bluuebunny/crossref_metadata_2025_split huggingface dataset:
Informing a European guidance framework on electronic informed consent in clinical research: a qualitative study
Authors: De Sutter Evelien , Borry Pascal , Huys Isabelle , Barbier Liese 
Published: February 2023

Abstract
Background
Electronic informed consent (eIC) may offer various advantages compared to paper-based informed consent. However, the regulatory and legal landscape related to eIC provides a diffuse image. By drawing from the perspectives of key stakeholders in the field, this study aims to inform the creation of a European guidance framework on eIC in clinical research.

Methods
Focus group discussions and semi-structured interviews were conducted with 20 participants from six stakeholder groups. The stakeholder groups included representatives of ethics committees, data infrastructure organizations, patient organizations, and the pharmaceutical industry as well as investigators and regulators. All were involved in or knowledgeable about clinical research and were active in one of the European Union Member States or at a pan-European or global level. The framework method was used for data analysis.

Results
Stakeholders underwrote the need for a multi-stakeholder guidance framework addressing practical elements related to eIC. According to the stakeholders, a European guidance framework should describe consistent requirements and procedures for implementing eIC on a pan-European level. Generally, stakeholders agreed with the definitions of eIC issued by the European Medicines Agency and the US Food and Drug Administration. Nevertheless, it was raised that, in a European guidance framework, it should be emphasized that eIC aims to support rather than replace the personal interaction between research participants and the research team. In addition, it was believed that a European guidance framework should include details on the legality of eIC across European Union Member States and the responsibilities of an ethics committee in the eIC assessment process. Although stakeholders supported the idea to include detailed information on the type of eIC-related materials to be submitted to an ethics committee, opinions varied on this regard.

Conclusion
The creation of a European guidance framework is a much needed factor to advance eIC implementation in clinical research. By collecting the views of multiple stakeholder groups, this study advances recommendations that may facilitate the development of such a framework. Particular consideration should go to harmonizing requirements and providing practical details related to eIC implementation on a European Union-wide level.
Health workforce perceptions on telehealth augmentation opportunities
Authors: Thomas L. T. , Lee C. M. Y. , McClelland K. , Nunis G. , Robinson S. , Norman R. 
Published: February 2023

Abstract
Background
The availability and use of telehealth to support health care access from a distance has expanded in response to the COVID-19 pandemic. Telehealth services have supported regional and remote health care access for many years and could be augmented to improve health care accessibility, acceptability and overall experiences for both consumers and clinicians. This study aimed to explore health workforce representatives’ needs and expectations to move beyond existing telehealth models and plan for the future of virtual care.

Methods
To inform recommendations for augmentation, semi-structured focus group discussions were held (November–December 2021). Health workforce representatives with experience in health care delivery via telehealth across country Western Australia were approached and invited to join a discussion.

Results
Focus group participants included 53 health workforce representatives, with between two and eight participants per discussion. In total, 12 focus groups were conducted: seven were specific to regions, three with staff in centralised roles, and two with a mixture of participants from regional and central roles. Findings identified four key areas for telehealth augmentation: improvements required to existing service practice and processes; equity and access considerations; health workforce-focussed opportunities; and consumer-focussed opportunities.

Conclusions
Following the onset of the COVID-19 pandemic and the rapid increase in health services delivered via telehealth modalities, it is timely to explore opportunities to augment pre-existing models of care. Workforce representatives consulted in this study suggested modifications to existing process and practice that would improve the current models of care, and recommendations on ways to improve clinician and consumer experiences with telehealth. Improving experiences with virtual delivery of health care is likely to support continued use and acceptance of this modality in health care delivery.
The impact of road safety strategy and policy on admissions to a national rehabilitation hospital; a 5-year retrospective review and reflection on trauma data
Authors: Carroll Áine , Sukumar Prasanth , O’Keeffe Aisling 
Published: February 2023

Abstract
Background
Globally, road traffic collisions (RTCs) are a common cause of death and disability. Although many countries, including Ireland, have road safety and trauma strategies, the impact on rehabilitation services is unclear. This study explores how admissions with RTC related injuries to a rehabilitation facility has changed over 5 years and how they contrast to major trauma audit (MTA) serious injury data from the same timeframe.

Methods
A retrospective review of healthcare records with data abstraction in accordance with best practice was performed. Fisher’s exact test and binary logistic regression were used to determine associations and statistical process control was used to analyse variation. All patients discharged with an International Classification of Diseases (ICD) 10 coded diagnosis of Transport accidents from 2014 to 2018 were included. In addition, serious injury data was abstracted from MTA reports.

Results
338 cases were identified. Of these, 173 did not meet the inclusion criteria (readmissions) and were excluded. The total number analyzed was 165. Of these, 121 (73%) were male and 44 (27%) were female and 115 (72%) were under 40 years of age. The majority [128 (78%)] had traumatic brain injuries (TBI), 33 (20%) had traumatic spinal cord injuries and 4 (2.4%) had traumatic amputation The numbers varied over the time period of the study but showed normal variation and not special cause variation which suggests no significant impact of policy in the time frame. There was a large discrepancy between the number of severe TBIs reported in the MTA reports and the numbers admitted with RTC related TBI to the National Rehabilitation University Hospital (NRH). This suggests there may be many people not accessing the specialist rehabilitation services they require.

Conclusion
Data linkage between administrative and health datasets does not currently exist but offers huge potential for understanding the trauma and rehabilitation ecosystem in detail. This is required to better understand the impact of strategy and policy.
HDAC inhibitor ITF2357 reduces resistance of mutant-KRAS non-small cell lung cancer to pemetrexed through a HDAC2/miR-130a-3p-dependent mechanism
Authors: Cui Jian , Xu Fei , Bai Wei , Zhao Tiantian , Hong Junbo , Zuo Wei 
Published: February 2023

Abstract
Background
Histone deacetylases (HDAC) contribute to oncogenic program, pointing to their inhibitors as a potential strategy against cancers. We, thus, studied the mechanism of HDAC inhibitor ITF2357 in resistance of mutant (mut)-KRAS non-small cell lung cancer (NSCLC) to pemetrexed (Pem).

Methods
We first determined the expression of NSCLC tumorigenesis-related HDAC2 and Rad51 in NSCLC tissues and cells. Next, we illustrated the effect of ITF2357 on the Pem resistance in wild type-KARS NSCLC cell line H1299, mut-KARS NSCLC cell line A549 and Pem-resistant mut-KARS cell line A549R in vitro and in xenografts of nude mice in vivo.

Results
Expression of HDAC2 and Rad51 was upregulated in NSCLC tissues and cells. Accordingly, it was revealed that ITF2357 downregulated HDAC2 expression to diminish the resistance of H1299, A549 and A549R cells to Pem. HDAC2 bound to miR-130a-3p to upregulate its target gene Rad51. The in vitro findings were reproduced in vivo, where ITF2357 inhibited the HDAC2/miR-130a-3p/Rad51 axis to reduce the resistance of mut-KRAS NSCLC to Pem.

Conclusion
Taken together, HDAC inhibitor ITF2357 restores miR-130a-3p expression by inhibiting HDAC2, thereby repressing Rad51 and ultimately diminishing resistance of mut-KRAS NSCLC to Pem. Our findings suggested HDAC inhibitor ITF2357 as a promising adjuvant strategy to enhance the sensitivity of mut-KRAS NSCLC to Pem.
Majorization and semidoubly stochastic operators on $L^{1}(X)$
Authors: Manjegani Seyed Mahmoud , Moein Shirin 
Published: February 2023

AbstractThis paper is devoted to a study of majorization based on semidoubly stochastic operators (denoted by $S\mathcal{D}(L^{1})$
S
D
(

L
1

)
) on $L^{1}(X)$

L
1

(
X
)
when X is a σ-finite measure space. We answer Mirsky’s question and characterize the majorization by means of semidoubly stochastic maps on $L^{1}(X)$

L
1

(
X
)
. We prove some results on semidoubly stochastic operators such as a strong relation of semidoubly stochastic operators and integral stochastic operators and relatively weak compactness of $S_{f}=\{Sf : S\in S\mathcal{D}(L^{1})\}$

S
f

=
{
S
f
:
S
∈
S
D
(

L
1

)
}
for a fixed element $f\in L^{1}(X)$
f
∈

L
1

(
X
)
by proving the equiintegrability of $S_{f}$

S
f

. We present a full characterization of majorization on a σ-finite measure space X.
Attitudes toward depression among Ecuadorian physicians using the Spanish-validated version of the Revised Depression Attitude Questionnaire (R-DAQ)
Authors: Valdevilla Figueira José Alejandro , Mautong Hans , Camacho L Genesis , Cherrez Michelle , Orellana Román Carlos , Alvarado-Villa Geovanny Efraín , Sarfraz Zouina , Sarfraz Azza , Agolli Arjola , Farfán Bajaña María José , Vanegas Emanuel , Felix Miguel , Michel Jack , Espinoza-Fuentes Fernando , Maquilón Jaime Rosero , Cherrez Ojeda Ivan 
Published: February 2023

Abstract
Purpose
Depression is inadequately recognized and managed, and physicians’ attitudes toward this condition and its treatment may play a part in this. This study aimed to assess Ecuadorian physicians' attitudes toward depression.

Methods
This was a cross-sectional study conducted using the validated Revised Depression Attitude Questionnaire (R-DAQ). The questionnaire was delivered to Ecuadorian physicians, and the response rate was 88.8%.

Results
76.4% of participants had never received previous training in depression, and 52.1% of them indicated neutral or limited professional confidence when dealing with depressed patients. More than two-thirds of the participants reported an optimistic attitude toward the generalist perspective of depression.

Conclusion
Overall, physicians in Ecuador's healthcare settings were optimistic and held positive attitudes toward patients with depression. However, a lack of confidence in the management of depression and a need for ongoing training were found, especially among medical professionals who are not in daily contact with patients with depression.
The time cost of physiologically ineffective intravenous fluids in the emergency department: an observational pilot study employing wearable Doppler ultrasound
Authors: Kenny Jon-Émile S. , Gibbs Stanley O. , Johnston Delaney , Yang Zhen , Hofer Lisa M. , Elfarnawany Mai , Eibl Joseph K. , Johnson Amanda , Buecker Anthony J. , Lau Vivian C. , Kemp Benjamin O. 
Published: February 2023

Abstract
Background
Little data exist on the time spent by emergency department (ED) personnel providing intravenous (IV) fluid to ‘responsive’ versus ‘unresponsive’ patients.

Methods
A prospective, convenience sample of adult ED patients was studied; patients were enrolled if preload expansion was indicated for any reason. Using a novel, wireless, wearable ultrasound, carotid artery Doppler was obtained before and throughout a preload challenge (PC) prior to each bag of ordered IV fluid. The treating clinician was blinded to the results of the ultrasound. IV fluid was deemed ‘effective’ or ‘ineffective’ based on the greatest change in carotid artery corrected flow time (ccFT∆) during the PC. The duration, in minutes, of each bag of IV fluid administered was recorded.

Results
53 patients were recruited and 2 excluded for Doppler artifact. There were 86 total PCs included in the investigation comprising 81.7 L of administered IV fluid. 19,667 carotid Doppler cardiac cycles were analyzed. Using ccFT∆ ≥  + 7 ms to discriminate ‘physiologically effective’ from ‘ineffective’ IV fluid, we observed that 54 PCs (63%) were ‘effective’, comprising 51.7 L of IV fluid, whereas, 32 (37%) were ‘ineffective’ comprising 30 L of IV fluid. 29.75 total hours across all 51 patients were spent in the ED providing IV fluids categorized as ‘ineffective.’

Conclusions
We report the largest-known carotid artery Doppler analysis (i.e., roughly 20,000 cardiac cycles) in ED patients requiring IV fluid expansion. A clinically significant amount of time was spent providing physiologically ineffective IV fluid. This may represent an avenue to improve ED care efficiency.
The strength and microstructure of cemented sand-gravel (CSG) mixture containing fine-grained particles
Authors: Karimi Sina , Farshbaf Aghajani Hamed 
Published: February 2023

AbstractThe hardfill embankments are composed of cemented sand-gravel (CSG) mixtures. In some cases, however, sand and gravel used in the mixture contain fine-grained fraction. This paper aimed to study the mechanical behavior and microstructure of CSG mixtures in which the base soil contains fine-grained particles with different plasticity specifications. Various contents of kaolinite and bentonite were added to a sand-cement mixture with different cement contents and uniaxial strength and deformation modulus in the mixtures were measured at two curing ages. According to the results, in low cement mixtures, the mixture containing 10% of the additive exhibited the maximum strength and deformation modulus, regardless of the additive type. In a family of bentonite-containing mixtures with higher cement, the strength of mixtures decreased with increasing the bentonite content. However, the mixture with higher cement and 10% of kaolinite presented the best performance from in terms of strength and stiffness. Analyzing the mineralogy and SEM images of mixtures showed that the structure of base soil attained the best packing and a strong matrix was devolved inside the mixture with 10% of fine additive. Furthermore, the kaolinite particles in the mixture containing 10% kaolinite contributed to the hydration process of cement.
A case of Hirschsprung’s disease with segmental dilatation of the colon
Authors: Yokokawa Hideyuki , Yoshida Mariko , Takazawa Shinya , Kutsukake Mai , Omata Kanako , Ogawa Shoko , Fujishiro Jun 
Published: February 2023

Abstract
Background
Segmental dilatation of the colon (SDC) is a rare disease that is characterized by an abrupt segment of dilated colon between regions of normal-sized colon. We herein report a case of SDC associated with Hirschsprung’s disease (HD).

Case presentation
The patient developed abdominal distension soon after birth, and enema examination showed localized intestinal dilatation from the descending colon to the sigmoid colon with significant caliber changes on both the oral and anal sides of the dilated colon. The findings of the rectal mucosal biopsy were consistent with HD. We considered this case to be a combination of HD and SDC and performed laparoscopic-assisted Soave pull-through with resection of the dilated colon when the patient was 7 months old. Resected specimens showed steep caliber changes on the oral and anal sides of the dilated colon. In the pathological examination, no ganglion cells were found in the submucosa on the anal side of the dilated colon. Based on the above findings, we finally made the diagnosis of HD with SDC.

Conclusion
In HD with a characteristic dilated colon, the possibility of SDC should be considered.
Novel variants of SYNGAP1 associated epileptic encephalopathy: two cases report and literature review
Authors: Zeng Xingying , Chen Yong , Yu Xiongying , Che Yuanyuan , Chen Hui , Yi Zhaoshi , Qin Jie , Zhong Jianmin 
Published: February 2023

Abstract
Background
SYNGAP1 is a significant genetic risk factor for global developmental delay, autism spectrum disorder, and epileptic encephalopathy. De novo loss-of-function variants in this gene cause a neurodevelopmental disorder, for example, early-onset and drug-refractory seizures. We report two children with global developmental delay and epileptic encephalopathy, which are caused by SYNGAP1 gene novel mutations, and drug treatment is effective.

Case presentation
We report a boy and a girl presented with global developmental delay when they were young babies; as they grew up, cognitive impairment and social-communication disorder became more and more prominent; unfortunately, the patients developed into various seizure types, including eyelid myoclonia, myoclonic and absences when the boy was 1 year 8 mouths old and the girl was 3 years old. The two patients were found two previously unknown mutations by high throughput sequencing [c.3271_ c.3272insT; (p.L1091L fs*62), c.2515A > T (p.K839*)] in exon 15 of the SYNGAP in the proband. Sanger sequencing confirmed the heterozygous nature, and neither of their parents carried the same mutation. The girl treated with valproic acid and prednisone became seizure-free, and valproic acid and levetiracetam combined with clonazepam were influential in the other.

Conclusions
The global developmental delay and epileptic encephalopathy of the children were probably due to the pathogenic mutation of the SYNGAP1 gene, and prednisone and clonazepam may be effective in achieving seizure-free.
The incidence and trends of laryngeal malignancies in Sri Lanka from 2001 to 2019: a Joinpoint analysis of the national cancer database
Authors: Jayarajah Umesh , Jayasinghe Ravindri , Fernando Ashan , Seneviratne Sanjeewa 
Published: February 2023

Abstract
Introduction
Laryngeal cancer is the ninth commonest cancer among Asian males. Global and regional epidemiological analyses have shown varying patterns in the incidence and risk factors for laryngeal cancer. Therefore, we aimed to analyse the trends in the incidence and histological patterns of laryngeal cancers for the first time in Sri Lanka.

Methods
We used the population-based Sri Lanka cancer registry data and pooled all newly diagnosed patients with laryngeal malignancies from 2001 to 2019 (a 19-year study period). The WHO age-standardised incidence rates (ASR) were calculated using the WHO standard pollution. We used the Joinpoint regression software to calculate the estimated annual percentage change (EAPC) and analysed the trends in the incidence by different age categories and sex.

Results
From 2001 to 2019, 9808 new cases of laryngeal cancers (males = 8927, 91%, mean age = 62 years) were registered. The incidence of laryngeal cancers was greatest in the 70–74-year followed by 65–69-year age groups. Around 7.9% were reported as carcinoma not otherwise specified (NOS). Squamous cell carcinoma (90.1%) was the commonest documented histology type. A rise in the WHO-ASR was noted from 1.91 per 100,000 in 2001 [95% confidence interval (95% CI): 1.69–2.12] to 3.59 per 100,000 in 2017 [(95% CI: 3.34–3.84); EAPC: 4.4 (95% CI: 3.7–5.2), p < 0.05 for trend] followed by a decrease in the incidence [2.97 per 100,000 in 2019 (95% CI: 2.74–3.2), EAPC: − 7.2 (95% CI: − 21.1–9.1, p > 0.05)]. From 2001 to 2017, the proportional increase in incidence was greater in males than females [EAPC: 4.9 (95% CI: 4.1–5.7 vs. 3.7 (95% CI: 1.7–5.6)].

Conclusions
We identified an increasing incidence of laryngeal cancer in Sri Lanka from 2001 to 2017 followed by a slight decrease. Further studies are essential to identify the aetiological factors. Development of laryngeal cancer prevention and screening programmes for high-risk populations may be considered.
Semaglutide in the treatment of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis
Authors: Mazurek Magdalena , Białowąs Edyta , Dybała Ewelina , Cuber Iwona , Aghadi Artur 
Published: February 2023

Background: Non-alcoholic fatty liver disease (NAFLD) is an increasing problem in the modern world due to increased morbidity and due to its clinical consequences. It is a chronic liver disease, histologically divided into non-alcoholic steatohepatitis (NAFL) with isolated steatosis to non-alcoholic steatohepatitis (NASH), which is characterized by hepatocyte injury, inflammation, and variable degrees of fibrosis that can progress to cirrhosis in a fraction of patients. Data on the prevalence of NAFLD vary depending on the population studied and the method used to establish the diagnosis, but the prevalence rate ranges from 6% to 35%, with a median of 20%. The prevalence of NASH in the European population is estimated at 5-6%, which makes NAFLD a new civilizational challenge.
Aim of the study: The following article as an analysis of the current medical knowledge on the effectiveness and safety of NAFLD and NASH treatment with semaglutide based on available publications.
Methods and materials: Literature review based on PubMed data using the following key words: NAFLD; NASH; semaglutide; Glucagon-like peptide-1 (GLP-1) analogues
State of knowledge: GLP-1 receptor agonists are incretin drugs. This class of drugs has been approved by the FDA for the treatment of type 2 diabetes.
Results: There is currently no approved therapy for NAFLD or nonalcoholic steatohepatitis (NASH). Beneficial effect of semaglutide on glycemia and weight loss makes them an attractive potential therapeutic form in NASH. However, there is a need for more clinical studies, on larger groups of people to recognize the effective form of semaglutide NAFLD therapy.
Ketogenic diet - a literature review
Authors: Cuber Iwona , Aghadi Artur , Białowąs Edyta , Dybała Ewelina , Mazurek Magdalena , Górna Marta 
Published: February 2023

Introduction: The ketogenic diet, originally used in the treatment of epilepsy, has recently attracted increasing interest from scientists. There are more and more reports about the possible benefits of using KD.
Aim of the study: The aim of the study is to present the assumptions of the ketogenic diet and the effects of its use in weight reduction, treatment of type 2 diabetes and the treatment of cancer and dementia.
Description of the state of knowledge: Beneficial effects of the use of a ketogenic diet related to weight reduction and improvement of the lipid profile have been described. The ketogenic diet also allows to reduce the intake of antidiabetic drugs and reduce or discontinue insulin therapy. Animal studies also suggest benefits of using KD in the treatment of cancer. However, studies involving humans are lacking. There are also reports of the effect of KD on delaying the onset of dementia symptoms.
Summary: Despite very promising scientific reports, there are no long-term studies on the impact of the ketogenic diet on cardiovascular risk. Therefore, it should be used after weighing the pros and cons.