bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations of inflammatory cytokines with inflammatory bowel disease: a Mendelian randomization study
Authors: Song Zhaoxiang , Li Xiangyu , Xie Jinlin , Han Fei , Wang Nan , Hou Yuhan , Yao Jianning
Published: January 2024

Objectives

Previous studies have confirmed a link between specific inflammatory cytokines and inflammatory bowel disease (IBD), but the causal relationship between them is not completely clear. This Mendelian Randomization (MR) study aims to evaluate the causal relationship between 18 inflammatory cytokines and inflammatory bowel disease.

Method

Two-sample Mendelian randomization utilized genetic variances associated with IBD from two extensive publicly available genome-wide association studies (GWAS) (Crohn’s Disease (CD): 12,194 cases and 28,072 controls; Ulcerative Colitis (UC): 12,336 cases and 33,609 controls). The data of inflammatory cytokines was acquired from a GWAS including 8,293 healthy participants. We used inverse variance weighted method, MR-Egger, weighted median, simple model and weighted model to evaluate the causal relationship between inflammatory cytokines and IBD. Sensitivity analysis includes heterogeneity and pleiotropy analysis to evaluate the robustness of the results.

Results

The findings indicated suggestive positive associations between Interleukin-13 (IL-13) and macrophage migration inhibitory factor (MIF) with CD (odds ratio, OR: 1.101, 95%CI: 1.021-1.188, p = 0.013; OR: 1.134, 95%CI: 1.024-1.255, p = 0.015). IL-13 also displayed a significant positive correlation with UC (OR: 1.099, 95%CI: 1.018-1.186, p = 0.016). Stem cell factor (SCF) was suggested to be associated with the development of both CD and UC (OR: 1.032, 95%CI: 0.973-1.058, p = 0.012; OR: 1.038, 95%CI: 1.005-1.072, p = 0.024).

Conclusion

This study proposes that IL-13 may be a factor correlated with the etiology of IBD (CD and UC), while MIF just be specifically associated with CD. Additionally, SCF appears more likely to be involved in the downstream development of IBD (CD and UC).
MicroRNA expression profile of chicken jejunum in different time points Eimeria maxima infection
Authors: Jebessa Endashaw , Bello Semiu Folaniyi , Guo Lijin , Tuli Merga Daba , Hanotte Olivier , Nie Qinghua
Published: January 2024

Coccidiosis stands as a protozoan disease of notable economic impact, characterized by an intracellular parasite that exerts substantial influence over poultry production. This invasion disrupts the integrity of the enteric mucosa, leading to the emergence of severe lesions and diminishing the efficiency of feed utilization in chickens. MicroRNA (miRNA) are short, non-coding RNA molecules with approximately 21–24 nucleotides long in size that play essential roles in various infectious diseases and inflammatory responses. However, the miRNA’s expression patterns and roles in the context of Eimeria maxima infection of chicken intestines remain unclear. miRNA sequencing was employed to assess the miRNA expression profile in chicken jejunum during E. maxima infection. In this study, we analyzed miRNA expression profiles related to the host’s immune response in the chicken jejunum during E. maxima infection. At 4 days infection and control (J4I versus J4C), 21 differentially expressed miRNAs in the jejunum were identified, comprising 9 upregulated and 12 downregulated miRNAs. Furthermore, in the jejunum, at 7 days infection and control (J7I versus J7C) groups, a total of 35 significantly differentially expressed miRNAs were observed, with 13 upregulated and 22 downregulated miRNAs. The regulatory networks were constructed between differentially expressed miRNA and mRNAs to offer insight into the interaction mechanisms between chickens and E. maxima coccidian infection. Furthermore, within the comparison group, we obtained 946, 897, and 281 GO terms that exhibited significant enrichment associated with host immunity in the following scenarios, J4I vs. J4C, J7I vs. J7C, and J4I vs. J7I, respectively. The KEGG pathway analysis indicated notable enrichment of differentially expressed miRNAs in the jejunum, particularly in J4I vs. J4C; enriched pathways included metabolic pathways, endocytosis, MAPK signaling pathway, regulation of actin cytoskeleton, and cytokine–cytokine receptor interaction. Moreover, in J7I vs. J7C, the KEGG pathway was significantly enriched, including metabolic pathways, protein processing in the endoplasmic reticulum, ubiquitin-mediated proteolysis, and FoxO signaling pathway. A comprehensive understanding of the host genetic basis of resistance with a combination of time-dependent infection to the Eimeria parasite is crucial for pinpointing resistance biomarkers for poultry production.
Induction PD-1 inhibitor toripalimab plus chemotherapy followed by concurrent chemoradiotherapy and consolidation toripalimab for bulky locally advanced non-small-cell lung cancer: protocol for a randomized phase II trial (InTRist study)
Authors: Wang Yu , Deng Lei , Wang Jianyang , Zhang Tao , Wang Wenqing , Wang Xin , Liu Wenyang , Wu Yuqi , Lv Jima , Feng Qinfu , Zhou Zongmei , Wang Jie , Wang Luhua , Wang Zhijie , Bi Nan
Published: January 2024

Background

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape for locally advanced non-small-cell lung cancer (LA-NSCLC), whereas responses to anti-programmed cell death-1 (PD-1) or anti-programmed death-ligand 1 (PD-L1) are heterogeneous. Though consolidation ICI following concurrent chemoradiotherapy (cCRT) improves survival of NSCLC, this regimen is challenging for patients with bulky tumors due to excessive target volumes and radiation-resistant hypoxia during upfront cCRT, leading to higher risk of pneumonitis and inferior local-regional control. Recent trials have demonstrated neoadjuvant ICI brought greater benefit to stage III than stage I-II NSCLC. Our previous study also supported the therapeutic advantage of 2-cycle induction ICI for patients with bulky unresectable stage III NSCLC. In the context of induction immunotherapy, radiotherapy is more likely to exert immune synergistic effects, reverse anti-PD-1 resistance, and activate abscopal immune responses. Prospective trials to determine the efficacy and safety of induction ICI for bulky LA-NSCLC are necessary.

Methods

This randomized, open-label, two-arm phase II study aims to explore whether 2 cycles of induction anti-PD-1 toripalimab plus chemotherapy can improve progression-free survival (PFS) in bulky LA-NSCLC. Bulky tumors are defined as primary lesion ≥5 cm in greatest dimension or metastatic lymph nodes ≥2 cm in shortest diameter. A total of 50 patients with bulky unresectable stage III NSCLC will be recruited and 1:1 randomized into the experimental arm: 2-cycle induction PD-1 inhibitor toripalimab plus chemotherapy followed by cCRT and consolidation toripalimab; or control arm: 2-cycle induction chemotherapy followed by cCRT and consolidation toripalimab. Patients are stratified by pathology (squamous versus non-squamous). The primary endpoint is PFS. Secondary endpoints are overall survival, overall response rate, disease control rate, duration of response, and incidence of adverse events. Exploratory analyses include PD-L1 expression and liquid biopsy-based biomarker testing, tumor microenvironment profiling at single-cell levels, and quality-of-life assessments.

Discussion

The InTRist study is the first randomized phase II trial to investigate the feasibility of induction anti-PD-1 toripalimab plus chemotherapy followed by cCRT and consolidation toripalimab in bulky LA-NSCLC, providing novel evidence for the synergistic strategy combining anti-PD-1 blockade with radiotherapy to prolong immunotherapy benefits, overcome resistance, and enhance abscopal immune response.

Clinical trial registration

ClinicalTrials.gov, identifier NCT05888402.
Microglia depletion/repopulation does not affect light-induced retinal degeneration in mice
Authors: Laudenberg Nils , Kinuthia Urbanus Muthai , Langmann Thomas
Published: January 2024

Reactive microglia are a hallmark of age-related retinal degenerative diseases including age-related macular degeneration (AMD). These cells are capable of secreting neurotoxic substances that may aggravate inflammation that leads to loss of photoreceptors and impaired vision. Despite their role in driving detrimental inflammation, microglia also play supporting roles in the retina as they are a crucial cellular component of the regulatory innate immune system. In this study, we used the colony stimulating factor 1 receptor (CSF1R)-antagonist PLX3397 to investigate the effects of microglia depletion and repopulation in a mouse model of acute retinal degeneration that mimics some aspects of dry AMD. Our main goal was to investigate whether microglia depletion and repopulation affects the outcome of light-induced retinal degeneration. We found that microglia depletion effectively decreased the expression of several key pro-inflammatory factors but was unable to influence the extent of retinal degeneration as determined by optical coherence tomography (OCT) and histology. Interestingly, we found prominent cell debris accumulation in the outer retina under conditions of microglia depletion, presumably due to the lack of efficient phagocytosis that could not be compensated by the retinal pigment epithelium. Moreover, our in vivo experiments showed that renewal of retinal microglia by repopulation did also not prevent rapid microglia activation or preserve photoreceptor death under conditions of light damage. We conclude that microglia ablation strongly reduces the expression of pro-inflammatory factors but cannot prevent photoreceptor loss in the light-damage paradigm of retinal degeneration.
Refining patient selection for next-generation immunotherapeutic early-phase clinical trials with a novel and externally validated prognostic nomogram
Authors: Losurdo Agnese , Dipasquale Angelo , Giordano Laura , Persico Pasquale , Lorenzi Elena , Di Muzio Antonio , Barigazzi Chiara , Korolewicz James , Mehan Aman , Mohammed Oreoluwa , Scheiner Benhard , Pinato David J. , Santoro Armando , Simonelli Matteo
Published: January 2024

Introduction

Identifying which patient may benefit from immunotherapeutic early-phase clinical trials is an unmet need in drug development. Among several proposed prognostic scores, none has been validated in patients receiving immunomodulating agents (IMAs)-based combinations.

Patients and methods

We retrospectively collected data of 208 patients enrolled in early-phase clinical trials investigating IMAs at our Institution, correlating clinical and blood-based variables with overall survival (OS). A retrospective cohort of 50 patients treated with IMAs at Imperial College (Hammersmith Hospital, London, UK) was used for validation.

Results

A total of 173 subjects were selected for analyses. Most frequent cancers included non-small cell lung cancer (26%), hepatocellular carcinoma (21.5%) and glioblastoma (13%). Multivariate analysis (MVA) revealed 3 factors to be independently associated with OS: line of treatment (second and third vs subsequent, HR 0.61, 95% CI 0.40-0.93, p 0.02), serum albumin as continuous variable (HR 0.57, 95% CI 0.36–0.91, p 0.02) and number of metastatic sites (<3 vs ≥3, HR 0.68, 95% CI 0.48-0.98, p 0.04). After splitting albumin value at the median (3.84 g/dL), a score system was capable of stratifying patients in 3 groups with significantly different OS (p<0.0001). Relationship with OS reproduced in the external cohort (p=0.008). Then, from these factors we built a nomogram.

Conclusions

Prior treatment, serum albumin and number of metastatic sites are readily available prognostic traits in patients with advanced malignancies participating into immunotherapy early-phase trials. Combination of these factors can optimize patient selection at study enrollment, maximizing therapeutic intent.
Improved prediction of extreme ENSO events using an artificial neural network with weighted loss functions
Authors: Kim Dong-Hoon , Moon Il-Ju , Lim Chaewook , Woo Seung-Buhm
Published: January 2024

The El Niño–Southern Oscillation (ENSO) causes a wide array of abnormal climates and extreme events, including severe droughts and floods, which have a major impact on humanity. With the development of artificial neural network techniques, various attempts are being made to predict ENSO more accurately. However, there are still limitations in accurately predicting ENSO beyond 6 months, especially for abnormal years with less frequent but greater impact, such as strong El Niño or La Niña, mainly due to insufficient and imbalanced training data. Here, we propose a new weighted loss function to improve ENSO prediction for abnormal years, in which the original (vanilla) loss function is multiplied by the weight function that relatively reduces the weight of high-frequency normal events. The new method applied to recurrent neural networks shows significant improvement in ENSO predictions for all lead times from 1 month to 12 months compared to using the vanilla loss function; in particular, the longer the prediction lead time, the greater the prediction improvement. This method can be applied to a variety of other extreme weather and climate events of low frequency but high impact.
The relationships between lens diameter and ocular biometric parameters: an ultrasound biomicroscopy-based study
Authors: Huang Zhiqian , Qi Jiao , Cheng Kaiwen , Liu Shuyu , Zhang Keke , Du Yu , Lu Yi , Zhu Xiangjia
Published: January 2024

Purpose

This study aims to explore the relationships between lens diameter (LD) measured with ultrasound biomicroscopy (UBM) and ocular biometric parameters.

Methods

Ocular biometric parameters including axial length (AL), white-to-white distance (WTW), anterior chamber depth (ACD), lens thickness (LT) and anterior segment length (ASL) were measured with IOL-Master 700, and the direct measurement of LD was conducted through UBM (ArcScan Insight 100). Relationships between LD and ocular biometric parameters were then investigated. Eyes with AL ≥ 28 mm were defined as eyes with extreme myopia, and eyes with AL < 28 mm were defined as eyes without extreme myopia.

Results

A total of 194 eyes from 194 subjects were included. The mean LD was 9.58 ± 0.49 mm, ranging from 8.60 to 10.96 mm. According to univariate analysis, larger LD was associated with elder age, male gender, larger WTW, ACD and ASL (all p < 0.05). Meanwhile, the LD was positively correlated with AL in eyes without extreme myopia (p < 0.05), but not in eyes with extreme myopia (p > 0.05). Backward stepwise regressions revealed that a larger LD was associated with larger WTW, ASL and AL in eyes without extreme myopia (all p < 0.05), while ASL was the only significant variable in eyes with extreme myopia (p < 0.05).

Conclusion

Larger WTW, ASL and AL in eyes without extreme myopia, as well as longer ASL in eyes with extreme myopia indicated a larger LD, which provides guidance in personalized surgical choice and promises ideal visual outcomes.
The potential of leveraging electrostatics for improved inhaled drug delivery to the lungs
Authors: Bessler Ron , Sznitman Josué
Published: January 2024

In this short perspective, we explore the potential of leveraging electrostatic forces in the lungs to enhance pulmonary drug delivery methods and optimize drug delivery efficiency and therapeutic outcomes. Alongside conventional mechanisms such as diffusion, gravitational sedimentation, and impaction, we delve into electrostatic mechanisms, utilizing a non-dimensional analysis approach for insights into aerosol drug delivery. While often overlooked in inhalation therapy, our considerations emphasize the significance of electrostatic interactions on drug deposition, particularly in the deep lung, where, in the future, tailored electrostatic charges can strategically offer new possibilities for localized therapeutic effects for respiratory diseases.
Effect of tea polyphenols supplement on growth performance, antioxidation, and gut microbiota in squabs
Authors: Chen Ailing , Ma Tingting , Zhong Yajing , Deng Shan , Zhu Shaoping , Fu Zhiqi , Huang Yanhua , Fu Jing
Published: January 2024

Early life nutritional supplementation can significantly improve pigeon health. Both the nutritional crops of parental pigeons and the intestinal development of squabs play key roles in the growth rate of squabs. Tea polyphenols (TPs), as natural plant extracts, exhibit potential biological activities. However, the impact of TPs on the intestinal function of squabs is not known. This study evaluated the effects of TPs on growth performance, immunity, antioxidation, and intestinal function in squabs. A total of 432 young pigeons (1 day old) were divided into four groups: a control group (fed a basic diet) and three treatment groups (low, medium, and high dose groups; 100, 200, and 400 mg/kg TPs, respectively). On the 28th day, samples of serum, mucosal tissue, and digests from the ileum of squabs were collected for analysis. The results revealed that TP supplementation significantly reduced the feed-to-meat ratio and improved the feed utilization rate and serum biochemical indices in squabs. Additionally, it enhanced the intestinal barrier function of birds by promoting intestinal development and integrity of tight junctions and regulating digestive enzyme activities and intestinal flora. Mechanistically, TPs activated the Nrf2-ARE signaling pathway, which may be associated with improved antioxidant and immune responses, correlating with an increased abundance of Candida arthritis and Corynebacterium in the ileum.
Exploration of oxidized phosphocholine profile in non-small-cell lung cancer
Authors: Godzien Joanna , Lopez-Lopez Angeles , Sieminska Julia , Jablonowski Kacper , Pietrowska Karolina , Kisluk Joanna , Mojsak Malgorzata , Dzieciol-Anikiej Zofia , Barbas Coral , Reszec Joanna , Kozlowski Miroslaw , Moniuszko Marcin , Kretowski Adam , Niklinski Jacek , Ciborowski Michal
Published: January 2024

Introduction: Lung cancer is one of the most frequently studied types of cancer and represents the most common and lethal neoplasm. Our previous research on non-small cell lung cancer (NSCLC) has revealed deep lipid profile reprogramming and redox status disruption in cancer patients. Lung cell membranes are rich in phospholipids that are susceptible to oxidation, leading to the formation of bioactive oxidized phosphatidylcholines (oxPCs). Persistent and elevated levels of oxPCs have been shown to induce chronic inflammation, leading to detrimental effects. However, recent reports suggest that certain oxPCs possess anti-inflammatory, pro-survival, and endothelial barrier-protective properties. Thus, we aimed to measure the levels of oxPCs in NSCLC patients and investigate their potential role in lung cancer.

Methods: To explore the oxPCs profiles in lung cancer, we performed in-depth, multi-level metabolomic analyses of nearly 350 plasma and lung tissue samples from 200 patients with NSCLC, including adenocarcinoma (ADC) and squamous cell carcinoma (SCC), the two most prevalent NSCLC subtypes and COPD patients as a control group. First, we performed oxPC profiling of plasma samples. Second, we analyzed tumor and non-cancerous lung tissues collected during the surgical removal of NSCLC tumors. Because of tumor tissue heterogeneity, subsequent analyses covered the surrounding healthy tissue and peripheral and central tumors. To assess whether the observed phenotypic changes in the patients were associated with measured oxPC levels, metabolomics data were augmented with data from medical records.

Results: We observed a predominance of long-chain oxPCs in plasma samples and of short-chain oxPCs in tissue samples from patients with NSCLC. The highest concentration of oxPCs was observed in the central tumor region. ADC patients showed higher levels of oxPCs compared to the control group, than patients with SCC.

Conclusion: The detrimental effects associated with the accumulation of short-chain oxPCs suggest that these molecules may have greater therapeutic utility than diagnostic value, especially given that elevated oxPC levels are a hallmark of multiple types of cancer.
Biochemical parameters as a tool to assess the nutritional status of patients with amyotrophic lateral sclerosis
Authors: Monov Dimitar , Molodozhnikova Natalia
Published: January 2024

Background

The research aimed to analyze blood biochemical parameters in patients with amyotrophic lateral sclerosis and to determine whether they can be used to assess their nutritional status.

Methods

The study included 45 patients diagnosed with amyotrophic lateral sclerosis (ALS): 28 (62.2%) were men and 17 (37.8%) were women. The mean age of the study participants was 50.69 ± 7.24 years. The control group consisted of 30 practically healthy individuals.

Results

Compared with practically healthy individuals, patients with ALS had significantly lower blood parameters, including total lymphocyte count (1.49 ± 0.11 vs. 2.86 ± 0.25, p < 0.05), total protein (60.55 ± 2.38 vs. 77.80 ± 4.41, p < 0.05), albumin (33.70 ± 2.03 vs. 46.49 ± 3.22, p < 0.05), urea (3.09 ± 0.36 vs. 5.37 ± 0.50, p < 0.05), creatinine (51.28 ± 4.42 vs. 70.91 ± 5.13, p < 0.05), and transferrin (1.84 ± 0.12 vs. 2.32 ± 0.10, p < 0.05). These parameters correspond to first-degree malnutrition. There were direct correlations between anthropometric and biochemical parameters in the ALS group. BMI correlated with the blood levels of total protein (r = 0.22, p < 0.05), albumin (r = 0.27, p < 0.05), urea (r = 0.33, p < 0.05), creatinine (r = 0.30, p < 0.05), transferrin (r = 0.18, p < 0.05), and total lymphocyte count (r = 0.20, p < 0.05). PNI correlated with the blood levels of total protein (r = 0.53, p < 0.05), albumin (r = 0.87, p < 0.05), total cholesterol (r = 0.34, p < 0.05), transferrin (r = 0.40, p < 0.05), total lymphocyte count (r = 0.79, p < 0.05), urea (r = 0, 37, p < 0.05), and creatinine (r = 0.32, p < 0.05).

Conclusion

The study presents compelling evidence supporting the utilization of biochemical parameters, including total protein, albumin, urea, creatinine, transferrin, and total lymphocyte count, for potentially evaluating the nutritional status of individuals diagnosed with ALS.
MRI-visible enlarged perivascular spaces in basal ganglia rather than centrum semiovale was associated with aneurysmal subarachnoid hemorrhage
Authors: Yu Qiuyue , Wang Haichao , Zhang Wenyi , Zhang Xiang , Zhao Jingjing , Gong Li , Liu Xueyuan
Published: January 2024

Background

The subarachnoid space is continuous with the perivascular compartment in the central nervous system. However, whether the topography and severity of enlarged perivascular spaces (EPVS) correlates with spontaneous subarachnoid hemorrhage (SAH) remains unknown. Based on the underlying arteriopathy distributions, we hypothesized that EPVS in basal ganglia (BG-EPVS) are more closely associated with aneurysmal subarachnoid hemorrhage (aSAH) than other SAH without aneurysm.

Methods

Magnetic resonance imaging (MRI) scans of 271 consecutive SAH survivors with and without aneurysm were analyzed for EPVS and other markers of imaging data. In the subgroup analysis, we compared the clinical characteristics and EPVS of SAH participants with and without pre-existing known risk factors (hypertension, diabetes, and smoking history) using multivariable logistic regression.

Results

Patients with aSAH (n = 195) had a higher severity of BG-EPVS and centrum semiovale EPVS (CSO-EPVS) than those without aneurysm (n = 76). Importantly, BG-EPVS predominance pattern (BG-EPVS>CSO-EPVS) only existed in aSAH survivors rather than other SAH without aneurysm. In the subgroup analysis, interestingly, we also found that a high degree of BG-EPVS showed an independent relationship with aSAH in patients without pre-existing risk factors (e.g., hypertension).

Conclusion

In this cohort study, BG-EPVS predominance pattern was associated with aSAH patients compared with those without aneurysm. Moreover, BG-EPVS still showed a strong association with aSAH survivors without pre-existing vascular risk factors. Our present study suggested the BG-EPVS as a potential MRI-visible characteristic would shed light on the pathogenesis of glymphatic function at the skull base for aSAH.
A study on the combination of functional connection features and Riemannian manifold in EEG emotion recognition
Authors: Wu Minchao , Ouyang Rui , Zhou Chang , Sun Zitong , Li Fan , Li Ping
Published: January 2024

Introduction

Affective computing is the core for Human-computer interface (HCI) to be more intelligent, where electroencephalogram (EEG) based emotion recognition is one of the primary research orientations. Besides, in the field of brain-computer interface, Riemannian manifold is a highly robust and effective method. However, the symmetric positive definiteness (SPD) of the features limits its application.

Methods

In the present work, we introduced the Laplace matrix to transform the functional connection features, i.e., phase locking value (PLV), Pearson correlation coefficient (PCC), spectral coherent (COH), and mutual information (MI), to into semi-positive, and the max operator to ensure the transformed feature be positive. Then the SPD network is employed to extract the deep spatial information and a fully connected layer is employed to validate the effectiveness of the extracted features. Particularly, the decision layer fusion strategy is utilized to achieve more accurate and stable recognition results, and the differences of classification performance of different feature combinations are studied. What's more, the optimal threshold value applied to the functional connection feature is also studied.

Results

The public emotional dataset, SEED, is adopted to test the proposed method with subject dependent cross-validation strategy. The result of average accuracies for the four features indicate that PCC outperform others three features. The proposed model achieve best accuracy of 91.05% for the fusion of PLV, PCC, and COH, followed by the fusion of all four features with the accuracy of 90.16%.

Discussion

The experimental results demonstrate that the optimal thresholds for the four functional connection features always kept relatively stable within a fixed interval. In conclusion, the experimental results demonstrated the effectiveness of the proposed method.
Cloud platform to improve efficiency and coverage of asynchronous multidisciplinary team meetings for patients with digestive tract cancer
Authors: Zhang Yu , Li Jie , Liao Min , Yang Yalan , He Gang , Zhou Zuhong , Feng Gang , Gao Feng , Liu Lihua , Xue Xiaojing , Liu Zhongli , Wang Xiaoyan , Shi Qiuling , Du Xaiobo
Published: January 2024

Background

Multidisciplinary team (MDT) meetings are the gold standard of cancer treatment. However, the limited participation of multiple medical experts and the low frequency of MDT meetings reduce the efficiency and coverage rate of MDTs. Herein, we retrospectively report the results of an asynchronous MDT based on a cloud platform (cMDT) to improve the efficiency and coverage rate of MDT meetings for digestive tract cancer.

Methods

The participants and cMDT processes associated with digestive tract cancer were discussed using a cloud platform. Software programming and cMDT test runs were subsequently conducted to further improve the software and processing. cMDT for digestive tract cancer was officially launched in June 2019. The doctor response duration, cMDT time, MDT coverage rate, National Comprehensive Cancer Network guidelines compliance rate for patients with stage III rectal cancer, and uniformity rate of medical experts’ opinions were collected.

Results

The final cMDT software and processes used were determined. Among the 7462 digestive tract cancer patients, 3143 (control group) were diagnosed between March 2016 and February 2019, and 4319 (cMDT group) were diagnosed between June 2019 and May 2022. The average number of doctors participating in each cMDT was 3.26 ± 0.88. The average doctor response time was 27.21 ± 20.40 hours, and the average duration of cMDT was 7.68 ± 1.47 min. The coverage rates were 47.85% (1504/3143) and 79.99% (3455/4319) in the control and cMDT groups, respectively. The National Comprehensive Cancer Network guidelines compliance rates for stage III rectal cancer patients were 68.42% and 90.55% in the control and cMDT groups, respectively. The uniformity rate of medical experts’ opinions was 89.75% (3101/3455), and 8.97% (310/3455) of patients needed online discussion through WeChat; only 1.28% (44/3455) of patients needed face-to-face discussion with the cMDT group members.

Conclusion

A cMDT can increase the coverage rate of MDTs and the compliance rate with National Comprehensive Cancer Network guidelines for stage III rectal cancer. The uniformity rate of the medical experts’ opinions was high in the cMDT group, and it reduced contact between medical experts during the COVID-19 pandemic.
Diagnosis, treatment, and prognosis of stage IB non-small cell lung cancer with visceral pleural invasion
Authors: Ruan Zegang , Zhuo Xin , Xu Chenyang
Published: January 2024

With the increasing implementation of early lung cancer screening and the increasing emphasis on physical examinations, the early-stage lung cancer detection rate continues to rise. Visceral pleural invasion (VPI), which denotes the tumor’s breach of the elastic layer or reaching the surface of the visceral pleura, stands as a pivotal factor that impacts the prognosis of patients with non-small cell lung cancer (NSCLC) and directly influences the pathological staging of early-stage cases. According to the latest 9th edition of the TNM staging system for NSCLC, even when the tumor diameter is less than 3 cm, the final T stage remains T2a if VPI is present. There is considerable controversy within the guidelines regarding treatment options for stage IB NSCLC, especially among patients exhibiting VPI. Moreover, the precise determination of VPI is important in guiding treatment selection and prognostic evaluation in individuals with NSCLC. This article aims to provide a comprehensive review of the current status and advancements in studies pertaining to stage IB NSCLC accompanied by VPI.
Positive outcomes with neoadjuvant chemotherapy in the management of colovesical fistula in cancer: a case report and literature review
Authors: Tang Song , Li Xinjun , Guo Donghua , Zhuo Fan
Published: January 2024

Colovesical fistula (CVF) is usually developed from colonic diverticulitis, followed by tumor. Traditional surgery is usually completed in one or more stages. For complex cancerous CVF, radical resection is more difficult. We report a 62-year-old male patient diagnosed with sigmoid colon cancer combined with sigmoid vesical fistula. In the course of treatment, in addition to conventional surgery, neoadjuvant chemotherapy (NAC) was innovatively used. The sigmoid tumor and fistula were significantly shrunken. Radical surgery achieved negative margins.
OTUD3 suppresses the mTORC1 signaling by deubiquitinating KPTN
Authors: Li Jiatao , Yang Dan , Lin Yan , Xu Wei , Zhao Shi-min , Wang Chenji
Published: January 2024

Background: Ubiquitination and deubiquitination modifications play pivotal roles in eukaryotic life processes, regulating protein dynamics via the ubiquitin-proteasome pathway. Dysregulation can impact disease development, including cancer and neurodegenerative disorders. Increasing evidence highlights their role in tumorigenesis, modulating key proteins. OTUD3, a deubiquitinase, stabilizes PTEN, suppressing tumor growth by inhibiting PI3K-AKT signaling. Yet, further OTUD3 substrates remain underexplored.

Methods: We employed the In vivo ubiquitination assay to investigate the ubiquitination role of OTUD3 on KPTN within the cellular context. Additionally, CRISPR/Cas9 editing and Immunofluorescence were utilized to study the impact of OTUD3 on the mTOR signaling pathway in cells. Furthermore, Cell proliferation assay and NMR were employed to explore the effects of OTUD3 on cellular growth and proliferation.

Results: OTUD3 serves as a deubiquitinase for KPTN. OTUD3 interacts with KPTN, facilitated by the OTU domain within OTUD3. Further investigations confirmed KPTN’s ubiquitination modification, primarily at lysine residue 49. Ubiquitination experiments demonstrated OTUD3’s ability to mediate KPTN’s deubiquitination without affecting its protein levels. This suggests KPTN’s ubiquitination is a function-regulated, non-degradable modification. Under various amino acid starvation or stimulation conditions, overexpressing OTUD3 reduces mTORC1 signaling activation, while knocking out OTUD3 further enhances it. Notably, OTUD3’s regulation of mTORC1 signaling relies on its deubiquitinase activity, and this effect is observed even in PTEN KO cells, confirming its independence from PTEN, a reported substrate. OTUD3 also promotes GATOR1’s lysosomal localization, a process requiring KPTN’s involvement. Ultimately, OTUD3 affects cellular metabolic pool products by downregulating the mTORC1 pathway, significantly inhibiting tumor cell growth and proliferation.

Discussion: Our experiments shed light on an alternative perspective regarding the intrinsic functions of OTUD3 in inhibiting tumor development. We propose a novel mechanism involving KPTN-mediated regulation of the mTORC1 signaling pathway, offering fresh insights into the occurrence and progression of tumor diseases driven by related genes. This may inspire new approaches for drug screening and cancer treatment, potentially guiding future therapies for relevant tumors.
Monitoring functional immune responses with a cytokine release assay: ISS flight hardware design and experimental protocol for whole blood cultures executed under microgravity conditions
Authors: Buchheim Judith-Irina , Feuerecker Matthias , Balsamo Michele , Vukich Marco , Van Walleghem Merel , Tabury Kevin , Quintens Roel , Vermeesen Randy , Baselet Bjorn , Baatout Sarah , Rattenbacher Bernd , Antunes Inês , Ngo-Anh Thu Jennifer , Crucian Brian , Choukér Alexander
Published: January 2024

Introduction: Long-term space missions trigger a prolonged neuroendocrine stress response leading to immune system dysregulation evidenced by susceptibility to infections, viral reactivation, and skin irritations. However, due to existing technical constraints, real-time functional immune assessments are not currently available to crew inflight. The in vitro cytokine release assay (CRA) has been effectively employed to study the stimulated cytokine response of immune cells in whole blood albeit limited to pre- and post-flight sessions. A novel two-valve reaction tube (RT) has been developed to enable the execution of the CRA on the International Space Station (ISS).

Methods: In a comprehensive test campaign, we assessed the suitability of three materials (silicone, C-Flex, and PVC) for the RT design in terms of biochemical compatibility, chemical stability, and final data quality analysis. Furthermore, we thoroughly examined additional quality criteria such as safety, handling, and the frozen storage of antigens within the RTs. The validation of the proposed crew procedure was conducted during a parabolic flight campaign.

Results: The selected material and procedure proved to be both feasible and secure yielding consistent and dependable data outcomes. This new hardware allows for the stimulation of blood samples on board the ISS, with subsequent analysis still conducted on the ground.

Discussion: The resultant data promises to offer a more accurate understanding of the stress-induced neuroendocrine modulation of immunity during space travel providing valuable insights for the scientific community. Furthermore, the versatile nature of the RT suggests its potential utility as a testing platform for various other assays or sample types.
Genome-wide identification, classification and expression analysis of MYB gene family in coconut (Cocos nucifera L.)
Authors: Li Jing , Guo Shukuan , Min Htwe Yin , Sun Xiwei , Zhou Lixia , Wang Fangyuan , Zeng Chunru , Chen Shuangyan , Iqbal Amjad , Yang Yaodong
Published: January 2024

MYB transcription factors regulate the growth, development, and secondary metabolism of plant species. To investigate the origin of color variations in coconut pericarp, we identified and analyzed the MYB gene family present in coconut. According to the sequence of MYB genes in Arabidopsis thaliana, homologous MYB gene sequences were found in the whole genome database of coconut, the conserved sequence motifs within MYB proteins were analyzed by Motif Elicitation (MEME) tool, and the sequences without conservative structure were eliminated. Additionally, we employed RNA-seq technology to generate gene expression signatures of the R2R3-MYB genes across distinctive coconut parts exhibiting diverse colors. To validate these profiles, we conducted quantitative PCR (qPCR). Through comprehensive genome-wide screening, we successfully identified a collection of 179 MYB genes in coconut. Subsequent phylogenetic analysis categorized these 179 coconut MYB genes into 4-subfamilies: 124 R2R3-MYB, 4 3R-MYB types, 4 4R-MYB type, and 47 unknown types. Furthermore, these genes were further divided into 34 subgroups, with 28 of these subgroups successfully classified into known subfamilies found in Arabidopsis thaliana. By mapping the CnMYB genes onto the 16 chromosomes of the coconut genome, we unveiled a collinearity association between them. Moreover, a preservation of gene structure and motif distribution was observed across the CnMYB genes. Our research encompassed a thorough investigation of the R2R3-MYB genes present in the coconut genome, including the chromosomal localization, gene assembly, conserved regions, phylogenetic associations, and promoter cis-acting elements of the studied genes. Our findings revealed a collection of 12 R2R3-MYB candidate genes, namely CnMYB8, CnMYB15, CnMYB27, CnMYB28, CnMYB61, CnMYB63, CnMYB68, CnMYB94, CnMYB101, CnMYB150, CnMYB153, and CnMYB164. These genes showed differential expressions in diverse tissues and developmental stages of four coconut species, such as CnMYB68, CnMYB101, and CnMYB28 exhibited high expression in majority of tissues and coconut species, while CnMYB94 and CnMYB164 showed lower expression. These findings shed light on the crucial functional divergence of CnMYB genes across various coconut tissues, suggesting these genes as promising candidate genes for facilitating color development in this important crop.
Genetics, genomics, and breeding of black gram [Vigna mungo (L.) Hepper]
Authors: Nair Ramakrishnan M. , Chaudhari Sunil , Devi Nagamallika , Shivanna Aparna , Gowda Abhishek , Boddepalli Venkata N. , Pradhan Hansaraj , Schafleitner Roland , Jegadeesan Souframanien , Somta Prakit
Published: January 2024

Black gram [Vigna mungo (L.) Hepper] is a highly nutritious grain legume crop, mainly grown in South and Southeast Asia, with the largest area in India, where the crop is challenged by several biotic and abiotic stresses leading to significant yield losses. Improving genetic gains to increase on-farm yields is the primary goal of black gram breeding programs. This could be achieved by developing varieties resistant to major diseases like mungbean yellow mosaic disease, urdbean leaf crinkle virus, Cercospora leaf spot, anthracnose, powdery mildew, and insect pests such as whitefly, cowpea aphids, thrips, stem flies, and bruchids. Along with increasing on-farm yields, incorporating market-preferred traits ensures the adoption of improved varieties. Black gram breeding programs rely upon a limited number of parental lines, leading to a narrow genetic base of the developed varieties. For accelerating genetic gain, there is an urgent need to include more diverse genetic material for improving traits for better adaptability and stress resistance in breeding populations. The present review summarizes the importance of black gram, the major biotic and abiotic stresses, available genetic and genomic resources, major traits for potential crop improvement, their inheritance, and the breeding approaches being used in black gram for the development of new varieties.
Chlorophyll a fluorescence as a tool to monitor physiological status in the leaves of Artemisia ordosica under root cutting conditions
Authors: Liu Ying , Gong Chuangang , Pei Weihao , Fan Kaixuan , Shen Wenjing
Published: January 2024

Background

Root cutting caused by underground coal mining subsidence is among the leading causes of plant damage in western China. Detection of root cutting stress is of great importance in evaluating the degree of plant damage and changes in physiological conditions in underground coal mining disturbance conditions.

Methods

The present study assessed the use of chlorophyll fluorescence OJIP transient data to evaluate the disturbance characteristics of root cutting stress on leaf photosynthetic mechanisms in the typical shrub Artemisia ordosica Krasch. Different root cutting ratios (10%, 20%, 30%, 50%, 75%, and 100%) were established on the roots of A. ordosica in the field, and the OJIP transient and JIP parameters of the leaves were measured.

Results

The overall OJIP curves and each OJIP step in leaves decreased as the root cutting ratio increased, but the impact was relatively small for root cutting ratios of less than 30%. Through the analysis of JIP parameters and the established energy pipeline model, it was found that the energy capture efficiency and electron transfer efficiency of photosystem II decreased as the root cutting ratio increased. Therefore, we also inferred that the threshold for the plant root cutting ratio at which leaf photosynthetic mechanisms begin to change is 30–50%.

Conclusion

These results indicate that OJIP transient analysis can serve as a non-destructive, rapid technique for detecting plant root cutting stress in coal mining subsidence areas, which is of great value for non-destructive monitoring of plant root damage.
The psychosocial functioning in adolescents with severe obesity evaluated throughout the strengths and difficulties questionnaire (SDQ): a preliminary report
Authors: Guerrini Usubini Anna , Bottacchi Michela , Morelli Giovanna , Caroli Diana , Marazzi Nicoletta , Castelnuovo Gianluca , Sartorio Alessandro
Published: January 2024

Introduction

Childhood obesity is associated with poor psychological adjustment. Severely impacts the psychological adjustment of young patients. To assess the psychological functioning of children and adolescents, several questionnaires have been proposed so far. Although the Strengths and Difficulties Questionnaire (SDQ) is one of the most well-used tools, its application in obesity research is scarce. The study is aimed at assessing the psychological profile of a sample of Italian children and adolescents seeking an in-hospital multidisciplinary body weight reduction program for obesity, via SDQ.

Methods

One hundred and fourteen consecutive Italian children and adolescents with obesity (43 males/71 females, age range: 11–17 years, mean age ± SD: 15.1 ± 1.66, body mass index-BMI ± SD: 37.4 ± 6.13 kg/m2), were recruited at the Division of Auxology, Istituto Auxologico Italiano IRCCS, Piancavallo (VB).

Results

Obese Females reported worse conditions of emotional symptoms (t = 5.48; p < 0.001) and peer problems (t = 2.34; p = 0.021), as well as higher which were associated with greater scores of pro-social behaviors than obese males (t = 3.07; p = 0.003). The total difficulties score (t = 4.00; p < 0.001) and the total impact score (t = 4.53; p < 0.001) were significantly higher in females than males. No statistically significant differences in SDQ variables were found in relation to the degree of obesity (BMI SDS: 2–2.99; BMI SDS: > 3).

Discussion

These findings can contribute to understand the psychological condition of adolescents with obesity in a better way and also to develop effective interventions for the treatment of pediatric obesity which not only take into account the medical and physical aspects but also the emotional and social difficulties expressed by adolescents with obesity.
Scarcity mindset among schoolteachers: how resource scarcity negatively impacts teachers’ cognition and behaviors
Authors: Denti Leif , Sturén Erik , Johansson Lars-Olof
Published: January 2024

A recent line of research investigates the negative cognitive effects – known as the scarcity mindset – that arise when people face a lack of resources. We expand on this research and show that these cognitive effects are present among Swedish schoolteachers facing a scarcity of time and social resources at work. From an initial interview study we developed novel survey scales to measure teachers’ subjective assessments of available resources and the extent of their scarcity mindset. We then related resource scarcity of time and social resources to the scarcity mindset using structural equation modeling (SEM) analysis in a survey study with a sample of Swedish schoolteachers. This research provides valuable insights for addressing resource constrained work environments in schools and contributes to the broader psychological research on cognitive effects resulting from resource scarcity.
PTCHD1 gene mutation/deletion: the cognitive-behavioral phenotyping of four case reports
Authors: Montanaro Federica Alice Maria , Mandarino Alessandra , Alesi Viola , Schwartz Charles , Sepulveda Daniela Judith Claps , Skinner Cindy , Friez Michael , Piccolo Gabriele , Novelli Antonio , Zanni Ginevra , Dentici Maria Lisa , Vicari Stefano , Alfieri Paolo
Published: January 2024

Introduction

X-linked PTCHD1 gene has recently been pointed as one of the most interesting candidates for involvement in neurodevelopmental disorders (NDs), such as intellectual disability (ID) and autism spectrum disorder (ASD). PTCHD1 encodes the patched domain-containing protein 1 (PTCHD1), which is mainly expressed in the developing brain and adult brain tissues. To date, major studies have focused on the biological function of the PTCHD1 gene, while the mechanisms underlying neuronal alterations and the cognitive-behavioral phenotype associated with mutations still remain unclear.

Methods

With the aim of incorporating information on the clinical profile of affected individuals and enhancing the characterization of the genotype–phenotype correlation, in this study, we analyze the clinical features of four individuals (two children and two adults) in which array-CGH detected a PTCHD1 deletion or in which panel for screening non-syndromal XLID (X-linked ID) detected a PTCHD1 gene variant. We define the neuropsychological and psychopathological profiles, providing quantitative data from standardized evaluations. The assessment consisted of clinical observations, structured interviews, and parent/self-reported questionnaires.

Results

Our descriptive analysis align with previous findings on the involvement of the PTCHD1 gene in NDs. Specifically, our patients exhibited a clinical phenotype characterized by psychomotor developmental delay- ID of varying severity. Interestingly, while ID during early childhood was associated with autistic-like symptomatology, this interrelation was no longer observed in the adult subjects. Furthermore, our cohort did not display peculiar dysmorphic features, congenital abnormalities or comorbidity with epilepsy.

Discussion

Our analysis shows that the psychopathological and behavioral comorbidities along with cognitive impairment interfere with development, therefore contributing to the severity of disability associated with PTCHD1 gene mutation. Awareness of this profile by professionals and caregivers can promote prompt diagnosis as well as early cognitive and occupational enhancement interventions.