bluuebunny/crossref_metadata_2025 huggingface dataset:
Semi-quantitative thigh magnetic resonance imaging scores in assessing disease activity and determining long-term clinical outcome in idiopathic inflammatory myopathies: a causal mediation analysis
Authors: Gorijavolu Mamatha , Bairwa Devender , Ganapathy Sachit , Dunga Saikumar , Gopal Aishwarya , Ananthakrishnan Ramesh , Thabah Molly Mary , Negi Vir Singh , Kavadichanda Chengappa G
Published: April 2023

Objectives

To evaluate the relationship of thigh MRI (t-MRI) with manual muscle testing-8 (MMT-8), muscle enzymes and autoantibodies. To determine the causal and mediating factors resulting in poor recovery of MMT-8 in inflammatory myositis (IIM).

Methods

This was a single-centre retrospective study in IIM patients. t-MRI was semi-quantitatively scored for muscle oedema, fascial oedema, muscle atrophy and fatty infiltration. Spearman correlation of t-MRI scores was done with muscle enzymes at baseline, and MMT-8 at baseline and on follow-up. Causal mediation analysis was performed with age, sex, symptom duration, autoantibodies, diabetes and BMI as independent variables, follow-up MMT-8 as dependent and t-MRI scores as mediating variables.

Results

Baseline evaluation was done on 59 and follow-up on 38 patients. Median follow-up of the cohort was 31 (10–57) months. Baseline MMT-8 negatively correlated with muscle oedema (r = –0755), fascial oedema (r = –0.443) and muscle atrophy (r = –0.343). Creatinine kinase (r = 0.422) and aspartate transaminase (r = 0.480) positively correlated with muscle oedema. Follow-up MMT-8 correlated negatively with baseline atrophy (r = –0.497) and fatty infiltration (r = –0.531). On follow-up, MMT-8 males had positive total effect (estimate (95%CI)) via atrophy [2.93 (0.44, 4.89)] and fatty infiltration [2.08 (0.54, 3.71)]. Antisynthetase antibody had a positive total effect via fatty infiltration [4.50 (0.37, 7.59)]. Age had a negative total effect via atrophy [–0.09 (0.19, –0.01)] and fatty infiltration [–0.07 (–0.15, –0.01)]. Disease duration had a negative total effect via fatty infiltration [–0.18 (–0.27, –0.02)].

Conclusion

Baseline fatty infiltration and muscle atrophy resulting from older age, female sex, longer disease duration and absent anti-synthetase antibodies, partly mediate muscle recovery in IIM.
CONQUER Scleroderma: association of gastrointestinal tract symptoms in early disease with resource utilization
Authors: Luebker Sarah , Frech Tracy M , Assassi Shervin , Skaug Brian , Gordon Jessica K , Lakin Kimberly , Bernstein Elana J , Luo Yiming , Steen Virginia D , Shah Ami A , Hummers Laura K , Richardson Carrie , Moore Duncan F , Khanna Dinesh , Castelino Flavia V , Chung Lorinda , Kapoor Puneet , Hant Faye N , Shanmugam Victoria K , VanBuren John M , Alvey Jessica , Harding Monica , Shah Ankoor , Makol Ashima , Lebiedz-Odrobina Dorota , Thomas Julie K , Volkmann Elizabeth R , Molitor Jerry A , Sandorfi Nora
Published: April 2023

Objectives

SSc is associated with increased health-care resource utilization and economic burden. The Collaborative National Quality and Efficacy Registry (CONQUER) is a US-based collaborative that collects longitudinal follow-up data on SSc patients with <5 years of disease duration enrolled at scleroderma centres in the USA. The objective of this study was to investigate the relationship between gastrointestinal tract symptoms and self-reported resource utilization in CONQUER participants.

Methods

CONQUER participants who had completed a baseline and 12-month Gastrointestinal Tract Questionnaire (GIT 2.0) and a Resource Utilization Questionnaire (RUQ) were included in this analysis. Patients were categorized by total GIT 2.0 severity: none-to-mild (0–0.49); moderate (0.50–1.00), and severe-to-very severe (1.01–3.00). Clinical features and medication exposures were examined in each of these categories. The 12-month RUQ responses were summarized by GIT 2.0 score categories at 12 months.

Results

Among the 211 CONQUER participants who met the inclusion criteria, most (64%) had mild GIT symptoms, 26% had moderate symptoms, and 10% severe GIT symptoms at 12 months. The categorization of GIT total severity score by RUQ showed that more upper endoscopy procedures and inpatient hospitalization occurred in the CONQUER participants with severe GIT symptoms. These patients with severe GIT symptoms also reported the use of more adaptive equipment.

Conclusion

This report from the CONQUER cohort suggests that severe GIT symptoms result in more resource utilization. It is especially important to understand resource utilization in early disease cohorts when disease activity, rather than damage, primarily contributes to health-related costs of SSc.
Pharmacological screening of glibenclamide solid dispersion in fructose-fed diabetic rats
Authors: Rahman Mahfuza , Barman Ranjan Kumar , Khan Rafiqul Islam , Ali Ashraf , Sarker Shahin , Wahed Imam Ibne
Published: April 2023

Objectives

In this study, our main objective was to estimate the therapeutic effectiveness of the formulated solid dispersion of glibenclamide (GSD) with improved dissolution profiles in comparison with pure glibenclamide (GLB) by means of a fructose-fed diabetic rat model.

Methods

To evaluate the pharmacological effectiveness of the formulated GSD, a fructose-fed diabetic rat model evolved and the obtained consequences were compared with the conventional GLB treatment.

Key findings

GSD exhibited improved glucose and lipid-lowering efficacy of GSD in contrast to pure GLB after 15 days of treatment. Low dose (0.5 mg/kg) and high dose (5 mg/kg) of GSD showed significant lowering of blood glucose which is 6 ± 0.2 mmol/L and 5.6 ± 0.3 mmol/L respectively after 15 days of treatment is much better than that of pure GLB (6.2 ± 0.4 mmol/L). Furthermore, low dose of GSD presented approximately comparable beneficiary effects in regard to triglycerides (72.00 ± 7.23 mg/dL), total cholesterol (110.33 ± 5.78 mg/dL), low-density lipoprotein (67.60 ± 5.21 mg/dL) and high-density lipoprotein (28.33 ± 1.53 mg/dL) as pure GLB after 15 days. Additionally, histological studies as well confirmed no fatty infiltration from the liver by GSD as compared with GLB which was consistent with the biochemical parameters.

Conclusions

For treating diabetes and hyperlipidaemia, the formulated GSD might be a potential substitute for traditional GLB.
It’s who, not what that matters: personal relevance and early face processing
Authors: Bayer Mareike , Johnstone Tom , Dziobek Isabel
Published: April 2023

The faces of our friends and loved ones are among the most pervasive and important social stimuli we encounter in our everyday lives. We employed electroencephalography to investigate the time line of personally relevant face processing and potential interactions with emotional facial expressions by presenting female participants with photographs of their romantic partner, a close friend and a stranger, displaying fearful, happy and neutral facial expressions. Our results revealed elevated activity to the partner’s face from 100 ms after stimulus onset as evident in increased amplitudes of P1, early posterior negativity, P3 and late positive component, while there were no effects of emotional expressions and no interactions. Our findings indicate the prominent role of personal relevance in face processing; the time course of effects further suggests that it might not rely solely on the core face processing network but might start even before the stage of structural face encoding. Our results suggest a new direction of research in which face processing models should be expanded to adequately capture the dynamics of the processing of real-life, personally relevant faces.
Evidence of Neurovascular Water Exchange and Endothelial Vascular Dysfunction in Schizophrenia: An Exploratory Study
Authors: Goldwaser Eric L , Wang Danny J J , Adhikari Bhim M , Chiappelli Joshua , Shao Xingfeng , Yu Jiaao , Lu Tong , Chen Shuo , Marshall Wyatt , Yuen Alexa , Kvarta Mark , Ma Yizhou , Du Xiaoming , Gao Si , Saeedi Osamah , Bruce Heather , Donnelly Patrick , O’Neill Hugh , Shuldiner Alan R , Mitchell Braxton D , Kochunov Peter , Hong L Elliot
Published: April 2023

Background and Hypothesis

Mounting evidence supports cerebrovascular contributions to schizophrenia spectrum disorder (SSD) but with unknown mechanisms. The blood–brain barrier (BBB) is at the nexus of neural-vascular exchanges, tasked with regulating cerebral homeostasis. BBB abnormalities in SSD, if any, are likely more subtle compared to typical neurological insults and imaging measures that assess large molecule BBB leakage in major neurological events may not be sensitive enough to directly examine BBB abnormalities in SSD.

Study Design

We tested the hypothesis that neurovascular water exchange (Kw) measured by non-invasive diffusion-prepared arterial spin label MRI (n = 27 healthy controls [HC], n = 32 SSD) is impaired in SSD and associated with clinical symptoms. Peripheral vascular endothelial health was examined by brachial artery flow-mediated dilation (n = 44 HC, n = 37 SSD) to examine whether centrally measured Kw is related to endothelial functions.

Study Results

Whole-brain average Kw was significantly reduced in SSD (P = .007). Exploratory analyses demonstrated neurovascular water exchange reductions in the right parietal lobe, including the supramarginal gyrus (P = .002) and postcentral gyrus (P = .008). Reduced right superior corona radiata (P = .001) and right angular gyrus Kw (P = .006) was associated with negative symptoms. Peripheral endothelial function was also significantly reduced in SSD (P = .0001). Kw in 94% of brain regions in HC positively associated with peripheral endothelial function, which was not observed in SSD, where the correlation was inversed in 52% of brain regions.

Conclusions

This study provides initial evidence of neurovascular water exchange abnormalities, which appeared clinically associated, especially with negative symptoms, in schizophrenia.
Synthetic biology regulation in Europe: containment, release and beyond
Authors: Sundaram Lalitha S , Ajioka James W , Molloy Jennifer C
Published: April 2023

While synthetic biology is hoped to hold promise and potential to address pressing global challenges, the issue of regulation is an under-appreciated challenge. Particularly in Europe, the regulatory frameworks involved are rooted in historical concepts based on containment and release. Through a series of case studies including a field-use biosensor intended to detect arsenic in well water in Nepal and Bangladesh, and insects engineered for sterility, we explore the implications that this regulatory and conceptual divide has had on the deployment of synthetic biology projects in different national contexts. We then consider some of the broader impacts that regulation can have on the development of synthetic biology as a field, not only in Europe but also globally, with a particular emphasis on low- and middle-income countries. We propose that future regulatory adaptability would be increased by moving away from a containment and release dichotomy and toward a more comprehensive assessment that accounts for the possibility of varying degrees of ‘contained release’.

Graphical Abstract
Genome-Wide Association Study of Asian and European Common Wheat Accessions for Yield-Related Traits and Stripe Rust Resistance
Authors: Yang Xiu , Cai Li , Wang Miaomiao , Zhu Wei , Xu Lili , Wang Yi , Zeng Jian , Fan Xing , Sha Lina , Wu Dandan , Cheng Yiran , Zhang Haiqin , Jiang Yunfeng , Chen Guoyue , Zhou Yonghong , Kang Houyang
Published: April 2023

Identifying novel loci of yield-related traits and resistance to stripe rust (caused by Puccinia striiformis f. sp. tritici) in wheat will help in breeding wheat that can meet projected demands in diverse environmental and agricultural practices. We performed a genome-wide association study with 24,767 single nucleotide polymorphisms (SNPs) in 180 wheat accessions that originated in 16 Asian or European countries between latitudes 30°N and 45°N. We detected seven accessions with desirable yield-related traits and 42 accessions that showed stable, high degrees of stripe rust resistance in multienvironment field assessments. A marker-trait association analysis of yield-related traits detected 18 quantitative trait loci (QTLs) in at least two test environments and two QTLs related to stripe rust resistance in at least three test environments. Five of these QTLs were identified as potentially novel QTLs by comparing their physical locations with those of known QTLs in the Chinese Spring (CS) reference genome RefSeq v1.1 published by the International Wheat Genome Sequencing Consortium; two were for spike length, one was for grain number per spike, one was for spike number, and one was for stripe rust resistance at the adult plant stage. We also identified 14 candidate genes associated with the five novel QTLs. These QTLs and candidate genes will provide breeders with new germplasm and can be used to conduct marker-assisted selection in breeding wheat with improved yield and stripe rust resistance.
The Cost of Living While Human
Authors: Brown Theresa
Published: April 2023

Observations on the craziness in American health care
Safe Practices for Medication Administration via Enteral Tubes
Authors: Aschenbrenner Diane S.
Published: April 2023

Medication errors are possible when drugs are given through enteral feeding tubes.

The Institute for Safe Medication Practices has suggested strategies for reducing the common errors that can occur through use of this route of administration.
Medical Mistrust Among Food Insecure Individuals in Appalachia
Authors: Thomas Melissa K. , Amstutz Ciara , Orr-Roderick Debra , Horter Julia , Holben David H.
Published: April 2023

This study focused on the relationship between food insecurity and medical mistrust within Appalachia. Food insecurity has negative consequences on health, while medical mistrust can lead to a decrease in health care use, creating additive consequences to already vulnerable populations. Medical mistrust has been defined in various ways, with measures addressing health care organizations and individual health care providers. To determine whether food insecurity has an additive impact on medical mistrust, a cross-sectional survey was completed by 248 residents in Appalachia Ohio while attending community or mobile clinics, food banks, or the county health department. More than one-quarter of the respondents had high levels of mistrust toward health care organizations. Those with high food insecurity levels were more likely to have higher levels of medical mistrust than those with lower levels of food insecurity. Individuals with higher self-identified health issues and older participants had higher medical mistrust scores. Screening for food insecurity in primary care can reduce the impact of mistrust on patient adherence and health care access by increasing patient-centered communication. These findings present a unique perspective on how to identify and mitigate medical mistrust within Appalachia and call attention to the need for further research on the root causes among food insecure residents.
Adherence to Ocular Hypotensive Medication in Patients With Primary Open Angle Glaucoma in Ghana
Authors: Kyei Samuel , Kwao Eric , Mashige Percy Khathutshelo , Listowell Abu Sampson , Racette Lyne
Published: April 2023

Précis:

There is a high rate of nonadherence to ocular hypotensive medications in a highly prevalent glaucoma setting, which warrants the attention of caregivers so as to inform their discussion of the possible barriers to adherence with their patients.

Purpose:

To assess adherence to ocular hypotensive medication objectively among glaucoma patients in Ghana and to identify factors associated with adherence.

Materials and Methods:

The prospective, observational cohort study included consecutive patients with primary open angle glaucoma treated with Timolol at the Christian Eye Centre, Cape Coast, Ghana. Adherence was assessed using Medication Event Monitoring System (MEMS) for a period of 3 months. MEMS adherence was defined as the number of doses taken divided by the number of doses prescribed, expressed in percent. Patients with adherence of 75% or less were classified as nonadherent. Associations with glaucoma medication self-efficacy, eyedrop-taking behaviors, and health beliefs were also assessed.

Results:

Of the 139 patients (mean age, 65 y [SD, 13 y]) included in the study, 107 (77.0%) were nonadherent when assessed with MEMS, compared with only 47 (33.8%) who self-reported being nonadherent. Overall, mean adherence was 48.5%±29.7. In univariate analysis, MEMS adherence was significantly associated with educational level (χ
2=9.18, P=0.01) and the number of systemic comorbidities (χ
2=6.03, P=0.049).

Conclusion:

Overall, mean adherence was low, and adherence was associated with educational level and number of systemic comorbidities in univariate analysis.
Oxygen saturation during donor warm ischemia time and outcome of donation after circulatory death (DCD) liver transplantation with static cold storage: A review of 1114 cases
Authors: Lee David D. , Joyce Cara , Duehren Sarah , Fernandez Luis
Published: April 2023

The donor operation and the hemodynamics during declaration resulting in donor warm ischemia time have been linked to the outcomes in donation after circulatory death (DCD) liver transplantation (LT). Scrutiny of the donor hemodynamics at the time of withdrawal of life support concluded that a functional donor warm ischemia time may be associated with LT graft failure. Unfortunately, the definition for functional donor warm ischemia time has not reached a consensus—but has almost always incorporated time spent in a hypoxic state. Herein, we reviewed 1114 DCD LT cases performed at the 20 highest volume centers during 2014 and 2018. Donor hypoxia began within 3 minutes of withdrawal of life support for 60% of cases and within 10 minutes for 95% of cases. Graft survival was 88.3% at 1 year and 80.3% at 3 years. Scrutinizing the time spent under hypoxic conditions (oxygen saturation ≤ 80%) during the withdrawal of life support, we found an increasing risk of graft failure as hypoxic time increased from 0 to 16 minutes. After 16 minutes and up to 50 minutes, we did not find any increased risk of graft failure. In conclusion, after 16 minutes of time in hypoxia, the risk of graft failure in DCD LT did not increase. The current evidence suggests that an over-reliance on hypoxia time may lead to an unnecessary increase in DCD liver discard and may not be as useful for predicting graft loss after LT.
Head-up cardiopulmonary resuscitation
Authors: Moore Johanna C.
Published: April 2023

Purpose of review

The purpose of this review was to provide an overview of head-up (HUP) CPR physiology, relevant preclinical findings, and recent clinical literature.

Recent findings

Recent preclinical findings have demonstrated optimal hemodynamics and improved neurologically intact survival in animals receiving controlled head and thorax elevation with circulatory adjuncts. These findings are compared with animals in the supine position and/or receiving conventional CPR with the HUP position. There are few clinical studies of HUP CPR. However, recent studies have shown safety and feasibility of HUP CPR and improved near-infrared spectroscopy changes in patients with head and neck elevation. Additional observational studies have shown that HUP CPR performed with head and thorax elevation and circulatory adjuncts has a time-dependent association with survival to hospital discharge, survival with good neurological function, and return of spontaneous circulation.

HUP CPR is a new and novel therapy increasingly used in the prehospital setting and discussed in the resuscitation community. This review provides a relevant review of HUP CPR physiology and preclinical work, and recent clinical findings. Further clinical studies are needed to further explore the potential of HUP CPR.
Pulse wave analysis: basic concepts and clinical application in intensive care medicine
Authors: Thomsen Kristen K. , Kouz Karim , Saugel Bernd
Published: April 2023

Purpose of review

The measurement of cardiac output (CO) is important in patients with circulatory shock. Pulse wave analysis (PWA) estimates CO continuously and in real-time using the mathematical analysis of the arterial pressure waveform. We describe different PWA methods and provide a framework for CO monitoring using PWA in critically ill patients.

Recent findings

PWA monitoring systems can be classified according to their invasiveness (into invasive, minimally invasive, and noninvasive systems) and their calibration method (into externally calibrated, internally calibrated, and uncalibrated systems). PWA requires optimal arterial pressure waveform signals. Marked alterations and rapid changes in systemic vascular resistance and vasomotor tone can impair the measurement performance of PWA.

Noninvasive PWA methods are generally not recommended in critically ill patients (who have arterial catheters anyway). PWA systems can be used to continuously track stroke volume and CO in real-time during tests of fluid responsiveness or during therapeutic interventions. During fluid challenges, continuous CO monitoring is important because – if CO decreases – a fluid challenge can be stopped early to avoid further unnecessary fluid administration. PWA externally calibrated to indicator dilution methods can be used – in addition to echocardiography – to diagnose the type of shock.
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

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

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

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.

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.

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.
How can graph theory inform the dual-stream model of speech processing? a resting-state fMRI study of post-stroke aphasia
Authors: Zhu Haoze , Fitzhugh Megan C. , Keator Lynsey M. , Johnson Lisa , Rorden Chris , Bonilha Leonardo , Fridriksson Julius , Rogalsky Corianne
Published: April 2023

The dual-stream model of speech processing has been proposed to represent the cortical networks involved in speech comprehension and production. Although it is arguably the prominent neuroanatomical model of speech processing, it is not yet known if the dual-stream model represents actual intrinsic functional brain networks. Furthermore, it is unclear how disruptions after a stroke to the functional connectivity of the dual-stream model’s regions are related to specific types of speech production and comprehension impairments seen in aphasia. To address these questions, in the present study, we examined two independent resting-state fMRI datasets: (1) 28 neurotypical matched controls and (2) 28 chronic left-hemisphere stroke survivors with aphasia collected at another site. Structural MRI, as well as language and cognitive behavioral assessments, were collected. Using standard functional connectivity measures, we successfully identified an intrinsic resting-state network amongst the dual-stream model’s regions in the control group. We then used both standard functional connectivity analyses and graph theory approaches to determine how the functional connectivity of the dual-stream network differs in individuals with post-stroke aphasia, and how this connectivity may predict performance on clinical aphasia assessments. Our findings provide strong evidence that the dual-stream model is an intrinsic network as measured via resting-state MRI, and that weaker functional connectivity of the hub nodes of the dual-stream network defined by graph theory methods, but not overall average network connectivity, is weaker in the stroke group than in the control participants. Also, the functional connectivity of the hub nodes predicted specific types of impairments on clinical assessments. In particular, the relative strength of connectivity of the right hemisphere’s homologues of the left dorsal stream hubs to the left dorsal hubs versus right ventral stream hubs is a particularly strong predictor of post-stroke aphasia severity and symptomology.
Financial conflicts of interest between pharmaceutical companies and executive board members of internal medicine subspecialty societies in Japan between 2016 and 2020
Authors: Murayama Anju , Saito Hiroaki , Tanimoto Tetsuya , Ozaki Akihiko
Published: April 2023

Using payment data disclosed by 92 major pharmaceutical companies, this study evaluated personal payments to executive board members (EBMs) among each specialized field of internal medicine in Japan. A total of 63,405 personal payments worth of $70,796,014 in payment amounts were made to 99.2% of all EBMs of the 15 leading professional societies of internal medicine in Japan between 2016 and 2020.
Sensitivity of temperature-based time since death estimation on measurement location
Authors: Subramaniam J. Shanmugam , Hubig M. , Muggenthaler H. , Schenkl S. , Ullrich J. , Pourtier G. , Weiser M. , Mall G.
Published: April 2023

Rectal temperature measurement (RTM) from crime scenes is an important parameter for temperature-based time of death estimation (TDE). Various influential variables exist in TDE methods like the uncertainty in thermal and environmental parameters. Although RTM depends in particular on the location of measurement position, this relationship has never been investigated separately. The presented study fills this gap using Finite Element (FE) simulations of body cooling. A manually meshed coarse human FE model and an FE geometry model developed from the CT scan of a male corpse are used for TDE sensitivity analysis. The coarse model is considered with and without a support structure of moist soil. As there is no clear definition of ideal rectal temperature measurement location for TDE, possible variations in RTM location (RTML) are considered based on anatomy and forensic practice. The maximum variation of TDE caused by RTML changes is investigated via FE simulation. Moreover, the influence of ambient temperature, of FE model change and of the models positioning on a wet soil underground are also discussed. As a general outcome, we notice that maximum TDE deviations of up to ca. 2-3 h due to RTML deviations have to be expected. The direction of maximum influence of RTML change on TDE generally was on the line caudal to cranial.