bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association between retina thinning and hippocampal atrophy in Alzheimer’s disease and mild cognitive impairment: a meta-analysis and systematic review
Authors: Chen Shuntai , Zhang Dian , Zheng Honggang , Cao Tianyu , Xia Kun , Su Mingwan , Meng Qinggang 
Published: August 2023

IntroductionThe retina is the “window” of the central nervous system. Previous studies discovered that retinal thickness degenerates through the pathological process of the Alzheimer’s disease (AD) continuum. Hippocampal atrophy is one of the typical clinical features and diagnostic criteria of AD. Former studies have described retinal thinning in normal aging subjects and AD patients, yet the association between retinal thickness and hippocampal atrophy in AD is unclear. The optical coherence tomography (OCT) technique has access the non-invasive to retinal images and magnetic resonance imaging can outline the volume of the hippocampus. Thus, we aim to quantify the correlation between these two parameters to identify whether the retina can be a new biomarker for early AD detection.MethodsWe systematically searched the PubMed, Embase, and Web of Science databases from inception to May 2023 for studies investigating the correlation between retinal thickness and hippocampal volume. The Newcastle-Ottawa Quality Assessment Scale (NOS) was used to assess the study quality. Pooled correlation coefficient r values were combined after Fisher’s Z transformation. Moderator effects were detected through subgroup analysis and the meta-regression method.ResultsOf the 1,596 citations initially identified, we excluded 1,062 studies after screening the titles and abstract (animal models, n = 99; irrelevant literature, n = 963). Twelve studies met the inclusion criteria, among which three studies were excluded due to unextractable data. Nine studies were eligible for this meta-analysis. A positive moderate correlation between the retinal thickness was discovered in all participants of with AD, mild cognitive impairment (MCI), and normal controls (NC) (r = 0.3469, 95% CI: 0.2490–0.4377, I2 = 5.0%), which was significantly higher than that of the AD group (r = 0.1209, 95% CI:0.0905–0.1510, I2 = 0.0%) (p &lt; 0.05). Among different layers, the peripapillary retinal nerve fiber layer (pRNFL) indicated a moderate positive correlation with hippocampal volume (r = 0.1209, 95% CI:0.0905–0.1510, I2 = 0.0%). The retinal pigmented epithelium (RPE) was also positively correlated [r = 0.1421, 95% CI:(−0.0447–0.3192), I2 = 84.1%]. The retinal layers and participants were the main overall heterogeneity sources. Correlation in the bilateral hemisphere did not show a significant difference.ConclusionThe correlation between RNFL thickness and hippocampal volume is more predominant in both NC and AD groups than other layers. Whole retinal thickness is positively correlated to hippocampal volume not only in AD continuum, especially in MCI, but also in NC.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, CRD42022328088.
Case Report: A rare case of recurrent ascites after anti-Claudin18.2 antibody therapy for metastatic gastric cancer while responding sustainingly
Authors: Liu Jinlu , Jiang Dan , Lei Qingqiang , Zhu Qing , Zhu Hong 
Published: August 2023

BackgroundGastric cancer remains one of the deadliest malignancies in the world, thus urgently requiring effective and safe therapeutics. Claudin18.2 is a member of the tight junction protein family specifically expressed in gastric cancer cells. Monoclonal antibodies targeting Claudin18.2 have been receiving increasing attention recently. ASKB589 is a humanized monoclonal antibody targeting Claudin18.2.Case presentationThis case described a 65-year-old Chinese man diagnosed with gastric cancer metastasizing to the liver and multiple lymph nodes. The biomarker examination revealed that he had proficient mismatch repair (pMMR), human epidermal growth factor receptor 2 (HER2) was negative, and the combined proportion score (CPS) of PD-L1 (22C3) was 1. After being proven to be moderately positive for Claudin18.2 expression, he received ASKB589 and CAPOX (oxaliplatin and capecitabine) chemotherapy. After a six-cycle therapy (from 14 July 2022 to 29 November 2022), the target tumor was evaluated for partial response (PR) by the investigator based on the enhanced CT scan according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. However, this patient also suffered from intolerable ascites that gradually aggravated during the therapy, which was not controlled well by the supporting therapy. Therefore, the patient stopped receiving the combined therapy in our hospital and did not receive any other anti-tumor treatment. After 4 months of discontinuation of the drug, the patient’s ascites almost disappeared, while the tumor continued to reduce and almost achieved clinically complete relapse (cCR). His progression-free survival (PFS) reached at least 10 months.ConclusionThis is the first case of severe ascites reported after anti-Claudin18.2 monoclonal antibody treatment for advanced gastric cancer. At the same time, the patient still benefited significantly from this incomplete treatment even after discontinuation of the drug and the PFS reached at least 10 months. The ascites might be an immune adverse effect related to the monoclonal antibody-induced antibody-dependent cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Further mechanisms remain to be investigated.
CT-based radiomics for predicting radio-chemotherapy response and overall survival in nonsurgical esophageal carcinoma
Authors: Li Chao , Pan Yuteng , Yang Xianghui , Jing Di , Chen Yu , Luo Chenhua , Qiu Jianfeng , Hu Yongmei , Zhang Zijian , Shi Liting , Shen Liangfang , Zhou Rongrong , Lu Shanfu , Xiao Xiang , Chen Tingyin 
Published: August 2023

BackgroundTo predict treatment response and 2 years overall survival (OS) of radio-chemotherapy in patients with esophageal cancer (EC) by radiomics based on the computed tomography (CT) images.MethodsThis study retrospectively collected 171 nonsurgical EC patients treated with radio-chemotherapy from Jan 2010 to Jan 2019. 80 patients were randomly divided into training (n=64) and validation (n=16) cohorts to predict the radiochemotherapy response. The models predicting treatment response were established by Lasso and logistic regression. A total of 156 patients were allocated into the training cohort (n=110), validation cohort (n=23) and test set (n=23) to predict 2-year OS. The Lasso Cox model and Cox proportional hazards model established the models predicting 2-year OS.ResultsTo predict the radiochemotherapy response, WFK as a radiomics feature, and clinical stages and clinical M stages (cM) as clinical features were selected to construct the clinical-radiomics model, achieving 0.78 and 0.75 AUC (area under the curve) in the training and validation sets, respectively. Furthermore, radiomics features called WFI and WGI combined with clinical features (smoking index, pathological types, cM) were the optimal predictors to predict 2-year OS. The AUC values of the clinical-radiomics model were 0.71 and 0.70 in the training set and validation set, respectively.ConclusionsThis study demonstrated that planning CT-based radiomics showed the predictability of the radiochemotherapy response and 2-year OS in nonsurgical esophageal carcinoma. The predictive results prior to treatment have the potential to assist physicians in choosing the optimal therapeutic strategy to prolong overall survival.
Refractory microsatellite stable metastatic colorectal cancer with ERBB2/ERBB3 mutation may be preferred population for regorafenib plus PD-1 inhibitor therapy: a real-world study
Authors: Dai Xuan , Ding Wenjun , He Yongshan , Huang Shiyong , Liu Yun , Wu Tingyu 
Published: August 2023

BackgroundMicrosatellite stable (MSS) colorectal cancer (CRC) has been referred to as the “cold tumor” because of almost no response to anti–programmed death-1 (PD-1) antibody. A recent REGONIVO trial showed that regorafenib plus nivolumab had an encouraging efficacy in MSS metastatic CRC (mCRC). However, only a small subset of patients may benefit from the combination therapy. We aim to evaluate the efficacy and safety data of immune checkpoint inhibitors combined with regorafenib in refractory MSS mCRC and to discover biomarkers that can effectively stratify the beneficial patient population.MethodsWe retrospectively analyzed patients with MSS mCRC who received regorafenib combined with anti–PD-1 antibody therapy. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and status of gene mutation were reviewed and evaluated.ResultsTwenty-one patients received combination treatment. At a median treatment duration of 4 months, one patient achieved complete response, three patients achieved partial response, and two patients achieved stable disease as the best response. The ORR and DCR were 19% and 28.5% in the overall population, respectively. The median PFS was 4 months, and the median OS was 25 months. Only erbb2 receptor tyrosine kinase 2/erbb3 receptor tyrosine kinase 3 (ERBB2/ERBB3) mutation status was confirmed to be a potential predictive factor for effective treatment. In patients with ERBB2/ERBB3 mutation, ORR, DCR, and PFS exhibited significant improvements in comparison with that in wild-type patients. Grade 3 or higher treatment-related adverse events occurred in three patients (14.3%).ConclusionsRegorafenib in combination with PD-1 inhibitor provides a feasible treatment regimen for refractory MSS mCRC with tolerated toxicity. Patients with ERBB2/ERBB3 mutation may be the preferred population for this combination regimen.
Interventional effects of oral microecological agents on perioperative indicators of colorectal cancer: a meta-analysis
Authors: Wang Xueyan , Pan Lijun , Wang Feiqing , Long Fengxi , Yang Bing , Tang Dongxin 
Published: August 2023

PurposeTo investigate the efficacy of the application of microecological agents in patients with perioperative colorectal cancer.MethodsThe seven electronic databases including PubMed, Cochrane Library, Excerpt Medica Database (Embase), Web of Science (WOS), Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), and Wan-fang Database were systematically searched for eligible studies from 2000 to February 2023.ResultsA total of 38 randomized controlled clinical trials were included in this study, with a total of 1765 patients in the microecological preparation group and 1769 patients in the control group. All data were analyzed using Review Manager 5.4 and R 4.2.2 software. Meta-analysis showed that in the perioperative period of colorectal cancer, the microecological agents group reduced patients’ adverse drug reactions, improved intestinal flora with Lactobacillus (SMD, 3.0858, [2.0197; 4.1520], p&lt; 0. 0001), Bifidobacterium (SMD, 2.1551, [1.6145; 2.6956], p&lt; 0.0001) and Escherichia coli (SMD, -1.1393, [-1.6247; -0.6538], p&lt; 0.0001); protection of intestinal mucosal barrier function, endotoxin (SMD, -2.6850 [-4.1399; -1.2301], p=0.0003), DAO (SMD, -2.5916, [-3.4694; -1.7137], p&lt;0.0001) and plasma D-lactate (SMD, -5.4726, [-9.8901; -1.0551], p= 0.0152), reduced inflammatory response, IL-6 (SMD, -3.1279 [-5.7706; -0.4852], p=0.0204) and CRP (SMD, -3.9698 [-7.6296; -0.3100], p=0.0335); improved the immune function of the organism, CD4+ (SMD, 1.5817 [1.0818; 2.0817], p&lt; 0.0001), CD4+/CD8+ (SMD, 1.2938 [0.9693; 1.6183] p&lt; 0.0001) and IgG (SMD, 1.1376 [0.2993; 1.9759] p=0.0078), improved short-term clinical efficacy, ORR (RR, 1.5105 [1.2306; 1.8541], p&lt; 0.0001) and DCR (RR, 0.3896 [0.2620; 0.5795], p&lt; 0.0001).ConclusionBy increasing the number of beneficial flora such as Lactobacillus and Bifidobacterium and decreasing the number of harmful flora such as Escherichia coli, the micro-ecological preparation group is beneficial in improving the ecological dysregulation in colorectal cancer patients receiving different treatments in the perioperative period. The microecological preparation group was able to reduce many types of adverse drug reactions, such as infections and gastrointestinal discomfort, compared to the control group. The microecological agents also reduced inflammatory responses, decreased the increase in harmful metabolites, enhanced patients’ immune function, protected intestinal mucosal barrier function, and improved short-term clinical outcomes.Systematic review registrationhttps://inplasy.com/inplasy-2023-4-0051/, identifier INPLASY202340051.
Longitudinal prospective anthropometric evaluation in Caucasian prepubertal children with lactose intolerance
Authors: Lizzi Mauro , Sgrazzutti Laura , Porreca Annamaria , Di Filippo Paola , Cauzzo Chiara , Di Pillo Sabrina , Chiarelli Francesco , Attanasi Marina 
Published: August 2023

IntroductionThe health consequences of lactose intolerance remain unclear. We studied the association of lactose intolerance with growth in children.MethodsIn this prospective case–control study, we compared Caucasian prepubertal children with lactose intolerance (LI) [n = 30, median age = 7.87 years (3.00–12.75)] to healthy controls [(n = 75, median age = 2.25 years (2.00–7.25)]. A lactose tolerance test was performed for lactose intolerance diagnosis. The gastrointestinal symptom score was administered at baseline and after a lactose-free diet for a median period of 9.0 months [range 5%–95% (6.0–24.0)]. The anthropometric parameters were measured at baseline and follow-up. All the anthropometric data were converted into standard deviation scores (SDS). A linear regression model was used to investigate the association of lactose intolerance with growth parameters.ResultsWe found no difference in height velocity SDS between the LI and control groups [SDS difference (95% CI): 0.52 (−1.86 to 2.90)]. In addition, we found a significant reduction in the clinical score of the LI group after a lactose-free diet [median (5%–95%): 7.5 (4.0–15.0) and 3 (0.0–8.0); p-value &lt;0.001].ConclusionsThe LI group exhibited no difference in height velocity compared with the control group. Nonetheless, due to the small sample size, the results on the anthropometric profile of the LI group require careful interpretation. More large-scale studies in the pediatric population are required to better understand the association of LI with anthropometric and metabolic profiles.
The changes of Treg and Th17 cells relate to serum 25(OH)D in patients with initial-onset childhood systemic lupus erythematosus
Authors: Jiang Li-jun , Rong Zan-hua , Zhang Hui-feng 
Published: August 2023

BackgroundT helper 17 (Th17) cells and regulatory T cells (Treg) are known to play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE). Improving the balance between Treg and Th17 cells can be a promising new therapeutic target in SLE patients. Vitamin D has a significant impact on the immune inflammatory process and the immune cells involved in this process. The purpose of this study is to investigate the relationship between Th17, Treg, cytokines, and serum 25 hydroxyvitamin D [25(OH)D] in patients with initial-onset childhood SLE.MethodsA total of 82 children aged &lt;18 years with initial-onset SLE were included, as well as 60 healthy subjects during the same period at the Pediatrics Department of the Second Hospital of Hebei Medical University. The chemiluminescence method was performed to detect serum 25(OH)D levels. Flow cytometry was used to evaluate Treg and Th17 cells. An enzyme-linked immunosorbent assay kit was used to evaluate plasma interleukin (IL)-23, IL-17, IL-10, IL-6, and tumor necrosis factor alpha (TNF-α) concentrations.ResultThe serum 25(OH)D levels in patients with initial-onset childhood SLE were significantly lower than those in the healthy controls. The proportion of lupus nephritis (LN) was higher in the vitamin D insufficiency group (71.4%) compared with the vitamin D sufficiency group (30.3%) (p &lt; 0.05). The SLE disease activity index (SLEDAI) was higher in the vitamin D insufficiency group (median = 14) than that in the vitamin D sufficiency group (median = 9) (p &lt; 0.05).The 25(OH)D level was positively correlated with the Treg ratio (r = 0.337, p = 0.002), and it was negatively correlated with the Th17 cell ratio (r = −0.370, p = 0.001). The serum 25(OH)D level had a negative correlation with IL-23 (r = −0.589, p &lt; 0.001), IL-17(r = −0.351, p = 0.001), TNF-α (r = −0.283, p = 0.01), IL-6 (r = −0.392, p &lt; 0.001), and IL-10 (r = −0.313, p = 0.004) levels.ConclusionThe serum 25(OH)D levels decreased in patients with initial-onset childhood SLE. There was a negative correlation between the serum 25(OH)D levels and SLEDAI. The serum 25(OH)D levels in patients with initial-onset childhood SLE were negatively correlated with the Th17 ratio and related cytokines, while positively correlated with the Treg ratio.
Body mass index-associated responses to an ABVD-like regimen in newly-diagnosed patients with Hodgkin lymphoma
Authors: Hu Min , Ding Yiduo , Zhang Haizhou , Guo Wei , Li Yun , Jin Zhengming , Qu Changju , Xia Fan 
Published: August 2023

Background: The role of body mass index (BMI) in the treatment outcomes of lymphoma patients is controversial. While investigating the efficacy of ABVD-like regimen in Hodgkin lymphoma (HL) patients, we observed that obese patients had poor responses. To better understand this clinical phenomenon, we evaluated the effect of BMI on responses to ABVD-like chemotherapy in HL patients.Methods: This retrospective cohort study evaluated the clinical outcomes of all 67 patients with confirmed HL who were treated at the First Affiliated Hospital of Soochow University from November 2016 to March 2023 with an ABVD-like regimen as first-line chemotherapy. Baseline patient characteristics and clinical outcomes were compared across different BMI categories. The primary end-point was the overall response rate defined as the proportion of the HL patients who achieved complete response or partial response. The additional end-points included progression-free survival and overall survival.Results: The median age of the HL patients was 31 years old. Of the patients, 10.4% were obese, and 17.9% patients were overweight. Interim and end-term response evaluations revealed overall response rates of 98.5% and 83.6%, respectively. The proportion of patients with potential poor prognostic factors (IPS risk factors) did not differ significantly in the responders versus non-responders. However, non-responders had a higher average BMI when compared with responders (p = 0.002). Poor overall response rates in higher BMI patients indeed manifested with shorter progression free survival (p = 0.013). The minimum relative dose of the ABVD-like regimen in the overweight and obese groups was significantly lower than in the normal weight group (p &lt; 0.001).Conclusion: Our analyses show that &gt;80% of newly-diagnosed HL patients responded to the ABVD-like regimen. We find that being obese or overweight at the time of diagnosis correlated with a poorer overall response rate and that BMI was an independent risk factor in HL patients treated with the ABVD-like regimen. Lower doses of ABVD-like regimen contributed to the discrepant findings of responses in the high BMI groups. These findings indicate that newly-diagnosed, obese HL patients receiving an ABVD-like regimen require personalized treatment.
Optical coherence tomography angiography allows longitudinal monitoring of angiogenesis in the critical-sized defect model
Authors: Shen Yiyang , Bu Jin , Yu Lan , Yao Lin , Feng Xiaoyan , Lin Jun , Li Peng 
Published: August 2023

Purpose: This study aims to evaluate the capability of optical coherence tomography angiography (OCTA) for imaging the microvasculature within a critical bone defect, to longitudinally observe vascular alterations, and quantify the microvascular density and morphology in a model of a critical-sized defect.Methods: An OCTA system was used to longitudinally monitor angiogenesis in four rat models presenting critical-sized defects with observations recorded on days 7, 14, and 28 post-defect creation. Simultaneously, angiogenesis in three additional rat models was evaluated through a conventional histological analysis involving hematoxylin and eosin staining.Results: OCTA was successful in acquiring in vivo 3D vascular perfusion mapping within the critical-sized defect, and it allowed for quantitative analysis of the microvasculature’s density and morphology. The OCTA imagery of the blood microvasculature revealed a noticeable augmentation in the number and size of vessels, with more extensive vessel convergence observed on day 14 compared to both days 7 and 28. Complementing these observations, quantitative analysis demonstrated that the vessel area density (VAD) and maximum vascular diameter index (MVDI) were significantly larger on day 14 in comparison to measurements taken on days 7 and 28.Conclusion: Leveraging its ability to capture high-resolution images, OCTA facilitated longitudinal monitoring of angiogenesis in models of critical-sized defects. Therefore, it potentially serves as a non-invasive experimental tool beneficial for bone regeneration research.
Integrated transcriptome and metabolome analysis reveals a possible mechanism for the regulation of lipid metabolism via vitamin A in rice field eel (Monopterus albus)
Authors: Huo Huanhuan , Hu Chonghua , Zhou Qiubai , Xiong Liufeng , Peng Mo 
Published: August 2023

To understand the effects of vitamin A on lipid deposition in rice field eels, integrated liver transcriptome and metabolome were conducted and the changes in the genes and metabolites were assessed. Three groups of rice field eel were fed with 0, 200, and 16,000 IU/kg vitamin A supplementations in their diets for 70 days. The total lipid content in the whole body of the rice field eels was significantly increased with the vitamin A supplementations (p &lt; 0.05). Comparative transcriptome analysis revealed 14 pathways and 46 differentially expressed genes involved in lipid metabolism. Sphingolipid metabolism, glycerolipid metabolism, primary bile acid biosynthesis and steroid hormone biosynthesis were significantly enriched pathways. In these pathways, three differential genes phospholipid phosphatase 1a (PLPP1a), phospholipid phosphatase 2b (PLPP2b), cytochrome P450 21a2 (CYP21a2) were consistent with the change trend of lipid content, and the other three differential genes aldo-keto reductase family 1 member D1 (AKR1D1), uridine diphosphate glucuronic acid transferase 1a1 (UGT1a1), cytochrome P450 1a (CYP1a) were opposite. Metabolomic analysis revealed that primary bile acid biosynthesis, sphingolipid metabolism, steroid hormone biosynthesis and biosynthesis of unsaturated fatty acids were all critical for rice field eel metabolic changes in response to vitamin A. Six important differential metabolites (eicosapentaenoic acid, sphinganine, 11-beta-hydroxyprogesterone, hydroxyeicosatetraenoic acid, cholic acid, and glycochenodeoxycholate) were identified and have provided new insights into how vitamin A regulates lipid deposition. Integrated transcriptome and metabolome analyses revealed that primary bile acid biosynthesis was the only remarkably enriched pathway in both the transcriptome and metabolome while that sphingosine was the main metabolite. Based on the above results, we have concluded that vitamin A promotes lipid deposition in the rice field eel through the primary bile acid synthesis pathway, and lipid deposits are widely stored in cell membranes, mainly in the form of sphingosine. These results will provide reference data to help improve our understanding of how vitamin A regulates lipid metabolism.