis, or advanced stages. A single biomarker is inadequate to predict CC prognosis or identify CC patients likely to benefit from immunotherapy, presumably owing to tumor complexity and heterogeneity.

Methods

Using advanced Olink proteomics, we analyzed 92 oncology-related proteins in plasma from CC patients receiving immunotherapy, based upon the comparison of protein expression levels of pre-therapy with those of therapy-Cycle 6 in the partial response (PR) group and progressive disease (PD) group, respectively.

Results

55 proteins were identified to exhibit differential expression trends across pre-therapy and post-therapy in both PR and PD groups. Enriched GO terms and KEGG pathways were associated with vital oncological and immunological processes. A logistic regression model, using 5 proteins (ITGB5, TGF-α, TLR3, WIF-1, and ERBB3) with highest AUC values, demonstrated good predictive performance for prognosis of CC patients undergoing immunotherapy and showed potential across different cancer types. The effectiveness of these proteins in prognosis prediction was further validated using TCGA-CESC datasets. A negative correlation and previously unidentified roles of WIF-1 in CC immunotherapy was also first determined.

Conclusion

Our findings reveal multi-biomarker profiles effectively predicting CC prognosis and identifying patients benefitting most from immunotherapy, especially for those with limited treatment options and traditionally poor prognosis, paving the way for personalized immunotherapeutic treatments and improved clinical strategies.
Dietary 5-hydroxytryptophan improves sheep growth performance by enhancing ruminal functions, antioxidant capacity, and tryptophan metabolism: in vitro and in vivo studies
Authors: Sun Zhe , Aschalew Natnael D. , Cheng Long , Xia Yuanhong , Zhang Longyu , Yin Guopei , Wang Shikun , Wang Ziyuan , Dong Jianan , Zhang Weigang , Zhao Wei , Qin Guixin , Zhang Xuefeng , Zhong Rongzhen , Wang Tao , Zhen Yuguo
Published: May 2024

Background

Hydroxytryptophan (5-HTP) can regulate the synthesis of 5-Hydroxytryptamine (5-HT) and melatonin (MT). In a previous metabolome analysis, we found that 5-HTP is an effective ingredient in yeast culture for regulating rumen fermentation. However, research on the effect of this microbial product (5-HTP) as a functional feed additive in sheep production is still not well explained. Therefore, this study examined the effects of 5-HTP on sheep rumen function and growth performance using in vitro and in vivo models.

Methods

A two-factor in vitro experiment involving different 5-HTP doses and fermentation times was conducted. Then, in the in vivo experiment, 10 sheep were divided into a control group which was fed a basal diet, and a 5-HTP group supplemented with 8 mg/kg 5-HTP for 60 days.

Results

The results showed that 5-HTP supplementation had a significant effect on in vitro DMD, pH, NH3-N, acetic acid, propionic acid, and TVFA concentrations. 5-HTP altered rumen bacteria composition and diversity indices including Chao1, Shannon, and Simpson. Moreover, the in vivo study on sheep confirmed that supplementing with 8 mg/kg of 5-HTP improved rumen fermentation efficiency and microbial composition. This led to enhanced sheep growth performance and increased involvement in the tryptophan metabolic pathway, suggesting potential benefits.

Conclusion

Dietary 5-HTP (8 mg/kg DM) improves sheep growth performance by enhancing ruminal functions, antioxidant capacity, and tryptophan metabolism. This study can provide a foundation for the development of 5-HTP as a functional feed additive in ruminants’ production.
Response of river delta hydrological connectivity to changes in river discharge and atmospheric frontal passage
Authors: Feizabadi Sajjad , Li Chunyan , Hiatt Matthew
Published: May 2024

Atmospheric frontal passage is a common meteorological event that can significantly affect hydrodynamics in coastal environments, including the hydrological connectivity between channels and floodplains that regulates material transport in river deltas. This study is focused on the influence of atmospheric cold fronts on the hydrological connectivity between channels and floodplains within the Wax Lake Delta using the Delft3D FM model. The results demonstrate a substantial effect of passing cold fronts on the exchange of water and transport fraction between the primary channels and floodplains. This impact is intricately connected to the morphodynamical characteristics of the floodplains, the intensity of cold fronts, river discharge, Coriolis force, and tidal currents. The passing cold fronts can enhance or reverse the direction of water exchange between channels and floodplains. For floodplains, the passage of cold fronts can lead to an increase in the rate of water exchange by as much as five times. In the WLD, a substantial fraction of water, 39-58%, is flowing through the floodplains to the bay at the delta front influenced by the prevailing discharge, although there is a significant spatial heterogeneity. Passing cold fronts can alter the transport distribution, depending on the phase of the front. An increase in river discharge tends to bolster floodplain connectivity and lessen the effects of cold fronts. Conversely, decreased river discharge results in reduced connectivity and exacerbates the fluctuations induced by cold fronts. Moreover, the findings indicate that from the apex to downstream, the contribution of channels decreases as they become shallower, while the role of the floodplains increases, leading to a less distinct demarcation between channels and floodplains. It has also been noted that an increase in river discharge correlates with an increased contribution from floodplains to transfer water to the bay.
Association between 23 drugs and inflammatory bowel disease: a two-sample Mendelian randomization study
Authors: He Lei , Deng Tuo , Huang Yurong , Yang Wangliu , Yang Jie , Song Gengqing
Published: May 2024

Background

Inflammatory bowel disease (IBD) is a group of diseases characterized by chronic and recurrent inflammation of the gastrointestinal tract. The etiology of IBD remains multifaceted and poorly understood, resulting in limited treatment options that primarily target disease induction and remission maintenance. Thus, the exploration of novel therapeutic options for IBD among existing medications is advantageous. Mendelian randomization analysis (MR) serves as a valuable tool in investigating the relationship between drugs and diseases. In this study, MR analysis was employed to investigate the potential causal relationship between 23 approved drugs for the treatment of various diseases and IBD.

Method

We performed a two-sample MR analysis using publicly available genome-wide association study (GWAS) statistics. The inverse variance weighting (IVW) method was used as the main analysis method, supplemented by the remaining four methods (weighted median, MR Egger regression, simple and weighted models), and Meta-analysis was performed to expand the sample size to obtain a more reliable composite causal effect. Finally, Cochran’s Q statistic and the MR-Egger test for directed pleiotropy were applied to determine whether significant heterogeneity or directed pleiotropy existed.

Results

In the main MR analysis (IVW), drugs with a negative causal association with the risk of IBD were immunosuppressant {OR (95% CI) = 0.7389 [0.6311–0.8651], p = 0.0046} and diabetes drugs {OR (95% CI) = 0.9266 [0.8876–0.9674], p = 0.0058}. A positive causal association with the risk of IBD was found for salicylic acid and derivatives {OR (95% CI) = 1.2737 [1.0778–1.5053], p = 0.0345}. Negative causal associations with UC risk were identified for immunosuppressants {OR (95% CI) = 0.6660 [0.5133–0.8640], p = 0.0169} and diabetes medications {OR (95% CI) = 0.9020 [0.8508–0.9551], p = 0.0046}; positive causal associations with UC risk were found for β-receptor blockers {OR (95% CI) = 1.1893 [1.0823–1.3070], p = 0.0046}. A negative causal association with the risk of CD was found for immunosuppressants {OR (95% CI) = 0.6957 [0.5803–0.8341], p = 0.0023}. There was no statistically significant association between the remaining 19 drugs and IBD and subtypes.

Conclusion

This MR study provides evidence suggesting that immunosuppressants have a mitigating effect on the risk of IBD and demonstrate consistent efficacy in subtypes of ulcerative colitis (UC) and Crohn’s disease (CD). Additionally, diabetes medications show potential in reducing the risk of IBD, particularly in cases of UC, while β-blockers may elevate the risk of UC. Conversely, salicylic acid and its derivatives may increase the risk of IBD, although this effect is not consistently observed in the subtypes of the disease. These findings offer new insights into the prevention and management of IBD.
Intervention with fructooligosaccharides, Saccharomyces boulardii, and their combination in a colitis mouse model
Authors: Wu Yan , Fu Hao , Xu Xu , Jin Hui , Kao Qing-jun , Teng Wei-lin , Wang Bing , Zhao Gang , Pi Xiong-e
Published: May 2024

Objective

To examine the effects of an intervention with fructooligosaccharides (FOS), Saccharomyces boulardii, and their combination in a mouse model of colitis and to explore the mechanisms underlying these effects.

Methods

The effects of FOS, S. boulardii, and their combination were evaluated in a DSS-induced mouse model of colitis. To this end, parameters such as body weight, the disease activity index (DAI), and colon length were examined in model mice. Subsequently, ELISA was employed to detect the serum levels of proinflammatory cytokines. Histopathological analysis was performed to estimate the progression of inflammation in the colon. Gas chromatography was used to determine the content of short-chain fatty acids (SCFAs) in the feces of model mice. Finally, 16S rRNA sequencing technology was used to analyze the gut microbiota composition.

Results

FOS was slight effective in treating colitis and colitis-induced intestinal dysbiosis in mice. Meanwhile, S. boulardii could significantly reduced the DAI, inhibited the production of IL-1β, and prevented colon shortening. Nevertheless, S. boulardii treatment alone failed to effectively regulate the gut microbiota. In contrast, the combined administration of FOS/S. boulardii resulted in better anti-inflammatory effects and enabled microbiota regulation. The FOS/S. boulardii combination (109 CFU/ml and 107 CFU/ml) significantly reduced the DAI, inhibited colitis, lowered IL-1β and TNF-α production, and significantly improved the levels of butyric acid and isobutyric acid. However, FOS/S. boulardii 109 CFU/ml exerted stronger anti-inflammatory effects, inhibited IL-6 production and attenuated colon shortening. Meanwhile, FOS/S. boulardii 107 CFU/ml improved microbial regulation and alleviated the colitis-induced decrease in microbial diversity. The combination of FOS and S. boulardii significantly increased the abundance of Parabacteroides and decreased the abundance of Escherichia–Shigella. Additionally, it promoted the production of acetic acid and propionic acid.

Conclusion

Compared with single administration, the combination can significantly increase the abundance of beneficial bacteria such as lactobacilli and Bifidobacteria and effectively regulate the gut microbiota composition. These results provide a scientific rationale for the prevention and treatment of colitis using a FOS/S. boulardii combination. They also offer a theoretical basis for the development of nutraceutical preparations containing FOS and S. boulardii.
Advances and challenges in gene therapy strategies for pediatric cancer: a comprehensive update
Authors: Moaveni Amir Kian , Amiri Maryam , Shademan Behrouz , Farhadi Arezoo , Behroozi Javad , Nourazarian Alireza
Published: May 2024

Pediatric cancers represent a tragic but also promising area for gene therapy. Although conventional treatments have improved survival rates, there is still a need for targeted and less toxic interventions. This article critically analyzes recent advances in gene therapy for pediatric malignancies and discusses the challenges that remain. We explore the innovative vectors and delivery systems that have emerged, such as adeno-associated viruses and non-viral platforms, which show promise in addressing the unique pathophysiology of pediatric tumors. Specifically, we examine the field of chimeric antigen receptor (CAR) T-cell therapies and their adaptation for solid tumors, which historically have been more challenging to treat than hematologic malignancies. We also discuss the genetic and epigenetic complexities inherent to pediatric cancers, such as tumor heterogeneity and the dynamic tumor microenvironment, which pose significant hurdles for gene therapy. Ethical considerations specific to pediatric populations, including consent and long-term follow-up, are also analyzed. Additionally, we scrutinize the translation of research from preclinical models that often fail to mimic pediatric cancer biology to the regulatory landscapes that can either support or hinder innovation. In summary, this article provides an up-to-date overview of gene therapy in pediatric oncology, highlighting both the rapid scientific progress and the substantial obstacles that need to be addressed. Through this lens, we propose a roadmap for future research that prioritizes the safety, efficacy, and complex ethical considerations involved in treating pediatric patients. Our ultimate goal is to move from incremental advancements to transformative therapies.
Rapid identification and prognosis evaluation by dual-phase computed tomography angiography for stroke patients with a large ischemic region in the anterior circulation treated with endovascular thrombectomy
Authors: E Yajun , Jiang Huigang , Yu Weifei , Chen Weiwei , He Hongfei
Published: May 2024

Purpose

To investigate the value of dual-phase head-and-neck computed tomography angiography (CTA) in assessing advantages and risks associated with mechanical thrombectomy for stroke with a large ischemic region in the anterior circulation within 6 h of onset.

Methods

We retrospectively analyzed the data of patients with acute occlusion of the internal carotid artery or middle cerebral artery-M1 segment. Baseline dual-phase CTA was performed for collateral grading using the 4-point visual collateral score (0, 0% filling; 1, >0% and ≤50% filling; 2, >50 and <100% filling; 3, 100% filling). The rates of modified Rankin score (MRS) ≤ 3 at 90 days, any intracranial hemorrhage (ICH) within 48 h, malignant cerebral edema within 24 h, and all-cause 90-day mortality were analyzed.

Results

Among the 69 study patients, 15, 26, 17, and 11 patients had collateral grades of 0, 1, 2, and 3, respectively. At 90 days, the MRS was ≤3 in 0, 8.33, 29.41, and 36.36% of patients with grades 0, 1, 2, and 3, respectively. ICH incidence was 73.33, 57.69, 29.41, and 18.18% for grades 0, 1, 2, and 3, respectively, while the incidence of malignant brain edema was 100, 76.92, 35.29, and 0%, respectively. All-cause 90-day mortality was 53.33% for grade 0 and 30.77% for grade 1; no deaths occurred at grades 2 and 3.

Conclusion

Collateral grading based on dual-phase CTA enables simple and rapid preoperative evaluation prior to mechanical thrombectomy for acute anterior-circulation stroke with a large ischemic focus, particularly for patients presenting within the 6-h time window.
Motor network dynamic resting state fMRI connectivity of neurotypical children in regions affected by cerebral palsy
Authors: Boerwinkle Varina L. , Sussman Bethany L. , de Lima Xavier Laura , Wyckoff Sarah N. , Reuther William , Kruer Michael C. , Arhin Martin , Fine Justin M.
Published: May 2024

Background

Normative childhood motor network resting-state fMRI effective connectivity is undefined, yet necessary for translatable dynamic resting-state-network-informed evaluation in pediatric cerebral palsy.

Methods

Cross-spectral dynamic causal modeling of resting-state-fMRI was investigated in 50 neurotypically developing 5- to 13-year-old children. Fully connected six-node network models per hemisphere included primary motor cortex, striatum, subthalamic nucleus, globus pallidus internus, thalamus, and contralateral cerebellum. Parametric Empirical Bayes with exhaustive Bayesian model reduction and Bayesian modeling averaging informed the model; Purdue Pegboard Test scores of hand motor behavior were the covariate at the group level to determine the effective-connectivity-functional behavior relationship.

Results

Although both hemispheres exhibited similar effective connectivity of motor cortico-basal ganglia-cerebellar networks, magnitudes were slightly greater on the right, except for left-sided connections of the striatum which were more numerous and of opposite polarity. Inter-nodal motor network effective connectivity remained consistent and robust across subjects. Age had a greater impact on connections to the contralateral cerebellum, bilaterally. Motor behavior, however, affected different connections in each hemisphere, exerting a more prominent effect on the left modulatory connections to the subthalamic nucleus, contralateral cerebellum, primary motor cortex, and thalamus.

Discussion

This study revealed a consistent pattern of directed resting-state effective connectivity in healthy children aged 5–13 years within the motor network, encompassing cortical, subcortical, and cerebellar regions, correlated with motor skill proficiency. Both hemispheres exhibited similar effective connectivity within motor cortico-basal ganglia-cerebellar networks reflecting inter-nodal signal direction predicted by other modalities, mainly differing from task-dependent studies due to network differences at rest. Notably, age-related changes were more pronounced in connections to the contralateral cerebellum. Conversely, motor behavior distinctly impacted connections in each hemisphere, emphasizing its role in modulating left sided connections to the subthalamic nucleus, contralateral cerebellum, primary motor cortex, and thalamus. Motor network effective connectivity was correlated with motor behavior, validating its physiological significance. This study is the first to evaluate a normative effective connectivity model for the pediatric motor network using resting-state functional MRI correlating with behavior and serves as a foundation for identifying abnormal findings and optimizing targeted interventions like deep brain stimulation, potentially influencing future therapeutic approaches for children with movement disorders.
Black tea preserves intestinal homeostasis through balancing barriers and microbiota in mice
Authors: Shi Yuxuan , Guo Shasha , Zhou Jihong , Xu Ping , Wang Yuefei
Published: May 2024

Introduction

Black tea, a beverage consumed worldwide, possesses favorable effects on gastrointestinal tract, including nourishing stomach and promoting digestion. Nevertheless, its specific effects on intestinal homeostasis remains inconclusive.

Methods

We applied black tea to mice prior to inducing colitis with DSS and then monitored their body weight and disease activity index (DAI) daily. When sacrificed, we measured intestinal permeability and conducted analyses of mucin and tight junction proteins. We detected inflammatory cytokines, immune cells, and related inflammatory signaling pathways. In addition, the gut microbiota was analyzed through 16S rRNA sequencing, and the concentrations of short-chain fatty acids (SCFAs) were also measured.

Results

The results showed that black tea-treated group significantly rescued the DSS-disrupted intestinal structure. It reduced the relative abundance of the pathogenic bacterium Turicibacter, while increased the abundance of beneficial bacteria norank_f_Muribaculaceae and restored the contents of SCFAs such as acetate, propionate, and butyrate. It also protected the intestinal barrier by reducing the levels of immune response-related factors (e.g., TNF-α, IL-6, IL-1β) and increasing the expression of tight junction proteins (TJs) (e.g., ZO-1, occludin). Furthermore, black tea exhibited the capacity to suppress the expression of MMP-9 and ICAM-1, as well as to inhibit the activation of NF-κB signaling pathway.

Discussion

Our findings provide a theoretical framework that elucidates the mechanisms by which black tea preserves intestinal homeostasis, highlighting its potential as a preventive strategy against intestinal disruptions. This study contributes to the understanding of the dietary effects of black tea on gastrointestinal health.
Metabolic availability of amino acids in humans
Authors: Paoletti Alyssa , Elango Rajavel , Courtney-Martin Glenda
Published: May 2024

Knowledge of amino acid bioavailability and the effect of combining complementary protein sources are required to determine how to best meet an individual’s protein and indispensable amino acid needs. Traditionally, protein quality of foods has been assessed using digestibility data. Digestibility may overestimate bioavailability of some amino acids particularly those more susceptible to heat and processing. The indicator amino acid oxidation (IAAO) method has been validated and applied to determine amino acid bioavailability termed metabolic availability of the first limiting amino acid of a proteinaceous food. The metabolic availability of the limiting amino acid in the test protein is determined as a ratio of the indicator amino acid oxidation response to graded intakes of the test protein compared to the indicator response to a reference protein (crystalline amino acid patterned after egg protein). The IAAO method has also been applied to assess the effect of protein complementation directly in humans on the overall protein quality of the diet. The results demonstrate that protein complementation augments the limiting amino acid supply and increases protein synthesis.
A missed case of intraductal oncocytic papillary neoplasm associated with missed stones in extrahepatic bile duct: a case report
Authors: Xie Cong , Zhang Hang , Meng Yushan , Cao Bin
Published: May 2024

The pathological features of intraductal oncocytic papillary neoplasm (IOPN) of the bile duct include tumor cells that are rich in eosinophilic cytoplasm and arranged in papillary structures. Herein, we report a missed case of IOPN of the bile duct because of concomitant gallstones. A 70-year-old woman was hospitalized with upper abdominal discomfort. The primary diagnosis was choledocholithiasis following imaging examination. However, an unidentified mass was detected after the gallstones were removed. The mass appeared as many papillary protuberances surrounded by fish-egg-like mucosa when viewed by the choledochoscope and was confirmed as IOPN by pathological examination. The patient underwent choledochectomy and no recurrence was observed at the 6-month follow-up examination. In this report, peroral choledochoscopy demonstrated its advantages for the diagnosis of biliary diseases and acquisition of tissue specimens. Therefore, it may solve the challenge related to the lack of preoperative pathological evidence for bile duct tumors.
Spinal myeloid sarcoma presenting as initial symptom in acute promyelocytic leukemia with a rare cryptic PLZF::RARα fusion gene: a case report and literature review
Authors: Zhang Xuejiao , Wang Tao , Chen Pu , Chen Yan , Wang Zhimei , Xu Tianhong , Yu Pengfei , Liu Peng
Published: May 2024

Background

Acute promyelocytic leukemia (APL) is rarely caused by the PLZF::RARα fusion gene. While APL patients with PLZF::RARα fusion commonly exhibit diverse hematologic symptoms, the presentation of myeloid sarcoma (MS) as an initial manifestation is infrequent.

Case presentation

A 61-year-old patient was referred to our hospital with 6-month history of low back pain and difficulty walking. Before this admission, spine magnetic resonance imaging (MRI) conducted at another hospital revealed multiple abnormal signals in the left iliac bone and vertebral bodies spanning the thoracic (T11-T12), lumbar (L1-L4), and sacral (S1/S3) regions. This led to a provisional diagnosis of bone tumors with an unknown cause. On admission, complete blood count (CBC) test and peripheral blood smear revealed a slightly increased counts of monocytes. Immunohistochemical staining of both spinal and bone marrow (BM) biopsy revealed positive expression for CD117, myeloperoxidase (MPO), and lysozyme. BM aspirate showed a significant elevation in the percentage of promyelocytes (21%), which were morphologically characterized by round nuclei and hypergranular cytoplasm. Multiparameter flow cytometry of BM aspirate revealed that blasts were positive for CD13, CD33, CD117, and MPO. Through the integrated application of chromosome analysis, fluorescence in situ hybridization (FISH), reverse transcriptase polymerase chain reaction (RT-PCR), and Sanger sequencing, it was determined that the patient possessed a normal karyotype and a rare cryptic PLZF::RARα fusion gene, confirming the diagnosis of APL.

Conclusion

In the present study, we report the clinical features and outcome of a rare APL patient characterized by a cryptic PLZF::RARα fusion and spinal myeloid sarcoma (MS) as the initial presenting symptom. Our study not only offers valuable insights into the heterogeneity of APL clinical manifestations but also emphasizes the crucial need to promptly consider the potential link between APL and MS for ensuring a timely diagnosis and personalized treatments.
Physician preferences for nonmetastatic castration-resistant prostate cancer treatment in China
Authors: Fan Yu , Guo Xuanjun , Campobasso Davide , He Zhisong
Published: May 2024

Introduction

The treatment preferences of Chinese physicians who treat nonmetastatic castration-resistant prostate cancer (nmCRPC) and how they weigh the benefits and risks of nmCRPC treatment are still unknown. This study aimed to evaluate Chinese physicians’ benefit–risk treatment preferences for nmCRPC and assist in setting nmCRPC treatment goals.

Methods

A paper-based discrete choice experiment (DCE) survey was administered to 80 nmCRPC-treating physicians. DCE responses were analyzed to produce the preference weight and the relative importance score for each attribute level. The marginal rate of substitution (MRS) was used to quantify the amount of overall survival (OS) physicians were willing to trade for a reduction in treatment-related adverse events (AEs). We further conducted the exploratory analysis, stratifying physicians from 5 perspectives into different subgroups and examining the treatment preferences and OS trade-off in each subgroup.

Results

In terms of efficacy attributes, physicians placed greater emphasis on OS than time to pain progression. With regard to safety attributes, serious fracture was perceived as the most important AE by physicians, followed by serious fall, cognitive problems, skin rash, and fatigue. In the exploratory analysis, we found generally that physicians with less clinical practice experience and those from more economically developed regions placed more emphasis on AEs and were willing to give up more of their patients’ OS to reduce the risk of AEs.

Conclusion

Physicians from mainland China value the importance of minimizing treatment-related AEs when considering different treatment options for patients with nmCRPC, and they are willing to trade a substantial amount of OS to avoid AEs.
Serum vitamin D and obesity among US adolescents, NHANES 2011–2018
Authors: Chen Zisu , Qiu Xiaojin , Wang Qiong , Wu Jing , Li Min , Niu Wenquan
Published: May 2024

Background and objectives

Childhood obesity is highly prevalent worldwide. We aimed to assess whether serum 25-hydroxyvitamin D was associated with general/central obesity among US adolescents, and further to explore the mediatory impact of homeostasis model assessment of insulin resistance (HOMA-IR) on this association.

Methods

This study is cross-sectional in design. Study adolescents were enrolled from the National Health and Nutrition Examination Survey (NHANES), 2011–2018. Serum 25-hydroxyvitamin D categories associated with general (indexed by body mass index) and central (indexed by waist circumference to height ratio) obesity were regressed. The possible mediatory effect of HOMA-IR on this association was explored. The nonlinear and dose-response association was examined by restricted cubic spline (RCS) test.

Results

Total 2,696 adolescents were eligible for inclusion, and the mean age of all adolescents was 15.4 years. Overall, the percentage of general and central obesity was 38.0% and 38.6%, respectively. Compared with adolescents with sufficient vitamin D, adolescent with deficient and insufficient vitamin D intake were associated with general obesity and central obesity; fully-adjusted OR for general obesity was 1.602 (95% CI: 1.161–2.211) and 1.659 (1.385–1.986), and fully-adjusted OR for central obesity was 2.025 (1.445–2.837) and 1.557 (1.287–1.884), respectively, while there was no observable significance in adolescents with possibly harmful vitamin D. The proportion mediated by HOMA-IR was estimated to be 31.7% for global obesity and 50.3% for central obesity (both P < 0.05). More stratified analyses were presented, and identified that the association with general obesity was particularly present among Mexican American, while with central obesity among Non-Hispanic Black adolescents.

Conclusions

Our findings indicate that deficient or insufficient 25-hydroxyvitamin D concentrations were associated with the significant risk of general and central obesity among US adolescents, and approximately 30% and 50%, respectively, of these associations were mediated by HOMA-IR.
Effects of cell-free DNA on kidney disease and intervention strategies
Authors: Zhang Mingying , Cai Yubin , Zhong Xiaoze , Liu Weijun , Lin Yuan , Qiu Zhanyi , Liang Ruihuang , Wei Huibo , Wu Kefei , Liu Qinghua
Published: May 2024

Kidney disease has become a global public health problem. Patients with end-stage kidney disease must rely on dialysis or undergo renal transplantation, placing heavy burdens on their families and society. Therefore, it is important to develop new therapeutic targets and intervention strategies during early stages of chronic kidney disease. The widespread application of liquid biopsy has led to an increasing number of studies concerning the roles of cell-free DNA (cfDNA) in kidney disease. In this review, we summarize relevant studies concerning the roles of cfDNA in kidney disease and describe various strategies for targeted removal of cfDNA, with the goal of establishing novel therapeutic approaches for kidney disease.
Predicting the PSQA results of volumetric modulated arc therapy based on dosiomics features: a multi-center study
Authors: Ni Qianxi , Chen Luqiao , Tan Jianfeng , Pang Jinmeng , Luo Longjun , Zhu Jun , Yang Xiaohua
Published: May 2024

Backgroud and objectives

The implementation of patient-specific quality assurance (PSQA) has become a crucial aspect of the radiation therapy process. Machine learning models have demonstrated their potential as virtual QA tools, accurately predicting the gamma passing rate (GPR) of volumetric modulated arc therapy (VMAT)plans, thereby ensuring safe and efficient treatment for patients. However, there is limited multi-center research dedicated to predicting the GPR. In this study, a dosiomics-based machine learning approach was employed to construct a prediction model for classifying GPR in multiple radiotherapy institutions. Additionally, the model’s performance was compared by evaluating the impact of two distinct feature selection methods.

Methods

A retrospective data collection was conducted on 572 VMAT patients across three radiotherapy institutions. Utilizing a three-dimensional dose verification technique grounded in real-time measurements, γ analysis was conducted according to the criteria of 3%/2 mm and 2%/2 mm, employing a dose threshold of 10% along with absolute dose and global normalization mode. Dosiomics features were extracted from the dose files, and distinct subsets of features were selected as inputs for the model using the random forest (RF) and RF combined with SHapley Additive exPlanations (SHAP) methods. The data underwent training using the extreme gradient boosting (XGBoost) algorithm, and the model’s classification performance was assessed through F1-score and area under the curve (AUC) values.

Results

The model exhibited optimal performance under the 3%/2 mm criteria, utilizing a subset of 20 features and attaining an AUC value of 0.88 and an F1-score of 0.89. Similarly, under the 2%/2 mm criteria, the model demonstrated superior performance with a subset of 10 features, resulting in an AUC value of 0.91 and an F1-score of 0.89. The feature selection methods of RF and RF + SHAP have achieved good model performance by selecting as few features as possible.

Conclusion

Based on the multi-center PSQA results, it is possible to utilize dosiomics features extracted from dose files to construct a machine learning predictive model. This model demonstrates excellent discriminative abilities, thus promoting the progress of gamma passing rate prognostic models in clinical application and implementation. Furthermore, it holds potential in providing patients with secure and efficient personalized QA management, while also reducing the workload of medical physicists.
Metabolic and molecular mechanisms of spine color formation in Chinese red chestnut
Authors: Qiao Qian , Gao Yun , Liu Qingzhong
Published: May 2024

The spines of Chinese red chestnut are red and the depth of their color gradually increases with maturity. To identify the anthocyanin types and synthesis pathways in red chestnut and to identify the key genes regulating the anthocyanin biosynthesis pathway, we obtained and analyzed the transcriptome and anthocyanin metabolism of red chestnut and its control variety with green spines at 3 different periods. GO and KEGG analyses revealed that photosynthesis was more highly enriched in green spines compared with red spines, while processes related to defense and metabolism regulation were more highly enriched in red spines. The analysis showed that the change in spine color promoted photoprotection in red chestnut, especially at the early growth stage, which resulted in the accumulation of differentially expressed genes involved in the defense metabolic pathway. The metabolome results revealed 6 anthocyanins in red spines. Moreover, red spines exhibited high levels of cyanidin, peonidin and pelargonidin and low levels of delphinidin, petunidin and malvidin. Compared with those in the control group, the levels of cyanidin, peonidin, pelargonidin and malvidin in red spines were significantly increased, indicating that the cyanidin and pelargonidin pathways were enriched in the synthesis of anthocyanins in red spines, whereas the delphinidin pathways were inhibited and mostly transformed into malvidin. During the process of flower pigment synthesis, the expression of the CHS, CHI, F3H, CYP75A, CYP75B1, DFR and ANS genes clearly increased, that of CYP73A decreased obviously, and that of PAL, 4CL and LAR both increased and decreased. Notably, the findings revealed that the synthesized anthocyanin can be converted into anthocyanidin or epicatechin. In red spines, the upregulation of BZ1 gene expression increases the corresponding anthocyanidin content, and the upregulation of the ANR gene also promotes the conversion of anthocyanin to epicatechin. The transcription factors involved in color formation included 4 WRKYs.
Regulation of root growth and elongation in wheat
Authors: Alrajhi Abdullah , Alharbi Saif , Beecham Simon , Alotaibi Fahad
Published: May 2024

Currently, the control of rhizosphere selection on farms has been applied to achieve enhancements in phenotype, extending from improvements in single root characteristics to the dynamic nature of entire crop systems. Several specific signals, regulatory elements, and mechanisms that regulate the initiation, morphogenesis, and growth of new lateral or adventitious root species have been identified, but much more work remains. Today, phenotyping technology drives the development of root traits. Available models for simulation can support all phenotyping decisions (root trait improvement). The detection and use of markers for quantitative trait loci (QTLs) are effective for enhancing selection efficiency and increasing reproductive genetic gains. Furthermore, QTLs may help wheat breeders select the appropriate roots for efficient nutrient acquisition. Single-nucleotide polymorphisms (SNPs) or alignment of sequences can only be helpful when they are associated with phenotypic variation for root development and elongation. Here, we focus on major root development processes and detail important new insights recently generated regarding the wheat genome. The first part of this review paper discusses the root morphology, apical meristem, transcriptional control, auxin distribution, phenotyping of the root system, and simulation models. In the second part, the molecular genetics of the wheat root system, SNPs, TFs, and QTLs related to root development as well as genome editing (GE) techniques for the improvement of root traits in wheat are discussed. Finally, we address the effect of omics strategies on root biomass production and summarize existing knowledge of the main molecular mechanisms involved in wheat root development and elongation.
A 12-month longitudinal naturalistic follow-up of cariprazine in schizophrenia
Authors: Carmassi Claudia , Dell’Oste Valerio , Fantasia Sara , Bordacchini Andrea , Bertelloni Carlo Antonio , Scarpellini Pietro , Pedrinelli Virginia
Published: May 2024

Background

Cariprazine, a third-generation antipsychotic (TGAs), has demonstrated efficacy in the treatment of schizophrenia with good tolerability profile. Actual real-world literature data are lacking, particularly when exploring its efficacy in the long term. The present study examined the effects of cariprazine treatment on specific psychopathological domains with a particular focus on outcomes and side effects in real-life experience, after a long-term treatment.

Methods

The present 12-month longitudinal naturalistic study included a sample of subjects with a DSM-5-TR diagnosis of schizophrenia, recruited in the outpatients’ psychiatric services of university and community hospitals in Italy, naturally treated with cariprazine. The assessments included: a sociodemographic data sheet, the Structured Clinical Interview for the DSM-5 (SCID-5), the Positive and Negative Symptom Scale (PANSS) and the St. Hans Rating Scale (SHRS). The PANSS was also administered after 6 (T1) and 12 (T2) months of treatment with cariprazine while the SHRS at T1.

Results

The total sample consisted of 31 patients, 15 males and 16 females. A significant decrease of the PANSS’ subscales, Marder factors and total mean scores emerged at both T1 and T2 with respect to T0. Extrapyramidal symptoms occurred in a minority of patients and in mild or mild/moderate forms: no patient showed moderate forms of psychic/motor akathisia or dystonia, three subjects showed moderate parkinsonism.

Conclusions

This study confirms a good efficacy profile of cariprazine in both positive and negative symptoms in patients with Schizophrenia, combined with a good tolerability profile in extrapyramidal symptoms.