bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pancreatic Apoplexy
Authors: Mintziras Ioannis , Stollenwerk Lisa , Uhl Waldemar , Niescery Jennifer , Belyaev Orlin , Luu Andreas Minh , Munding Johanna , Tannapfel Andrea , Künzli Beat , Herzog Torsten 
Published: April 2023

Objectives
Patient characteristics with postoperative acute necrotizing pancreatitis and completion pancreatectomy (CP) after pancreaticoduodenectomy (PD) remain unclear.

Methods
Data from all patients who underwent a PD with need for CP (January 2011–December 2019) at a German University Hospital were analyzed regarding the indications and timing of CP, laboratory and histopathological findings, and overall outcome.

Results
Six hundred twelve patients underwent PD, 33 (5.4%) of them needed a CP. Indications were grade C pancreatic fistula with or without biliary leak (46% and 12%), biliary leak (6%), and hemorrhage due to pancreatic fistula (36%). Eight patients (24%) underwent CP within 3 days after PD. These fulminant courses (“pancreatic apoplexy”) were accompanied by significantly higher levels of lactate dehydrogenase, C-reactive protein, serum amylase, serum lipase, drain amylase, and drain lipase compared with patients with CP after the third day. Pancreatic apoplexy was histologically associated with higher rates of pancreatic necrosis (P = 0.044) and hemorrhage (P = 0.001). A trend toward higher mortality was observed (75% vs 36%, P = 0.058).

Conclusions
Pancreatic apoplexy, defined as fulminant necrotizing pancreatitis after PD leading to CP within 3 days, is associated with characteristic laboratory and histopathological findings and a trend to higher mortality.
Pancreatic Adenocarcinoma With Strong Expression of Interleukin-13 Receptor α2 Shows a Poor Response to Gemcitabine-Based Chemotherapy
Authors: Tomishima Ko , Fujisawa Toshio , Fukumura Yuki , Ushio Mako , Fukuma Taito , Takahashi Sho , Takasaki Yusuke , Suzuki Akinori , Ito Koichi , Ishii Shigeto , Yao Takashi , Nagahara Akihito , Isayama Hiroyuki 
Published: April 2023

Objectives
Pancreatic ductal adenocarcinoma with strong expression of interleukin-13 receptor α2 (IL-13Rα2) was associated with poor prognosis and gemcitabine resistance in an orthotopic mouse model. We evaluated the influence of IL-13Rα2 expression in the endoscopic ultrasound–fine needle aspiration (EUS-FNA) specimen.

Methods
We included patients with pancreatic ductal adenocarcinoma, as diagnosed by EUS-FNA, who received gemcitabine-based chemotherapy (G-CTX). Tumor expression of IL-13Rα2 was assessed by immunohistochemistry and classified using a three scale (negative, weak, or strong) in a blinded fashion. The effect of G-CTX was assessed by tumor reduction rate by computed tomography after 3 months.

Results
A total of 95 patients were enrolled, and 63 and 32 cases were determined with strong and weak/negative expression of IL-13Rα2. The IL-13Rα2–strong group showed significantly poorer progression-free and overall survival rates than weak/negative group (P = 0.0191 and P = 0.0062, respectively). Strong expression of IL-13Rα2 was associated with progression factor after 3 months of the first G-CTX (odds ratio, 13.72; P = 0.0143).

Conclusions
Pancreatic ductal adenocarcinoma with strong expression of IL-13Rα2 in EUS-FNA specimens showed poor prognosis and poor response to G-CTX.
Clinically Relevant Biology of Hyaluronic Acid in the Desmoplastic Stroma of Pancreatic Ductal Adenocarcinoma
Authors: Jahedi Hossein , Ramachandran Anassuya , Windsor John , Knowlton Nicholas , Blenkiron Cherie , Print Cristin G. 
Published: April 2023

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is notorious for its poor outcome. The presence of a dense desmoplastic stroma is a hallmark of this malignancy, and abundant hyaluronic acid (HA) within this stroma is a common feature of PDAC. At the end of 2019, an HA-targeting drug, after initial promise, failed phase 3 clinical trials in PDAC. This failure in the face of such strong evidence for biological importance forces us to turn back to the research and seek a better understanding of HA biology in PDAC. Therefore, in this review, we reexamine what is known about HA biology, the methods used to detect and quantify HA, and the ability of the biological models in which HA has been investigated to recapitulate an HA-rich desmoplastic tumor stroma. The role of HA in PDAC relies on its complex interplay with a range of HA-associated molecules, which have not been as extensively investigated as HA itself. Therefore, using large genomic data sets, we cataloged the abundance and activity in PDAC of molecules that modulate HA synthesis, degradation, protein interactions, and receptor binding. Based on their association with clinical characteristics and individual patient outcomes, we suggest a small number of HA-associated molecules that warrant further investigation as biomarkers and drug targets.
Challenges in Recruitment and Retention
Authors: Coffin Tara B. , Kenner Barbara J. 
Published: April 2023

Abstract
Advancements in pancreatic ductal adenocarcinoma (PDAC) prevention, diagnosis, and treatment rely on representative and robust clinical trial participation. Given the severity of PDAC, along with the lack of effective early detection approaches, the need for accessible screening tools and new treatments is dire. Unfortunately, enrollment barriers often result in low participant accrual rates for PDAC studies and illustrate the challenging terrain researchers are facing. Research participation along with access to preventative care has been further impacted by the coronavirus disease 2019 pandemic. In this review, we use the Comprehensive Model for Information Seeking to discuss underexplored factors that influence patient participation in clinical studies. Adequate staffing, flexible scheduling, effective patient and physician communication, and culturally responsive messaging, along with the use of telehealth, can support enrollment objectives. Clinical research studies are a key component of health care, informing medical advancements, and improving outcomes. By leveraging health-related antecedents and information carrier factors, researchers can more effectively address barriers to participation and implement potential evidence-based mitigating strategies. While this work focuses on the PDAC research context, the lessons delineated here are applicable to the wider cancer research setting.
DPP10-AS1–Mediated Downregulation of MicroRNA-324-3p Is Conducive to the Malignancy of Pancreatic Cancer by Enhancing CLDN3 Expression
Authors: Jiang Fengru , Li Sumei , Wang Xiaoyun , Deng Yingzhao , Peng Shuying 
Published: April 2023

Objectives
Network of long noncoding RNA-microRNA (miRNA)-mRNA is becoming increasingly pivotal roles in carcinogenesis mechanism. Herein, we aim to delineate the mechanistic understanding of dipeptidyl peptidase like 10-antisense RNA 1 (DPP10-AS1)/miRNA-324-3p/claudin 3 (CLDN3) axis in the malignancy of pancreatic cancer (PC).

Methods
Microarray profiling and other bioinformatics methods were adopted to predict differentially expressed long noncoding RNA-miRNA-mRNA in PC, followed by verification of expression of DPP10-AS1, microRNA-324-3p (miR-324-3p), and CLDN3 in PC cells. The relationship among DPP10-AS1, miR-324-3p, and CLDN3 were further assessed. The PC cell invasion and migration were evaluated by scratch test and transwell assay. Tumor formation and lymph node metastasis were assessed in nude mice

Results
Highly expressed DPP10-AS1 and CLDN3 and poorly expressed miR-324-3p were identified in PC cells. The competitively binding between DPP10-AS1 and miR-324-3p was identified, and CLDN3 was targeted and downregulated by miR-324-3p. In addition, DPP10-AS1 was found to sequester miR-324-3p to release CLDN3 expression. DPP10-AS1 knockdown or miR-324-3p restoration diminished migration, invasion, tumor formation, microvessel density, and lymph node metastasis of PC cells, which was associated with CLDN3 downregulation.

Conclusions
Taken together, the study identified the regulatory role of DPP10-AS1/miR-324-3p/CLDN3 axis in PC, offering a mechanistic basis suggesting DPP10-AS1 ablation as a therapeutic target against PC.
The Efficacy and Safety of Treatment Regimens Used in the First-Line Setting in Metastatic Pancreatic Cancer Patients
Authors: Akdeniz Nadiye , Kaplan Muhammet Ali , İnanç Mevlüde , Uncu Doğan , Ergün Yakup , Küçüköner Mehmet , Demirci Ayşe , Şendur Mehmet Ali Nahit , Beşiroğlu Mehmet , Topçu Atakan , Yerlikaya Halis , Urakçi Zuhat , Kiliçkap Saadettin , Işikdoğan Abdurrahman 
Published: April 2023

Objective
The aim of the study is to compare the efficacy and safety of 3 chemotherapy regimens used as first-line treatments in the real-life management of metastatic pancreatic cancer.

Methods
A total of 218 patients were included in this multicenter study. Gemcitabine (Gem, n = 71), gemcitabine-cisplatin (Gem-Cis, n = 91), and FOLFIRINOX (a combination of leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin [FFX], n = 56) treatments were compared.

Results
Overall response rate was significantly higher in the FFX group (50.0%) than in the Gem (28.2%) and Gem-Cis (27.5%) groups (P = 0.010). Median progression-free survival (8.4 vs 4.6 and 5.5 months, respectively, P < 0.001) and overall survival (16.4 vs 8.1 and 8.7 months, respectively, P = 0.002) were significantly longer in the FFX group than in the Gem and Gem-Cis groups. Toxicity of any grade was noted in 46 (64.8%), 56 (61.5%), and 49 (87.5%) patients in the Gem, Gem-Cis, and FFX groups, respectively (P = 0.003).

Conclusions
In our study, FFX regimen provides a significant advantage over the other treatment regimens in terms of response rates and survival. Treatment toxicity was more frequent but manageable with the FFX regimen.
Toll-Like Receptor 9 Signaling Pathway Contributes to Intestinal Mucosal Barrier Injury in Mice With Severe Acute Pancreatitis
Authors: Ni Wei , Ma Yu-Feng , Chen Tao , Chen Xia 
Published: April 2023

Objectives
The purpose of this study was to investigate the role and mechanism of toll-like receptor 9 (TLR9) in intestinal mucosal barrier injury in mice with severe acute pancreatitis (SAP).

Methods
The mice were randomly divided into 3 groups: control group, SAP group, and TLR9 antagonist–treated group. The expression of tumor necrosis factor-α, interleukin-1β, interleukin-6, diamine oxidase, and endotoxin core antibodies were detected by enzyme-linked immunosorbent assay. The protein expression of zonula occluden-1 (ZO)-1, occludin, TLR9, myeloid differentiation factor 88 (MyD88), tumor necrosis factor receptor–associated factor 6 (TRAF6), p-nuclear factor (NF)-κB p65, and NF-κB p65 were detected by Western blot. TdT-mediated dUTP nick-end labeling staining was used for detecting intestinal epithelial cell apoptosis.

Results
The expression of TLR9 and its related pathway proteins MyD88, TRAF6, and p-NF-κB p65 in the intestinal tract of SAP mice were significantly increased compared with that of control mice. Inhibition of the TLR9 expression could reduce the level of serum proinflammatory cytokines, reduce the apoptosis of intestinal epithelial cells, improve intestinal permeability, and ultimately reduce the damage of intestinal mucosal barrier function in SAP.

Conclusions
Toll-like receptor 9/MyD88/TRAF6/NF-κB signaling pathway plays an important role in intestinal mucosal barrier injury of SAP.
Negative p53 Expression Confers Worse Prognosis in Patients With Resected Pancreatic Ductal Adenocarcinoma
Authors: Li Bo , Wang Yang , Wang Jian , Zhang Guoxiao , Yin Xiaoyi , Wang Huan , Jiang Hui , Jin Gang , Guo Shiwei 
Published: April 2023

Abstract

Objective
The aim of the study is to reinterpret the prognostic prediction of p53 expression categories in pancreatic ductal adenocarcinoma with exploration of the relationship between TP53 mutation genotype and p53 expression pattern.

Methods
Data were retrospectively collected from consecutive patients who underwent primary pancreatic resection. Complete loss of function of TP53 is defined as nonsense and frameshift mutations. A tissue microarray was used to evaluate p53 expression by immunohistochemistry and was categorized as regulated, high, or negative.

Results
The κ coefficient for agreement between p53 expression and TP53 was 0.761. Cox regression analyses revealed that p53 expression (high vs regulated: hazard ratio [HR], 2.225; P < 0.001; negative vs regulated: HR, 2.788; P < 0.001), tumor-node-metastasis stage (II vs I: HR, 3.471; P < 0.001; III vs I: HR, 6.834; P < 0.001), and tumor grade (G3/4 vs G1/2: HR, 1.958; P < 0.001) were independent prognostic factors in developing cohort and validation cohort. In subgroups of stage I, II, and III, compared with regulated expression, the patients with negative expression had a worse prognosis in both cohorts (P < 0.05).

Conclusions
Our findings indicate that 3-tier p53 expression in resectable pancreatic ductal adenocarcinoma provided independent prognostic information complementary to the tumor-node-metastasis staging system and facilitated patient stratification for personalized therapy.
Equity and Inclusion in Pediatric Gastroenterology Telehealth: A Study of Demographic, Socioeconomic, and Digital Disparities
Authors: Mougey Edward B. , Judy Wesley C. , Venkatesh Rajitha D. , Berg Elizabeth , Lee Jennifer A. , Rosen John M. , Li B.U.K. , Koster Alex , Maiden Kristin , Gao Zhongcui , Franciosi James P. 
Published: April 2023

Objectives:The purpose of our study is to compare in-person and telehealth pediatric care ambulatory visits for gastroenterology (GI) at the Nemours Children’s Health System in the Delaware Valley (NCH-DV) based on geospatial, demographic, socioeconomic, and digital disparities.Methods:Characteristics of 26,565 patient encounters from January 2019 to December 2020 were analyzed. U.S. Census Bureau geographic identifiers were assigned to each participant and aligned with the American Community Survey (2015–2019) socioeconomic and digital outcomes. Reported odds ratios (OR) are telehealth encounter/in-person encounter.Results:GI telehealth usage increased 145-fold in 2020 compared to 2019 for NCH-DV. Comparing telehealth to in-person usage in 2020 revealed that GI patients who required a language translator were 2.2-fold less likely to choose telehealth [individual level adjusted OR (I-ORa) [95% confidence interval, CI], 0.45 [0.30–0.66],P< 0.001]. Individuals of Hispanic ethnicity or non-Hispanic Black or African American race are 1.3–1.4-fold less likely to utilize telehealth than non-Hispanic Whites (I-ORa[95% CI], 0.73 [0.59–0.89],P= 0.002 and 0.76 [0.60–0.95],P= 0.02, respectively). Households in census block groups (BG) that are more likely to utilize telehealth: have broadband access (BG-OR = 2.51 [1.22–5.31],P= 0.014); are above the poverty level (BG-OR = 4.44 [2.00–10.24],P< 0.001); own their own home (BG-OR = 1.79 [1.25–2.60],P= 0.002); and have a bachelor’s degree or higher (BG-OR = 6.55 [3.25–13.80],P< 0.001).Conclusions:Our study is the largest reported pediatric GI telehealth experience in North America that describes racial, ethnic, socioeconomic, and digital inequities. Advocacy and research for pediatric GI focused on telehealth equity and inclusion is urgently needed.
Perceived shared decision-making among patients undergoing lower-limb amputation and their care teams: A qualitative study
Authors: Leonard Chelsea , Sayre George , Williams Sienna , Henderson Alison , Norvell Dan , Turner Aaron P. , Czerniecki Joseph 
Published: April 2023

Background:
Shared decision-making (SDM) is increasingly advocated in the care of vascular surgery patients. The goal of this investigation was to gain a greater understanding of the patient and provider experience of SDM during clinical decision-making around the need for lower-extremity amputation and amputation level related to chronic limb-threatening ischemia (CLTI) in the Veterans Health Administration.

Methods:
Semistructured interviews in male Veterans with CLTI, vascular surgeons, physical medicine and rehabilitation physicians, and podiatric surgeons. Interviews were analyzed using team-based content analysis to identify themes related to amputation-level decisions.

Results:
We interviewed 22 patients and 21 surgeons and physicians and identified 4 themes related to SDM: (1) providers recognize the importance of incorporating patient preferences into amputation-level decisions and strive to do so; (2) patients do not perceive that they are included as equal partners in decisions around amputation or amputation level; (3) providers perceive several obstacles to including patients in amputation level decisions; and (4) patients describe facilitators to their involvement in SDM.

Conclusions:
Despite the recognized importance SDM in amputation decision-making, patients often perceived that their opinion was not solicited. This may result from provider perception of significant challenges to SDM posed by the clinical context of amputation. Patients identified key features that might enhance SDM including presentation of clear, concise information, and the importance of communicating concern during the discussion. These findings point to gaps in the provision of patient-centric care through SDM discussions at the time of amputation.
Biliary Adverse Events during Neoadjuvant Therapy for Pancreatic Cancer
Authors: Thalji Sam Z. , Fernando Deemantha , Dua Kulwinder S. , Madhavan Srivats , Chisholm Phillip , Smith Zachary L. , Aldakkak Mohammed , Christians Kathleen K. , Clarke Callisia N. , George Ben , Kamgar Mandana , Erickson Beth A. , Hall William A. , Evans Douglas B. , Tsai Susan 
Published: April 2023

Objective:
To describe a high-volume experience with biliary drainage prior to neoadjuvant therapy (NAT) for patients with operable pancreatic cancer (PC) and characterize the association between biliary adverse events (BAE) and patient outcome.

Background:
Patients with PC presenting with biliary obstruction require durable decompression prior to NAT.

Methods:
Patients with operable PC and tumor-associated biliary obstruction were examined and grouped by the presence or absence of a BAE during NAT. The incidence, timing, and management of BAE are described and outcomes, including the completion of all treatment and overall survival (OS), were compared.

Results:
Of 426 patients who received pre-treatment biliary decompression, 92 (22%) experienced at least one BAE during NAT and 56 (13%) required repeat intervention on their biliary stent. The median duration of NAT was 161 days for all patients and was not different in the group that experienced BAE. Median time from initial stent placement to BAE was 64 days. An interruption in the delivery of NAT (median 7 days) occurred in 25 (6%) of 426 patients. Among 426 patients, 290 (68%) completed all NAT including surgery: 60 (65%) of 92 patients with BAE and 230 (69%) of 334 patients without BAE (P=0.51). Among 290 patients who completed NAT and surgery, the median OS was 39 months; 26 months for the 60 patients with BAE and 43 months for the 230 patients without BAE (P=0.02).

Conclusions:
During extended multimodal NAT for PC, 22% of patients experienced a BAE. Although BAE were not associated with a significant interruption of treatment, patients who experienced a BAE had worse OS.
Imaging cortical lesions in multiple sclerosis
Authors: Mainero Caterina , Treaba Constantina A. , Barbuti Elena 
Published: April 2023

Purpose of review
Cortical lesions are an established pathological feature of multiple sclerosis, develop from the earliest disease stages and contribute to disease progression. Here, we discuss current imaging approaches for detecting cortical lesions in vivo and their contribution for improving our understanding of cortical lesion pathogenesis as well as their clinical significance.

Recent findings
Although a variable portion of cortical lesions goes undetected at clinical field strength and even at ultra-high field MRI, their evaluation is still clinically relevant. Cortical lesions are important for differential multiple sclerosis (MS) diagnosis, have relevant prognostic value and independently predict disease progression. Some studies also show that cortical lesion assessment could be used as a therapeutic outcome target in clinical trials. Advances in ultra-high field MRI not only allow increased cortical lesion detection in vivo but also the disclosing of some interesting features of cortical lesions related to their pattern of development and evolution as well to the nature of associated pathological changes, which might prove relevant for better understanding the pathogenesis of these lesions.

Summary
Despite some limitations, imaging of cortical lesions is of paramount importance in MS for elucidating disease mechanisms as well as for improving patient management in clinic.
Chronic and delayed neurological manifestations of persistent infections
Authors: Pandya Darshan , Johnson Tory P. 
Published: April 2023

Purpose of the review
Persistent infections capable of causing central nervous system (CNS) complications months or years after the initial infection represent a major public health concern. This concern is particularly relevant considering the ongoing coronavirus disease 2019 pandemic, where the long-term neurological effects are still being recognized.

Recent findings
Viral infections are a risk factor for the development of neurodegenerative diseases. In this paper, we provide an in-depth exploration of the prevalent known and suspected persistent pathogens and their epidemiological and mechanistic links to later development of CNS disease. We examine the pathogenic mechanisms involved, including direct viral damage and indirect immune dysregulation, while also addressing the challenges associated with detecting persistent pathogens.

Summary
Viral encephalitis has been closely associated with the later development of neurodegenerative diseases and persistent viral infections of the CNS can result in severe and debilitating symptoms. Further, persistent infections may result in the development of autoreactive lymphocytes and autoimmune mediated tissue damage. Diagnosis of persistent viral infections of the CNS remains challenging and treatment options are limited. The development of additional testing modalities as well as novel antiviral agents and vaccines against these persistent infections remains a crucial research goal.