bluuebunny/crossref_metadata_2025_split huggingface dataset:
Update on the clinical trial landscape: analysis of ClinicalTrials.gov registration data, 2000–2020
Authors: Gresham Gillian , Meinert Jill L. , Gresham Arthur G. , Piantadosi Steven , Meinert Curtis L. 
Published: October 2022

Abstract
Background
The clinical trial landscape has evolved over the last two decades, shaped by advances in therapeutics and drug development and innovation in trial design and methods. The tracking of such changes became possible with trial registration, providing the public with a window into the massive clinical research enterprise. The ClinicalTrials.gov website was launched in 2000 by the NIH National Library of Medicine and is the largest clinical trial registry worldwide. The purpose of this analysis is to describe the composition and methodologic features of clinical trials as registered on ClinicalTrials.gov and to identify trends over time.

Methods
We analyzed data from the publicly available Clinical Trials Transformation Initiative Aggregate Analysis of ClinicalTrials.gov (AACT) database, focusing on trials (interventional studies) started between 1 January 2000 through 31 December 2020. Characteristics of design (e.g., phase, randomization, use of masking, number of treatment groups, sample size), eligibility criteria (age groups, gender), interventions, conditions, and funders (primary sponsor) were tabulated over time, by year trial started.

Results
There were 274,043 registered interventional studies (trials) included in the analysis. Most trials were reported as randomized (65%); single site (60%); parallel-group (56%); funded by other sources (e.g., individuals, universities, and community-based organizations) (65%); and involving drug interventions (55%). Notable trends include an increase in the proportion of registered trials without FDA-defined phases (“Phase N/A”) over time, a decrease in proportion of trials that involve drugs or report treatment as a primary purpose, declining sample size and time to complete trials, and an increase in proportion of trials reporting results among completed trials. The proportion of missing registration fields has also decreased over time and more trials make protocols and other documents available. There is a current need to expand the registration fields in ClinicalTrials.gov to adapt to the evolving trial designs and reduce the number of trials categorized as “other.” Observed trends may be explained by changes in trial regulations as well as expanding and evolving trial designs, interventions, and outcome types.

Conclusions
Clinical trial registration has transformed how trial information is accessed, disseminated, and used. As clinical trials evolve and regulations change, trial registries, including ClinicalTrials.gov, will continue to provide a means to access and follow trials over time, thus informing future trial design and highlighting the value of this tremendous resource.
Neuroleptic malignant syndrome secondary to olanzapine, a presentation with severe acute kidney injury requiring hemodialysis: a case report
Authors: Chang Chee Keong , Payus Alvin Oliver , Noh Malehah Mohd , Lansing Meryl Grace , Sumpat Doreen , Lu Sooth Jiun Andrea , Yew Boon Teong 
Published: October 2022

Abstract
Background
We present this case to draw attention to the importance of early diagnosis in terms of life-saving, noting that greater awareness is important among healthcare professionals. Our patient developed neuroleptic malignant syndrome (NMS) after his neuroleptic drug dosage was increased. His condition was complicated by acute kidney injury (AKI) which required hemodialysis. The uniqueness of this case is that the causative agent of NMS is an atypical antipsychotic, and atypical antipsychotics are generally considered to be safer than typical antipsychotics.

Case presentation
A 31-year-old Chinese man with underlying schizophrenia presented to our hospital with aggressive behavior. He was admitted to the psychiatric hospital and started on his regular medications, with an increase in the dose of olanzapine tablet from 5 to 10 mg daily. After 5 days in the ward, the patient was noted to have high fever, restlessness, confusion, increased muscle rigidity, tachycardia and tachypnoea. Antipsychotic therapy was stopped in view of suspected NMS. The first laboratory test for serum creatine kinase (CK) showed a markedly high level of this molecule. His renal profile showed raised serum creatinine in comparison to 2 months prior when the baseline serum creatinine was within the normal range. A diagnosis of NMS with AKI was made. Although the patient was given adequate intravenous fluid hydration with close monitoring of urine output, his renal function did not show improvement but continued to show a worsening trend. In view of this, he was started on urgent hemodialysis. The patient was dependent on intermittent hemodialysis before his AKI showed complete recovery. After 2 weeks, his blood test results returned to normal. He was discharged well.

Conclusion
Neuroleptic malignant syndrome is a life-threatening iatrogenic medical emergency in which high index of clinical suspicion is required for diagnosis and prompt treatment.
Perceptions and attitudes about antibiotic resistance in the general public and general practitioners in France
Authors: Menard Colette , Fégueux Sophie , Heritage Zoë , Nion-Huang Michèle , Berger-Carbonne Anne , Bonmarin Isabelle 
Published: October 2022

Abstract
Background
During the last 20 years, France has taken important steps to tackle antibiotic resistance. These include national awareness campaigns for the general public, and supporting changes in terms of antibiotic prescription for healthcare practitioners. To prepare the upcoming 2022/2023 campaign, we conducted two surveys to assess (1) the general public’s knowledge, attitudes and behaviours regarding antibiotics and (2) the perceptions and practices of general practitioners (GPs).

Methods
Two quantitative telephone surveys were conducted using the same methodology as that used in 2010 by the National Health Insurance Authority. The first was conducted in 2019 in a national representative quota sample of 1204 persons aged over 15 years living in metropolitan France, including an over-sample of 332 parents of children aged six years or under. The second was conducted in 2020 in a national representative sample of 388 GPs.

Results
Twenty-seven percent of respondents reported taking antibiotics during the previous year. Sixty-five percent of GPs declared prescribing fewer antibiotics during the previous five years. However, 33% of GPs reported they often had patients who put high pressure to get antibiotics. The pressure from elderly patients, especially those with comorbidities was notable. Three percent of respondent patients reported putting often pressure on their GP. All respondents expressed total trust in their GP irrespective of whether s/he had prescribed them antibiotics. Half knew that antibiotics act only on bacteria, and 38% said they understood precisely what antibiotic resistance is.

Conclusion
Although antibiotic use is decreasing in France, patient pressure on GPs to prescribe antibiotics is very high. GPs are key ambassadors in reducing antibiotic use. Awareness campaigns must target elderly patients in particular.
Adaptation of Food Craving Inventory to Turkish culture: a validity and reliability study
Authors: Özel İrem Çağla , Yabancı Ayhan Nurcan , Çetiner Özlem 
Published: October 2022

Abstract
Introduction
The Food Craving Inventory is a 28-item self-report measure of specific food cravings. The inventory consists of 4 factors: high fats, sweets, carbohydrates/starches and fast-food fats.

Purpose
This study was carried out to evaluate the Turkish validity and reliability of the Food Craving Inventory, and to determine the psychometric properties and factor structure of the Turkish version.

Methods
The sample of the study consists of 621 individuals between the ages of 19–50 who voluntarily agree to participate in online survey. Validity and reliability analyses were performed for the Turkish version of Food Craving Inventory (FCI-TR). Confirmatory factor analysis was performed to evaluate the factor structure of the Turkish version of FCI.

Results
Confirmatory factor analysis yielded a four-factor structure as “sweets,” “high-fats,” “carbohydrates/starches” and “fast food fats”. The Cronbach-alpha coefficient for the total score was 0.84; subfactors were calculated as 0.74 for “sweets”, 0.64 for “high-fat foods”, 0.65 for “carbohydrates/starches”, and 0.66 for “fast-food fats”. The scores of the FCI-TR factors and its total score significantly correlated with the sub-factors of Three Factor Eating Questionnaire (TFEQ). A significant correlation was found between body mass index (BMI) and high fats and fast-food fats factor score. Also total and factor scores of the FCI-TR were different between BMI groups.

Conclusions
This study demonstrates that the Turkish version of the FCI is a valid and reliable tool to measure food cravings in the Turkish population. FCI is also correlated with sub-factors of TFEQ.
Trend analyses of TIMSS 2015 and 2019: school factors related to declining performance in mathematics
Authors: Nilsen Trude , Kaarstein Hege , Lehre Anne-Catherine 
Published: October 2022

AbstractGaining knowledge of what contextual factors may contribute to changes in student achievement across cycles of international large-scale assessments (ILSA), is important for educational policy and practice. Addressing this necessitates advanced methodology that utilizes the trend design of the ILSAs. The Trends in International Mathematics and Science Study (TIMSS) data is suitable for such analyses as it measures students’ competence based on the participating countries curricula. In Norway, students’ performance in mathematics decreased from 2015 to 2019 as evidenced by TIMSS. During this time-period, there are indications that also school climate, student motivation and self-concept decreased. This study investigates whether school climate (including bullying, a safe environment, school emphasis on academic success, and students’ sense of school belonging and well-being), student motivation (including interest-enjoyment and utility value), and self-concept declined from 2015 to 2019, and whether this possible decline is related to the decline in mathematics performance in Norway. The present study utilized a trend approach with mediation structural equation modelling. The results showed that school climate, the utility value of the subject and students’ self-concept declined during this period, and that a safe environment and student self-concept mediated the changes in achievement from TIMSS 2015 to 2019. Hence, declines in a safe school climate and student self-concept were associated with declining achievements. While the study cannot prove a causal relation, it is discussed whether this could indicate that the decline in these predictors may explain the decline in mathematics achievement. The usefulness of the methodological approach for other countries, as well as the implications of the results for policy, practice, and research are discussed.
Role of multi-walled carbon nanotubes as a growth regulator for Basella alba (Malabar spinach) plant and its soil microbiota
Authors: Singh Garima , Ghosh Sayantan , Dinakar B. , Nayak Bismita 
Published: October 2022

AbstractThe effect of pure multi-walled carbon nanotubes (MWCNTs) was studied on the development and morphology of theBasella albaplant. The plants were treated with varying sonicated concentrations of MWCNTs. The parameters taken into consideration were germination percentage of seeds, protein content in the plant, estimation of chlorophyll concentration, and the effect on the soil microbial community after treatment with MWCNTs. A boost in vigour index was recorded with the 200 µg ml−1concentration of MWCNTs. Increment in other parameters like protein content, chlorophyll concentration, and microbial community in soil samples have also been observed. All parameters showed higher efficiency in a concentration-dependent manner of MWCNTs compared to control by testing the significance of results through statistical one-way ANOVA analysis. The uptake of MWCNTs by plants was confirmed by SEM–EDX analysis of treated and control leaf tissue sections. This study concludes that MWCNTs exhibit significant growth effects with no toxicity toBasella alba.Graphical Abstract
Parental COVID-19 vaccination hesitancy among parents of children aged 5–18 years in Thailand: a cross-sectional survey study
Authors: Parinyarux Pantira , Sunkonkit Kanokkarn , Yotsombut Kitiyot 
Published: October 2022

Abstract
Background
To promote an acceptance rate of COVID-19 immunization among Thai children, concerns about parental vaccination hesitancy should be urgently studied. This study aimed to examine the parental COVID-19 vaccination hesitancy (PVh) level and influencing factors among Thai parents of children 5–18 years of age.

Methods
This cross-sectional survey was conducted in Thailand during May and June of 2022. The Google forms for data collection were distributed to parents (a father, a mother, or one who nurtures and raises a child) via various online social media. Data regarding PVh level, relevant attitudes, experiences of COVID-19 and COVID-19 vaccination (EC&V), and family contexts (FC) were collected and analyzed using descriptive statistics. Mann–Whitney U test was used to compare the differences among groups of parents based on EC&V and FC. The factors influencing PVh were assessed by multiple regression analysis.

Results
Four hundred and eighty-eight parents completed the online questionnaire. Their median (IQR) age was 41 (35–47) years. They lived in different provinces from all regions across Thailand. Ninety percent of them were authorized persons to make decision about children vaccination. Fifty-eight percent of the respondents had vaccine hesitancy, defined as PVh level at moderate or above. Parents who had ever refused COVID-19 vaccination for themselves or refused to vaccinate their children against any other diseases had statistically significant higher levels of PVh (p value < 0.001). Conversely, the parents who had finished the initial COVID-19 vaccine had lower PVh levels with statistical significance (p value = 0.001). Attitude towards COVID-19 (AC), attitude towards COVID-19 vaccine (AV), and perceived behavioral control (PC) of the parents negatively influenced PVh with statistical significance, according to the results of the multiple regression analysis (Betas = − 0.307, − 0.123, and − 0.232, respectively).

Conclusions
COVID-19 vaccination hesitancy was commonly found among Thai parents. The factors of the hesitancy were multifaceted. Different experiences regarding COVID-19 vaccination for themselves and any vaccinations for their children were associated with different PVhs. The attitudes especially AC, AV, and PC statistically influenced PVh. These findings should be exploited for national and local policy planning as well as public campaigns.
Associations between traumatic event experiences, psychiatric disorders, and suicidal behavior in the general population of Afghanistan: findings from Afghan National Mental Health Survey
Authors: Sabawoon Ajmal , Keyes Katherine M. , Karam Elie , Kovess-Masfety Viviane 
Published: October 2022

Abstract
Background
The role of traumatic event exposure and psychiatric disorders as central risk factors for suicidal behavior has been established, but there are limited data in high conflict regions with significant trauma exposures such as Afghanistan.

Methods
A nationally representative, cross-sectional survey was conducted through systematic stratified random sampling in 8 regions of Afghanistan in 2017 (N = 4474). Well-validated instruments were used to establish trauma exposure, psychiatric disorders. Death preference, suicidal ideation, plan, and attempts were assessed.

Results
In the total sample, 2.2% reported suicidal ideation in the past 12 months, and 7.1% of respondents reported that they had suicidal ideation at some point in their lives; 3.4% reported a suicide attempt. Women were at higher risk than men. All traumatic event exposures were strongly associated with suicidal behavior. Respondents who reported experiencing sexual violence were 4.4 times more likely to report lifetime suicide attempts (95% CI 2.3–8.4) and 5.8 times more likely to report past 12-month suicidal ideation (95% CI 2.7–12.4). Associations were strong and significant for all psychiatric disorders related to suicidal behavior. Respondents who met criteria for major depressive episodes (OR = 7.48; 95% CI 4.40–12.72), generalized anxiety disorder (OR = 6.61; 95% CI 3.54–12.33), and PTSD (OR = 7.26; 95% CI 4.21–12.51) had the highest risk of past 12-month suicidal ideation.

Conclusion
Traumatic event exposures and psychiatric disorders increase risk of suicidal behavior in the Afghan general population; women are at high risk. Interventions to reduce trauma exposure, including expansion of a mental health workforce in the region, are critically important.
Historical account and current ecological knowledge of the southernmost lizard in the world, Liolaemus magellanicus (Squamata: Liolaemidae)
Authors: Jaksic Fabian M. 
Published: October 2022

AbstractBackgroundThe systematics ofLiolaemus magellanicushas been relatively well researched, but despite its recognition as the southernmost lizard in the world, scant attention has been paid to the discovery, distribution, biogeography, and ecology of this lizard at the southern tip of South America. I hereby research such aspects and collate the most relevant information reported in the primary literature.Methods and ResultsI conducted a selective review of the history of discovery, distributional records, biogeography, and ecological features ofL. magellanicus, as recorded in mainstream journals and landmark monographs and books. I specifically omitted the work on the systematics of the species and genus because its complexity warrants separate treatment. I found scattered references to this lizard starting with the chronicles of several overseas expeditions (British, French, and Swedish), with Darwin, Jacquinot and Guichenot, and Anderson and Ohlin acting as informers; and culminating with Skottsberg, a traveler, and Bridges, an early settler in Tierra del Fuego Island. Modern treatment of this species started with Hellmich in the 1930s and Donoso-Barros in the 1960s in Chile, and with Cei in Argentina in the 1960s and has continued chiefly in the latter country until today.DiscussionI propose this species as a model ectothermic vertebrate that may serve to test hypotheses about: (a) Resource allocation strategies to deal with a harsh environment that affords limited opportunities for foraging and reproductive activities of a lizard. (b) Behavioral strategies for dealing with thermoregulation, food, and mate acquisition, and care –if any—of offspring. (c) Its place within the rather impoverished food web of which this species forms part of. This relatively new species, which persisted in glacial refuges before being cut off into two subpopulations—one mainlander, another islander—also offers fertile ground for testing population genetic, evolutionary, and phylogeographic hypotheses. I think that biogeographers, systematists, evolutionists, physiologists, and ecologists should take advantage of this uniquely positioned species in the southernmost margin of the world.
BRCA1/2Variants Identified Through Tumor Genomic Profiling: Assessing Genetic Counseling Outcomes
Authors: Harriman Jamie W. , Espinel Whitney F. , Vagher Jennie , Gammon Amanda 
Published: October 2022

PURPOSEAs tumor genomic profiling (TGP) is increasingly used to help guide cancer treatment, BRCA variants, which may or may not be reflective of the germline genome, are being identified. As TGP use increases, it is becoming an important tool for referral to genetic counseling and identifying patients with hereditary cancer syndromes such as hereditary breast and ovarian cancer. This study explores genetic counseling referral patterns and germline implications of patients found to have pathogenic BRCA1/2 variants identified through TGP.METHODSParticipants include patients at Huntsman Cancer Institute undergoing TGP through a single commercial laboratory between March 2014 and July 2018. A retrospective chart review was conducted for 62 patients found to have pathogenic variants (PVs) in BRCA1/2 on TGP. Data on genetic counseling referrals and uptake, germline test results, family history, and patient demographics were collected.RESULTSIn the study time frame, 1,899 patients underwent TGP. Testing identified 67 PVs in BRCA1 (23 variants) or BRCA2 (44 variants) in 62 patients. Thirty-five patients first received a referral to a genetic counselor following TGP with 33 patients completing genetic counseling. Of the 30 patients who pursued germline genetic testing following TGP, 11 were discovered to have a previously unknown germline BRCA PV. Nine of these patients were the first in their family diagnosed with hereditary breast and ovarian cancer.CONCLUSIONThis study represents one institution's experience with genetic counseling referrals, uptake, and germline results following TGP. For some patients, TGP will be the first indicator of an underlying hereditary condition. Identifying patients with PVs (which may be germline) through TGP is an important new genetic counseling referral tool that can have important implications for the patient and their family.
Follicle-Stimulating Hormone Glycosylation Variants Distinctly Modulate Pre-antral Follicle Growth and Survival
Authors: Johnson Gillian P , Onabanjo Caitlan G A , Hardy Kate , Butnev Viktor Y , Bousfield George R , Jonas Kim C 
Published: October 2022

Abstract
Follicle-stimulating hormone (FSH) is a key endocrine regulator of ovarian function. FSH is secreted as 2 macroglycosylation variants: partially glycosylated FSH (FSH21/18) and fully glycosylated FSH (FSH24). FSH21/18 is more potent than FSH24 at binding to and activating the FSH receptor (R). The ratio of FSH21/18:FSH24 has been shown to change with age, with FSH21/18 predominant at reproductive prime, and FSH24 predominant during perimenopause/menopause. How these FSH glycosylation variants modulate ovarian follicle functions remains largely unknown. The aim of this study was to investigate the effect of FSH glycosylation variants of pre-antral follicle function. Pre-antral follicles were isolated from 3- to 5-week-old C57BL/6 mice and treated ±10 ng/mL FSH21/18, FSH24, a ratio of 80:20 FSH21/18:FSH24 (to mimic reproductive prime), 50:50 FSH21/18:FSH24 (perimenopause), or 20:80 FSH21/18:FSH24 (menopause) for up to 96 hours. FSH21/18 and 80:20 FSH21/18:FSH24 increased follicle growth, in comparison with control, contrasting with FSH24 and 20:80 FSH21/18:FSH24. Survival rates were decreased in follicles treated with FSH24 or 20:80 FSH21/18:FSH24, with follicles undergoing basement membrane rupture and oocyte extrusion, increased Caspase3 gene and protein expression, and decreased markers of cell proliferation in FSH24 or 20:80 FSH21/18:FSH24–treated follicles. Moreover, this correlated with differential regulation of key genes modulating follicular functions. Pharmacological inhibitors of key FSH signal pathways suggests FSH21/18 and FSH24 initiate different FSHR signal pathway activation, which may determine their differential effects on follicle growth and survival. These data suggest that the nature of FSH glycosylation modulates the follicular cellular environment to regulate follicle growth and survival and may underpin the increasing ovarian resistance to FSH observed during aging.