bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted sequencing and clinical strategies in children with autism spectrum disorder: A cohort study
Authors: Hu Chunchun , Wang Yi , Li Chunyang , Mei Lianni , Zhou Bingrui , Li Dongyun , Li Huiping , Xu Qiong , Xu Xiu
Published: March 2023

Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with genetic and clinical heterogeneity. Owing to the advancement of sequencing technologies, an increasing number of ASD-related genes have been reported. We designed a targeted sequencing panel (TSP) for ASD based on next-generation sequencing (NGS) to provide clinical strategies for genetic testing of ASD and its subgroups.

Methods: TSP comprised 568 ASD-related genes and analyzed both single nucleotide variations (SNVs) and copy number variations (CNVs). The Autism Diagnostic Observation Schedule (ADOS) and the Griffiths Mental Development Scales (GMDS) were performed with the consent of ASD parents. Additional medical information of the selected cases was recorded.

Results: A total of 160 ASD children were enrolled in the cohort (male to female ratio 3.6:1). The total detection yield was 51.3% for TSP (82/160), among which SNVs and CNVs accounted for 45.6% (73/160) and 8.1% (13/160), respectively, with 4 children having both SNVs and CNV variants (2.5%). The detection rate of disease-associated variants in females (71.4%) was significantly higher than that in males (45.6%, p = 0.007). Pathogenic and likely pathogenic variants were detected in 16.9% (27/160) of the cases. SHANK3, KMT2A, and DLGAP2 were the most frequent variants among these patients. Eleven children had de novo SNVs, 2 of whom had de novo ASXL3 variants with mild global developmental delay (DD) and minor dysmorphic facial features besides autistic symptoms. Seventy-one children completed both ADOS and GMDS, of whom 51 had DD/intellectual disability (ID). In this subgroup of ASD children with DD/ID, we found that children with genetic abnormalities had lower language competence than those without positive genetic findings (p = 0.028). There was no correlation between the severity of ASD and positive genetic findings.

Conclusion: Our study revealed the potential of TSP, with lower cost and more efficient genetic diagnosis. We recommended that ASD children with DD or ID, especially those with lower language competence, undergo genetic testing. More precise clinical phenotypes may help in the decision-making of patients with genetic testing.
Genetics of destemming in pepper: A step towards mechanical harvesting
Authors: Hill Theresa , Cassibba Vincenzo , Joukhadar Israel , Tonnessen Bradley , Havlik Charles , Ortega Franchesca , Sripolcharoen Sirisupa , Visser Bernard Jurriaan , Stoffel Kevin , Thammapichai Paradee , Garcia-Llanos Armando , Chen Shiyu , Hulse-Kemp Amanda , Walker Stephanie , Van Deynze Allen
Published: March 2023

Introduction: The majority of peppers in the US for fresh market and processing are handpicked, and harvesting can account for 20–50% of production costs. Innovation in mechanical harvesting would increase availability; lower the costs of local, healthy vegetable products; and perhaps improve food safety and expand markets. Most processed peppers require removal of pedicels (stem and calyx) from the fruit, but lack of an efficient mechanical process for this operation has hindered adoption of mechanical harvest. In this paper, we present characterization and advancements in breeding green chile peppers for mechanical harvesting. Specifically, we describe inheritance and expression of an easy-destemming trait derived from the landrace UCD-14 that facilitates machine harvest of green chiles.

Methods: A torque gauge was used for measuring bending forces similar to those of a harvester and applied to two biparental populations segregating for destemming force and rate. Genotyping by sequencing was used to generate genetic maps for quantitative trait locus (QTL) analyses.

Results: A major destemming QTL was found on chromosome 10 across populations and environments. Eight additional population and/or environment-specific QTL were also identified. Chromosome 10 QTL markers were used to help introgress the destemming trait into jalapeño-type peppers. Low destemming force lines combined with improvements in transplant production enabled mechanical harvest of destemmed fruit at a rate of 41% versus 2% with a commercial jalapeńo hybrid. Staining for the presence of lignin at the pedicel/fruit boundary indicated the presence of an abscission zone and homologs of genes known to affect organ abscission were found under several QTL, suggesting that the easy-destemming trait may be due to the presence and activation of a pedicel/fruit abscission zone.

Conclusion: Presented here are tools to measure the easy-destemming trait, its physiological basis, possible molecular pathways, and expression of the trait in various genetic backgrounds. Mechanical harvest of destemmed mature green chile fruits was achieved by combining easy-destemming with transplant management.
Advances in the development of antivirals for rotavirus infection
Authors: Jiang Lin , Tang Ao , Song Lihua , Tong Yigang , Fan Huahao
Published: March 2023

Rotavirus (RV) causes 200,000 deaths per year and imposes a serious burden to public health and livestock farming worldwide. Currently, rehydration (oral and intravenous) remains the main strategy for the treatment of rotavirus gastroenteritis (RVGE), and no specific drugs are available. This review discusses the viral replication cycle in detail and outlines possible therapeutic approaches including immunotherapy, probiotic-assisted therapy, anti-enteric secretory drugs, Chinese medicine, and natural compounds. We present the latest advances in the field of rotavirus antivirals and highlights the potential use of Chinese medicine and natural compounds as therapeutic agents. This review provides an important reference for rotavirus prevention and treatment.
Treatment of refractory lupus nephritis using leflunomide: A prospective study
Authors: Zhang Shuo , Chen Yiran , Chen Xin , Zhao Yan , Zeng Xiaofeng , Zhang Fengchun , Wang Li , Li Mengtao
Published: March 2023

Introduction

The condition of refractory lupus nephritis (LN) negatively affects the prognosis and life expectancy of the patients, posing a challenge to manage in clinical. This interventional study evaluated the efficacy as well as safety of leflunomide in patients with refractory LN.

Methods

Twenty patients with refractory LN were enrolled in this study. A daily dose of 20–40 mg of leflunomide was given to the patients orally. Meanwhile, immunosuppressives were withdrawn, and corticosteroids were gradually tapered. There was an average follow-up period of 3, 6, and 12 months for most patients while some were observed for as long as 24 months. We recorded biochemical parameters and side effects. We calculated the response rate using intention-to-treat analysis.

Results

Eighteen patients (90%) completed the study. At 3 months, 80% (16/20) of the patients achieved more than a 25% decrease in 24-hour urine protein quantity. At 6 months, three patients (15%) achieved a partial response, and five patients (25%) achieved a complete response. However, by 12 months and 24 months, the complete response rate dropped to 15% and 20%, respectively. The objective responses were 30% (6/20), 40% (8/20), 40% (8/20), and 30% (6/20) at 3, 6, 12, and 24 months, respectively. Two patients withdrew from the study due to developing cytopenia and leucopenia.

Conclusion

In patients diagnosed with refractory LN, our study shows that leflunomide could be a promising treatment option owing to its response rate and safety profile.
Role and mechanism of fibroblast-activated protein-α expression on the surface of fibroblast-like synoviocytes in rheumatoid arthritis
Authors: Wang Zihan , Wang Jinping , Lan Tianyi , Zhang Liubo , Yan Zeran , Zhang Nan , Xu Yuan , Tao Qingwen
Published: March 2023

Fibroblast-activated protein-α (FAP) is a type II integrated serine protease expressed by activated fibroblasts during fibrosis or inflammation. Fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA) synovial sites abundantly and stably overexpress FAP and play important roles in regulating the cellular immune, inflammatory, invasion, migration, proliferation, and angiogenesis responses in the synovial region. Overexpression of FAP is regulated by the initial inflammatory microenvironment of the disease and epigenetic signaling, which promotes RA development by regulating FLSs or affecting the signaling cross-linking FLSs with other cells at the local synovium and inflammatory stimulation. At present, several treatment options targeting FAP are in the process of development. This review discusses the basic features of FAP expressed on the surface of FLSs and its role in RA pathophysiology and advances in targeted therapies.
Optical remote sensing (Sentinel-3 OLCI) used to monitor dissolved organic carbon in the Lena River, Russia
Authors: El Kassar Jan , Juhls Bennet , Hieronymi Martin , Preusker Rene , Morgenstern Anne , Fischer Jürgen , Overduin Pier Paul
Published: March 2023

In the past decades the Arctic has experienced stronger temperature increases than any other region globally. Shifts in hydrological regimes and accelerated permafrost thawing have been observed and are likely to increase mobilization of organic carbon and its transport through rivers into the Arctic Ocean. In order to better quantify changes to the carbon cycle, Arctic rivers such as the Lena River in Siberia need to be monitored closely. Since 2018, a sampling program provides frequent in situ observations of dissolved organic carbon (DOC) and colored dissolved organic matter (CDOM) of the Lena River. Here, we utilize this ground truth dataset and aim to test the potential of frequent satellite observations to spatially and temporally complement and expand these observations. We explored all available overpasses (~3250) of the Ocean and Land Colour Instrument (OLCI) on Sentinel-3 within the ice-free periods (May – October) for four years (2018 to 2021) to develop a new retrieval scheme to derive concentrations of DOC. OLCI observations with a spatial resolution of ~300 m were corrected for atmospheric effects using the Polymer algorithm. The results of this study show that using this new retrieval, remotely sensed DOC concentrations agree well with in situ DOC concentrations (MAPD=10.89%, RMSE=1.55 mg L−1, r²=0.92, n=489). The high revisit frequency and wide swath of OLCI allow it to capture the entire range of DOC concentrations and their seasonal variability. Estimated satellite-derived DOC export fluxes integrated over the ice-free periods of 2018 to 2021 show a high interannual variability and agree well with flux estimates from in situ data (RMSD=0.186 Tg C, MAPD=4.05%). In addition, 10-day OLCI composites covering the entire Lena River catchment revealed increasing DOC concentration and local sources of DOC along the Lena from south to north. We conclude that moderate resolution satellite imagers such as OLCI are very capable of observing DOC concentrations in large/wide rivers such as the Lena River despite the relatively coarse spatial resolution. The global coverage of remote sensing offers the expansion to more rivers in order to improve our understanding of the land-ocean carbon fluxes in a changing climate.
Influence of Marangoni convection, solar radiation, and viscous dissipation on the bioconvection couple stress flow of the hybrid nanofluid over a shrinking surface
Authors: Rehman Ali , Khan Waris , Abdelrahman Anas , Jan Rashid , Khan Muhammad Sohail , Galal Ahmed M.
Published: March 2023

The heat transfer ratio plays an important role in the industrial and engineering sectors; in this model, the authors used the hybrid nanofluid because the heat transfer ratio of the hybrid nanofluid is more than that of the base fluid. The key objective of this research work is to boost up the heat transfer ratio, for example, not only the accomplishment of energy is enough but is also expected to regulate the feeding of energy, and this is possible only to approve the development of heat transmission liquids to the mechanism of the expenditures of energy and improvement. The current research study investigates the influence of Marangoni convection, solar radiation, and viscous dissipation on the bioconvection couple stress flow of the hybrid nanofluid over a shrinking surface. This type of flow has some important application in the industrial and engineering sectors for the purpose of cooling and heating effect. To transform the non-dimensionless form of the differential equation to the dimensionless form, the authors used the defined similarity transformation. The transformed dimensionless form of the differential equation is solved by the homotopic analysis method. The obtained important result is determined with the help of graphs which is obtained from velocity and temperature equations. The impression of different parameters such as couple stress parameter, Marangoni convection parameter, nanoparticle volume fraction, solar radiation parameter, magnetic field parameter, thermophoresis parameter, Eckert number, and Prandtl number is taken over graphs. The skin friction coefficient and Nusselt number are described in the form of tables.
The impact of the image conversion factor and image centration on retinal vessel geometric characteristics
Authors: Schanner Carolin , Hautala Nina , Rauscher Franziska G. , Falck Aura
Published: March 2023

Background

This study aims to use fundus image material from a long-term retinopathy follow-up study to identify problems created by changing imaging modalities or imaging settings (e.g., image centering, resolution, viewing angle, illumination wavelength). Investigating the relationship of image conversion factor and imaging centering on retinal vessel geometric characteristics (RVGC), offers solutions for longitudinal retinal vessel analysis for data obtained in clinical routine.

Methods

Retinal vessel geometric characteristics were analyzed in scanned fundus photographs with Singapore-I-Vessel-Assessment using a constant image conversion factor (ICF) and an individual ICF, applying them to macula centered (MC) and optic disk centered (ODC) images. The ICF is used to convert pixel measurements into μm for vessel diameter measurements and to establish the size of the measuring zone. Calculating a constant ICF, the width of all analyzed optic disks is included, and it is used for all images of a cohort. An individual ICF, in turn, uses the optic disk diameter of the eye analyzed. To investigate agreement, Bland-Altman mean difference was calculated between ODC images analyzed with individual and constant ICF and between MC and ODC images.

Results

With constant ICF (n = 104 eyes of 52 patients) the mean central retinal equivalent was 160.9 ± 17.08 μm for arteries (CRAE) and 208.7 ± 14.7.4 μm for veins (CRVE). The individual ICFs resulted in a mean CRAE of 163.3 ± 15.6 μm and a mean CRVE of 219.0 ± 22.3 μm. On Bland–Altman analysis, the individual ICF RVGC are more positive, resulting in a positive mean difference for most investigated parameters. Arteriovenous ratio (p = 0.86), simple tortuosity (p = 0.08), and fractal dimension (p = 0.80) agreed well between MC and ODC images, while the vessel diameters were significantly smaller in MC images (p < 0.002).

Conclusion

Scanned images can be analyzed using vessel assessment software. Investigations of individual ICF versus constant ICF point out the asset of utilizing an individual ICF. Image settings (ODC vs. MC) were shown to have good agreement.
Using simulated wildland fire to assess microbial survival at multiple depths from biocrust and bare soils
Authors: Palmer Brianne , Pietrasiak Nicole , Cobb Polina , Lipson David
Published: March 2023

Introduction

Surface soil microbial communities are directly exposed to the heat from wildland fires. Due to this, the microbial community composition may be stratified within the soil profile with more heat tolerant microbes near the surface and less heat tolerant microbes, or mobile species found deeper in the soil. Biological soil crusts, biocrusts, are found on the soil surface and contain a diverse microbial community that is directly exposed to the heat from wildland fires.

Methods

Here, we used a simulated fire mesocosm along with a culture-based approach and molecular characterization of microbial isolates to understand the stratification of biocrust and bare soil microbes after low severity (450°C) and high severity (600°C) fires. We cultured and sequenced microbial isolates from 2 to 6 cm depth from both fire types.

Results

The isolates were stratified along the soil depth. Green algal isolates were less thermotolerant and found in the deeper depths (4–6 cm) and the control soils, while several cyanobacteria in Oscillatoriales, Synechococcales, and Nostocales were found at 2–3 cm depth for both fire temperatures. An Alphaproteobacteria isolate was common across several depths, both fire types, and both fire temperatures. Furthermore, we used RNA sequencing at three depths after the high severity fire and one control to determine what microbial community is active following a fire. The community was dominated by Gammaproteobacteria, however some Cyanobacteria ASVs were also present.

Discussion

Here we show evidence of stratification of soil and biocrust microbes after a fire and provide evidence that these microbes are able to survive the heat from the fire by living just below the soil surface. This is a steppingstone for future work on the mechanisms of microbial survival after fire and the role of soil insulation in creating resilient communities.
The analysis of gut microbiota in patients with bile acid diarrhoea treated with colesevelam
Authors: Kumar Aditi , Quraishi Mohammed Nabil , Al-Hassi Hafid O. , El-Asrag Mohammed E. , Segal Jonathan P. , Jain Manushri , Steed Helen , Butterworth Jeffrey , Farmer Adam , Mclaughlin John , Beggs Andrew , Brookes Matthew J.
Published: March 2023

Introduction

Bile acid diarrhoea (BAD) is a common disorder that results from an increased loss of primary bile acids and can result in a change in microbiome. The aims of this study were to characterise the microbiome in different cohorts of patients with BAD and to determine if treatment with a bile acid sequestrant, colesevelam, can alter the microbiome and improve microbial diversity.

Materials and methods

Patients with symptoms of diarrhoea underwent 75-selenium homocholic acid (75SeHCAT) testing and were categorised into four cohorts: idiopathic BAD, post-cholecystectomy BAD, post-operative Crohn’s disease BAD and 75SeHCAT negative control group. Patients with a positive 75SeHCAT (<15%) were given a trial of treatment with colesevelam. Stool samples were collected pre-treatment, 4-weeks, 8-weeks and 6–12 months post-treatment. Faecal 16S ribosomal RNA gene analysis was undertaken.

Results

A total of 257 samples were analysed from 134 patients. α-diversity was significantly reduced in patients with BAD and more specifically, in the idiopathic BAD cohort and in patients with severe disease (SeHCAT <5%); p < 0.05. Colesevelam did not alter bacterial α/β-diversity but patients who clinically responded to treatment had a significantly greater abundance of Fusobacteria and Ruminococcus, both of which aid in the conversion of primary to secondary bile acids.

Conclusion

This is the first study to examine treatment effects on the microbiome in BAD, which demonstrated a possible association with colesevelam on the microbiome through bile acid modulation in clinical responders. Larger studies are now needed to establish a causal relationship with colesevelam and the inter-crosstalk between bile acids and the microbiome.
Biomarker of early neurological deterioration in minor stroke and proximal large vessel occlusion: A pilot study
Authors: Wang Zhiqiang , Wang Shuai , Li Yuxia , Wang Rongyu , Jiang Lianyan , Zheng Bo , Zhang Yaodan , Wang Qingsong , Wang Jian
Published: March 2023

Background

Plasma neurofilament light chain (pNFL) represents one of the scaffolding proteins of central nervous system axonal injury. The aim of this study was to evaluate pNFL as a predictive biomarker for early neurological deterioration (END) in medically managed patients with large vessel occlusion (LVO) and mild presentation (NIHSS < 6).

Methods

This retrospective study was developed from a prospectively collected stroke database, which was conducted at a large academic comprehensive stroke center in western China. Patients who first presented with acute ischemic stroke (AIS) within 24 h of symptom onset were continuously included. Stroke severity was analyzed at admission using the NIHSS score. The pNFL drawn on admission was analyzed with a novel ultrasensitive single-molecule array.

Results

Thirty-nine consecutive patients were included in the analysis, and 19 (48.72%) patients experienced END. Patients who experienced END had significantly higher pNFL levels (mean, 65.20 vs. 48.28 pg/mL; P < 0.001) and larger infarct volume (mean, 15.46 vs. 9.56 mL; P < 0.001). pNFL was valuable for the prediction of END (OR, 1.170; 95% CI, 1.049–1.306; P = 0.005), even after adjusted for age and sex (OR, 1.178; 95% CI, 1.038–1.323; P = 0.006), blood sampling time, baseline NIHSS, TOAST classification, and infarct volume (OR, 1.168; 95% CI, 1.034–1.320; P = 0.012). The area under the ROC curve was 85.0% (95% CI, 0.731–0.970; P < 0.001). The sensitivity was 73.7%, and the specificity was 80%.

Conclusion

END in minor stroke with LVO was distinguishable from those without END following the determination of pNFL in the blood samples within 24 h of onset. The pNFL is a promising biomarker of END in minor stroke with LVO.

Clinical trial registration

ChiCTR1800020330.
Alcohol flushing syndrome is significantly associated with intracranial aneurysm rupture in the Chinese Han population
Authors: Chen Xiheng , Gui Siming , Deng Dingwei , Dong Linggen , Zhang Longhui , Wei Dachao , Jiang Jia , Ge Huijian , Liu Peng , Lv Ming , Li Youxiang
Published: March 2023

Objective

Although alcohol flushing syndrome (AFS) has been associated with various diseases, its association with intracranial aneurysm rupture (IAR) is unclear. We aimed to examine this association in the Chinese Han population.

Methods

We retrospectively reviewed Chinese Han patients with intracranial aneurysms who were evaluated and treated at our institution between January 2020 and December 2021. AFS was determined using a semi-structured telephone interview. Clinical data and aneurysm characteristics were assessed. Univariate and multivariate logistic regression were conducted to determine independent factors associated with aneurysmal rupture.

Results

A total of 1,170 patients with 1,059 unruptured and 236 ruptured aneurysms were included. The incidence of aneurysm rupture was significantly higher in patients without AFS (p < 0.001). Meanwhile, there was a significantly difference between the AFS and non-AFS group in habitual alcohol consumption (10.5 vs. 27.2%, p < 0.001). In the univariate analyses, AFS [odds ratio (OR) 0.49; 95% confidence interval (CI), 0.34–0.72] was significantly associated with IAR. In the multivariate analysis, AFS was an independent predictor of IAR (OR 0.50; 95%, CI, 0.35–0.71). Multivariate analysis revealed that AFS was an independent predictor of IAR in both habitual (OR 0.11; 95% CI, 0.03–0.45) and non-habitual drinkers (OR 0.69; 95% CI, 0.49–0.96).

Conclusion

Alcohol flushing syndrome may be a novel clinical marker to assess the risk of IAR. The association between AFS and IAR exists independently of alcohol consumption. Further single nucleotide polymorphism testing and molecular biology studies are warranted.
Case report: Multiple disconnection patterns revealed by a multi-modal analysis explained behavior after a focal frontal damage
Authors: Monai Elena , Silvestri Erica , Bisio Marta , Cagnin Annachiara , Aiello Marco , Cecchin Diego , Bertoldo Alessandra , Corbetta Maurizio
Published: March 2023

Introduction

There is overwhelming evidence that focal lesions cause structural, metabolic, functional, and electrical disconnection of regions directly and indirectly connected with the site of injury. Unfortunately, methods to study disconnection (positron emission tomography, structural and functional magnetic resonance imaging, electroencephalography) have been applied primarily in isolation without capturing their interaction. Moreover, multi-modal imaging studies applied to focal lesions are rare.

Case report

We analyzed with a multi-modal approach the case of a patient presenting with borderline cognitive deficits across multiple domains and recurrent delirium. A post-surgical focal frontal lesion was evident based on the brain anatomical MRI. However, we were able to acquire also simultaneous MRI (structural and functional) and [18F]FDG using a hybrid PET/MRI scan along with EEG recordings. Despite the focality of the primary anatomical lesion, structural disconnection in the white matter bundles extended far beyond the lesion and showed a topographical match with the cortical glucose hypometabolism seen both locally and remotely, in posterior cortices. Similarly, a right frontal delta activity near/at the region of structural damage was associated with alterations of distant occipital alpha power. Moreover, functional MRI revealed even more widespread local and distant synchronization, involving also regions not affected by the structural/metabolic/electrical impairment.

Conclusion

Overall, this exemplary multi-modal case study illustrates how a focal brain lesion causes a multiplicity of disconnection and functional impairments that extend beyond the borders of the anatomical irrecoverable damage. These effects were relevant to explain patient’s behavior and may be potential targets of neuro-modulation strategies.
Cultivation, nutritional value, bioactive compounds of morels, and their health benefits: A systematic review
Authors: Li Yitong , Chen Hongyu , Zhang Xi
Published: March 2023

Morels are valuable mushrooms being used as foods and medical substances for a long history. The commonly cultivated morel species include M. eximia, M. importuna, and M. sextelata in China, M. conica and M. esculenta in the US. Morels' nutritional profile mainly consists of carbohydrates, proteins, fatty acids, vitamins, minerals, and organic acids, which are also responsible for its complex sensory attributes and health benefits. The bioactive compounds in morels including polysaccharides, phenolics, tocopherols, and ergosterols contribute to the anti-oxidative abilities, anti-inflammation, immunoprotection, gut health preservation, and anti-cancer abilities. This review depicted on the cultivation of morels, major bioactive compounds of different morel species both from fruit bodies and mycelia, and their health benefits to provide a comprehensive understanding of morels and support the future research and applications of morels as high-value functional food sources.
Development and validation of prognostic index based on immunogenic cell death-related genes with melanoma
Authors: Han Yajun , Cai Qinqin , Xie Xiaolin , Gao Shilong , Fan Xiwen
Published: March 2023

Although immune checkpoint inhibitors have improved the overall survival rate of skin cutaneous melanoma (SKCM) patients, there is a wide variation and low response rate to these treatments in clinical immunotherapy for melanoma patients. These problems can be addressed through the induction of immunogenic cell death (ICD).We constructed an ICD-based prognostic model to predict the prognosis of SKCM patients and the efficacy of immunotherapy. Information on melanoma and normal samples obtained by TCGA and GTEx was stratified by ICD-related genes. The samples were divided into two subtypes according to high and low expression of ICD using an unsupervised clustering method (K-means). Patients with ICD-high subtype showed longer overall survival. We found that the ICD-related differential genes were associated with several cell death and immune-related pathways through GO, KEGG and GSEA. Immunoscore and tumor purity of ICD-associated genes was calculated using ESTIMATE, and ICD-high subtypes had higher immunoscore and lower tumor purity than ICD-low subtypes. Seven ICD-associated genes were obtained by one-way Cox regression and Lasso regression of ICD genes. Risk models were constructed to classify melanoma patients into high- risk and low-risk groups. The expression of ICD-related pivotal genes was lower in the high-risk group than in the low-risk group, and the survival time was significantly higher in the low-risk group than in the high-risk group. We then found that ICD risk characteristics had predictive value for the clinical efficacy of immunotherapy, with higher ICD risk scores in the immunotherapy non-responsive group. Combined with clinicopathological factors, a nomogram was established. the ROC and calibration curves assessed the ability of the nomogram to predict prognosis. We developed a new classification system for SKCM based on the characteristics of ICDs. This stratification has important clinical implications for estimating the prognosis and immunotherapy of SKCM patients.
Single versus multiple hyperthermic intraperitoneal chemotherapy applications for T4 gastric cancer patients: Efficacy and safety profiles
Authors: Zhang Jing , Sun Yuemin , Bai Xiaofeng , Wang Peng , Tian Liang , Tian Yantao , Zhong Yuxin
Published: March 2023

Objective

To explore the clinical safety and efficacy of single and multiple applications of lobaplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with T4 gastric cancer and to evaluate the impact of HIPEC on peritoneal metastasis.

Materials and methods

We retrospectively reviewed prospectively collected data from T4 gastric cancer patients who underwent radical gastric resection plus HIPEC between March 2018 and August 2020 from the National Cancer Center and Huangxing Cancer Hospital. Patients who underwent radical surgery and HIPEC were divided into two groups: the single-HIPEC group (radical resection + a single application of intraoperative HIPEC with lobaplatin 50 mg/m2 at 43.0 ± 0.5°C for 60 min), and a multi-HIPEC group (two more HIPEC applications were performed after radical surgery).

Results

A total of 78 patients were enrolled in this two-center study; among them, 40 patients were in the single-HIPEC group, and 38 patients were in the multi-HIPEC group. The baseline characteristics were well balanced between the two groups. There was no significant difference in the postoperative complication rates between the two groups (P > 0.05). Mild renal dysfunction, mild liver dysfunction, low platelet levels and low white blood cell levels were recorded in both groups, without significant differences between the two groups (P > 0.05). After a mean follow-up of 36.8 months, 3 (7.5%) patients in the single-HIPEC group and 2 (5.2%) patients in the multi-HIPEC group experienced peritoneal recurrence (P > 0.05). Both groups had comparable 3-year overall survival (OS) (51.3% vs. 54.5%, P = 0.558) and 3-year disease-free survival (DFS) rates (44.1% vs. 45.7%, P = 0.975). Multivariate analysis showed that an age > 60 years and low preoperative albumin levels were independent risk factors for postoperative complications.

Conclusion

Single and multiple applications of HIPEC in patients with T4 gastric cancer were safe and feasible. Both groups had similar postoperative complication rates, 3-year OS rates and 3-year DFS rates. Special attention should be given to HIPEC for patients aged > 60 years and patients with low preoperative albumin levels.
Identification of LSM family members as potential chemoresistance predictive and therapeutic biomarkers for gastric cancer
Authors: Liu Qianhui , Lian Qinghai , Song Yingqiu , Yang Shangbin , Jia Changchang , Fang Jiafeng
Published: March 2023

Introduction

The Like-Smith (LSM) family plays a critical role in the progression of several cancers. However, the function of LSMs in chemoresistance of gastric cancer (GC) is still elusive.

Methods

The Cancer Genome Atlas (TCGA) database, Gene Expression Omnibus (GEO) database and Tumor Immune Estimation Resource Analysis (TIMER) were utilized to analyze the expression, prognostic value and immune infiltration of LSMs in GC patients. Moreover, qPCR and immunohistochemistry (IHC) experiment were conducted with clinical samples.

Results

The expression of LSMs was upregulated in GC tissues and most of LSMs were negatively correlated with overall survival of GC patients with 5-fluorouracil (5-FU) treatment. We further revealed that LSM5, 7 and 8 were hub genes of GEO (GSE14210). Besides, the qPCR results demonstrated that a higher level of LSM5 and LSM8 was associated with 5-FU chemoresistance in GC. Moreover, both TIMER and IHC revealed that a lower expression of LSM5 and LSM8 was correlated with high infiltration of T cells, regulatory T cells, B cells, macrophages, and neutrophils.

Discussion

Our study systematically investigated the expression pattern and biological features of LSM family members in GC, and identified LSM5 and LSM8 as potential biomarkers in GC with 5-FU chemotherapy.
A novel nomogram predicting the early recurrence of hepatocellular carcinoma patients after R0 resection
Authors: Wang Huanhuan , Liu Runkun , Mo Huanye , Li Runtian , Lian Jie , Liu Qingguang , Han Shaoshan
Published: March 2023

Background

Early tumor recurrence is one of the most significant poor prognostic factors for patients with HCC after R0 resection. The aim of this study is to identify risk factors of early recurrence, in addition, to develop a nomogram model predicting early recurrence of HCC patients.

Methods

A total of 481 HCC patients after R0 resection were enrolled and divided into a training cohort (n = 337) and a validation cohort (n = 144). Risk factors for early recurrence were determined based on Cox regression analysis in the training cohort. A nomogram incorporating independent risk predictors was established and validated.

Results

Early recurrence occurred in 37.8% of the 481 patients who underwent curative liver resection of HCC. AFP ≥ 400 ng/mL (HR: 1.662; P = 0.008), VEGF-A among 127.8 to 240.3 pg/mL (HR: 1.781, P = 0.012), VEGF-A > 240.3 pg/mL (HR: 2.552, P < 0.001), M1 subgroup of MVI (HR: 2.221, P = 0.002), M2 subgroup of MVI (HR: 3.120, P < 0.001), intratumor necrosis (HR: 1.666, P = 0.011), surgical margin among 5.0 to 10.0 mm (HR: 1.601, P = 0.043) and surgical margin < 5.0 mm (HR: 1.790, P = 0.012) were found to be independent risk factors for recurrence-free survival in the training cohort and were used for constructing the nomogram. The nomogram indicated good predictive performance with an AUC of 0.781 (95% CI: 0.729-0.832) and 0.808 (95% CI: 0.731-0.886) in the training and validation cohorts, respectively.

Conclusions

Elevated serum concentrations of AFP and VEGF-A, microvascular invasion, intratumor necrosis, surgical margin were independent risk factors of early intrahepatic recurrence. A reliable nomogram model which incorporated blood biomarkers and pathological variables was established and validated. The nomogram achieved desirable effectiveness in predicting early recurrence in HCC patients.
Associations between unit workloads and outcomes of first extubation attempts in extremely premature infants below a gestational age of 26 weeks
Authors: Ohnstad Mari Oma , Stensvold Hans Jørgen , Pripp Are Hugo , Tvedt Christine Raaen , Jelsness-Jørgensen Lars-Petter , Astrup Henriette , Eriksen Beate Horsberg , Lunnay Mai Linn , Mreihil Khalaf , Pedersen Tanja , Rettedal Siren Irene , Selberg Terje Reidar , Solberg Rønnaug , Støen Ragnhild , Rønnestad Arild Erland
Published: March 2023

Objective

The objective was to explore whether high workloads in neonatal intensive care units were associated with short-term respiratory outcomes of extremely premature (EP) infants born <26 weeks of gestational age.

Methods

This was a population-based study using data from the Norwegian Neonatal Network supplemented by data extracted from the medical records of EP infants <26 weeks GA born from 2013 to 2018. To describe the unit workloads, measurements of daily patient volume and unit acuity at each NICU were used. The effect of weekend and summer holiday was also explored.

Results

We analyzed 316 first planned extubation attempts. There were no associations between unit workloads and the duration of mechanical ventilation until each infant’s first extubation or the outcomes of these attempts. Additionally, there were no weekend or summer holiday effects on the outcomes explored. Workloads did not affect the causes of reintubation for infants who failed their first extubation attempt.

Conclusion

Our finding that there was no association between the organizational factors explored and short-term respiratory outcomes can be interpreted as indicating resilience in Norwegian neonatal intensive care units.
Identification of a pediatric acute hypoxemic respiratory failure signature in peripheral blood leukocytes at 24 hours post-ICU admission with machine learning
Authors: Grunwell Jocelyn R. , Rad Milad G. , Ripple Michael J. , Yehya Nadir , Wong Hector R. , Kamaleswaran Rishikesan
Published: March 2023

Background

There is no generalizable transcriptomics signature of pediatric acute respiratory distress syndrome. Our goal was to identify a whole blood differential gene expression signature for pediatric acute hypoxemic respiratory failure (AHRF) using transcriptomic microarrays within twenty-four hours of diagnosis. We used publicly available human whole-blood gene expression arrays of a Berlin-defined pediatric acute respiratory distress syndrome (GSE147902) cohort and a sepsis-triggered AHRF (GSE66099) cohort within twenty-four hours of diagnosis and compared those children with a PaO2/FiO2 < 200 to those with a PaO2/FiO2 ≥ 200.

Results

We used stability selection, a bootstrapping method of 100 simulations using logistic regression as a classifier, to select differentially expressed genes associated with a PaO2/FiO2 < 200 vs. PaO2/FiO2 ≥ 200. The top-ranked genes that contributed to the AHRF signature were selected in each dataset. Genes common to both of the top 1,500 ranked gene lists were selected for pathway analysis. Pathway and network analysis was performed using the Pathway Network Analysis Visualizer (PANEV) and Reactome was used to perform an over-representation gene network analysis of the top-ranked genes common to both cohorts. Changes in metabolic pathways involved in energy balance, fundamental cellular processes such as protein translation, mitochondrial function, oxidative stress, immune signaling, and inflammation are differentially regulated early in pediatric ARDS and sepsis-induced AHRF compared to both healthy controls and to milder acute hypoxemia. Specifically, fundamental pathways related to the severity of hypoxemia emerged and included (1) ribosomal and eukaryotic initiation of factor 2 (eIF2) regulation of protein translation and (2) the nutrient, oxygen, and energy sensing pathway, mTOR, activated via PI3K/AKT signaling.

Conclusions

Cellular energetics and metabolic pathways are important mechanisms to consider to further our understanding of the heterogeneity and underlying pathobiology of moderate and severe pediatric acute respiratory distress syndrome. Our findings are hypothesis generating and support the study of metabolic pathways and cellular energetics to understand heterogeneity and underlying pathobiology of moderate and severe acute hypoxemic respiratory failure in children.
Ciprofol attenuates the isoproterenol-induced oxidative damage, inflammatory response and cardiomyocyte apoptosis
Authors: Yang Yunzhao , Xia Zhongyuan , Xu Cheng , Zhai Chunchun , Yu Xi , Li Siqi
Published: March 2023

Background and Purpose: Ciprofol (HSK3486), a novel 2,6-disubstituted phenol derivative, is a new intravenous anesthetic compound with a similar chemical structure to propofol. Animal studies have also shown that propofol plays a protective role in a variety of cardiovascular diseases, including myocardial infarction, myocardial ischemia-reperfusion injury and takotsubo syndrome. However, whether ciprofol exerts cardioprotective effects on myocardial infarction remains unclear. Thus, the aim of this work was to explore the potential cardioprotective mechanism of ciprofol on isoproterenol (ISO)-induced myocardial infarction.

Experimental Approach: In the present study, male C57BL/6 mice were subjected to subcutaneous injection of ISO (100 mg/kg) for 2 consecutive days to induce experimental myocardial infarction. Herein, we found that ciprofol could inhibit the abnormal increase in myocardial injury enzymes, the area of myocardial infarction and cardiac dysfunction in ISO-treated mice. Ciprofol administration increased the activity of superoxide dismutase and reduced the levels of NADPH oxidase and malondialdehyde in ISO-treated hearts. Additionally, ciprofol administration markedly reduced the expression of pro-inflammatory cytokines and cardiomyocyte apoptosis. In an in vitro model, the results also confirmed that ciprofol could inhibit ISO-induced oxidative damage, the inflammatory response and cardiomyocyte apoptosis. Moreover, ciprofol can activate the sirtuin1 (Sirt1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and Sirt1 and Nrf2 inhibition almost abolished ciprofol-mediated cardioprotective effects.

Interpretation: Ciprofol protects the heart against ISO-induced myocardial infarction by reducing cardiac oxidative stress, the inflammatory response and cardiomyocyte apoptosis.
Vanadium oxide metal-insulator phase transition in different types of one-dimensional photonic microcavities
Authors: Scotognella Francesco
Published: March 2023

The optical properties of vanadium dioxide (VO2) can be tuned via metal-insulator transition. In this work, different types of one-dimensional photonic structure-based microcavities that embed vanadium dioxide have been studied in the spectral range between 900 nm and 2000 nm. In particular, VO2 has been sandwiched between: i) two photonic crystals made of SiO2 and ZrO2; ii) two aperiodic structures made of SiO2 and ZrO2 that follow the Thue-Morse sequence; iii) two disordered photonic structures, made of SiO2 and ZrO2 in which the disorder is introduced either by a random sequence of the two materials or by a random variation of the thicknesses of the layers; iv) two four material-based photonic crystals made of SiO2, Al2O3, Y2O3, and ZrO2. The ordered structures i and iv show, respectively, one and two intense transmission valleys with defect modes, while the aperiodic and disordered structures ii and iii show a manifold of transmission valleys due to their complex layered configurations. The metal-insulator transition of VO2, controlled by temperature, results in a modulation of the optical properties of the microcavities.
Iron accumulation and partitioning in hydroponically grown wild and cultivated chickpea (Cicer arietinum L)
Authors: Jahan Tamanna A. , Kalve Shweta , Belak Zachery , Eskiw Christopher , Tar’an Bunyamin
Published: March 2023

Chickpea (Cicer arietinum L.) is a staple food in many developing countries where iron (Fe) deficiency often occurs in their population. The crop is a good source of protein, vitamins, and micronutrients. Fe biofortification in chickpea can be part of long-term strategy to enhance Fe intake in human diet to help to alleviate Fe deficiency. To develop cultivars with high Fe concentration in seeds, understanding the mechanisms of absorption and translocation of Fe into the seeds is critical. An experiment was conducted using a hydroponic system to evaluate Fe accumulation in seeds and other organs at different growth stages of selected genotypes of cultivated and wild relatives of chickpea. Plants were grown in media with Fe zero and Fe added conditions. Six chickpea genotypes were grown and harvested at six different growth stages: V3, V10, R2, R5, R6, and RH for analysis of Fe concentration in roots, stems, leaves, and seeds. The relative expression of genes related to Fe-metabolism including FRO2, IRT1, NRAMP3, V1T1, YSL1, FER3, GCN2, and WEE1 was analyzed. The results showed that the highest and lowest accumulation of Fe throughout the plant growth stages were found in the roots and stems, respectively. Results of gene expression analysis confirmed that the FRO2 and IRT1 were involved in Fe uptake in chickpeas and expressed more in roots under Fe added condition. All transporter genes: NRAMP3, V1T1, YSL1 along with storage gene FER3 showed higher expression in leaves. In contrast, candidate gene WEE1 for Fe metabolism expressed more in roots under Fe affluent condition; however, GCN2 showed over-expression in roots under Fe zero condition. Current finding will contribute to better understanding of Fe translocation and metabolism in chickpea. This knowledge can further be used to develop chickpea varieties with high Fe in seeds.
Genome-wide identification and expression analysis of the U-box E3 ubiquitin ligase gene family related to salt tolerance in sorghum (Sorghum bicolor L.)
Authors: Cui Jianghui , Ren Genzeng , Bai Yuzhe , Gao Yukun , Yang Puyuan , Chang Jinhua
Published: March 2023

Plant U-box (PUB) E3 ubiquitin ligases play essential roles in many biological processes and stress responses, but little is known about their functions in sorghum (Sorghum bicolor L.). In the present study, 59 SbPUB genes were identified in the sorghum genome. Based on the phylogenetic analysis, the 59 SbPUB genes were clustered into five groups, which were also supported by the conserved motifs and structures of these genes. SbPUB genes were found to be unevenly distributed on the 10 chromosomes of sorghum. Most PUB genes (16) were found on chromosome 4, but there were no PUB genes on chromosome 5. Analysis of cis-acting elements showed that SbPUB genes were involved in many important biological processes, particularly in response to salt stress. From proteomic and transcriptomic data, we found that several SbPUB genes had diverse expressions under different salt treatments. To verify the expression of SbPUBs, qRT-PCR analyses also were conducted under salt stress, and the result was consistent with the expression analysis. Furthermore, 12 SbPUB genes were found to contain MYB-related elements, which are important regulators of flavonoid biosynthesis. These results, which were consistent with our previous multi-omics analysis of sorghum salt stress, laid a solid foundation for further mechanistic study of salt tolerance in sorghum. Our study showed that PUB genes play a crucial role in regulating salt stress, and might serve as promising targets for the breeding of salt-tolerant sorghum in the future.
Integrated transcriptome and metabonomic analysis of key metabolic pathways in response to cadmium stress in novel buckwheat and cultivated species
Authors: Huo Dongao , Hao Ying , Zou Juan , Qin Lixia , Wang Chuangyun , Du Dengxiang
Published: March 2023

Introduction

Buckwheat (Fagopyrum tataricum), an important food crop, also has medicinal uses. It is widely planted in Southwest China, overlapping with planting areas remarkably polluted by cadmium (Cd). Therefore, it is of great significance to study the response mechanism of buckwheat under Cd stress and further develop varieties with excellent Cd tolerance.

Methods

In this study, two critical periods of Cd stress treatment (days 7 and 14 after Cd treatment) of cultivated buckwheat (Pinku-1, named K33) and perennial species (F. tatari-cymosum Q.F. Chen) (duoku, named DK19) were analyzed using transcriptome and metabolomics.

Results

The results showed that Cd stress led to changes in reactive oxygen species (ROS) and the chlorophyll system. Moreover, Cd-response genes related to stress response, amino acid metabolism, and ROS scavenging were enriched or activated in DK19. Transcriptome and metabolomic analyses highlighted the important role of galactose, lipid (glycerophosphatide metabolism and glycerophosphatide metabolism), and glutathione metabolism in response to Cd stress in buckwheat, which are significantly enriched at the gene and metabolic levels in DK19.

Discussion

The results of the present study provide valuable information for a better understanding of the molecular mechanisms underlying Cd tolerance in buckwheat and useful clues for the genetic improvement of drought tolerance in buckwheat.