bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infiltrating pattern and prognostic value of tertiary lymphoid structures in resected non-functional pancreatic neuroendocrine tumors
Authors: Zhang Wu-Hu , Wang Wen-Quan , Han Xuan , Gao He-Li , Xu Shuai-Shuai , Li Shuo , Li Tian-Jiao , Xu Hua-Xiang , Li Hao , Ye Long-Yun , Lin Xuan , Wu Chun-Tao , Long Jiang , Yu Xian-Jun , Liu Liang 
Published: October 2020

BackgroundTertiary lymphoid structures (TLS) are associated with favorable survival and play a critical role in most solid tumors. However, investigations of TLS are lacking in patients with grade 1 or grade 2 (G1/G2) non-functional pancreatic neuroendocrine tumors (NF-PanNETs). This study aimed to investigate the presence, cellular composition, association with tumor-infiltrating immune cells, and prognostic value of TLS in G1/G2 NF-PanNETs.MethodsTumor tissues from a 182-patient Fudan cohort and a 125-patient external validation set were assessed by H&E staining, immunohistochemistry, and/or multispectral fluorescent immunohistochemistry.ResultsTLS were identified in more than one-third of patients with G1/G2 NF-PanNETs and were located peritumorally, either just outside the tumor tissue or in the stromal area. TLS were mainly composed of B-cell follicles with germinal centers and T-cell zones with dendritic cells. Kaplan-Meier analyses showed that the presence of TLS correlated with both longer recurrence-free survival (RFS, p<0.001) and overall survival (OS, p=0.001), but the number of TLS had no prognostic significance. Multivariate Cox-regression analyses demonstrated that the presence of TLS, WHO classification, and 8th edition American Joint Committee on Cancer (AJCC8th) tumor-node-metastasis (TNM) stage were independent prognostic factors for RFS (p=0.004, p=0.001, and p<0.001, respectively) and OS (p=0.009, p=0.008, and p=0.019, respectively). These results were confirmed using an external validation set. Finally, a nomogram incorporating the presence of TLS was constructed to predict the probability of 5-year RFS of resected G1/G2 NF-PanNETs, which improved on the current WHO classification and AJCC8th TNM stage.ConclusionsThe presence of TLS is an independent and favorable predictor of resected G1/G2 NF-PanNETs, which may play a role in cancer immunobiology.
Clinical effectiveness of different natalizumab interval dosing schedules in a large Italian population of patients with multiple sclerosis
Authors: Chisari Clara Grazia , Grimaldi Luigi Maria , Salemi Giuseppe , Ragonese Paolo , Iaffaldano Pietro , Bonavita Simona , Sparaco Maddalena , Rovaris Marco , D'Arma Alessia , Lugaresi Alessandra , Ferrò Maria Teresa , Grossi Paola , Di Sapio Alessia , Cocco Eleonora , Granella Franco , Curti Erica , Lepore Vito , Trojano Maria , Patti Francesco 
Published: October 2020

Introduction
Natalizumab (NTZ) is one of the most effective treatment options for multiple sclerosis (MS) treatment. Our study aimed to evaluate the effectiveness of NTZ when administered according to the extended dosing strategy compared with standard 4-weekly administration in a large Italian MS population.

Materials and methods
This retrospective multicentre study included patients with relapsing-remitting MS (RR-MS) who received NTZ administrations between the 1 June 2012 and the 15 May 2018 and were followed by the ‘Italian MS Register’. All patients with MS were stratified into two groups based on NTZ administration schedule: standard interval dosing (SID) patients who received infusions on average from 28 to 32 days (median 30) and extended interval dosing (EID) including patients who have been infused with interval between 33 and 49 days (median 43). Clinical data were assessed at baseline (before starting NTZ), after 12 (T1) and 24 months (T2) of treatment.

Results
Out of 5231 patients with RR-MS screened, 2092 (mean age 43.2±12.0, 60.6% women) were enrolled. A total of 1254 (59.9%) received NTZ according to SID, and 838 (40.1%) according to EID. At 12 and 24 months, no differences in terms of annualised relapse rate and disability status were found between the two groups. Progression index and confirmed disability worsening were similar between the two groups.

Discussion
The use of NTZ with an extended interval schedule showed similar effectiveness compared with SID. Unchanged clinical efficacy of EID schedule may raise the question of a possible advantage in terms of tolerability and safety.
Platelets Promote Thromboinflammation in SARS-CoV-2 Pneumonia
Authors: Taus Francesco , Salvagno Gianluca , Canè Stefania , Fava Cristiano , Mazzaferri Fulvia , Carrara Elena , Petrova Varvara , Barouni Roza Maria , Dima Francesco , Dalbeni Andrea , Romano Simone , Poli Giovanni , Benati Marco , De Nitto Simone , Mansueto Giancarlo , Iezzi Manuela , Tacconelli Evelina , Lippi Giuseppe , Bronte Vincenzo , Minuz Pietro 
Published: October 2020

Objective:
Pulmonary thrombosis is observed in severe acute respiratory syndrome coronavirus 2 pneumonia. Aim was to investigate whether subpopulations of platelets were programmed to procoagulant and inflammatory activities in coronavirus disease 2019 (COVID-19) patients with pneumonia, without comorbidities predisposing to thromboembolism.

Approach and Results:

Overall, 37 patients and 28 healthy subjects were studied. Platelet-leukocyte aggregates, platelet-derived microvesicles, the expression of P-selectin, and active fibrinogen receptor on platelets were quantified by flow cytometry. The profile of 45 cytokines, chemokines, and growth factors released by platelets was defined by immunoassay. The contribution of platelets to coagulation factor activity was selectively measured. Numerous platelet-monocyte (mean±SE, 67.9±4.9%, n=17 versus 19.4±3.0%, n=22;
P
<0.0001) and platelet-granulocyte conjugates (34.2±4.04% versus 8.6±0.7%;
P
<0.0001) were detected in patients. Resting patient platelets had similar levels of P-selectin (10.9±2.6%, n=12) to collagen-activated control platelets (8.7±1.5%), which was not further increased by collagen activation on patient platelets (12.4±2.5%,
P
=nonsignificant). The agonist-stimulated expression of the active fibrinogen receptor was reduced by 60% in patients (
P
<0.0001 versus controls). Cytokines (IL [interleukin]-1α, IL-1β, IL-1RA, IL-4, IL-10, IL-13, IL, 17, IL-27, IFN [interferon]-α, and IFN-γ), chemokines (MCP-1/CCL2 [monocyte chemoattractant protein 1]), and growth factors (VEGF [vascular endothelial growth factor]-A/D) were released in significantly larger amounts upon stimulation of COVID-19 platelets. Platelets contributed to increased fibrinogen, VWF (von Willebrand factor), and factor XII in COVID-19 patients. Patients (28.5±0.7 s, n=32), unlike controls (31.6±0.5 s, n=28;
P
<0.001), showed accelerated factor XII–dependent coagulation.

Conclusions:
Platelets in COVID-19 pneumonia are primed to spread proinflammatory and procoagulant activities in systemic circulation.
The Materialist Dialectic in Boris Hessen’s Newton Papers (1927 and 1931)
Authors: Winkler Sean 
Published: October 2020

Abstract
Boris Hessen’s ‘The Social and Economic Roots of Newton’s Principia’ (see https://doi.org./10.1163/1569206X-00002041) is considered a pioneering work in the historiography of the natural sciences. For some, it marks the founding moment of the ‘externalist’ approach to this field of study. Previously, Hessen published another paper on Newton entitled ‘Preface to Articles by A. Einstein and J.J. Thomson’, which, some maintain, bears a stronger resemblance to works in the ‘internalist’ camp of the historiography of the natural sciences. For decades, scholars have puzzled over why Hessen chose to argue for, seemingly, diametrically opposed positions. In this paper, however, I argue that Hessen does not advance two different historiographical methods, but a single, dialectical-materialist approach that accounts for the ‘unity in opposition’ of the external and internal dimensions of natural-scientific theory. I draw from Hessen’s two papers on Newton, his previously untranslated writings, as well as selections from the secondary literature.
Using the figure-of-8 tape technique to place neonates and infants in the lithotomy position
Authors: Abbas Tariq O 
Published: October 2020

Cystourethroscopy in children can be conducted in a significant variety of patient sizes, ranging from newborns to adolescents. In order to have adequate visualization of both the urethra and the bladder, suitable positioning needs to be achieved. We describe a method for positioning the legs of infants for cystoscopy using skin-friendly tape. The benefit of this technique is that it is adaptable and cheap without the requirement for wedges, stirrups or boots. Level of evidence: Level IV.
smORFunction: a tool for predicting functions of small open reading frames and microproteins
Authors: Ji Xiangwen , Cui Chunmei , Cui Qinghua 
Published: October 2020

Abstract
Background
Small open reading frame (smORF) is open reading frame with a length of less than 100 codons. Microproteins, translated from smORFs, have been found to participate in a variety of biological processes such as muscle formation and contraction, cell proliferation, and immune activation. Although previous studies have collected and annotated a large abundance of smORFs, functions of the vast majority of smORFs are still unknown. It is thus increasingly important to develop computational methods to annotate the functions of these smORFs.

Results
In this study, we collected 617,462 unique smORFs from three studies. The expression of smORF RNAs was estimated by reannotated microarray probes. Using a speed-optimized correlation algorism, the functions of smORFs were predicted by their correlated genes with known functional annotations. After applying our method to 5 known microproteins from literatures, our method successfully predicted their functions. Further validation from the UniProt database showed that at least one function of 202 out of 270 microproteins was predicted.

Conclusions
We developed a method, smORFunction, to provide function predictions of smORFs/microproteins in at most 265 models generated from 173 datasets, including 48 tissues/cells, 82 diseases (and normal). The tool can be available at https://www.cuilab.cn/smorfunction.
DNA methylation of CpG sites in the chicken KLF7 promoter and Exon 2 in association with mRNA expression in abdominal adipose tissue and blood metabolic indicators
Authors: Zhang Zhiwei , Nie Cunxi , Chen Yuechan , Dong Yanzhe , Lin Tao 
Published: October 2020

Abstract
Background
Our previous study found that chicken KLF7 was an important regulator in formation of adipose tissue. In the present study, we analyzed the association for DNA methylation in chicken KLF7 with its transcripts of abdominal adipose tissue and blood metabolic indicators.

Results
The KLF7 transcripts of the adipose tissue of Chinese yellow broilers were associated with age (F = 6.67, P = 0.0035). In addition, the KLF7 transcripts were negatively correlated with blood glucose levels (r = − 0.61841, P = 0.0140). The DNA methylation levels of 26 CpG loci in the chicken KLF7 promoter and Exon 2 were studied by Sequenom MassArray. A total of 22 valid datasets were obtained. None of them was significantly different in relation to age (P > 0.05). However, the DNA methylation levels in the promoter were lower than those in Exon 2 (T = 40.74, P < 0.01). Correlation analysis showed that the DNA methylation levels of PCpG6 and E2CpG9 were significantly correlated with KLF7 transcripts and blood high-density lipoprotein levels, respectively, and many CpG loci were correlated with each other (P < 0.05). The methylation data were subjected to principal component analysis and factor analysis. The six principal components (z1–z6) were extracted and named Factors 1–6, respectively. Factor analysis showed that Factor 1 had a higher load on the loci in the promoter, and Factors 2–6 loaded highly on quite different loci in Exon 2. Correlation analysis showed that only z1 was significantly correlated to KLF7 transcripts (P < 0.05). In addition, an established regression equation between z1 and KLF7 transcripts was built, and the contribution of z1 to the variation on KLF7 transcripts was 34.29%.

Conclusions
In conclusion, the KLF7 transcripts of chicken abdominal adipose tissue might be inhibited by DNA methylation in the promoter, and it might be related to the DNA methylation level of PCpG6.
Comparing two methods for deriving dietary patterns associated with risk of metabolic syndrome among middle-aged and elderly Taiwanese adults with impaired kidney function
Authors: Kurniawan Adi Lukas , Hsu Chien-Yeh , Lee Hsiu-An , Rau Hsiao-Hsien , Paramastri Rathi , Syauqy Ahmad , Chao Jane C.-J. 
Published: October 2020

Abstract
Background
Dietary patterns were associated with the risk of chronic disease development and outcome-related diseases. In this study, we aimed to compare the correlation between dietary patterns and metabolic syndrome (MetS) using two methods for identifying dietary patterns.

Methods
The participants (n = 25,569) aged ≥40 years with impaired kidney function were retrieved from Mei Jau (MJ) Health Screening database from 2008 to 2010. Dietary patterns were identified by principal component analysis (PCA) and reduced rank regression (RRR) from twenty-two food groups using PROC FACTOR and PROC PLS functions.

Results
We identified two similar dietary pattern characteristics (high intakes of deep fried foods, preserved or processed foods, dipping sauce, meat, sugary drinks, organ meats, jam/honey, fried rice/flour products, instant noodles and eggs) derived by PCA and RRR. Logistic regression analysis revealed that RRR-derived dietary pattern scores were positively associated with an odds ratio (OR = 1.70, 95% CI: 1.56, 1.86) of having MetS than PCA-derived dietary pattern scores (OR = 1.38, 95% CI: 1.27, 1.51). The correlations between RRR-derived dietary pattern scores and elevated systolic and diastolic blood pressure (OR = 1.30 for both) or low high density lipoprotein cholesterol in women (OR = 1.32) were statistically significant but not significant in PCA-derived dietary pattern scores.

Conclusions
Our findings suggest that RRR gives better results when studying behavior related dietary patterns in association with MetS. RRR may be more preferable to provide dietary information for developing dietary guidelines among people with MetS. Further studies with prospective measurements are needed to verify whether RRR is a useful analytic tool for the association between dietary patterns and other chronic diseases.
Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract: a tricky diagnosis of a gastric case
Authors: Zanelli Magda , Zizzo Maurizio , Sanguedolce Francesca , Martino Giovanni , Soriano Alessandra , Ricci Stefano , Castro Ruiz Carolina , Annessi Valerio , Ascani Stefano 
Published: October 2020

Abstract
Background
Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract is a rare low-grade clonal lymphoid proliferation, included as a provisional entity in the current World Health Organization classification. The disease is generally localized to the gastrointestinal tract, mainly small bowel and colon. Involvement of other organs is infrequently reported. The majority of patients show a protracted clinical course with persistent disease. A prolonged survival, even without treatment, is common.

Case presentation
A 28-year-old woman had a 2-year history of dyspepsia and lactose intolerance. Autoimmune diseases and celiac disease were excluded. No gross lesions were identified by endoscopy. Multiple gastric biopsies showed a small-sized lymphoid infiltrate, expanding the lamina propria, with a non-destructive appearance. The lymphoid cells were positive for CD3, CD4, CD5, CD7 and negative for CD20, CD8, CD56, CD103, PD1, CD30, ALK1, CD10, BCL6, perforin, TIA-1, Granzyme B and Epstein-Barr virus-encoded RNA. KI-67 index was low (5%). Molecular analysis revealed a clonal T-cell receptor γ rearrangement. Bone marrow was microscopically free of disease, but molecular testing identified the same T-cell receptor γ rearrangement present in the gastric biopsies. After the diagnosis of indolent T-cell lymphoproliferative disorder of the gastrointestinal tract, the patient received steroid therapy, only for 2 months. She is alive, with a stable disease restricted to the stomach, at 12 months from diagnosis.

Conclusions
Indolent T-cell lymphoproliferative disorder is usually a disease of adulthood (median age: 51 yrs). The small bowel and colon are the sites most commonly involved. Our case occurred in a young woman and affected the stomach, sparing small intestine and colon. Clonality testing identified involvement of bone marrow, a site infrequently affected in this disease. Our aim is focusing on the main diagnostic issues. If appropriate immunostainings and molecular analysis are not performed, the subtle infiltrate may be easily overlooked. The risk of misdiagnosis as more aggressive lymphomas, causing patient overtreatment, needs also to be considered.
Multiple polypoid colonic metastases from rectal adenocarcinoma with signet ring cells features: a case report
Authors: Wu Yunlong , Zhou Jiaolin , Liu Tongtong , Xu Lai , Xiao Yi 
Published: October 2020

Abstract
Background
Multiple polypoid colonic metastases are very rare which mainly originated from gastric carcinoma or melanoma. For rectal cancers, liver, lung and peritoneum are the most common metastatic sites. Here we present an unusual case with rectal adenocarcinoma and metachronous multiple colonic polypoid metastases.

Case presentation
A 53-year-old man who underwent radical resection for rectal cancer 2 years ago was admitted to our department for an elevation of CEA level of 18.4 ng/ml. Colonoscopy revealed ten ivory rubbery colonic polypoid lesions (about 5 mm in diameters) in the large bowel which were confirmed as signet ring cell carcinomas (SRCC) by biopsy, but full-body contrast enhanced CT and PET-CT showed no other suspicious lesion. Seven weeks later, a laparoscopic total colectomy was performed and more than 50 polypoid lesions were observed throughout the mucosal surface of the large intestine which were confirmed as metastatic SRCC by postoperative pathological examination. All the 34 paracolic lymph nodes retrieved were involved. After 4 months, diffuse abdominopelvic and multiple bone metastases were identified by CT and the patient died of the disease 1 month later.

Conclusion
Here we present an unusual case of multiple colonic polypoid metastases of rectal adenocarcinoma. For SRCC that is prone to have disseminated micrometastases, colonic ‘polyps’ may be the early noticeable sign of undetectable and extensive tumor spread. Instead of surgical resection of ‘the confined disease in colon’, systemic treatment maybe a more appropriate choice.
Physical frailty predicts the development of social frailty: a prospective cohort study
Authors: Nagai Koutatsu , Tamaki Kayoko , Kusunoki Hiroshi , Wada Yosuke , Tsuji Shotaro , Itoh Masako , Sano Kyoko , Amano Manabu , Hayashitani Seiya , Yokoyama Ryota , Yonezawa Ryo , Kamitani Tsukasa , Shinmura Ken 
Published: October 2020

Abstract
Background
It has not been clarified whether physical frailty symptoms predict social.
frailty. The purpose of this study was to elucidate the effect of physical frailty on social frailty, and to determine which domains of physical frailty predict the development of social frailty.

Methods
We employed a two-year prospective cohort study. A total of 342 socially robust community-dwelling older adults were recruited. We used a modified social frailty screening index consisting of four social domains including financial difficulties, living alone, social activity, and contact with neighbors. Physical frailty status was also assessed at baseline. At the two-year follow-up, we assessed the development of social frailty. Social status was assessed using four social subdomains for the primary analysis. Social status was assessed using the two social subdomains of social activity and contact with neighbors, which would be affected by the physical frailty component, for the secondary analysis. The risk ratios (RR) of physical frailty for the development of social frailty were estimated.

Results
Although physical frailty symptoms were not a significant risk factor for future development of social frailty as assessed by four social subdomains (adjusted RR 1.39, 95% CI 0.95–2.15), it became significant when development of social frailty was assessed by the two social subdomains (adjusted RR 1.78, 95% CI 1.10–2.88). An analysis using the physical frailty subdomain showed that slow gait speed (adjusted RR 3.41, 95% CI 1.10–10.53) and weakness (adjusted RR 1.06, 95% CI 1.01–1.12) were independent risk factors for development of social frailty as assessed by two social subdomains.

Conclusions
Physical frailty symptoms predict the development of social frailty. Among physical frailty subdomains, gait speed and muscle strength are critical independent risk factors for future decline in the social aspect. The prevention of physical frailty, especially by maintaining gait ability and muscle strength, may be effective for avoiding social frailty.
Epigastric pain associated with herpes esophagitis: case report
Authors: Antaki Nabil , Aljarad Ziad , Dabbas Howayda , Haddad Walid , Akil M. Amin , Tarabishi Ahmad Sankari 
Published: October 2020

Abstract
Background
Herpes esophagitis is uncommon disease caused by Herpes simplex virus (HSV). While the disease most often occurs in immunocompromised patients, including post-chemotherapy, immunosuppression with organ transplants, and in AIDS, Herpes esophagitis can also occur in immunocompetent individuals.

Case presentation
We report a case of herpes esophagitis in a 72 year- old woman who was presumed to be immunocompromised following prolonged radiotherapy and chemotherapy for lymphoma. Her main symptom was epigastric pain.
Upper endoscopy showed multiple rounded ulcers in lower esophagus. The diagnosis was confirmed histologically by multiple biopsies. The patient received Valacyclovir for 2 weeks and started to get better within 3 days of treatment.

Conclusion
Although there are few published cases of Herpes esophagitis disease in the medical literature, we recommend that this disease should be considered as one of the differential diagnoses when assessing immuno-compromised patients presenting with non-specific abdominal symptoms.