bluuebunny/crossref_metadata_2025 huggingface dataset:
Case Report: Camrelizumab combined with gemcitabine and oxaliplatin in the treatment of advanced intrahepatic cholangiocarcinoma: a case report and literature review
Authors: Zhang Zhongyan , Wang Xin , Li Hehe , Sun Huimin , Chen Jianhong , Lin Hongfeng
Published: August 2023

Intrahepatic cholangiocarcinoma (ICC) is one of the most common invasive malignant tumors, with a 5-year survival rate of less than 5%. Currently, radical surgical resection is the preferred treatment for ICC. However, most patients are only diagnosed at an advanced stage and are therefore not eligible for surgery. Herein, we present a case of advanced ICC in which radical surgery was not possible due to tumor invasion of the second porta hepatis and right hepatic artery. Six treatment cycles with a gemcitabine and oxaliplatin (GEMOX) regimen combined with camrelizumab immunotherapy achieved a partial response and successful tumor conversion, as tumor invasion of the second porta hepatis and right hepatic artery was no longer evident. The patient subsequently underwent successful radical surgical resection, including hepatectomy, caudate lobe resection, and cholecystectomy combined with lymph node dissection. Cases of patients with advanced ICC undergoing surgical resection after combined immunotherapy and chemotherapy are rare. The GEMOX regimen combined with camrelizumab demonstrated favorable antitumor efficacy and safety, suggesting that it might be a potential feasible and safe conversion therapy strategy for patients with advanced ICC.
Revealing the role of regulatory T cells in the tumor microenvironment of lung adenocarcinoma: a novel prognostic and immunotherapeutic signature
Authors: Zhang Pengpeng , Zhang Xiao , Cui Yanan , Gong Zetian , Wang Wei , Lin Shengrong
Published: August 2023

Background

Regulatory T cells (Tregs), are a key class of cell types in the immune system. In the tumor microenvironment (TME), the presence of Tregs has important implications for immune response and tumor development. Relatively little is known about the role of Tregs in lung adenocarcinoma (LUAD).

Methods

Tregs were identified using but single-cell RNA sequencing (scRNA-seq) analysis and interactions between Tregs and other cells in the TME were investigated. Next, we used multiple bulk RNA-seq datasets to construct risk models based on marker genes of Tregs and explored differences in prognosis, mutational landscape, immune cell infiltration and immunotherapy between high- and low-risk groups, and finally, qRT-PCR and cell function experiments were performed to validate the model genes.

Results

The cellchat analysis showed that MIF-(CD74+CXCR4) pairs play a key role in the interaction of Tregs with other cell subpopulations, and the Tregs-associated signatures (TRAS) could well classify multiple LUAD cohorts into high- and low-risk groups. Immunotherapy may offer greater potential benefits to the low-risk group, as indicated by their superior survival, increased infiltration of immune cells, and heightened expression of immune checkpoints. Finally, the experiment verified that the model genes LTB and PTTG1 were relatively highly expressed in cancer tissues, while PTPRC was relatively highly expressed in paracancerous tissues. Colony Formation assay confirmed that knockdown of PTTG1 reduced the proliferation ability of LUAD cells

Conclusion

TRAS were constructed using scRNA-seq and bulk RNA-seq to distinguish patient risk subgroups, which may provide assistance in the clinical management of LUAD patients.
Controlling viral inflammatory lesions by rebalancing immune response patterns
Authors: Mulik Sachin , Berber Engin , Sehrawat Sharvan , Rouse Barry Tyrrell
Published: August 2023

In this review, we discuss a variety of immune modulating approaches that could be used to counteract tissue-damaging viral immunoinflammatory lesions which typify many chronic viral infections. We make the point that in several viral infections the lesions can be largely the result of one or more aspects of the host response mediating the cell and tissue damage rather than the virus itself being directly responsible. However, within the reactive inflammatory lesions along with the pro-inflammatory participants there are also other aspects of the host response that may be acting to constrain the activity of the damaging components and are contributing to resolution. This scenario should provide the prospect of rebalancing the contributions of different host responses and hence diminish or even fully control the virus-induced lesions. We identify several aspects of the host reactions that influence the pattern of immune responsiveness and describe approaches that have been used successfully, mainly in model systems, to modulate the activity of damaging participants and which has led to lesion control. We emphasize examples where such therapies are, or could be, translated for practical use in the clinic to control inflammatory lesions caused by viral infections.
Review of algorithms estimating export production from satellite derived properties
Authors: Jönsson Bror F. , Kulk Gemma , Sathyendranath Shubha
Published: August 2023

Whereas the vertical transport of biomass from productive surface waters to the deep ocean (the biological pump) is a critical component of the global carbon cycle, its magnitude and variability is poorly understood. Global-scale estimates of ocean carbon export vary widely, ranging from ∼5 to ∼20 Gt C y – 1 due to uncertainties in methods and unclear definitions. Satellite-derived properties such as phytoplankton biomass, sea surface temperature, and light attenuation at depth provide information about the oceanic ecosystem with unprecedented coverage and resolution in time and space. These products have been the basis of an intense effort over several decades to constrain different biogeochemical production rates and fluxes in the ocean. One critical challenge in this effort has been to estimate the magnitude of the biological pump from satellite-derived properties by establishing how much of the primary production is exported out of the euphotic zone, a flux that is called export production. Here we present a review of existing algorithms for estimating export production from satellite-derived properties, available in-situ datasets that can be used for testing the algorithms, and earlier evaluations of the proposed algorithms. The satellite-derived products used in the algorithm evaluation are all based largely on the Ocean Colour Climate Change Initiative (OC-CCI) products, and carbon products derived from them. The different resources are combined in a meta-analysis.
Uncertainties in wave-driven longshore sediment transport projections presented by a dynamic CMIP6-based ensemble
Authors: Zarifsanayei Amin Reza , Antolínez José A. A. , Cartwright Nick , Etemad-Shahidi Amir , Strauss Darrell , Lemos Gil , Semedo Alvaro , Kumar Rajesh , Dobrynin Mikhail , Akpinar Adem
Published: August 2023

In this study four experiments were conducted to investigate uncertainty in future longshore sediment transport (LST) projections due to: working with continuous time series of CSIRO CMIP6-driven waves (experiment #1) or sliced time series of waves from CSIRO-CMIP6-Ws and CSIRO-CMIP5-Ws (experiment #2); different wave-model-parametrization pairs to generate wave projections (experiment #3); and the inclusion/exclusion of sea level rise (SLR) for wave transformation (experiment #4). For each experiment, a weighted ensemble consisting of offshore wave forcing conditions, a surrogate model for nearshore wave transformation and eight LST models was used. The results of experiment # 1 indicated that the annual LST rates obtained from a continuous time series of waves were influenced by climate variability acting on timescales of 20-30 years. Uncertainty decomposition clearly reveals that for near-future coastal planning, a large part of the uncertainty arises from model selection and natural variability of the system (e.g., on average, 4% scenario, 57% model, and 39% internal variability). For the far future, the total uncertainty consists of 25% scenario, 54% model and 21% internal variability. Experiment #2 indicates that CMIP6 driven wave climatology yield similar outcomes to CMIP5 driven wave climatology in that LST rates decrease along the study area’s coast by less than 10%. The results of experiment #3 indicate that intra- and inter-annual variability of LST rates are influenced by the parameterization schemes of the wave simulations. This can increase the range of uncertainty in the LST projections and at the same time can limit the robustness of the projections. The inclusion of SLR (experiment #4) in wave transformation, under SSP1-2.6 and SSP5-8.5 scenarios, yields only meagre changes in the LST projections, compared to the case no SLR. However, it is noted that future research on SLR influence should include potential changes in nearshore profile shapes.
Progressive high-fluence epithelium-on accelerated corneal crosslinking: a novel corneal photodynamic therapy for early progressive keratoconus
Authors: Mazzotta Cosimo , Pandolfi Anna , Ferrise Marco
Published: August 2023

Purpose

To assess the preliminary clinical results of a new, progressively higher fluence-pulsed light Epi-On accelerated crosslinking nomogram (PFPL M Epi-On ACXL) in the treatment of progressive keratoconus (KC).

Setting

Siena Crosslinking Center, Siena, Italy.

Methods

A prospective pilot open, non-randomized interventional study, including 32 eyes of 32 young-adult patients over 26 years old with Stages I-III progressive KC undergoing PFPL M Epi-On ACXL, was conducted. Riboflavin loading was performed by using Paracel I 0.25% for 4 min and Paracel II 0.22% for 6 min. The Avedro KXL System (Glaukos-Avedro, Burlington, USA) was used for pulsed-light accelerated crosslinking (ACXL) at air room 21% oxygenation and 13 min of UV-A irradiation. The treatment fluence was set at 7.2 J/cm2, 8.6 J/cm2, and 10.0 J/cm2 in corneas with baseline pachymetry <420 μm (group 1: 8 eyes), ≥ 420 μm <460 μm (group 2, 11 eyes), and ≥ 460 μm (group 3, 13 eyes), respectively. Uncorrected distance visual acuity (UDVA), best-spectacle corrected visual acuity (BSCVA), Scheimpflug corneal tomography, and anterior segment OCT (AS-OCT) data were collected at baseline and postoperatively at 1, 3, and 6 months.

Results

UDVA and BSCVA improved in all groups (P ≤ 0.05). Maximum keratometry values (K max) showed a significant decrease in the 10.0 J/cm2 group (Δ −1.68 D). The coma (HOAs) value improved significantly by the sixth month in all groups. OCT average demarcation lines were 211 ± 19 μm in group 1, 245 ± 23 μm in group 2, and 267 ± 21 μm in group 3.

Conclusions

The preliminary results show that pachymetry-based PFPL M Epi-On ACXL nomogram stabilizes ectasia progression. Higher fluence Epi-On ACXL increases CXL penetration, with better functional outcomes in the absence of complications.
The role of the gut microbiome and microbial metabolism in mediating opioid-induced changes in the epigenome
Authors: Kolli Udhghatri , Roy Sabita
Published: August 2023

The current opioid pandemic is a major public health crisis in the United States, affecting millions of people and imposing significant health and socioeconomic burdens. Preclinical and clinical research over the past few decades has delineated certain molecular mechanisms and identified various genetic, epigenetic, and environmental factors responsible for the pathophysiology and comorbidities associated with opioid use. Opioid use-induced epigenetic modifications have been identified as one of the important factors that mediate genetic changes in brain regions that control reward and drug-seeking behavior and are also implicated in the development of tolerance. Recently, it has been shown that opioid use results in microbial dysbiosis, leading to gut barrier disruption, which drives systemic inflammation, impacting the perception of pain, the development of analgesic tolerance, and behavioral outcomes. In this review, we highlight the potential role of microbiota and microbial metabolites in mediating the epigenetic modifications induced by opioid use.
Identification and distribution of new candidate T6SS effectors encoded in Salmonella Pathogenicity Island 6
Authors: Blondel Carlos J. , Amaya Fernando A. , Bustamante Paloma , Santiviago Carlos A. , Pezoa David
Published: August 2023

The type VI secretion system (T6SS) is a contact-dependent contractile multiprotein apparatus widely distributed in Gram-negative bacteria. These systems can deliver different effector proteins into target bacterial and/or eukaryotic cells, contributing to the environmental fitness and virulence of many bacterial pathogens. Salmonella harbors five different T6SSs encoded in different genomic islands. The T6SS encoded in Salmonella Pathogenicity Island 6 (SPI-6) contributes to Salmonella competition with the host microbiota and its interaction with infected host cells. Despite its relevance, information regarding the total number of effector proteins encoded within SPI-6 and its distribution among different Salmonella enterica serotypes is limited. In this work, we performed bioinformatic and comparative genomics analyses of the SPI-6 T6SS gene cluster to expand our knowledge regarding the T6SS effector repertoire and the global distribution of these effectors in Salmonella. The analysis of a curated dataset of 60 Salmonella enterica genomes from the Secret6 database revealed the presence of 23 new putative T6SS effector/immunity protein (E/I) modules. These effectors were concentrated in the variable regions 1 to 3 (VR1-3) of the SPI-6 T6SS gene cluster. VR1-2 were enriched in candidate effectors with predicted peptidoglycan hydrolase activity, while VR3 was enriched in candidate effectors of the Rhs family with C-terminal extensions with predicted DNase, RNase, deaminase, or ADP-ribosyltransferase activity. A global analysis of known and candidate effector proteins in Salmonella enterica genomes from the NCBI database revealed that T6SS effector proteins are differentially distributed among Salmonella serotypes. While some effectors are present in over 200 serotypes, others are found in less than a dozen. A hierarchical clustering analysis identified Salmonella serotypes with distinct profiles of T6SS effectors and candidate effectors, highlighting the diversity of T6SS effector repertoires in Salmonella enterica. The existence of different repertoires of effector proteins suggests that different effector protein combinations may have a differential impact on the environmental fitness and pathogenic potential of these strains.
Novel chlorinated and nitrogenated azaphilones with cytotoxic activities from the marine algal-derived fungus Chaetomium globosum 2020HZ23
Authors: Gao Zhong-Jie , Cao Lu-Lu , Ren Hai-Ping , Yu Hua , Wang Yan
Published: August 2023

Two novel chlorinated and nitrogenated azaphilones, namely N-butyl-2-aza-2-deoxychaetoviridin A (1) and N-hexyl-2-aza-2-deoxychaetoviridin A (2), along with a previously identified analogue, chaetoviridin A (3), were successfully obtained from Chaetomium globosum 2020HZ23, a marine algal-sourced endophytic fungus. The planar structures as well as the absolute configurations of these new metabolites were determined utilizing a synergistic approach that involved both spectroscopic techniques (1D/2D NMR and HRESIMS) and Density Functional Theory (DFT) calculations. Each compound was subject to in vitro cytotoxicity evaluation toward the A549 cancer cell line. Both compounds 1 and 2 demonstrated significant cytotoxicity, as evidenced by their respective IC50 values of 13.6 and 17.5 μM. Furthermore, 1 and 2 demonstrated potent cell migration inhibition, which elevated with increasing dose concentration. In contrast, compound 3 exhibited less cytotoxic activity relative to 1 and 2, suggesting that the cytotoxic potency escalates with N-substitution at the C-2 position and the introduction of a side chain. This finding could offer implications for future studies aimed at designing and refining lead compounds within this class.
Effective TME-related signature to predict prognosis of patients with head and neck squamous cell carcinoma
Authors: Wan Lingfei , Li Yuanshuai , Pan Wenting , Yong Yuting , Yang Chao , Li Chen , Zhao Xingxing , Li Ruihong , Yue Wen , Yan Xinlong
Published: August 2023

Introduction: The tumor microenvironment (TME) is crucial for the development of head and neck squamous cell carcinoma (HNSCC). However, the correlation of the characteristics of the TME and the prognosis of patients with HNSCC remains less known.

Methods: In this study, we calculated the immune and stromal cell scores using the “estimate” R package. Kaplan-Meier survival and CIBERSORT algorithm analyses were applied in this study.

Results: We identified seven new markers: FCGR3B, IGHV3-64, AC023449.2, IGKV1D-8, FCGR2A, WDFY4, and HBQ1. Subsequently, a risk model was constructed and all HNSCC samples were grouped into low- and high-risk groups. The results of both the Kaplan-Meier survival and receiver operating characteristic curve (ROC) analyses showed that the prognosis indicated by the model was accurate (0.758, 0.756, and 0.666 for 1-, 3- and 5-year survival rates). In addition, we applied the CIBERSORT algorithm to reveal the significant differences in the infiltration levels of immune cells between the two risk groups.

Discussion: Our study elucidated the roles of the TME and identified new prognostic biomarkers for patients with HNSCC.
Impact of a pyridazine derivative on tripartite synapse ultrastructure in hippocampus: a three-dimensional analysis
Authors: Xu Zan , Foster Joshua B. , Lashley Rashelle , Wang Xueqin , Benson Emily , Kidd Grahame , Lin Chien-liang Glenn
Published: August 2023

Introduction

We previously discovered a pyridazine derivative compound series that can improve cognitive functions in mouse models of Alzheimer’s disease. One of the advanced compounds from this series, LDN/OSU-0215111-M3, was selected as the preclinical development candidate. This compound activates local protein translation at the perisynaptic astrocytic process (PAP) and enhances synaptic plasticity sequentially. While biochemical evidence supports the hypothesis that the compound enhances the structural plasticity of the tripartite synapse, its direct structural impact has not been investigated.

Methods

Volume electron microscopy was used to study the hippocampal tripartite synapse three-dimensional structure in 3-month-old wild-type FVB/NJ mice after LDN/OSU-0215111-M3 treatment.

Results

LDN/OSU-0215111-M3 increased the size of tertiary apical dendrites, the volume of mushroom spines, the proportion of mushroom spines containing spine apparatus, and alterations in the spine distribution across the surface area of tertiary dendrites. Compound also increased the number of the PAP interacting with the mushroom spines as well as the size of the PAP in contact with the spines. Furthermore, proteomic analysis of the isolated synaptic terminals indicated an increase in dendritic and synaptic proteins as well as suggested a possible involvement of the phospholipase D signaling pathway. To further validate that LDN/OSU-0215111-M3 altered synaptic function, electrophysiological studies showed increased long-term potentiation following compound treatment.

Discussion

This study provides direct evidence that pyridazine derivatives enhance the structural and functional plasticity of the tripartite synapse.
Which headache disorders can be diagnosed concurrently? An analysis of ICHD3 criteria using prime encoding system
Authors: Zhang Pengfei
Published: August 2023

Introduction

Real-life headache presentations may fit more than one ICHD3 diagnosis. This project seeks to exhaustively list all logically consistent “co-diagnoses” according to the ICHD3 criteria. We limited our project to cases of two concurrent diagnoses.

Methods

We included the criteria for “Migraine” (1.1, 1.2, 1.3), “Tension-type headache” (2.1, 2.2, 2.3, 2.4), “Trigeminal autonomic cephalalgias” (3.1, 3.2, 3.3, 3.4, 3.5), and “Other primary headache disorders.” We also excluded “probable” diagnosis criteria. Each characteristic in the above criteria is assigned a unique prime number. We then encoded each ICHD3 criteria into integers through multiplication in a list format; we called these criteria representations. “Codiagnoses representations” were generated by multiplying all possible pairings of criteria representations. We then manually encoded a list of logically inconsistent characteristics through multiplication. All co-diagnoses representations divisible by any inconsistency representations were filtered out, generating a list of co-diagnoses representations that were logically consistent. This list was then translated back into ICHD3 diagnoses.

Results

We used a total of 103 prime numbers to encode 578 ICHD3 criteria. Once illogical characteristics were excluded, we obtained 145 dual diagnoses. Of the dual diagnoses, two contained intersecting characteristics due to subset relationships, 14 contained intersecting characteristics without subset relationships, and 129 contained dual diagnoses as a result of non-intersecting characteristics.

Conclusion

Analysis of dual diagnosis in headaches offers insight into “loopholes” in the ICHD3 as well as a potential explanation for the source of a number of controversies regarding headache disorders. The existence of dual diagnoses and their identification may carry implications for future developments and testing of machine-learning diagnostic algorithms for headaches.
The clinical predictive value of geriatric nutritional risk index in elderly rectal cancer patients received surgical treatment after neoadjuvant therapy
Authors: Zhang Lei , Hu Chenhao , Li Ruizhe , Zhang Zhe , Wang Ya , Zhao Jiamian , Liu Ruihan , Li Zhenghui , She Junjun , Shi Feiyu
Published: August 2023

Objective

The assessment of nutritional status has been recognized as crucial in the treatment of geriatric cancer patients. The objective of this study is to determine the clinical predictive value of the geriatric nutritional risk index (GNRI) in predicting the short-term and long-term prognosis of elderly rectal cancer (RC) patients who undergo surgical treatment after neoadjuvant therapy.

Methods

Between January 2014 and December 2020, the clinical materials of 639 RC patients aged ≥70 years who underwent surgical treatment after neoadjuvant therapy were retrospectively analysed. Propensity score matching was performed to adjust for baseline potential confounders. Logistic regression analysis and competing risk analysis were conducted to evaluate the correlation between the GNRI and the risk of postoperative major complications and cumulative incidence of cancer-specific survival (CSS). Nomograms were then constructed for postoperative major complications and CSS. Additionally, 203 elderly RC patients were enrolled between January 2021 and December 2022 as an external validation cohort.

Results

Multivariate logistic regression analysis showed that GNRI [odds ratio = 1.903, 95% confidence intervals (CI): 1.120–3.233, p = 0.017] was an independent risk factor for postoperative major complications. In competing risk analysis, the GNRI was also identified as an independent prognostic factor for CSS (subdistribution hazard ratio = 3.90, 95% CI: 2.46–6.19, p < 0.001). The postoperative major complication nomogram showed excellent performance internally and externally in the area under the receiver operating characteristic curve (AUC), calibration plots and decision curve analysis (DCA). When compared with other models, the competing risk prognosis nomogram incorporating the GNRI achieved the highest outcomes in terms of the C-index, AUC, calibration plots, and DCA.

Conclusion

The GNRI is a simple and effective tool for predicting the risk of postoperative major complications and the long-term prognosis of elderly RC patients who undergo surgical treatment after neoadjuvant therapy.
COVID−19 hospitalization increases the risk of developing glioblastoma: a bidirectional Mendelian-randomization study
Authors: Dong Jiajun , Wang Shengnan , Xie Haoqun , Mou Yanhao , Zhu Hao , Peng Yilong , Xi Jianxin , Zhong Minggu , Xie Zhengyuan , Jiang Zongyuan , Wang Kang , Chen Hongyu , Yang Wenzhuo , Zhu Mingqin , Wen Yufeng , Wu Yi
Published: August 2023

Background

As a result of the COVID-19 pandemic, patients with glioblastoma (GBM) are considered a highly vulnerable population. Despite this, the extent of the causative relationship between GBM and COVID-19 infection is uncertain.

Methods

Genetic instruments for SARS-CoV-2 infection (38,984 cases and 1,644,784 control individuals), COVID-19 hospitalization (8,316 cases and 1,549,095 control individuals), and COVID-19 severity (4,792 cases and 1,054,664 control individuals) were obtained from a genome-wide association study (GWAS) from European populations. A total of 6,183 GBM cases and 18,169 controls from GWAS were enrolled in our study. Their associations were evaluated by applying Mendelian randomization (MR) including IVW meta-analysis, MR-Egger regression, and weighted-median analysis. To make the conclusions more robust and reliable, sensitivity analyses were performed.

Results

Our results showed that genetically predicted COVID−19 hospitalization increases the risk of GBM (OR = 1.202, 95% CI = 1.035–1.395, p = 0.016). In addition, no increased risk of SARS-CoV-2 infection, COVID-19 hospitalization and severity were observed in patients with any type of genetically predicted GBM.

Conclusion

Our MR study indicated for the first time that genetically predicted COVID−19 hospitalization was demonstrated as a risk factor for the development of GBM.
Stromal-epithelial interaction induces GALNT14 in prostate carcinoma cells
Authors: Czyrnik Elena D. , Wiesehöfer Marc , Dankert Jaroslaw T. , Wach Sven , Wagner Mathias , Spahn Martin , Kruithof de Julio Marianna , Wennemuth Gunther
Published: August 2023

Introduction

Cell-cell communication is an important process in healthy tissue but also gains enhanced attention regarding pathological tissue. To date, the tumor microenvironment is gradually brought into focus when studying tumorigenesis. In the prostate gland, stromal and epithelial cells greatly interact to maintain homeostasis or tissue integrity. This study focuses on an indirect communication via soluble factors.

Methods

To investigate the cell-cell interaction via soluble factors, the prostate carcinoma cell line LNCaP and the stromal primary cells p21 were co-cultured without direct contact and RNA was isolated at defined time points. Differences in gene expression were finally analyzed by RNA sequencing.

Results

RNA sequencing revealed a time-depending differential expression profile. Selected factors were subsequently characterized at molecular level and analyzed in human prostate tissue of different developmental stages as well as pathology. GALNT14 was one of the highest induced co-culture-specific genes in LNCaP cells. Detection in healthy tissue and BPH revealed an age-dependent decrease in GALNT14 expression. Moreover, in prostate carcinoma, GALNT14 expression heavily varied independent of the Gleason score.

Conclusion

Overall, this work provides a basis for further studies related to paracrine stromal-epithelial interaction in prostate carcinoma and highlights the importance of GALNT14.
Visceral obesity and anastomotic leakage rates in colorectal cancer: a systematic review and meta-analysis
Authors: Yu Linchong , Wu Wenjiang , Xia Shijun , Li Yue , Xu Zhigang
Published: August 2023

Background

Numberous studies have heatedly discussed whether obesity is a risk factor for anastomotic leakage (AL) because of the increasing number of colorectal cancer (CRC) cases and high incidence of CRC in patients with obesity.

Objective

We aimed to explore the relationship between visceral obesity(VO) and AL after CRC surgery. The databases of Pubmed, Embase, and the Cochrane Library were searched for relevant data and articles published until November 1, 2022. We identified the difference in the incidence of AL after CRC surgery between patients with and without VO. The quality of included studies was evaluated using the Newcastle- Ottawa Scale, and odds ratio (OR) and 95% CI were used to assess the association between VO and AL.

Results

This meta-analysis included 7 studies with 2,136 patients. The OR of patients with VO versus those without VO was 2.15 (95%CIs = 1.46–3.15, test for heterogeneity: P = 0.29, I2 = 18%) based on the fixed-effect model in seven studies. Notably, the difference between the two groups was statistically significant (Z = 3.91 P < 0.0001). Patients with VO in the colon cancer group exhibited a higher incidence of AL (OR = 2.88, 95% CIs = 1.38–5.99, test for heterogeneity: P = 0.27, I2 = 20%) than those in the rectal cancer group (OR = 2.74, 95% CIs = 1.13–6.65, test for heterogeneity: P = 0.20, I2 = 38%). In the studies in the relevant literature, heterogeneity was low. Regarding patients with VO, four Asian studies reported increased morbidity due to AL (OR = 2.79, 95% CIs = 1.35–5.78, test for heterogeneity: P = 0.35, I2 = 9%) compared with three non-Asian studies.

Conclusions

Our findings confirmed the significant relationship between VO and AL. Thus, VO could be considered a reliable risk factor of surgery for colon cancer.
Identifying central symptom clusters and correlates in children with acute leukemia undergoing chemotherapy: a network analysis
Authors: Fang Jia , Wong Cho-Lee , Liu Chun-Qin , Huang Hai-Ying , Qi Yi-Shu , Xu Li-Ling , Wang Mei-Xiang , Lin Yan
Published: August 2023

Background

Previous studies have examined symptom clusters in children with acute leukemia, yet a knowledge gap persists regarding central symptom clusters and their influencing factors. By identifying these central clusters and associated factors, healthcare providers can enhance their understanding and effective management of symptoms. Our study seeks to address this gap by identifying symptom clusters, exploring central clusters, and investigating the demographic and health-related factors associated with these clusters in children with acute leukemia undergoing chemotherapy.

Methods

A total of 586 children with acute leukemia from January 2021 to April 2023 were recruited from China. They were investigated using Memorial Symptom Assessment Scale 10-18 during chemotherapy. The principal component analysis was used to identify the symptom clusters. An association network was conducted to describe the relationships among symptoms and clusters. A multiple linear model was used to investigate the associated factors for the severity of overall symptoms and each symptom cluster.

Results

Five clusters were identified, including oral and skin cluster, somatic cluster, self-image disorder cluster, gastrointestinal cluster and psychological cluster. Gastrointestinal cluster was the most central symptom cluster. Age, sex, clinical classification, number of having chemotherapy and education degree and marital status of the primary caregiver are associated with the severity of these five symptom clusters.

Conclusion

Our study highlights the importance of evaluating symptom clusters in children with acute leukemia during chemotherapy. Specifically, addressing gastrointestinal symptoms is crucial for effective symptom management and overall care.
Bryum billardieri Schwaegr. against EV71 infection: in vitro and in vivo antiviral effects, identification of molecular mechanisms and active monomers
Authors: Wang Yun-Yu , Li Qian , Han Xiu-Wei , Wan Xin-Huan , Zhang Li , Niu Feng-Jv , Xin Yi-Zhou , Zhou Chang-Zheng
Published: August 2023

Graphical Abstract
Exploring the natural products chemical space through a molecular search to discover potential inhibitors that target the hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD)
Authors: Sayaf Abrar Mohammad , Ullah Khalid Saif , Hameed Jawad Ahmed , Alshammari Abdulrahman , Khan Abbas , Mohammad Anwar , Alghamdi Saeed , Wei Dong-Qing , Yeoh KarKheng
Published: August 2023

Introduction: Hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD) enzymes are major therapeutic targets of anemia and ischemic/hypoxia diseases. To overcome safety issues, liver failure, and problems associated with on-/off-targets, natural products due to their novel and unique structures offer promising alternatives as drug targets.

Methods: In the current study, the Marine Natural Products, North African, South African, East African, and North-East African chemical space was explored for HIF-PHD inhibitors discovery through molecular search, and the final hits were validated using molecular simulation and free energy calculation approaches.

Results: Our results revealed that CMNPD13808 with a docking score of −8.690 kcal/mol, CID15081178 with a docking score of −8.027 kcal/mol, CID71496944 with a docking score of −8.48 kcal/mol and CID11821407 with a docking score of −7.78 kcal/mol possess stronger activity than the control N-[(4-hydroxy-8-iodoisoquinolin-3-yl)carbonyl]glycine, 4HG (−6.87 kcal/mol). Interaction analysis revealed that the target compounds interact with Gln239, Tyr310, Tyr329, Arg383 and Trp389 residues, and chelate the active site iron in a bidentate manner in PHD2. Molecular simulation revealed that these target hits robustly block the PHD2 active site by demonstrating stable dynamics. Furthermore, the half-life of the Arg383 hydrogen bond with the target ligands, which is an important factor for PHD2 inhibition, remained almost constant in all the complexes during the simulation. Finally, the total binding free energy of each complex was calculated as CMNPD13808-PHD2 −72.91 kcal/mol, CID15081178-PHD2 −65.55 kcal/mol, CID71496944-PHD2 −68.47 kcal/mol, and CID11821407-PHD2 −62.06 kcal/mol, respectively.

Conclusion: The results show the compounds possess good activity in contrast to the control drug (4HG) and need further in vitro and in vivo validation for possible usage as potential drugs against HIF-PHD2-associated diseases.
Efficacy and safety of ciprofol for long-term sedation in patients receiving mechanical ventilation in ICUs: a prospective, single-center, double-blind, randomized controlled protocol
Authors: Sun Xiaoxiao , Zhang Meixian , Zhang Hui , Fei Xuejie , Bai Gang , Li Cheng
Published: August 2023

Introduction: Critically ill patients who receive mechanical ventilation after endotracheal intubation commonly experience discomfort and pressure. The major sedative drugs that are currently used in clinical practice present with many complications, such as hypotension, bradycardia, and respiratory depression. Ciprofol (HSK3486), which is a newly developed structural analog of propofol, is a short-acting gamma-aminobutyric acid (GABA) receptor agonist, and its mechanism of action is sedation or anesthesia by enhancing GABA-mediated chloride influx. The high efficacy of ciprofol for short-term sedation is comparable to that of propofol, and it has a relatively low incidence of adverse effects and high level of safety, which has been confirmed by multiple clinical studies. However, few studies have examined its safety and efficacy for long-term sedation. The purpose of the study is to evaluate the efficacy and safety of ciprofol for long-term sedation in mechanically ventilated patients.

Methods: A prospective, single-center, double-blind, randomized, propofol-controlled, non-inferiority trial is proposed. The study will enroll 112 mechanically ventilated patients hospitalized in the intensive care unit (ICU) of the Shanghai Fourth People’s Hospital affiliated with Tongji University based on the inclusion and exclusion criteria of the study, and randomly assign them to a group sedated with either ciprofol or propofol. The primary outcome is the percentage of time spent under target sedation, and secondary outcomes include drug dose, number of cases requiring additional dextrometropine, incidence of systolic blood pressure <80 or >180 mmHg, incidence of diastolic blood pressure <50 or >100 mmHg, incidence of heart rate <50 beats per minute (bpm) or >120 bpm, inflammatory indicators, blood lipid levels, liver and kidney functions, nutritional indicators, ventilator-free days within the 7-day period after enrollment, 28-day mortality, ICU stay duration, and hospitalization costs.

Discussion: We hypothesize that the efficacy and safety of ciprofol for long-term sedation in mechanically ventilated ICU patients will not be inferior to that of propofol.

Trial registration: Chinese Clinical Trials Registry identifier ChiCTR2200066951.
The teleost fish PepT1-type peptide transporters and their relationships with neutral and charged substrates
Authors: Vacca Francesca , Gomes Ana S. , De Gennaro Marco , Rønnestad Ivar , Bossi Elena , Verri Tiziano
Published: August 2023

In teleosts, two PepT1-type (Slc15a1) transporters, i.e., PepT1a and PepT1b, are expressed at the intestinal level. They translocate charged di/tripeptides with different efficiency, which depends on the position of the charged amino acid in the peptide and the external pH. The relation between the position of the charged amino acid and the capability of transporting the dipeptide was investigated in the zebrafish and Atlantic salmon PepT1-type transporters. Using selected charged (at physiological pH) dipeptides: i.e., the negatively charged Asp-Gly and Gly-Asp, and the positively charged Lys-Gly and Gly-Lys and Lys-Met and Met-Lys, transport currents and kinetic parameters were collected. The neutral dipeptide Gly-Gln was used as a reference substrate. Atlantic salmon PepT1a and PepT1b transport currents were similar in the presence of Asp-Gly and Gly-Asp, while zebrafish PepT1a elicited currents strongly dependent on the position of Asp in the dipeptide and zebrafish PepT1b elicited small transport currents. For Lys- and Met-containing dipeptides smaller currents compared to Gly-Gln were observed in PepT1a-type transporters. In general, for zebrafish PepT1a the currents elicited by all tested substrates slightly increased with membrane potential and pH. For Atlantic salmon PepT1a, the transport current increased with negative potential but only in the presence of Met-containing dipeptides and in a pH-dependent way. Conversely, large currents were shown for PepT1b for all tested substrates but Gly-Lys in Atlantic salmon. This shows that in Atlantic salmon PepT1b for Lys-containing substrates the position of the charged dipeptides carrying the Lys residue defines the current amplitudes, with larger currents observed for Lys in the N-terminal position. Our results add information on the ability of PepT1 to transport charged amino acids and show species-specificity in the kinetic behavior of PepT1-type proteins. They also suggest the importance of the proximity of the substrate binding site of residues such as LysPepT1a/GlnPepT1b for recognition and specificity of the charged dipeptide and point out the role of the comparative approach that exploits the natural protein variants to understand the structure and functions of membrane transporters.
Fast screening of total nutrient contents in strawberry leaves and spent growing media using NIRS
Authors: Vandecasteele Bart , Van Waes Chris
Published: August 2023

Introduction

In closed-loop soilless cultivation, the main nutrient sinks are nutrients retained either by the crop or in spent growing media. Measurement of nutrients in spent growing media and in the aboveground vegetative plant biomass at crop termination can be a tool for assessing and optimizing nutrient efficiency. The first aim of this study was to test the potential of near-infrared reflectance spectroscopy (NIRS) to forecast the various nutrient contents in strawberry leaves, which would then allow for assessment of crop nutrient status and total nutrient uptake by strawberry plants. The second aim was to test NIRS as a high throughput technique for assessing the N, K, Ca, Mg and organic matter (OM) content and the pH, EC and C:N and C:P ratios for a dataset of composts, plant fibers and spent growing media. The NIRS prediction model for fast screening of the total nutrient contents in spent growing media was compared with a single extraction method.

Methods

A database with 369 dried and ground strawberry leaf samples with known contents of N, P, K, Ca, and Mg were scanned using NIRS. The database covered a range of leaf contents of 6-35 g N/kg dry matter (DM), 0.7-6.3 g P/kg DM and 2-29 g K/kg DM. A dataset of 458 samples of different types of materials used in growing media was validated with a dataset of 109 samples.

Results

Validation for the strawberry leaves indicated potential for this application, with R2 values of 0.90 or higher for N, K and Ca, and R2 values higher than 0.85 for P and Mg. Validation for the dataset of composts, plant fibers and spent growing media also indicated the potential for this application, with R2 values of 0.90 or higher for organic matter, and with R2 values of 0.85 or higher for total Ca, pH and C:N. A first test indicated potential for the calibration based on fresh samples of compost, plant fiber as well as spent growing media or dried (not ground) samples.

Discussion

Use of NIRS on fresh samples would eliminate the need for drying and grinding the samples and would reduce screening time. The ammonium acetate extraction is a reliable alternative to NIRS for fast screening of the total P, K, Ca, and Mg contents in composts, plant fibers and spent growing media.
Genome-wide analysis of cold imbibition stress in soybean, Glycine max
Authors: Haidar Siwar , Lackey Simon , Charette Martin , Yoosefzadeh-Najafabadi Mohsen , Gahagan A. Claire , Hotte Thomas , Belzile Francois , Rajcan Istvan , Golshani Ashkan , Morrison Malcolm J. , Cober Elroy R. , Samanfar Bahram
Published: August 2023

In Canada, the length of the frost-free season necessitates planting crops as early as possible to ensure that the plants have enough time to reach full maturity before they are harvested. Early planting carries inherent risks of cold water imbibition (specifically less than 4°C) affecting seed germination. A marker dataset developed for a previously identified Canadian soybean GWAS panel was leveraged to investigate the effect of cold water imbibition on germination. Seed from a panel of 137 soybean elite cultivars, grown in the field at Ottawa, ON, over three years, were placed on filter paper in petri dishes and allowed to imbibe water for 16 hours at either 4°C or 20°C prior to being transferred to a constant 20°C. Observations on seed germination, defined as the presence of a 1 cm radicle, were done from day two to seven. A three-parameter exponential rise to a maximum equation (3PERM) was fitted to estimate germination, time to the one-half maximum germination, and germination uniformity for each cultivar. Genotype-by-sequencing was used to identify SNPs in 137 soybean lines, and using genome-wide association studies (GWAS - rMVP R package, with GLM, MLM, and FarmCPU as methods), haplotype block analysis, and assumed linkage blocks of ±100 kbp, a threshold for significance was established using the qvalue package in R, and five significant SNPs were identified on chromosomes 1, 3, 4, 6, and 13 for maximum germination after cold water imbibition. Percent of phenotypic variance explained (PVE) and allele substitution effect (ASE) eliminated two of the five candidate SNPs, leaving three QTL regions on chromosomes 3, 6, and 13 (Chr3-3419152, Chr6-5098454, and Chr13-29649544). Based on the gene ontology (GO) enrichment analysis, 14 candidate genes whose function is predicted to include germination and cold tolerance related pathways were identified as candidate genes. The identified QTLs can be used to select future soybean cultivars tolerant to cold water imbibition and mitigate risks associated with early soybean planting.
Simultaneous editing of two DMR6 genes in grapevine results in reduced susceptibility to downy mildew
Authors: Giacomelli Lisa , Zeilmaker Tieme , Giovannini Oscar , Salvagnin Umberto , Masuero Domenico , Franceschi Pietro , Vrhovsek Urska , Scintilla Simone , Rouppe van der Voort Jeroen , Moser Claudio
Published: August 2023

The reduction of pesticide treatments is of paramount importance for the sustainability of viticulture, and it can be achieved through a combination of strategies, including the cultivation of vines (Vitis vinifera) that are resistant or tolerant to diseases such as downy mildew (DM). In many crops, the knock-out of Downy Mildew Resistant 6 (DMR6) proved successful in controlling DM-resistance, but the effect of mutations in DMR6 genes is not yet known in grapevine.

Today, gene editing serves crop improvement with small and specific mutations while maintaining the genetic background of commercially important clones. Moreover, recent technological advances allowed to produce non-transgenic grapevine clones by regeneration of protoplasts edited with the CRISPR/Cas9 ribonucleoprotein. This approach may revolutionize the production of new grapevine varieties and clones, but it requires knowledge about the targets and the impact of editing on plant phenotype and fitness in different cultivars.

In this work we generated single and double knock-out mutants by editing DMR6 susceptibility (S) genes using CRISPR/Cas9, and showed that only the combined mutations in VviDMR6-1 and VviDMR6-2 are effective in reducing susceptibility to DM in two table-grape cultivars by increasing the levels of endogenous salicylic acid. Therefore, editing both genes may be necessary for effective DM control in real-world agricultural settings, which could potentially lead to unwanted phenotypes. Additional research, including trials conducted in experimental vineyards, is required to gain a deeper understanding of DMR6-based resistance.
Norwegian music students’ perceptions and experiences of challenges and resources for health
Authors: Ege Grete , Ottemöller Fungisai Puleng Gwanzura , Frisk Bente
Published: August 2023

Introduction

Music students in higher education experience health-related challenges linked to practice and performance, while an understanding of these challenges and access to resources to deal with them are required to promote the students´ health. Health literacy and health education are integral parts of health promotion and resources for health, which encompasses health-related knowledge and competence aiming to improve health. The aim of this study was to explore Norwegian music students’ perceptions and experiences of resources and challenges for health and address the following research question: What health-related challenges do music students in higher music education meet, and what health promoting resources do they need and use to deal with these challenges and promote their health?

Methods

We conducted a qualitative study including three focus group interviews with 13 music students aged between 19 and 31 years studying classical, folk, jazz or rhythmic genres from five different music departments in Norwegian universities. The Salutogenic model of health was used as theoretical framework and a few questions regarding the concept of health literacy were included in the interviews. We used thematic network analysis to analyze the data.

Results

Main health challenges were related to performance pressure and difficulties implementing good health habits in the students` daily lives. Furthermore, the findings revealed several resources that promoted the students’ health: (1) Personal resources included situational understanding, using adequate coping strategies, high motivation and participating in regular physical activity. (2) Social resources involved an understanding of the importance of social support from peers and teachers and synergy created between themselves and the audience through sharing of music. (3) Environmental resources were linked to access to good rehearsal rooms. The music students expressed a need for increased competence in health promoting routines during practice and performance and suggested that health-related topics should be an integrated part of education.