bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pancreatic ductal adenocarcinoma and distal cholangiocarcinoma: a proposal of preoperative diagnostic score for differential diagnosis
Authors: Muttillo Edoardo Maria , Ciardi Antonio , Troiano Raffaele , Saullo Paolina , Masselli Gabriele , Guida Marianna , Tortora Alessandra , Sperduti Isabella , Marinello Giulio , Chirletti Piero , Caronna Roberto 
Published: January 2021

Abstract
Purpose
The differential diagnosis between primary adenocarcinoma of the pancreas head and distal cholangiocarcinoma remains a clinical challenge. Recent studies have shown important differences in terms of survival between these tumors. Therefore, different treatments should be considered, but the preoperative histological diagnosis is still difficult. Aim of this study is to create a preoperative diagnostic score for differential diagnosis between primary pancreatic adenocarcinoma and primary distal cholangiocarcinoma.

Methods
One hundred eighty consecutive patients who underwent pancreaticoduodenectomy at Sapienza University of Rome from January 2010 to December 2019 were retrospectively analyzed. Inclusion criteria were pancreatic or biliary histologic origin obtained by definitive postoperative histological examination. Exclusion criteria were diagnosis of ampullary carcinoma, non-ampullary duodenal adenocarcinoma, pancreatic metastasis, and benign disease. One hundred one patients were considered eligible for the retrospective study. Preoperative biological, clinical, and radiological parameters were considered.

Results
CRP > 10 mg/dL (p = 0.001), modified Glasgow Prognostic Score 2 (p = 0.002), albumin < 35 g/L (p = 0.05), CA 19-9 > 230 U/mL (p = 0.001), and Wirsung diameter > 3 mm (p < 0.001) were significant at univariate logistic analysis. Multivariate logistic analysis has shown that parameters independently associated with primary pancreatic adenocarcinoma were CRP > 10 mg/dL (p = 0.012), CA 19-9 > 230 U/mL (p = 0.043), and diameter of the Wirsung > 3 mm (p = 0.005). Through these parameters, a diagnostic score has been developed to predict a primary pancreatic adenocarcinoma when > 1 and a primary distal cholangiocarcinoma when < 1.

Conclusion
This feasible and low-cost diagnostic score could have a potential impact to differentiate pancreatic cancer histologic origin and to improve target therapeutic strategy.
Cytokine profile during occult hepatitis B virus infection in chronic hepatitis C patients
Authors: Ribeiro Camilla Rodrigues de Almeida , de Almeida Nathalia Alves Araújo , Martinelli Katrini Guidolini , Pires Marcia Amendola , Mello Carlos Eduardo Brandao , Barros José J. , de Paula Vanessa Salete 
Published: January 2021

AbstractBackgroundThe hepatitis B virus (HBV) is one of the leading causes of acute, chronic and occult hepatitis (OBI) representing a serious public health threat. Cytokines are known to be important chemical mediators that regulate the differentiation, proliferation and function of immune cells. Accumulating evidence indicate that the inadequate immune responses are responsible for HBV persistency. The aim of this study were to investigate the cytokines IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10 and IL-17A in patients with OBI and verify if there is an association between the levels of these cytokines with the determination of clinical courses during HBV occult infection.Methods114 patients with chronic hepatitis C were investigated through serological and molecular tests, the OBI coinfected patients were subjected to the test for cytokines using the commercial human CBA kit. As controls, ten healthy donors with no history of liver disease and 10 chronic HBV monoinfected patients of similar age to OBI patients were selected.ResultsAmong 114 HCV patients investigated, 11 individuals had occult hepatitis B. The levels of cytokines were heterogeneous between the groups, most of the cytokines showed higher levels of production detection among OBI/HCV individuals when compared to control group and HBV monoinfected pacients. We found a high level of IL-17A in the HBV monoinfected group, high levels of TNF-α, IL-10, IL-6, IL-4 and IL-2 in OBI/HCV patients.ConclusionThese cytokines could be involved in the persistence of HBV DNA in hepatocytes triggers a constant immune response, inducing continuous liver inflammation, which can accelerate liver damage and favor the development of liver cirrhosis in other chronic liver diseases.
TCF7L2 polymorphisms, nut consumption, and the risk of metabolic syndrome: a prospective population based study
Authors: Hosseinpour-Niazi Somayeh , Bakhshi Bahar , Zahedi Asiyeh-Sadat , Akbarzadeh Mahdi , Daneshpour Maryam S. , Mirmiran Parvin , Azizi Fereidoun 
Published: January 2021

Abstract
Background
The aim of this study was to investigate whether two variants of the TCF7L2 (rs7903146 and rs12255372) modify the association between nut consumption and the risk of metabolic syndrome (MetS). Additionally, the modifying effect of weight change during follow-up on these associations was investigated.

Material and methods
We prospectively studied 1423 participants of the Tehran Lipid and Glucose study aged 19–74 years who were followed-up for dietary assessment using a validated, semi-quantitative food frequency questionnaire. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) for MetS events. Genotyping was performed by Human Omni Express-24-v1-0 chip.

Results
Over a median 8.9 years of follow-up, 415 new cases of MetS were documented. The median nut consumption was 20.0 g/week (Interquartile Range (IQR): 8.6–38.9 g/week). Regarding the rs7903146 genotype, in carriers of T allele (CT + TT), highest tertile of nut consumption was associated with a reduced risk of MetS after adjusting for confounders (HR: 0.67 (0.50–0.91)). Regarding the rs12255372 genotype, highest versus lowest tertile of nut consumption in participants with T allele (GT + TT) resulted in 34% reduction of MetS risk after adjustment for confounders (HR: 0.66 (0.49–0.69)). After stratification by weigh change (< 7% or ≥ 7% weight gain), in individuals with ≥ 7% weight gain, highest tertile of nut consumption was associated with reduced risk of MetS among the risk allele of rs7903146. In the risk allele of rs12255372, among individuals with < 7% weight gain, third tertile of nuts intake reduced the risk of MetS, after adjustment for confounders.

Conclusion
Higher consumption of nuts may reduces the risk of MetS in T-risk allele of the TCF7L2 rs7903146 and rs12255372 variants and weight change may modify this association.
Three-month outcomes from a patient-centered program to treat opioid use disorder in Iowa, USA
Authors: Lynch Alison C. , Weber Andrea N. , Hedden Suzy , Sabbagh Sayeh , Arndt Stephan , Acion Laura 
Published: January 2021

Abstract
Background
Opioid use disorder (OUD), a chronic disease, is a major public health problem. Despite availability of effective treatment, too few people receive it and treatment retention is low. Understanding barriers and facilitators of treatment access and retention is needed to improve outcomes for people with OUD.

Objectives
To assess 3-month outcomes pilot data from a patient-centered OUD treatment program in Iowa, USA, that utilized flexible treatment requirements and prioritized engagement over compliance.

Methods
Forty patients (62.5% female: mean age was 35.7 years, SD 9.5) receiving medication, either buprenorphine or naltrexone, to treat OUD were enrolled in an observational study. Patients could select or decline case management, counseling, and peer recovery groups. Substance use, risk and protective factors, and recovery capital were measured at intake and 3 months.

Results
Most participants reported increased recovery capital. The median Assessment of Recovery Capital (ARC) score went from 37 at enrollment to 43 (p < 0.01). Illegal drug use decreased, with the median days using illegal drugs in the past month dropping from 10 to 0 (p < 0.001). Cravings improved: 29.2% reported no cravings at intake and 58.3% reported no cravings at 3 months (p < 0.001). Retention rate was 92.5% at 3 months. Retention rate for participants who were not on probation/parole was higher (96.9%) than for those on probation/parole (62.5%, p = 0.021).

Conclusion
This study shows preliminary evidence that a care model based on easy and flexible access and strategies to improve treatment retention improves recovery capital, reduces illegal drug use and cravings, and retains people in treatment.
Distribution of the T12 erector spinal muscle plane block in the dorsal region guided by ultrasound
Authors: Zhang Jin-Feng , Zhang Wei-Wei , Wang Jia , Guo Hao , Wang Ting 
Published: January 2021

Abstract
Background
This study aimed to explore the distribution of the erector spinal muscle plane block of the thoracic 12 vertebral body (T12) in the dorsal region guided by ultrasound.

Methods
A total of 28 patients, who underwent elective lumbar surgery, were enrolled in the present study. These patients were aged between 18 and 65 years, and the American Society of Anesthesiologists (ASA) grade was 1 or 2. The block of the T12 transverse process erector spinal muscle was performed under the guidance of ultrasound, and each side was injected with 25 ml of 0.4% ropivacaine hydrochloride + 2 mg of dexamethasone. The back areas were measured using the cold-warm method (the back area was divided into 11 areas [T7–S1] with the body surface marker). At 10, 20, 30, 40, 50, and 60 min after the drug injection, the effectiveness of the regional block was recorded. The presence of puncture hematoma, local anesthesia drug poisoning, nausea, vomiting, headache, and dizziness after the block was recorded.

Results
The range of the T12 transverse process block was basically fixed at 30 min after the single injection. No pneumothorax, hematoma, or local anesthetic poisoning occurred in any of the patients.

Conclusion
The effective longitudinal plane of the T12 transverse process erector spinal muscle block was mainly distributed in the T9–L5 dorsal cutaneous branches, and the distribution of the block area was safe and stable.
Stakeholder perspectives on clinical research related to therapies for rare diseases: therapeutic misconception and the value of research
Authors:   In collaboration with the Canadian Inherited Metabolic Diseases Research Network, Tingley Kylie , Coyle Doug , Graham Ian D. , Chakraborty Pranesh , Wilson Kumanan , Potter Beth K. 
Published: January 2021

Abstract
Background
For many rare diseases, few treatments are supported by strong evidence. Patients, family members, health care providers, and policy-makers thus have to consider whether to accept, recommend, or fund treatments with uncertain clinical effectiveness. They must also consider whether and how to contribute to clinical research that may involve receiving or providing the therapy being evaluated.

Objective
To understand why and how patients and families with rare metabolic diseases, specialist metabolic physicians, and health policy advisors choose whether to participate in studies and how they use and value research.

Methods
We conducted separate focus group interviews with each stakeholder group (three groups in total); two groups were conducted by telephone and the third was held in-person. Participants were recruited using purposive sampling. We analyzed each interview transcript sequentially using a qualitative description approach to inductively identify key themes. Several strategies to ensure credibility and trustworthiness were used including debriefing sessions after each focus group and having multiple team members review transcripts.

Results
Four patients/caregivers, six physicians, and three policy advisors participated. Our findings did not support conventional perspectives that therapeutic misconception (gaining access to treatment) is the main motivating factor for patients/caregivers to participate in clinical research. Rather, patients’/caregivers’ expressed reasons for participating in research included advancing science for the next generation and having an opportunity to share their experiences. Patients/caregivers and physicians described the difficulties in weighing risks versus benefits of accepting treatments not well-supported by evidence. Physicians also reported feeling conflicted in their dual role as patient advisor/advocate and evaluator of the evidence. Policy advisors were primarily focused on critically appraising the evidence to make recommendations for the health system.

Conclusions
Stakeholders differ in their perspectives on rare disease research but share concerns about the risks versus benefits of therapies when making individual- and population-level decisions.
Scaling‐up school mental health services in low resource public schools of rural Pakistan: the Theory of Change (ToC) approach
Authors: Hamdani Syed Usman , Huma Zill-e- , Suleman Nadia , Warraitch Azza , Muzzafar Naila , Farzeen Midhat , Minhas Fareed Aslam , Rahman Atif , Wissow Lawrence S. 
Published: January 2021

Abstract
Background
Ninety percent of children with mental health problems live in low or middle-income countries (LMICs). School-based programs offer opportunities for early identification and intervention, however implementation requires cross-sector collaboration to assure sustainable delivery of quality training, ongoing supervision, and outcomes monitoring at scale. In Pakistan, 35% of school-aged children are reported to have emotional and behavioral problems. As in many other LMICs, the government agencies who must work together to mount school-based programs have limited resources and a limited history of collaboration. The “Theory of Change” (ToC) process offers a way for new partners to efficiently develop mutual goals and long-term prospects for sustainable collaboration.

Objective
Develop a model for scale-up of school based mental health services in public schools of Pakistan.

Methods
We used ToC workshops to develop an empirically supported, ‘hypothesized pathway’ for the implementation of WHO’s School Mental Health Program in the public schools of rural Pakistan. Three workshops included 90 stakeholders such as policy makers from education and health departments, mental health specialists, researchers, head teachers, teachers and other community stakeholders including non-governmental organizations.

Results
The ToC process linked implementers, organizations, providers and consumers of school mental health services to develop common goals and relate them (improved child socioemotional wellbeing, grades and participation in activities) to interventions (training, monitoring and supervision of teachers; collaboration with parents, teachers and primary health care facilities and schools). Key testable assumptions developed in the process included buy-in from health care providers, education officials and professionals, community-based organizations and families. For example, teachers needed skills for managing children’s problems, but their motivation might come from seeking improved school performance and working conditions. Poverty, stigma and lack of child mental health literacy among teachers, administration, and parents were identified as key hypothesized barriers. Children and their families were identified as key stakeholders to make such a program successful.

Discussion
ToC workshops assisted in team building and served as a stakeholders’ engagement tool. They helped to develop and support testable hypotheses about the structures, collaborations, and knowledge most important to scaling-up school based mental health services in Pakistan.
Distinct role of 5′UTR sequences in dendritic trafficking of BDNF mRNA: additional mechanisms for the BDNF splice variants spatial code
Authors: Colliva Andrea , Tongiorgi Enrico 
Published: January 2021

AbstractThe neurotrophin Brain-derived neurotrophic factor (BDNF) is encoded by multiple bipartite transcripts. Each BDNF transcript is composed by one out of 11 alternatively spliced exons containing the 5′untranslated region (UTR), and one common exon encompassing the coding sequence (CDS) and the 3′UTR with two variants (short and long). In neurons, BDNF mRNA variants have a distinct subcellular distribution, constituting a “spatial code”, with exon 1, 3, 5, 7 and 8 located in neuronal somata, exon 4 extending into proximal dendrites, and exon 2 and 6 reaching distal dendrites. We previously showed that the CDS encodes constitutive dendritic targeting signals (DTS) and that both the 3′UTR-short and the 3′UTR-long contain activity-dependent DTS. However, the role of individual 5′UTR exons in mRNA sorting remains unclear. Here, we tested the ability of each different BDNF 5′UTRs to affect the subcellular localization of the green fluorescent protein (GFP) reporter mRNA. We found that exon 2 splicing isoforms (2a, 2b, and 2c) induced a constitutive dendritic targeting of the GFP reporter mRNA towards distal dendritic segments. The other isoforms did not affect GFP-mRNA dendritic trafficking. Through a bioinformatic analysis, we identified five unique cis-elements in exon 2a, 2b, and 2c which might contribute to building a DTS. This study provides additional information on the mechanism regulating the cellular sorting of BDNF mRNA variants.
Efficacy and safety of geptanolimab (GB226) for relapsed or refractory peripheral T cell lymphoma: an open-label phase 2 study (Gxplore-002)
Authors: Shi Yuankai , Wu Jianqiu , Wang Zhen , Zhang Liling , Wang Zhao , Zhang Mingzhi , Cen Hong , Peng Zhigang , Li Yufu , Fan Lei , Guo Ye , Ma Liping , Cui Jie , Gao Yuhuan , Yang Haiyan , Zhang Hongyu , Wang Lin , Zhang Weihua , Zhang Huilai , Xie Liping , Jiang Ming , Zhou Hui , Shuang Yuerong , Su Hang , Ke Xiaoyan , Jin Chuan , Du Xin , Du Xin , Liu Li , Xi Yaming , Ge Zheng , Feng Ru , Zhang Yang , Zhou Shengyu , Xie Fan , Wang Qian 
Published: January 2021

Abstract
Background
Peripheral T cell lymphoma (PTCL) is a rare disease and recent approved drugs for relapsed/refractory (r/r) PTCL provided limited clinical benefit. We conducted this study to evaluate the efficacy and safety of geptanolimab (GB226), an anti-PD-1 antibody, in r/r PTCL patients.

Methods
We did this single-arm, multicenter phase 2 study across 41 sites in China. Eligible patients with r/r PTCL received geptanolimab 3 mg/kg intravenously every 2 weeks until disease progression or intolerable toxicity. All patients who received at least one dose of geptanolimab and histological confirmed PTCL entered full analysis set (FAS). The primary endpoint was objective response rate (ORR) in FAS assessed by the independent radiological review committee (IRRC) per Lugano 2014 criteria.

Results
Between July 12, 2018, and August 15, 2019, 102 patients were enrolled and received at least one dose of geptanolimab. At the data cutoff date (August 15, 2020), the median follow-up was 4.06 (range 0.30–22.9) months. For 89 patients in FAS, 36 achieved objective response (40.4%, 95% CI 30.2–51.4), of which 13 (14.6%) were complete response and 23 (25.8%) had partial response assessed by IRRC. The median duration of response (DOR) was 11.4 (95% CI 4.8 to not reached) months per IRRC. Patients with PD-L1 expression ≥ 50% derived more benefit from geptanolimab treatment compared to < 50% ones (ORR, 53.3% vs. 25.0%, p = 0.013; median PFS 6.2 vs. 1.5 months, p = 0.002). Grade ≥ 3 treatment-related adverse events occurred in 26 (25.5%) patients, and the most commonly observed were lymphocyte count decreased (n = 4) and platelet count decreased (n = 3). Serious adverse events were observed in 45 (44.1%) patients and 19 (18.6%) were treatment related.

Conclusions
In this study, geptanolimab showed promising activity and manageable safety profile in patients with r/r PTCL. Anti-PD-1 antibody could be a new treatment approach for this patient population.
Trial registration: This clinical trial was registered at the ClinicalTrials.gov (NCT03502629) on April 18, 2018.
The integration of immune checkpoint inhibitors with VEGF targeted agents in advanced gastric and gastroesophageal adenocarcinoma: a review on the rationale and results of early phase trials
Authors: Saeed Anwaar , Park Robin , Sun Weijing 
Published: January 2021

AbstractSeveral targeted therapies have shown efficacy in patients with advanced gastric cancer (GC) and gastroesophageal junction adenocarcinoma (GEJC), including anti-angiogenic agents and immune checkpoint inhibitors. Ramucirumab, an anti-VEGFR2 antibody, has shown efficacy in GC, but the benefits are limited, in part due to MET-mediated resistance. Other VEGF targeted agents like VEGF tyrosine kinase inhibitors (TKIs) with broad multi-kinase inhibitory spectrum like regorafenib and cabozantinib have also shown modest single agent activity in early phase trials. For immune checkpoint inhibitors, pembrolizumab (anti-PD-1) monotherapy confers survival advantage as 3rd line therapy for the PD-L1 expressing GC and GEJC population and has been approved for use in this setting. Extensive tumor microenvironment immune modulatory effects from antiangiogenic agents have been demonstrated from preclinical data which support the clinical study rationale of dual blockade of VEGF and immune checkpoint. In addition, FDA has approved combinations of anti-VEGF/VEGFR with anti-PD-1/PD-L1 agents in hepatocellular carcinoma and renal cell carcinoma. Promising clinical activity has been demonstrated in patients with refractory GC/GEJC when treated with dual blockade combination with antiangiogenic agents and immune checkpoint inhibitors like PD-1/PD-L1 inhibitors in several phase I/II trials. This review highlights the trials investigating these novel combinations as well as their preclinical rationale.