bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial architecture of regulatory T-cells correlates with disease progression in patients with nasopharyngeal cancer
Authors: Zhou Fengge , Shayan Gulidanna , Sun Shiran , Huang Xiaodong , Chen Xuesong , Wang Kai , Qu Yuan , Wu Runye , Zhang Ye , Liu Qingfeng , Zhang Jianghu , Luo Jingwei , Shi Xinqi , Liu Yang , Liang Bin , Li Ye-Xiong , Wang Jingbo , Yi Junlin 
Published: November 2022

PurposeThis study aims to investigate the prognostic value of composition and spatial architecture of tumor-infiltrating lymphocytes (TILs) as well as PDL1 expression on TILs subpopulations in nasopharyngeal carcinoma (NPC).MethodsA total of 121 patients with NPC were included and divided into two groups: favorable (n = 68) and unfavorable (n = 53). The archived tumor tissues of the included patients were retrieved, and a tissue microarray was constructed. The density and spatial distribution of TILs infiltration were analyzed using the multiplex fluorescent immunohistochemistry staining for CD3, CD4, CD8, Foxp3, cytokeratin (CK), PDL1, and 4′,6-diamidino-2-phenylindole (DAPI). The infiltration density of TILs subpopulations and PDL1 expression were compared between the two groups. The Gcross function was calculated to quantify the relative proximity of any two types of cells. The Cox proportional hazards regression model was used to identify factors associated with overall survival (OS) and disease-free survival (DFS).ResultsThe densities of regulatory T-cells (Tregs), effector T-cells (Teffs), PDL1+ Tregs, and PDL1+ Teffs were significantly higher in patients with unfavorable outcomes. PDL1 expression on tumor cells (TCs) or overall TILs was not associated with survival. Multivariate analysis revealed that higher PDL1+ Tregs infiltration density was independently associated with inferior OS and DFS, whereas Tregs infiltration density was only a prognostic marker for DFS. Spatial analysis revealed that unfavorable group had significantly stronger Tregs and PDL1+ Tregs engagement in the proximity of TCs and cytotoxic T lymphocyte (CTLs). Gcross analysis further revealed that Tregs and PDL1+ Tregs were more likely to colocalize with CTLs. Moreover, increased GTC : Treg (Tregs engagement surrounding TCs) and GCTL : PDL1+ Treg were identified as independent factors correlated with poor outcomes.ConclusionTILs have a diverse infiltrating pattern and spatial distribution in NPC. Increased infiltration of Tregs, particularly PDL1+ Tregs, as well as their proximity to TCs and CTLs, correlates with unfavorable outcomes, implying the significance of intercellular immune regulation in mediating disease progression.
Difference in aqueous concentration and vitreous mass of cytokines in high myopias with and without choroidal neovascularization
Authors: Zhang Shian , Mao Jianbo , Chen Nuo , Fang Yuyan , Chen Yijing , Zheng Zicheng , Chen Yiqi , Shen Lijun 
Published: November 2022

PurposeTo investigate and compare the aqueous humor (AH) concentration and vitreous mass of cytokines in high myopias (HM) with and without myopic choroidal neovascularization (mCNV). And the correlations between cytokines and the size of CNVs on optical coherence tomography angiography (OCTA) images were also be analyzed.MethodsThis observational study included 56 highly myopic eyes with and without CNV and 57 control eyes with cataracts. AH samples were obtained prior to the intravitreal injection of anti-VEGF and cataract surgery. This study measured multiple inflammatory cytokines including VEGF, interleukin (IL)-6, IL-8, IL-10, interferon-inducible protein-10 (IP-10), and monocyte chemotactic protein-1 (MCP-1) by multiplex bead assay. AH cytokine level, axial length, and vitreous volume were used to calculate the vitreous mass of cytokines.ResultsThe vitreous mass of VEGF in eyes with mCNV was significantly higher than that in control group. However, the difference in AH concentration of VEGF between high myopias with mCNV was not observed. Inflammatory cytokines were upregulated (IL-6, IL-10, and MCP-1) in highly myopic eyes both with and without mCNV (all P&lt;0.05). There was also a significant difference in the vitreous mass of IL-8 and IP-10 among all three groups (P&lt;0.05).ConclusionWe confirmed the secretion of VEGF increased in eyes with mCNV from a new perspective. The development of both HM and mCNV were related to inflammatory cytokines and the upregulation of inflammatory cytokines may precede upregulation of VEGF. The vitreous mass might be tried as a more reliable potential biomarker in eyes with longer axial length.
Amniotic membrane transplantation and conjunctival autograft combined with mitomycin C for the management of primary pterygium: A systematic review and meta-analysis
Authors: Taher Nada Omar , Alnabihi Ahmed Naji , Hersi Reem Mahmoud , Alrajhi Rawan Khalid , Alzahrani Reham Ahmad , Batais Waleed Talib , Mofti Alaa Hesham , Alghamdi Saeed Abdullah 
Published: November 2022

BackgroundPterygium is a common ocular surface disease. Recurrence is the greatest concern in the treatment of pterygium. Thus, a standardized and effective treatment modality with minimal risk for complications is needed for the management of pterygium. The aim of this systematic review and meta-analysis was to evaluate different tissue grafting options, including conjunctival autograft (CAG) with mitomycin C (MMC), CAG alone, and amniotic membrane transplantation (AMT), for the management of primary pterygium.MethodsWe searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases for relevant studies. We included randomized controlled trials (RCTs) in which CAG + MMC and AMT were compared with surgical excision with CAG alone for the treatment of primary pterygium. The rates of recurrence and adverse events reported in the studies were also evaluated. Risk ratio (RR) was used to represent dichotomous outcomes. The data were pooled using the inverse variance weighting method. The quality of the evidence derived from the analysis was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials.ResultsTwelve RCTs (n= 1144) were deemed eligible and included for analysis. Five RCTs had a low risk of bias, five had some concerns, and two had a high risk of bias. Subgroup analysis showed a statistically significant reduction in the rate of pterygium recurrence after CAG + MMC (RR = 0.12; 95% confidence interval [CI], 0.02–0.63). This outcome was rated as high-quality evidence according to the GRADE criteria. There were insignificant differences between the rates of recurrence after AMT and CAG (RR = 1.51; 95% CI, 0.63–3.65). However, this result was rated as low-quality evidence. Regarding adverse events, patients treated using AMT showed significantly lower rates of adverse events than those treated using CAG (RR = 0.46; 95% CI, 0.22–0.95). However, this finding was rated as low-quality evidence as well. CAG + MMC showed a safety profile comparable to that of surgical excision with CAG alone (RR = 1.81; 95% CI, 0.40–8.31). This result was also rated as low-quality evidence.ConclusionA single intraoperative topical application of 0.02% MMC during excision of pterygium followed by CAG has significantly shown to decrease the rate of pterygium recurrence to 1.4% with no severe complications.
Stability of motor-nonmotor subtype in early-stage Parkinson’s disease
Authors: Xiao Yi , Wei Qianqian , Ou Ruwei , Hou Yanbing , Zhang Lingyu , Liu Kuncheng , Lin Junyu , Yang Tianmi , Jiang Qirui , Shang Huifang 
Published: November 2022

BackgroundThe different clinical characteristics and prognostic values of the motor-nonmotor subtypes of Parkinson’s disease (PD) have been established by previous studies. However, the consistency of motor-nonmotor subtypes in patients with early-stage Parkinson’s disease required further investigation. The present study aimed to evaluate the consistency of motor-nonmotor subtypes across five years of follow-up in a longitudinal cohort.Materials and methodsPatients were classified into different subtypes (mild-motor–predominant, intermediate, diffuse malignant; or tremor-dominant, indeterminate, postural instability and gait difficulty) according to previously verified motor-nonmotor and motor subtyping methods at baseline and at every year of follow-up. The agreement between subtypes was examined using Cohen’s kappa and total agreement. The determinants of having the diffuse malignant subtype as of the fifth-year visit were explored using logistic regression.ResultsA total of 421 patients were included. There was a fair degree of agreement between the baseline motor-nonmotor subtype and the subtype recorded at the one-year follow-up visit (κ = 0.30 ± 0.09; total agreement, 60.6%) and at following years’ visits. The motor-nonmotor subtype had a lower agreement between baseline and follow-up than did the motor subtype. The baseline motor-nonmotor subtype was the determinant of diffuse malignant subtype at the fifth-year visit.ConclusionMany patients experienced a change in their motor-nonmotor subtype during follow-up. Further studies of consistency in PD subtyping methods should be conducted in the future.
Longitudinal SARS-CoV-2 humoral response in MS patients with and without SARS-CoV-2 infection prior to vaccination
Authors: van Dam Koos P. J. , Hogenboom Laura , Stalman Eileen W. , Kummer Laura Y. L. , Steenhuis Maurice , Keijser Jim B. D. , Brinke Anja ten , van Ham S. Marieke , Kuijpers Taco W. , Rispens Theo , Wieske Luuk , Eftimov Filip , Strijbis Eva M. , Killestein Joep , van Kempen Zoé L. E. 
Published: November 2022

IntroductionDuring the COVID-19 pandemic, certain disease modifying therapies (DMTs) used in multiple sclerosis (MS), such as anti-CD20 therapies, have been associated with decreased humoral responses after SARS-CoV-2 vaccination. Hybrid immunity, referring to immunity after both vaccination and SARS-CoV-2 infection might increase humoral responses.MethodsThis was a substudy of two prospective cohort studies on SARS-CoV-2 antibodies after SARS-CoV-2 infection and vaccination. RBD-specific IgG titers of patients with MS and healthy controls who had experienced SARS-CoV-2 infection prior to the first vaccination were compared with those patients and healthy controls without prior infection. Humoral responses were measured at various time points after SARS-CoV-2 infection in convalescent patients and all patients prior to the first vaccination, 28 days after the first vaccination, and 28 days after the second vaccination.ResultsOne hundred and two individuals [of which 34 patients with MS and DMTs (natalizumab or ocrelizumab), 30 patients without DMTs, and 38 healthy controls] were included. Fifty one of these individuals were convalescent. Median SARS-CoV-2 antibody titers were higher after the first vaccination in convalescent individuals compared with individuals without infection prior to vaccination. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody titers were comparable after the second vaccination in patients with MS with and without prior infection. However, in the convalescent ocrelizumab-treated patients, SARS-CoV-2 antibody titers did not increase after vaccinations.ConclusionIn patients with MS without anti-CD20 therapies, SARS-CoV-2 infection before vaccination increases humoral responses after the first vaccination, similar to the healthy controls. In patients with MS treated with ocrelizumab (convalescent and non-convalescent), humoral responses remained low.
Clinical and cortical similarities identified between bipolar disorder I and schizophrenia: A multivariate approach
Authors: Rootes-Murdy Kelly , Edmond Jesse T. , Jiang Wenhao , Rahaman Md A. , Chen Jiayu , Perrone-Bizzozero Nora I. , Calhoun Vince D. , van Erp Theo G. M. , Ehrlich Stefan , Agartz Ingrid , Jönsson Erik G. , Andreassen Ole A. , Westlye Lars T. , Wang Lei , Pearlson Godfrey D. , Glahn David C. , Hong Elliot , Buchanan Robert W. , Kochunov Peter , Voineskos Aristotle , Malhotra Anil , Tamminga Carol A. , Liu Jingyu , Turner Jessica A. 
Published: November 2022

BackgroundStructural neuroimaging studies have identified similarities in the brains of individuals diagnosed with schizophrenia (SZ) and bipolar I disorder (BP), with overlap in regions of gray matter (GM) deficits between the two disorders. Recent studies have also shown that the symptom phenotypes associated with SZ and BP may allow for a more precise categorization than the current diagnostic criteria. In this study, we sought to identify GM alterations that were unique to each disorder and whether those alterations were also related to unique symptom profiles.Materials and methodsWe analyzed the GM patterns and clinical symptom presentations using independent component analysis (ICA), hierarchical clustering, and n-way biclustering in a large (N ∼ 3,000), merged dataset of neuroimaging data from healthy volunteers (HV), and individuals with either SZ or BP.ResultsComponent A showed a SZ and BP &lt; HV GM pattern in the bilateral insula and cingulate gyrus. Component B showed a SZ and BP &lt; HV GM pattern in the cerebellum and vermis. There were no significant differences between diagnostic groups in these components. Component C showed a SZ &lt; HV and BP GM pattern bilaterally in the temporal poles. Hierarchical clustering of the PANSS scores and the ICA components did not yield new subgroups. N-way biclustering identified three unique subgroups of individuals within the sample that mapped onto different combinations of ICA components and symptom profiles categorized by the PANSS but no distinct diagnostic group differences.ConclusionThese multivariate results show that diagnostic boundaries are not clearly related to structural differences or distinct symptom profiles. Our findings add support that (1) BP tend to have less severe symptom profiles when compared to SZ on the PANSS without a clear distinction, and (2) all the gray matter alterations follow the pattern of SZ &lt; BP &lt; HV without a clear distinction between SZ and BP.
Red, white, and processed meat consumption related to inflammatory and metabolic biomarkers among overweight and obese women
Authors: Shiraseb Farideh , Hosseininasab Dorsa , Mirzababaei Atieh , Bagheri Reza , Wong Alexei , Suzuki Katsuhiko , Mirzaei Khadijeh 
Published: November 2022

BackgroundConsidering that a high meat intake is directly associated with obesity, it is critical to address the relationship between consuming different types of meat with inflammation and metabolism in overweight and obese cohorts. Thus, we evaluated the association between red, white, and processed meat consumption with inflammatory and metabolic biomarkers in overweight and obese women.MethodsThe current cross-sectional study was conducted on 391 overweight and obese Iranian women. Dietary intake was obtained from a food frequency questionnaire (FFQ) with 147 items. The anthropometric measurements, serum lipid profile, and inflammatory markers were measured by standard protocols. All associations were assessed utilizing one-way analysis of variance (ANOVA), analysis of covariance (ANCOVA), and linear regression models.ResultsIn the adjusted model, it was established that higher intake of processed meat had a significant positive association with leptin levels (β: 0.900, 95% CI: 0.031;1.233, p = 0.015). Moreover, after considering the confounders, a significant positive association between processed meat and macrophage inflammatory protein (MCP-1) levels was observed (β: 0.304, 95% CI:0.100;1.596, p = 0.025). Positive significant associations between high-sensitivity C-reactive protein (hs-CRP) (β:0.020, 95% CI:0.000;0.050, P = 0.014) and plasminogen activator inhibitor 1 (PAI-1) (β:0.263, 95% CI:0.112;0.345, p = 0.053) and MCP-1 (β:0.490, 95% CI: 0.175;1.464, p = 0.071) levels with red meat were also shown; while there was a significant negative association between red meat and the homeostasis model assessment of insulin resistance (HOMA-IR) (β: −0.016, 95% CI: −0.022, −0.001, p = 0.033). Furthermore, a significant negative association were established following confounding adjustment between Galectin-3 (Gal-3) (β: −0.110, 95% CI: −0.271;0.000, p = 0.044), MCP-1 (β: −1.933, 95% CI: −3.721;0.192, p = 0.022) and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (β: −0.011, 95% CI: −0.020,0.000, p = 0.070) levels with high adherence of white meat intake. In contrast, a significant marginally positive association between PAI-1 levels and high adherence to white meat intake (β: −0.340, 95% CI: −0.751;0.050, p = 0.070) has been shown.ConclusionsHigher red and processed meat consumption were positively associated with inflammatory and metabolic markers in overweight and obese women. In contrast, negative relationships between high adherence to white meat and various inflammatory and metabolic parameters were established. Further studies are needed to confirm the causality of these associations and potential mediating pathways.
Zinc agronomic biofortification of staple crops may be a cost-effective strategy to alleviate zinc deficiency in Ethiopia
Authors: Abdu Abdu Oumer , De Groote Hugo , Joy Edward J. M. , Kumssa Diriba B. , Broadley Martin R. , Gashu Dawd 
Published: November 2022

BackgroundInadequate dietary zinc (Zn) supplies and Zn deficiency (ZnD) are prevalent in Ethiopia, where cereals are major dietary sources, yet low in bioavailable Zn. Zinc agronomic biofortification (ZAB) of staple crops through application of Zn fertilizers may contribute to alleviating ZnD. However, large-scale promotion and adoption of ZAB requires evidence of the feasibility and public health benefits. This paper aimed to quantify the potential cost-effectiveness of ZAB of staple crops for alleviating ZnD in Ethiopia.MethodsCurrent burden of ZnD among children in Ethiopia was quantified using a disability-adjusted life years (DALYs) framework. Evidence on baseline dietary Zn intake, cereal consumption, and fertilizer response ratio was compiled from existing literature and secondary data sources. Reduction in the burden of ZnD attributable to ZAB of three staple cereals (maize, teff, and wheat) via granular and foliar Zn fertilizer applications was calculated under optimistic and pessimistic scenarios. The associated costs for fertilizer, labor, and equipment were estimated in proportion to the cropping area and compared against DALYs saved and the national Gross Domestic Product capita–1.ResultsAn estimated 0.55 million DALYs are lost annually due to ZnD, mainly due to ZnD-related mortality (91%). The ZAB of staple cereals via granular Zn fertilizer could reduce the burden of ZnD by 29 and 38% under pessimistic and optimistic scenarios, respectively; the respective values for ZAB via foliar application were 32 and 40%. The ZAB of staple cereals via granular fertilizer costs US$502 and US$505 to avert each DALY lost under optimistic and pessimistic scenarios, respectively; the respective values for ZAB via foliar application were US$226 and US$ 496. Foliar Zn application in combination with existing pesticide use could reduce costs to US$260–353 for each DALY saved. Overall, ZAB of teff and wheat were found to be more cost-effective in addressing ZnD compared to maize, which is less responsive to Zn fertilizer.ConclusionZAB of staple crops via granular or foliar applications could be a cost-effective strategy to address ZnD, which can be integrated with the existing fertilizer scheme and pesticide use to minimize the associated costs.
Intrahepatic biliary cystadenoma: Confusion, experience, and lessons learned from our center
Authors: Yang Yongguang , Chen Weihuang , Cen Haiqiang , Li Zuobiao , Di Xiaoqing , Wu Yongjun , Liu Lijuan 
Published: November 2022

BackgroundIntrahepatic biliary cystadenoma (IBC) is a rare benign cystic tumor of the liver. So far, it has not been comprehensively understood, which causes incorrect diagnosis, treatment confusion, and even inappropriate treatment. Here, we reviewed clinical data of IBC patients in our center, shared our experiences and lessons learned, and improved the level of diagnosis and treatment.MethodsThe clinical data of 10 patients with pathologically diagnosed IBC, admitted to the Department of Hepatobiliary Surgery of the Affiliated Hospital of Guangdong Medical University from January, 2007, to January, 2022 were retrospectively analyzed.Results10 patients underwent surgery and were discharged successfully. Cyst morphology: multiple cysts: 6 cases (6/10), monocular cyst: four cases(4/10). Six patients (6/10) were diagnosed as IBC preoperatively and received hepatectomy. Four patients with monocular cyst IBC underwent intraoperative frozen section examination, except one case showed IBC; the rest were misdiagnosed as simple liver cyst. In three misdiagnosed patients, one underwent open left hepatectomy seven days after the initial operation. The other patient refused to undergo reoperation and required follow-up observation. The last patient could not tolerate hepatectomy due to insufficient residual liver volume and chose follow-up observationConclusionFor IBC, especially monocular IBC, it is easy to be misdiagnosed as simple hepatic cyst, which brings great confusion to clinical treatment. We propose strengthening communication with pathologists to deepen understanding of IBC. Attention should be paid to the cyst wall’s shape and the cyst fluid’s properties during the operation to avoid the missed diagnosis, misdiagnosis, or even improper operation. For suspicious cases, directly choose hepatectomy to avoid reoperation after thoroughly evaluating the patient’s condition.
Expanding the molecular spectrum of tenosynovial giant cell tumors
Authors: Gauduchon Thibault , Vanacker Helene , Pissaloux Daniel , Cassier Philippe , Dufresne Armelle , Karanian Marie , Meurgey Alexandra , Bouhamama Amine , Gouin François , Ray-Coquard Isabelle , Blay Jean-Yves , Tirode Franck , Brahmi Mehdi 
Published: November 2022

BackgroundWhile great advances in clinical and pathological description of tenosynovial giant cell tumors (TGCT) have been made, TGCT molecular heterogeneity represents an ongoing challenge. The canonical oncogenic fusion CSF1::COL6A3 is not systematically observed, suggesting that other oncogenic mechanisms are involved in tumorigenesis. This study aims to explore by RNA sequencing a retrospective series of tumors diagnosed as TGCT, in order to provide a better description of their molecular landscape and to correlate molecular features with clinical data.MethodsWe analyzed clinicopathological data and performed whole-exome RNA sequencing on 41 TGCT samples.ResultsRNAseq analysis showed significant higher CSF1 and CSF1-R expression than a control panel of 2642 solid tumors. RNA sequencing revealed fusion transcripts in 14 patients including 6 not involving CSF1 and some previously unreported fusions. Unsupervised clustering on the expression profiles issued from this series suggested two distinct subgroups: one composed of various molecular subtypes including CSF1 and FN1 rearranged samples and one composed of four tumors harboring an HMGA2::NCOR2 fusion, suggesting distinct tumor entities. Overall, 15 patients received at least one systemic anti-CSF1R treatment and clinical improvement was observed in 11 patients, including patients from both clusters.DiscussionThis study reported molecular heterogeneity in TGCT, contrasting with the clinical and pathological homogeneity and the ubiquitous high CSF1 and CSF1R expression levels. Whether molecular diversity may impact the efficacy of systemic treatments needs to be further investigated.