bluuebunny/crossref_metadata_2025_split huggingface dataset:
Honoring The Voices Of Families: An Interpretive Description Of Parent’s Understanding And Insights Into Preventing Type 2 Diabetes In Adolescents
Authors: Spurr Shelley , Bally Jill , Nahia Nalwooga 
Published: February 2022

Abstract
Background: The incidence of type 2 diabetes (T2D) in adolescents in increasing, affecting the overall health and quality of life of adolescents and their families. Despite the serious health consequences of T2D, few studies have explored the role of parents in the prevention of prediabetes and T2D in adolescents. Thus, the purpose was to better understand parents’ insights into strategies needed for the development of interventions to prevent prediabetes and T2D in their adolescents and families.Methods: Thorne’s Interpretive Description approach was used to guide this second of two-phase study. Using purposeful sampling, parents (n=12) of adolescents at high risk for developing T2D were interviewed. This study was conducted in accordance with the standards for reporting qualitative research.Results: Two themes and multiple subthemes emerged: Parents’ Understanding of T2D (High Blood Sugar, Severe Health Impacts, and Managing Your Diet) and It Takes a Village (The Onus is on the Adolescent, Starts at Home with the Parents, We Need More Support, and Getting the Message in Their Face). Conclusions: These qualitative data were insightful as findings highlighted the parents’ predominant lack of basic knowledge, life skills, and/or resources to prevent prediabetes and T2D in adolescents. The results provided target areas for education and emphasized the importance of using social media as an approach to disseminate important information to adolescents. Parents also identified strategies for prevention interventions for adolescents surrounding prediabetes and T2D that may be effective. Given the increased prevalence of T2D in adolescents, these results are timely and confirm the urgent need for interventions to prevent pediatric prediabetes and T2D. Future research will include the co-design, piloting, and evaluation of feasible family-centered interventions grounded in participants’ experiences and suggestions that are reflective of person-centred goals and needs of adolescents.
Correlation of PD-L1 Expression on Tumour Cells Between Diagnostic Biopsies and Surgical Specimens of Lung Cancer in Real Life With Respect to Biopsy Techniques and Neoadjuvant Treatment
Authors: Gompelmann Daniela , Sinn Katharina , Brugger Jonas , Bernitzky Dominik , Mosleh Berta , Prosch Helmut , Geleff Silvana , Blessing Alissa , Tiefenbacher Andreas , Hoetzenecker Konrad , Idzko Marco , Hoda Mir Alireza 
Published: February 2022

Abstract
Purposes: Programmed death-ligand 1 (PD-L1) testing is performed mainly on biopsy specimens in patients with advanced lung cancer. It is questionable whether the small amount of tissue analysed in biopsies may represent the true PD-L1 expression of a tumour.Methods: In this retrospective study, PD-L1 expression on tumour cells derived from bronchoscopy brush cytology, endobronchial-ultrasound guided transbronchial needle aspiration (EBUS-TBNA), endobronchial biopsy, transbronchial biopsy (TBB) and computed tomography (CT)-guided transthoracic biopsy was compared to the PD-L1 expression of the corresponding surgical resection in lung cancer patients with regard to neoadjuvant treatment in-between.Results: A quantitative comparison between the diagnostic biopsy of the primary tumour with corresponding resected surgical specimens in a total of 113 lung cancer patients (60% male, mean age 65 ± 9 years) revealed a statistically significant correlation of PD-L1 expression on tumour cells (r=0.58, p<0.001), for patients without neoadjuvant treatment in-between and for patients who underwent neoadjuvant treatment (both p<0.001). Using a cut-off value of ≥50% PD-L1 TPS for comparing the biopsy samples and resected specimens, the concordance rate was 78% with a Cohen´s Kappa of 0.45.Conclusion: A statistically significant concordance for PD-L1 expression on tumour cells between biopsies from primary lung tumour and resected specimen was found, but of uncertain clinical accuracy. The use of a cut-off value of ≥50% PD-L1 TPS resulted only in a moderate agreement. Therefore, the interpretation of the PD-L1 determined form biopsy specimens status should only be considered with caution for treatment decisions.
Realization of an Efficient Optical Interconnect Using L-Shape Photonic Waveguide via Finite Difference Time Domain Method
Authors: Nayak Sangram Kumar , Panigrahi Pratap Kumar , Palai Gopinath 
Published: February 2022

Abstract
The present research focuses on two dimensional L-shape waveguide for the realisation of optical interconnect at the signal of 1550 nm, which will help for the transformation of signals from one chip to another. In this article, graphene based light emitting diode generates the wavelength of 1550 nm, where PIN photodiode converts the optical signal (wavelength 1550 nm) to its electrical counterpart. The proposed wave guide (11×11 silicon rods) with L shape defect allows the signal from source to detector. The principle of mechanism relies on the propagation of field along with the defect path which is made through finite difference time domain method. Moreover, there is no loss associated with the structure during the transformation of signals. The computational result infers that the efficiency of LED is about 99.98 % where the efficiency of photodiode is 99.94 %. Finally, the suggested silicon based waveguide acts as a good candidate for the realisation of an efficient optical interconnect.
R132H IDH1 sensitizes glioma to the antiproliferative and cytotoxic effects of BET inhibition
Authors: Sears Thomas K , Woolard Kevin D 
Published: February 2022

Abstract
IntroductionMutations in isocitrate dehydrogenase 1/2 (IDHmut) identify a subset of gliomas that exhibit epigenetic dysregulation via aberrant DNA methylation. These tumors are ultimately fatal and lack effective therapeutic strategies. Considering the epigenetic dysregulation of IDHmut gliomas, we hypothesized that epigenetic-targeting drugs may yield therapeutic benefits in gliomas bearing IDHmut. One set of targets includes the Bromodomain and Extraterminal (BET) family of transcriptional coactivators.MethodsWe used TCGA data from glioma patients to determine whether BET proteins affect patient survival differently based on IDH status. Follow-up experiments using a set of IDH wildtype/mutant glioma cultures, as well as an IDH wildtype glioblastoma cell line expressing exogenous R132H IDH1, focused on cell health assays to investigate whether IDHmut was associated with increased sensitivity to the BET inhibitor JQ1. Immunoblots were used to evaluate the molecular response to JQ1 in these cultures.ResultsWe identified that high BRD4 expression associated with decreased survival only in IDHmut glioma patients. Cell viability analysis showed that IDHmut sensitized glioma cells to delayed cytotoxicity (10 days) in response to JQ1. Early effects of JQ1 (3 days) were primarily antiproliferative, with IDHmut glioma exhibiting a modest increase in sensitivity. Finally, exogenous R132H IDH1 expression in a resistant IDH wildtype cell line recapitulated the JQ1-mediated delayed cytotoxicity seen in our endogenous IDHmut glioma cells.ConclusionOverall, these data suggest that BRD4 enhances malignancy primarily in gliomas bearing IDHmut and is associated with greater sensitivity to BET inhibition. The finding that BET inhibition primarily exhibits delayed cytotoxicity may be overlooked in conventional short endpoint dose-response assays. Follow-up mechanistic and animal studies will help address the translational potential of these findings.
Resilience to chronic mild stress-induced anhedonia preserves the ability of the ventral hippocampus to respond to an acute challenge
Authors: Brivio Paola , Gallo Maria Teresa , Gruca Piotr , Lason Magdalena , Litwa Ewa , Fumagalli Fabio , Papp Mariusz , Calabrese Francesca 
Published: February 2022

Abstract
Stress is one of the main precipitating factors for psychiatric disorders and its effects may depend on its duration and intensity. Interestingly, the ability to react to stressful life events may alter the response to a subsequent novel stressor. However, there are differences in the individual susceptibility to stress, with some individuals displaying vulnerability and others showing resistance. Hence, we investigated whether the vulnerability and resilience to the chronic mild stress (CMS) paradigm, in terms of hedonic phenotype, may alter the ability to cope with a novel acute restraint stress by focusing on neuroplastic mechanisms within the ventral (vHip) and dorsal (dHip) hippocampus, the amygdala (Amy) and the prefrontal cortex (Pfc) of adult male rats. At molecular level, we found that the resilience to CMS was critical to preserving the ability to face a novel challenge measured as neuronal activation. Indeed, the resilient phenotype positively correlated with the enhancement of early response genes specifically in vHip. These results highlight the role of this hippocampal subregion for the development of therapeutic strategies to promote resilience against stress.
A prospective study assessing the pattern of response of local disease at DCE-MRI after salvage radiotherapy for prostate cancer
Authors: Bottero Marta , Faiella Adriana , Giannarelli Diana , Farneti Alessia , D’Urso Pasqualina , Bertini Luca , Landoni Valeria , Vici Patrizia , Sanguineti Giuseppe 
Published: February 2022

Abstract
Background: To assess the pattern of response of presumed local lesions at dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) after salvage radiotherapy (sRT).Methods: This is a prospective study conducted at a single Institution accruing patients with one or more local failures at DCE-MRI after radical prostatectomy between August 2017 and June 2020. Patients underwent exclusive sRT delivering 66-69 Gy and 73.5 Gy in 30 fractions to the whole prostatic fossa and to the local failure(s) seen at DCE-MRI, respectively. Patients were offered DCE-MRI at 3 month-intervals after sRT until complete dis-appearance (CR) of the lesion(s) or up to a maximum of 4 re-evaluations. Results: 62 patients with 72 nodules were enrolled. All patients underwent the 1st re-evaluation, and 33 patients (53.2%) showed a CR. The median time to CR was 4.7 months. Four patients did not undergo further testing before achieving a CR and even considering these patients as no responses, the vast majority (87.1%, 95%CI: 78.5-94.4%) of lesions would have completely disappeared by 12 months from the end of sRT. The volume of the lesion at pre-sRT DCE-MRI was an independent predictor of CR at the 1st re-evaluation (OR: 0.076, 95%CI: 0.009-0.667; p=0.020) along with time elapsed from sRT (OR: 3.399, 95% CI: 1.156-9.993, p=0.026). Conclusions: The present study documents the complete dis-appearance of the vast majority of local lesions after dose-escalated sRT though this requires several months after sRT; timing of CR is at least in part predictable based on the volume of the lesion.Trial registration: Clinicaltrials.gov NCT04703543, registered July 15 2020, retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04703543.
The Impact of the Coronavirus Disease - 19 Pandemic on the Treatment of Acute Appendicitis: Presentation, Outcomes, Strategies of Acute Appendicitis During Coronavirus Disease -19 Pandemic
Authors: An Sanghyun , Kim Hae-Rim , Jang Sungwoo , Kim Kwangmin 
Published: February 2022

Abstract
Background: This study aimed to investigate the characteristics, severity, and treatment of patients with acute appendicitis in Korea over a 2-year period during the coronavirus disease (COVID-19) pandemic compared to those before the pandemic. We also investigated whether there were any changes in clinical characteristics of acute appendicitis before and after vaccination against the coronavirus.Methods: We retrospectively reviewed the medical records of patients who were diagnosed with acute appendicitis at our institution between March 1, 2019, and August 31, 2021. We divided the patients into three groups (pre-pandemic, before vaccination, and after vaccination) and analyzed the clinical outcomes.Results: The time from symptom onset to hospital arrival and the time from symptom onset to operation increased during the COVID-19 pandemic period compared to the pre-pandemic period. The rate of complicated appendicitis during the pandemic was higher than that before the pandemic. In addition, the number of new daily cases showed a positive correlation with the time from symptom onset to hospital arrival (OR, 0.03; 95% CI, 0.02 to 0.04; P<0.001) and complicated appendicitis (OR, 1.002; 95% CI, 1.001–1.002; P=0.0017). The vaccination rate showed a negative correlation with the time from symptom onset to hospital arrival (OR, -2.26; 95% CI, -3.42 to -1.11; P<0.001) and complicated appendicitis (OR, 0.915; 95% CI, 0.84 to 0.996; P=0.0404).Conclusions: Employing hospital-wide efforts, such as screening by rapid PCR testing, to avoid further time delays, and nationwide efforts, such as vaccination, to shorten the time from symptom onset to hospital arrival, are necessary to maintain the quality of treatment of acute appendicitis during an infectious disease pandemic.
FGFR1 is a Potential Therapeutic Target in Neuroblastoma
Authors: Cimmino Flora , Montella Annalaura , Tirelli Matilde , Avitabile Marianna , Lasorsa Vito Alessandro , Visconte Feliciano , Cantalupo Sueva , Maiorino Teresa , Angelis Biagio , Morini Martina , Castellano Aurora , Locatelli Franco , Capasso Mario , Iolascon Achille 
Published: February 2022

Abstract
Background: FGFR1 regulates cell-cell adhesion and extracellular matrix architecture and acts as oncogene in several cancers. Potential cancer driver mutations of FGFR1 occur in neuroblastoma NB, a neural crest-derived pediatric tumor arising in sympathetic nervous system but so far, they have not been studied experimentally. We investigated the driver-oncogene role of FGFR1 and the implication of N546K mutation in therapy-resistance in NB cells.Methods: Public datasets were used to predict the correlation of FGFR1 expression with NB clinical outcomes. Whole genome sequencing data of 19 paired diagnostic and relapse NB samples were used to find somatic mutations. In NB cell lines, silencing and transient overexpression of FGFR1 by short hairpin RNA were performed to evaluate the effect of the found mutation by cell growth, invasion and cologenicity assays. HEK293, SHSY5Y and SKNBE2 were selected to investigate subcellular wildtype and mutated protein localization. FGFR1 inhibitor (AZD4547), alone or in combination with PI3K inhibitor (GDC0941), was used to rescue malignant phenotypes induced by overexpression of FGFR1 wildtype and mutated protein.Results: High FGFR1 expression correlated with low relapse-free survival in two independent NB gene expression datasets. In addition, we found the somatic mutation N546K, the most recurrent point mutation of FGFR1 in all cancers and already reported in NB, in one out of 19 matched primary and recurrent tumors. Loss of FGFR1 function attenuated invasion and cologenicity in NB cells, whereas FGFR1 overexpression enhanced oncogenicity. The overexpression of FGFR1N546K protein showed a higher nuclear localization compared to wildtype protein and increased cellular invasion and cologenicity. Moreover, N546K mutation caused the failure in response to treatment with FGFR1 inhibitor by activation of ERK, STAT3 and AKT pathways. The combination of FGFR1 and PI3K pathway inhibitors was effective in reducing the invasive and colonigenic ability of cells overexpressing FGFR1 mutated protein.Conclusion: FGFR1 is an actionable driver oncogene in NB and a promising therapy may consist in targeting FGFR1 mutations in patients with therapy-resistant NB.
Molecular effects of the consumption of margarine and butter varying in trans fat composition: a parallel human intervention study
Authors: Vergères Guy , Guggisberg Dominik , Burton-Pimentel Kathryn J. , Walther Barbara , Portmann Reto , Schmid Alexandra , Radtke Thomas , Saner Hugo , Zangger Nadine , Bütikofer Ueli , Badertscher René , Blaser Carola 
Published: February 2022

Abstract
Background: Dietary intake of industrial trans fatty acids (iTFA) is associated with inflammation, cardiovascular disease and type 2 diabetes but it is unclear whether naturally occurring trans fatty acids (TFA) exert these effects.Methods: In a parallel study, the molecular effects of consuming dairy fat containing ruminant TFA (rTFA) or margarine containing iTFA were investigated. After a run-in period of margarine without TFA (wTFA), 42 healthy volunteers (45 to 69 y), were randomly assigned to diets enriched with margarine wTFA (control), margarine with iTFA, or alpine butter (rTFA) for 4 weeks. Changes in fasting blood values of lipid profiles (GC with flame-ionization detection), metabolome profiles (LC-MS, GC-MS) and gene expression (microarray) were measured.Results: Eighteen fatty acids, as well as 242 additional features measured by LC-MS (185) and GC-MS (54) showed significantly different responses to the diets (PFDR-adjusted < 0.05), mainly distinguishing butter from the margarines while gene expression was not differentially affected. The most abundant TFA in the dietary fats (elaidic and vaccenic acids) were reflected in the significantly different serum TFAs after the TFA interventions.Conclusions: The TFA interventions did not appear to regulate a common molecular pathway. This could be attributable to the different TFAs present in rTFA and iTFA, which could differentially affect cholesterol and lipid metabolism.Trial registration: ClinicalTrials.gov NCT00933322
Application of a new mathematical description of Epidemics to the COVID-19 Omicron wave in few strongly affected countries by the beginning of 2022: USA, UK and France
Authors: Petkov Pavel 
Published: February 2022

Abstract
Purpose By means of mathematical modeling, we studied the COVID-19 Omicron waves in the USA, the UK and France which were strongly affected in the beginning of 2022.The aims were to test a new tracking model and by using the derived parameters, learn more about the new variant properties and the consequences for the population.Methods A newly developed [6] mathematical modeling of Epidemics is applied together with a day by day normalization correction accounting for the different number of tests.Results The new infection cases per day are reasonably described before and around the peak maximum. There are indications that the decreasing part may be well described too. The position of the calculated peaks in time within the Omicron waves indicates everywhere a transition only from the 3th to the 4th generation of infected people. The small impact of the next, 5th generation and the decrease of the new cases per day seem to be related to the combined effect of vaccination and the acquired immunity in a very large part of the population due to Omicron in a short period of time. The calculated cumulative curves support such interpretation.Conclusions The tracking model describes well the Omicron wave after normalization. The results suggest that a very large part of the population in the three countries have (will have) got some protection against the virus. Therefore, controlling/stopping the Pandemic might be soon possible.
Distribution Characteristics of New AO Classification in Different Age Groups of Patients with Femoral Neck Fracture
Authors: Jiang Yuxuan , Feng Dongxu , Huang Wei , Wang Xiaolong , Jiang Wuqiang , Wu Chengxi , Zhu Yangjun 
Published: February 2022

Abstract
Objective: Femoral neck fractures(FNFs) patients from 2018 to 2020 were classified according to the new AO classification. To observe the proportion of new AO classification and provide reference for improving the upper age limit of internal fixation(IF) treatmentMethods: In this study, patients with femoral neck fracture hospitalized in Xi 'an Honghui Hospital from January 2018 to January 2021 were divided into four groups according to age: the young group (≤44 years old), the middle-aged group (45-59 years old),the young elderly group (60-74 years old), and the elderly group (≥75 years old) to analyze age,sex,side,injury mechanism,new AO classification and other features . A total of 2071 patients were included for analysis.Results: There were 742 males (35.8%) and 1,329 females (64.2%).There were 1,106 patient s(53.4%) on the left side and 965 on the right side (46.6%).There were 1781 patients of low energy injury (86%) and 290 patients of high energy injury (14%), and the main injury mechanism was falling.The number of patients with femoral neck fracture in each year was 719 patients in 2018, 694 patients in 2019, and 661 patients in 2020, respectively. The number of patients showed a decreasing trend year by year, and the gender ratio and injury mechanism showed no significant trend of change. In the age group, the proportion of the young group was increasing year by year.Among the new AO classification, there were 1023 patients of B1.3, accounting for the highest proportion of 49.4%.The proportion of B2.2 was the highest in the young group (32.4%) .B1.3 and B2.2 were the main types in the middle-aged group, accounting for 31.7% and 32.0, respectively.B1.3 was dominant in the young elderly and elderly group (47.1% and 63.4%, respectively).Conclusion: The new AO classification is more detailed and practical. 1/3 of the fracture types of middle aged and young elderly people may achieve satisfactory results through IF.Level of evidence: III.
No Effect of PXR (8055C>T) Polymorphism on the Pharmacokinetic Profiles of
Piperaquine in Healthy Chinese Subjects
Authors: Liu Huixiang , Xie Yuewu , Cai Tianyu , Xing Jie 
Published: February 2022

Background:
Significant inter-subject variability in pharmacokinetics and clinical outcomes has been
observed for the antimalarial agent piperaquine (PQ). PQ is metabolized by CYP3A4, mainly regulated by the pregnane
X receptor (PXR). CYP3A4(*1B) polymorphism did not affect PQ clearance.

Objectives:
The effect of PXR (8055C>T) polymorphism on the pharmacokinetic profiles of PQ was investigated.

Method:
The pharmacokinetic profiles of PQ and its major metabolite PQ N-oxide (PQM) were studied in healthy
Chinese subjects after recommended oral doses of artemisinin-PQ. Twelve subjects were genotyped using PCRRFLP
(six in each group with PXR 8055CC and 8055TT), and plasma concentrations were determined by a validated
LC/MS/MS method. The dose-adjusted exposure (AUC and Cmax) to PQ or PQM was investigated, and the metabolic
capability of PQ N-oxidation was determined by AUCPQM/AUCPQ. The antimalarial outcome of PQ was evaluated
using its day 7 concentration.

Results:
PQM formation was mediated by CYP3A4/3A5. Interindividual variability in dose-adjusted AUC of PQ and
PQM was relatively low (%CV, <30.0%), whereas a larger inter-variability was observed for Cmax values (%CV,
68.1% for PQ). No polymorphic effect was found for PXR (C8055T) on the pharmacokinetic profiles of PQ or its
Cday 7 concentrations.

Conclusions:
Both CYP3A4 and CYP3A5 were involved in PQ clearance. The genotypes of PXR (C8055T) may not
contribute to the variability in PQ pharmacokinetics as well as antimalarial outcomes. There might be a low risk of
variable exposures to PQ in malaria patients carrying mutated PXR (8055C>T) genes, which deserves further study,
especially in a larger sample size.