bluuebunny/crossref_metadata_2025_split huggingface dataset:
BT24 Use of specialist advice and guidance for dermatology services: the importance of high-quality images in reducing double activity
Authors: Schofield Julia , Scharrer Krisztina 
Published: June 2023

Abstract
The use of specialist advice and guidance (A&G), where primary care healthcare professionals request diagnostic and management advice from specialists, is advocated as the ‘front door’ to dermatology services, to optimize referral management. This approach provides the opportunity for a two-way interchange between primary and specialist services, and can facilitate triage to appropriate dermatology services in a timely fashion. For A&G to work effectively, the expectation is that images will accompany the A&G interaction. Ideally, dermoscopic images would accompany skin lesion A&G requests. It is important that the images are of a high enough quality to enable the reviewing clinician to provide a diagnosis and management plan so that ‘double activity’, where an A&G request is reviewed and the patient needs to be seen because of poor-quality images, is avoided. We introduced specialist A&G in August 2021 and developed referral forms for skin lesions. Dermatoscopes were provided to practices. The aim of this study was to review the quality of skin lesion A&G requests and, in particular, to identify whether a diagnosis and management plan was possible based on the information and images provided. Consecutive skin lesion A&G requests were reviewed over a 4-week period, and information was collected on the images accompanying the request and whether the reviewing clinician was able to make a diagnosis and management plan. In total, 160 skin lesion A&G requests were reviewed over the 4-week period. A skin lesion referral form accompanied 42% of the requests, and 92% were accompanied by macroscopic images (42% clearly labelled) and 59.5% by dermoscopic images. In 32% of the requests, it was not possible to make a diagnosis and management plan. This study highlights the fact that the quality of images accompanying A&G skin lesion referrals is often not good enough to make a diagnosis and management plan. Many of these patients will therefore need to be seen for a face-to-face appointment, which leads to ‘double activity’. If A&G services are to work effectively, then it is essential that high-quality images, ideally including dermoscopy images for skin lesions, accompany the A&G requests. Systems need to identify appropriate models to support image-taking services. Such models can be developed locally and might include community image-taking hubs based in agreed primary care settings or community diagnostic centres. A suitably trained workforce needs to be developed to take and send the images.
Non-alcoholic fatty liver disease: pathophysiological concepts and treatment options
Authors: Grander Christoph , Grabherr Felix , Tilg Herbert 
Published: June 2023

Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD) is continually increasing due to the global obesity epidemic. NAFLD comprises a systemic metabolic disease accompanied frequently by insulin resistance and hepatic and systemic inflammation. Whereas simple hepatic steatosis is the most common disease manifestation, a more progressive disease course characterized by liver fibrosis and inflammation (i.e. non-alcoholic steatohepatitis) is present in 10–20% of affected individuals. NAFLD furthermore progresses in a substantial number of patients towards liver cirrhosis and hepatocellular carcinoma. Whereas this disease now affects almost 25% of the world’s population and is mainly observed in obesity and type 2 diabetes, NAFLD also affects lean individuals. Pathophysiology involves lipotoxicity, hepatic immune disturbances accompanied by hepatic insulin resistance, a gut dysbiosis, and commonly hepatic and systemic insulin resistance defining this disorder a prototypic systemic metabolic disorder. Not surprisingly many affected patients have other disease manifestations, and indeed cardiovascular disease, chronic kidney disease, and extrahepatic malignancies are all contributing substantially to patient outcome. Weight loss and lifestyle change reflect the cornerstone of treatment, and several medical treatment options are currently under investigation. The most promising treatment strategies include glucagon-like peptide 1 receptor antagonists, sodium–glucose transporter 2 inhibitors, Fibroblast Growth Factor analogues, Farnesoid X receptor agonists, and peroxisome proliferator–activated receptor agonists. Here, we review epidemiology, pathophysiology, and therapeutic options for NAFLD.
Impact of Supplementary Immunization Activities using Novel Oral Polio Vaccine Type 2 during a Large outbreak of Circulating Vaccine-Derived Poliovirus in Nigeria
Authors: Voorman Arend , Lyons Hil , Shuaib Faisal , Adamu Usman S , Korir Charles , Erbeto Tesfaye , Bandyopadhyay Ananda S , Okiror Samuel 
Published: June 2023

Abstract

Background
Novel oral poliovirus vaccine (OPV) type 2 (nOPV2) has been made available for outbreak response under an emergency use listing authorization based on supportive clinical trial data. Since 2021 more than 350 million doses of nOPV2 were used for control of a large outbreak of circulating vaccine-derived poliovirus type 2 (cVDPV2) in Nigeria.

Methods
Using a bayesian time-series susceptible-infectious-recovered model, we evaluate the field effectiveness of nOPV2 immunization campaigns in Nigeria compared with campaigns using monovalent OPV type 2 (mOPV2).

Results
We found that both nOPV2 and mOPV2 campaigns were highly effective in reducing transmission of cVDPV2, on average reducing the susceptible population by 42% (95% confidence interval, 28–54%) and 38% (20–51%) per campaign, respectively, which were indistinguishable from each other in this analysis (relative effect, 1.1 [.7–1.9]). Impact was found to vary across areas and between immunization campaigns.

Conclusions
These results are consistent with the comparable individual immunogenicity of nOPV2 and mOPV2 found in clinical trials but also suggest that outbreak response campaigns may have small impacts in some areas requiring more campaigns than are suggested in current outbreak response procedures.
Learning to Live with an Unruly Consuming Body
Authors: Bhatnagar Kushagra , Tillotson Jack S , Toyoki Sammy , Laker Benjamin 
Published: June 2023

AbstractPast research shows that successful consumer learning takes place in environments that support cooperative communities of practice, that enable access to refined didactic resources, and that provide a safe, sympathetic backstage for a controllable and able learning body to durably transition from one repertoire to another. This study complements existing research by investigating a group of lactose-intolerant consumers who must learn to transition to a new consumption repertoire because of socially embarrassing symptoms. Consumers must engage in high-risk, unguided, experiential learning pathways in a less than sympathetic frontstage, without the support of a cooperative community or a well-developed vocabulary, and while grappling with an impaired and unruly body in a dynamic marketplace. The findings demonstrate that consumers adapt to this hostile learning environment by surfing between different consumption repertoires in a fluid, impermanent manner.
CDK12 alterations and ARID1A mutations are predictors of poor prognosis and therapeutic targets in high-grade salivary gland carcinoma: analysis of the National Genomic Profiling Database
Authors: Kobayashi Kenya , Saito Yuki , Kage Hidenori , Fukuoka Osamu , Yamamura Koji , Mukai Toshiyuki , Oda Katsutoshi , Yamasoba Tatsuya 
Published: June 2023

Abstract

Background
Due to the diversity of histopathologic types in salivary gland carcinoma, genomic analysis of large cohorts with next-generation sequencing by histologic type has not been adequately performed.

Methods
We analysed data from 93 patients with salivary duct carcinoma and 243 patients with adenoid cystic carcinoma who underwent comprehensive genomic profiling testing in the Center for Cancer Genomics and Advanced Therapeutics database, a Japanese national genome profiling database. We visualised gene mutation profiles using the OncoPrinter platform. Fisher’s exact test, Kaplan–Meier analysis, log-rank test and Cox regression models were used for statistical analysis.

Results
In salivary duct carcinoma, a population with CDK12 and ERBB2 co-amplification was detected in 20 of 37 (54.1%) patients with ERBB2 amplification. We identified five loss-of-function variants in genes related to homologous recombination deficiency, such as BRCA2 and CDK12. Cox survival analysis showed that CDK12 and ERBB2 co-amplification is associated with overall survival (hazard ratio, 3.597; P = 0.045). In salivary duct carcinoma, NOTCH1 mutations were the most common, followed by mutations in chromatin modification genes such as KMT2D, BCOR, KDM6A, ARID1A, EP300 and CREBBP. In the multivariate Cox analysis, activating NOTCH1 mutations (hazard ratio, 3.569; P = 0.009) and ARID1A mutations (hazard ratio, 4.029; P = 0.034) were significantly associated with overall survival.

Conclusion
CDK12 and ERBB2 co-amplification is associated with a poor prognosis in salivary duct carcinoma. Chromatin remodelling genes are deeply involved in tumour progression in adenoid cystic carcinoma. One such gene, ARID1A, was an independent prognostic factor. In salivary duct carcinoma and adenoid cystic carcinoma, there might be minor populations with mutations that could be targeted for treatment with the synthetic lethality approach.
The room where it happens: addressing diversity, equity, and inclusion in National Clinical Trials Network clinical trial leadership
Authors: Snyder Rebecca A , Burtness Barbara , Cho May , Del Rivero Jaydira , Doroshow Deborah B , Hitchcock Kathryn E , Kalyan Aparna , Kim Christina A , Lukovic Jelena , Parikh Aparna R , Sanford Nina N , Singh Bhuminder , Shen Chan , Shroff Rachna T , Vijayvergia Namrata , Goodman Karyn A , Kunz Pamela L 
Published: June 2023

Abstract
Many multicenter randomized clinical trials in oncology are conducted through the National Clinical Trials Network (NCTN), an organization consisting of 5 cooperative groups. These groups are made up of multidisciplinary investigators who work collaboratively to conduct trials that test novel therapies and establish best practice for cancer care. Unfortunately, disparities in clinical trial leadership are evident. To examine the current state of diversity, equity, and inclusion across the NCTN, an independent NCTN Task Force for Diversity in Gastrointestinal Oncology was established in 2021, the efforts of which serve as the platform for this commentary. The task force sought to assess existing data on demographics and policies across NCTN groups. Differences in infrastructure and policies were identified across groups as well as a general lack of data regarding the composition of group membership and leadership. In the context of growing momentum around diversity, equity, and inclusion in cancer research, the National Cancer Institute established the Equity and Inclusion Program, which is working to establish benchmark data regarding diversity of representation within the NCTN groups. Pending these data, additional efforts are recommended to address diversity within the NCTN, including standardizing membership, leadership, and publication processes; ensuring diversity of representation across scientific and steering committees; and providing mentorship and training opportunities for women and individuals from underrepresented groups. Intentional and focused efforts are necessary to ensure diversity in clinical trial leadership and to encourage design of trials that are inclusive and representative of the broad population of patients with cancer in the United States.
Identification of the perpetrator imperatorin in Xin-yi-san-theophylline interaction: observed and predicted herb-drug interaction in rats
Authors: Wang Hong-Jaan , Chen An-Chi , Chen Hsin-Ying , Cheng Hsin-Chung , Kao Li-Ting , Lu Chung-Kuang , Tsai Keng-Chang , Lee I-Jung , Ueng Yune-Fang 
Published: June 2023

Abstract

Objectives
Theophylline is a bronchodilator with a narrow therapeutic index and primarily metabolised by cytochrome P450 (CYP) 1A2. Xin-yi-san (XYS) is a herbal formula frequently used to ameliorate nasal inflammation. This study aimed to investigate the effects of XYS and its ingredient, imperatorin, on theophylline pharmacokinetics in rats.

Methods
The kinetics of XYS- and imperatorin-mediated inhibition of theophylline oxidation were determined. Pharmacokinetics of theophylline were analysed. Comparisons were made with the CYP1A2 inhibitor, fluvoxamine.

Key findings
XYS extract and its ingredient, imperatorin, non-competitively inhibited theophylline oxidation. Fluvoxamine (50 and 100 mg/kg) and XYS (0.5 and 0.9 g/kg) significantly prolonged the time to reach the maximum plasma concentration (tmax) of theophylline by 3–10 fold. In a dose-dependent manner, XYS and imperatorin (0.1–10 mg/kg) treatments significantly decreased theophylline clearance by 27–33% and 19–56%, respectively. XYS (0.9 g/kg) and imperatorin (10 mg/kg) significantly prolonged theophylline elimination half-life by 29% and 142%, respectively. Compared with the increase (51–112%) in the area under curve (AUC) of theophylline by fluvoxamine, the increase (27–57%) by XYS was moderate.

Conclusions
XYS decreased theophylline clearance primarily through imperatorin-suppressed theophylline oxidation. Further human studies are essential for the dose adjustment in the co-medication regimen.
Transcriptional and post-translational regulation of plant autophagy
Authors: Agbemafle William , Wong Min May , Bassham Diane C 
Published: June 2023

Abstract
In response to changing environmental conditions, plants activate cellular responses to enable them to adapt. One such response is autophagy, in which cellular components, for example proteins and organelles, are delivered to the vacuole for degradation. Autophagy is activated by a wide range of conditions, and the regulatory pathways controlling this activation are now being elucidated. However, key aspects of how these factors may function together to properly modulate autophagy in response to specific internal or external signals are yet to be discovered. In this review we discuss mechanisms for regulation of autophagy in response to environmental stress and disruptions in cell homeostasis. These pathways include post-translational modification of proteins required for autophagy activation and progression, control of protein stability of the autophagy machinery, and transcriptional regulation, resulting in changes in transcription of genes involved in autophagy. In particular, we highlight potential connections between the roles of key regulators and explore gaps in research, the filling of which can further our understanding of the autophagy regulatory network in plants.
Intracystic papillary neoplasm diagnosis following an extended cholecystectomy: a case report … and literature review
Authors: Kitasaki Nao , Inoue Masashi , Abe Tomoyuki , Kohata Akihiro , Kochi Masatoshi , Hotta Ryuichi , Kobayashi Tsuyoshi , Ohdan Hideki , Toyota Kazuhiro , Takahashi Tadateru 
Published: June 2023

Abstract
We report a case of intracystic papillary neoplasms (ICPN) that was difficult to differentiate from adenocarcinoma of the gallbladder. A 64-year-old man visited our hospital for an examination of gallbladder tumors. At the preoperative examination, the tumor was revealed a papillary type of tumor in the body of the gallbladder without the findings that without the findings that suggested the tumor invasion into the deep subserosal layer. The patient underwent an extended cholecystectomy. Papillary lesions were observed mainly in the body of the gallbladder, with flattened elevated lesions at the gallbladder fundus. Within each of these tumors, cells corresponding to intraepithelial adenocarcinoma were irregularly interspersed, leading to a diagnosis of ICPN. The patient is currently undergoing follow-up with no recurrence postoperatively. The prognosis of ICPN is generally good; however, preoperative diagnosis remains challenging. Therefore, a treatment plan for gallbladder cancer should be applied.
A rare synchronous of dual primary genitourinary carcinoma manifested with a rapidly progressive renal failure
Authors: Affas Athar , AlBitar Sami , Alyyan Fatemah , Affas Mohammad Nasser 
Published: June 2023

Abstract
Non-urothelial carcinoma accounts for &lt;5% of urinary bladder tumors, and primary bladder adenocarcinoma accounts for 0.5–2%, but the variant primary signet-ring cell is extremely rare. We present a rare case of a synchronous of dual primary malignancy from a rare variant of urinary bladder adenocarcinoma (signet-ring cell) with indolent prostate adenocarcinoma in a 61-year-old male. The patient presented with a rapidly progressive renal failure due to a non-dilated obstructive uropathy that formed a dilemma in the course of diagnosiswhich was relieved transiently by a high-dose methylprednisolone. Primary signet-ring cell adenocarcinoma of the urinary bladder is a very rare malignancy manifests as a high-grade, high-stage lesion, which takes a vague course and has a poor prognosis. It is often managed with radical cystectomy due to its aggressive nature.
Key messages Non-dilated urinary obstruction should be considered as a possible rare cause of rapidly progressive renal failure, and often, it is related to an indolent and progressive urinary malignancy.
Pembrolizumab Every 6 Weeks Versus Every 3 Weeks in Advanced Non-Small Cell Lung Cancer
Authors: Dubé-Pelletier Maude , Labbé Catherine , Côté Jimmy , Pelletier-St-Pierre Audrey-Ann 
Published: June 2023

Abstract

Background
The survival benefits and adverse effects of pembrolizumab 2 mg/kg intravenously (IV) every 3 weeks (Q3W) in advanced non-small lung cancer (NSCLC) are well documented in the literature. Based on pharmacokinetic models, a pembrolizumab 4 mg/kg IV every 6 weeks (Q6W) dosing regimen is also approved in some countries. To date, there is no direct comparison in the literature between these 2 regimens in advanced NSCLC.

Methods
This retrospective study included 80 patients with advanced NSCLC who received pembrolizumab monotherapy 4 mg/kg Q6W between March 1, 2020 and December 31, 2021 and 80 patients with advanced NSCLC who received pembrolizumab monotherapy 2 mg/kg Q3W between January 1, 2017 and January 15, 2019 at Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ). The primary outcomes of this study were to compare overall survival (OS), progression-free survival (PFS) as well as the occurrence and severity of immune-mediated adverse events (AEs) in patients with advanced NSCLC who received pembrolizumab Q6W vs Q3W. Data cutoff date was December 15, 2022.

Results
Median follow-up was 14.5 ± 8.6 months in the Q6W group and 18.3 ± 19.6 months in the Q3W group. Median PFS was 6.9 months (CI 95% 5.0-10.7) in the Q6W group vs 8.9 months (CI 95% 5.6-14.1) in the Q3W group (adjusted HR 1.27 (CI 95% 0.85-1.89), P = .25). Median OS was not reached in the Q6W group vs 20.5 months (CI 95% 13.7-29.8) in the Q3W group (adjusted HR 0.80 (CI 95% 0.50-1.29), P = .36). Immune-mediated AEs of grade ≥ 3 occurred in 18% of patients in the Q6W group and in 19% of those in the Q3W group.

Conclusions
In this unicentric retrospective study, the pembrolizumab Q6W dosing regimen was comparable to the Q3W in terms of OS, PFS, and toxicity.
Hypersensitivity to gadolinium-based contrast
Authors: Sáenz de Santa María Rocío , Labella Marina , Bogas Gádor , Doña Inmaculada , Torres María José 
Published: June 2023

Purpose of review
The use of contrast media is increasing in recent decades. Although gadolinium-based contrast agents (GBCAs) are generally well tolerated, adverse reactions, including hypersensitivity reactions (HSRs), although infrequent, may occur. It is important to perform a thorough allergological evaluation in patients with suspected GBCA-HSRs to avoid potentially serious reactions in subsequent exposures.

Recent findings
Data on GBCA-HSRs are scarce. Most published articles dealing with skin tests and drug provocation tests (DPTs) with GBCAs are case series and small cohorts. Controversies exist about the role of premedication for preventing HSRs on subsequent exposures. Selection of well tolerated alternatives is based on potential cross-reactivity among GBCAs; however, the extent of cross-reactivity among them remains unclear.

Summary
As premedication is not useful because breakthrough reactions are frequent in patients with GBCA-HSRs in subsequent exposures, an allergological evaluation is required. Available data suggest a high negative predictive value of skin tests, being crucial for guiding the selection of an alternative GBCA. However, DPTs are still necessary to confirm or exclude the diagnosis or find alternative GBCAs. Cross-reactivity is high among GBCAs belonging from the same group, mainly among macrocyclic compounds, so this must be taken into account for selecting alternatives.
Vagueness in Goals-of-Care Conferences for Critically Ill Patients: Types of Hedge Language Used by Physicians*
Authors: Mittal Vaishali , Hakes Nicholas A. , Magnus David , Batten Jason N. 
Published: June 2023

OBJECTIVES:
Hedge language is a category of language that refers to words or phrases that make statements “fuzzier.” We sought to understand how physicians use hedge language during goals-of-care conferences in the ICU.

DESIGN:
Secondary analysis of transcripts of audio-recorded goals-of-care conferences in the ICU.

SETTING:
Thirteen ICUs at six academic and community medical centers in the United States.

PATIENTS:
Conferences were between clinicians and surrogates of incapacitated, critically ill adults.

INTERVENTIONS:
Four investigators performed a qualitative content analysis of transcripts using deductive followed by inductive methods to identify types of hedge language used by physicians, then coded all instances of hedge language across 40 transcripts to characterize general patterns in usage.

MEASUREMENTS AND MAIN RESULTS:
We identified 10 types of hedge language: numeric probabilistic statement (“there’s an 80% chance”), qualitative probabilistic statement (“there’s a good chance”), nonprobabilistic uncertainty statement (“hard to say for her”), plausibility shield (“we expect”), emotion-based statement (“we’re concerned”), attribution shield (“according to Dr. X”), adaptor (“sort of”), metaphor (“the chips are stacking up against her”), time reference (“too soon to tell”), and contingency statement (“if we are lucky”). For most types of hedge language, we identified distinct subtypes. Physicians used hedge language frequently in every transcript (median: 74 hedges per transcript) to address diagnosis, prognosis, and treatment. We observed large variation in how frequently each type and subtype of hedge language was used.

CONCLUSIONS:
Hedge language is ubiquitous in physician-surrogate communication during goals-of-care conferences in the ICU and can be used to introduce vagueness to statements in ways beyond expressing uncertainty. It is not known how hedge language impacts decision-making or clinician-surrogate interactions. This study prioritizes specific types of hedge language for future research based on their frequency and novelty.