bluuebunny/crossref_metadata_2025_split huggingface dataset:
Malignancy risk of hyperfunctioning thyroid nodules compared with non-toxic nodules: systematic review and a meta-analysis
Authors: Lau Lorraine W. , Ghaznavi Sana , Frolkis Alexandra D. , Stephenson Alexandra , Robertson Helen Lee , Rabi Doreen M. , Paschke Ralf 
Published: February 2021

Abstract
Background
Hyperfunctioning or hot nodules are thought to be rarely malignant. As such, current guidelines recommend that hot nodules be excluded from further malignancy risk stratification. The objective of this systematic review and meta-analysis is to compare the malignancy risk in hot nodules and non-toxic nodules in observational studies.

Methods
Ovid MEDLINE Daily and Ovid MEDLINE, EMBASE, Scopus, and Web of Science databases were searched. Observational studies which met all of the following were included: (1) use thyroid scintigraphy for nodule assessment, (2) inclusion of both hyperfunctioning and non-functioning nodules based on scintigraphy, (3) available postoperative histopathologic nodule results, (4) published up to November 12, 2020 in either English or French. The following data was extracted: malignancy outcomes include malignancy rate, mapping of the carcinoma within the hot nodule, inclusion of microcarcinomas, and presence of gene mutations.

Results
Among the seven included studies, overall incidence of malignancy in all hot thyroid nodules ranged from 5 to 100% in comparison with non-toxic nodules, 3.8–46%. Odds of malignancy were also compared between hot and non-toxic thyroid nodules, separated into solitary nodules, multiple nodules and combination of the two. Pooled odds ratio (OR) of solitary thyroid nodules revealed a single hot nodule OR of 0.38 (95% confidence interval (CI) 0.25, 0.59), toxic multinodular goiter OR of 0.51 (95% CI 0.34, 0.75), and a combined hot nodule OR of 0.45 (95% CI 0.31, 0.65). The odds of malignancy are reduced by 55% in hot nodules; however, the incidence was not zero.

Conclusions
Odds of malignancy of hot nodules is reduced compared with non-toxic nodules; however, the incidence of malignancy reported in hot nodules was higher than expected. These findings highlight the need for further studies into the malignancy risk of hot nodules.
Differences between manual CPR and corpuls cpr in regard to quality and outcome: study protocol of the comparing observational multi‐center prospective registry study on resuscitation (COMPRESS)
Authors: Seewald S. , Dopfer S. , Wnent J. , Jakisch B. , Heller M. , Lefering R. , Gräsner JT 
Published: February 2021

Abstract
Background
The effect of mechanical CPR is diversely described in the literature. Different mechanical CPR devices are available. The corpuls cpr is a new generation of piston-driven devices and was launched in 2015. The COMPRESS-trial analyzes quality of chest compression and CPR-related injuries in cases of mechanical CPR by the corpuls cpr and manual CPR.

Methods
This article describes the design and study protocol of the COMPRESS-trial. This observational multi-center study includes all patients who suffered an out-of-hospital cardiac arrest (OHCA) where CPR is attempted in four German emergency medical systems (EMS) between January 2020 and December 2022. EMS treatment, in-hospital-treatment and outcome are anonymously reported to the German Resuscitation Registry (GRR). This information is linked with data from the defibrillator, the feedback system and the mechanical CPR device for a complete dataset.
Primary endpoint is chest compression quality (complete release, compression rate, compression depth, chest compression fraction, CPR-related injuries). Secondary endpoint is survival (return of spontaneous circulation (ROSC), admission to hospital and survival to hospital discharge). The trial is sponsored by GS Elektromedizinische Geräte G. Stemple GmbH.

Discussion
This observational multi-center study will contribute to the evaluation of mechanical chest compression devices and to the efficacy and safety of the corpuls cpr.

Trial registration
DRKS, DRKS-ID DRKS00020819. Registered 31 July 2020.
Quality of focused thoracic ultrasound performed by emergency medical technicians and paramedics in a prehospital setting: a feasibility study
Authors: Pietersen Pia Iben , Mikkelsen Søren , Lassen Annmarie T. , Helmerik Simon , Jørgensen Gitte , Nadim Giti , Christensen Helle Marie , Wittrock Daniel , Laursen Christian B. 
Published: February 2021

Abstract
Background
In a prehospital setting, the severity of respiratory symptoms in patients calling for an ambulance differ. The initial evaluation, diagnosing, and thereby management can be challenging because respiratory symptoms can be caused by disease in many organs. Ultrasound examinations can contribute with important information and support the clinical decision-making. However, ultrasound is user-dependent and requires sufficient knowledge and training. The aim of this study was to explore the quality of thoracic ultrasound examinations performed on patients by emergency medical technicians and paramedics in a prehospital, clinical setting.

Methods
From November 2018 – April 2020, Danish emergency medical technicians and paramedics (n = 100) performed thoracic ultrasound examinations on patients with respiratory symptoms using a portable ultrasound device. The ultrasound examinations were stored and retrospectively assessed by a reviewer blinded to the patients’ symptoms and history, as well as the emergency medical technicians’ and paramedics’ findings. The image quality was scored from 1 to 5. The findings determined by the reviewer was then correlated with a questionnaire filled out by the emergency medical technicians and paramedics regarding ultrasonic findings and potential change in treatment or management of the patient. The agreement in percentage and as Cohen’s kappa was explored.

Results
A total of 590 ultrasound examinations were assessed, resulting in a median image quality score of 3 (IQ1 = 4, IQ3 = 3). The overall agreement in percentage between the emergency medical technicians and paramedics and reviewer was high (87.7% for a normal scan, 89.9% for interstitial syndrome, 97.3% for possible pneumothorax, and 96.3% for pleural effusion). Cohen’s kappa varied from 0.01 for possible pneumothorax to 0.69 for pleural effusion. Based on the questionnaires (n = 406), the ultrasound examination entailed a change in treatment or visitation in 48 cases (11.7%) which in this study population encompasses a number-needed-to-scan of 8.5.

Conclusion
Emergency medical technicians and paramedics perform focused thoracic ultrasound examinations with adequate image quality sufficient to determine if pathology is present or not. The emergency medical technicians’ and paramedics’ assessment correlates to some extent with an experienced reviewer and their findings are most reliable for the inclusion of a normal scan or inclusion of pleural effusion. Implementation could possibly impact the number of patients receiving correct prehospital treatment and optimal choice of receiving facility.
Age at menarche, eating disorders, and their relationships with some parameters in female adolescents in Iran
Authors: Daeie-Farshbaf Lida , Ebrahimi-Mameghani Mehrangiz , Sarbakhsh Parvin , Roshanravan Neda , Tarighat-Esfanjani Ali 
Published: February 2021

Abstract
Objective
Adolescence as one of the most challenging periods of humans’ growth is accompanied with major physical, behavioural, social-emotional, and neuroendocrine changes. Early maturation and eating disorders (EDs) have been reported to be associated with adverse health conditions. Therefore, the present study was conducted to assess age of onset of menarche (AM), EDs, and their possible relationships with weight, body mass index (BMI), waist circumference (WC), and socioeconomic status (SES) in the Iranian female adolescents.

Results
In the study population, mean ± standard deviation (SD) of AM was 12.95 ± 1.14 years. Inverse significant relationships were found between weight and AM, also BMI and AM (p < 0.05). There was a negative association between weight and anorexia nervosa (AN), BMI and AN, also WC and AN (p < 0.001). A significant positive correlation was found between SES and AM, also EDs and AM (p < 0.05) then between weight and bulimia nervosa (BN) & binge-eating disorder (BED), BMI and BN & BED, also WC and BD & BED (p < 0.001). Our results also revealed that AM in mothers had a significant positive relationship with AM in their daughters (p < 0.001, r = 0.34).
Assessment of corn starch as substitute for agarose in DNA gel electrophoresis
Authors: Djankpa Francis Tanam , Wiafe Gideon Akuamoah , Boateng Bernard Ntim , Tsegah Korantema Mawuena , Essien-Baidoo Samuel , Ulanja Mark Bilinyi , Affram Kwame Ofori , Ussif Abdala Mumuni , Agyeman Desmond Owusu , Asante Gabriel 
Published: February 2021

Abstract
Objective
The use of agarose in nucleic acid electrophoresis is the gold standard. However, agarose is very expensive and not readily available in resource limited developing countries like Ghana. Hence, finding a more affordable and readily available alternative to agarose will be a major boost to molecular research in developing countries. This study was aimed at investigating the use of corn starch as a potential substitute for agarose in DNA gel electrophoresis.

Results
Genomic deoxyribonucleic acid (DNA) extracted from Plasmodium falciparum and primers were obtained from the West African Centre for Cell Biology of Infectious Pathogens and amplified using polymerase chain reaction. The amplicon was run on agarose gel to ascertain the molecular weight (as a positive control). When visualized under both blue light and ultraviolet light, the DNA and ladder showed clear and clean bands with the expected molecular weight. Corn starch was then modified with sodium borate buffer, casted into a gel and used to run the same DNA sample. Our findings indicated that similar to agarose, the DNA sample and ladder migrated successfully through the modified starch gel but no bands were visible when visualized under blue and ultra-violet light.
Trunk and lower limb muscularity in sprinters: what are the specific muscles for superior sprint performance?
Authors: Tottori Nobuaki , Suga Tadashi , Miyake Yuto , Tsuchikane Ryo , Tanaka Takahiro , Terada Masafumi , Otsuka Mitsuo , Nagano Akinori , Fujita Satoshi , Isaka Tadao 
Published: February 2021

Abstract
Objective
The major purpose of this study was to determine the specific muscle(s) for superior sprint performance in sprinters. The cross sectional areas (CSAs) of ten muscles of the trunk and lower limb were measured using magnetic resonance images in 56 male sprinters and 40 male non-sprinters. In addition to the absolute CSA, to minimize the effect of difference in body size among participants, the relative CSA normalized to body mass was used for analysis of this study.

Results
Absolute and relative CSAs of most trunk and lower limb muscles, including the psoas major (PM) and gluteus maximus (GM), were significantly larger in sprinters than in non-sprinters (all P < 0.001, d = 0.91 to 1.82). The absolute and relative CSAs of the PM and GM correlated significantly with personal best 100-m sprint time in sprinters (r =  − 0.363 to − 0.388, all P < 0.01). A stepwise multiple regression analysis revealed that both CSAs of absolute PM and relative GM were predictive variables for the personal best 100 m sprint time in sprinters (β =  − 0.289 and − 0.287, respectively, both P < 0.05). These findings suggest that the PM and GM may be specific muscles for superior sprint performance in sprinters.
FK228 sensitizes radioresistant small cell lung cancer cells to radiation
Authors: Li Hong , Ma Liying , Bian Xing , Lv Yang , Lin Wenchu 
Published: February 2021

AbstractBackgroundConcurrent thoracic radiation plus chemotherapy is the mainstay of first-line treatment for limited-stage small cell lung cancer (LS-SCLC). Despite initial high responsiveness to combined chemo- and radiotherapy, SCLC almost invariably relapses and develops resistance within one year, leading to poor prognosis in patients with LS-SCLC. Developing new chemical agents that increase ionizing radiation’s cytotoxicity against SCLC is urgently needed.ResultsDual histone deacetylase (HDAC) and PI3K inhibitor FK228 not only displayed potent anticancer activity, but also enhanced the therapeutic effects of radiotherapy in SCLC cells. Mechanistically, radioresistant SCLC cells exhibit a lower level of histone H3K9 acetylation and a higher expression level of the MRE11-RAD50-NBS1 (MRN) complex and show more efficient and redundant DNA damage repair capacities than radiosensitive SCLC cells. FK228 pretreatment resulted in marked induction of H3k9 acetylation, attenuated homologous recombination (HR) repair competency and impaired non-homologous end joining (NHEJ) repair efficacy, leading to the accumulation of radiation-induced DNA damage and radiosensitization.ConclusionThe study uncovered that FK228 sensitized human radioresistant SCLC cells to radiation mainly through induction of chromatin decondensation and suppression of DNA damage signaling and repair. Our study provides a rational basis for a further clinical study to test the potential of FK228 as a radiosensitizing agent to increase the radiation-induced tumor cell kill in LS-SCLC patients.
Association of cardiovascular health and epigenetic age acceleration
Authors: Pottinger Tess D. , Khan Sadiya S. , Zheng Yinan , Zhang Wei , Tindle Hilary A. , Allison Matthew , Wells Gretchen , Shadyab Aladdin H. , Nassir Rami , Martin Lisa Warsinger , Manson JoAnn E. , Lloyd-Jones Donald M. , Greenland Philip , Baccarelli Andrea A. , Whitsel Eric A. , Hou Lifang 
Published: February 2021

Abstract
Background
Cardiovascular health (CVH) has been defined by the American Heart Association (AHA) as the presence of the “Life’s Simple 7” ideal lifestyle and clinical factors. CVH is known to predict longevity and freedom from cardiovascular disease, the leading cause of death for women in the United States. DNA methylation markers of aging have been aggregated into a composite epigenetic age score, which is associated with cardiovascular morbidity and mortality. However, it is unknown whether poor CVH is associated with acceleration of aging as measured by DNA methylation markers in epigenetic age.

Methods and results
We performed a cross-sectional analysis of racially/ethnically diverse post-menopausal women enrolled in the Women’s Health Initiative cohort recruited between 1993 and 1998. Epigenetic age acceleration (EAA) was calculated using DNA methylation data on a subset of participants and the published Horvath and Hannum methods for intrinsic and extrinsic EAA. CVH was calculated using the AHA measures of CVH contributing to a 7-point score. We examined the association between CVH score and EAA using linear regression modeling adjusting for self-reported race/ethnicity and education. Among the 2,170 participants analyzed, 50% were white and mean age was 64 (7 SD) years. Higher or more favorable CVH scores were associated with lower extrinsic EAA (~ 6 months younger age per 1 point higher CVH score, p < 0.0001), and lower intrinsic EAA (3 months younger age per 1 point higher CVH score, p < 0.028).

Conclusions
These cross-sectional observations suggest a possible mechanism by which ideal CVH is associated with greater longevity.
Chromatin remodeling by the histone methyltransferase EZH2 drives lung pre-malignancy and is a target for cancer prevention
Authors: Tellez Carmen S. , Picchi Maria A. , Juri Daniel , Do Kieu , Desai Dhimant H. , Amin Shantu G. , Hutt Julie A. , Filipczak Piotr T. , Belinsky Steven A. 
Published: February 2021

Abstract
Background
Trimethylation of lysine 27 and dimethylation of lysine 9 of histone-H3 catalyzed by the histone methyltransferases EZH2 and G9a impede gene transcription in cancer. Our human bronchial epithelial (HBEC) pre-malignancy model studied the role of these histone modifications in transformation. Tobacco carcinogen transformed HBEC lines were characterized for cytosine DNA methylation, transcriptome reprogramming, and the effect of inhibiting EZH2 and G9a on the transformed phenotype. The effects of targeting EZH2 and G9a on lung cancer prevention was assessed in the A/J mouse lung tumor model.

Results
Carcinogen exposure induced transformation and DNA methylation of 12–96 genes in the four HBEC transformed (T) lines that was perpetuated in malignant tumors. In contrast, 506 unmethylated genes showed reduced expression in one or more HBECTs with many becoming methylated in tumors. ChIP-on-chip for HBEC2T identified 327 and 143 genes enriched for H3K27me3 and H3K9me2. Treatment of HBEC2T and HBEC13T with DZNep, a lysine methyltransferase inhibitor depleted EZH2, reversed transformation, and induced transcriptional reprogramming. The EZH2 small molecule inhibitor EPZ6438 also affected transformation and expression in HBEC2T, while a G9a inhibitor, UNC0642 was ineffective. Genetic knock down of EZH2 dramatically reduced carcinogen-induced transformation of HBEC2. Only DZNep treatment prevented progression of hyperplasia to adenomas in the NNK mouse lung tumor model through reducing EZH2 and affecting the expression of genes regulating cell growth and invasion.

Conclusion
These studies demonstrate a critical role for EZH2 catalyzed histone modifications for premalignancy and its potential as a target for chemoprevention of lung carcinogenesis.
Sleep disorders in rare genetic syndromes: a meta-analysis of prevalence and profile
Authors: Agar Georgie , Brown Chloe , Sutherland Daniel , Coulborn Sean , Oliver Chris , Richards Caroline 
Published: February 2021

AbstractBackgroundSleep disorders are common in people with intellectual disability (ID) and autism, with growing evidence of diverse sleep profiles across ID associated genetic syndromes. Documenting the prevalence and profile of specific sleep disorders in syndromes will quantify syndrome-driven ‘risk’, inform prognosis and enhance understanding of aetiology of sleep disorders.MethodFollowing PRISMA guidelines for meta-analysis, we searched Ovid PsycINFO, Ovid MEDLINE, Ovid Embase, Web of Science and PubMed Central with use of syndrome-specific keywords and 60 sleep-related search terms. We screened and extracted papers that reported sleep disorder prevalence data for five or more individuals within a genetic syndrome, and applied quality criteria to produce a quality-effects prevalence model of six types of sleep disorder across nineteen syndromes. Relative risk estimates were calculated for the prevalence of each sleep disorder in each syndrome.ResultsTwo hundred and seventy three papers were identified, generating 463 prevalence estimates for Angelman, CHARGE, Cornelia de Lange, Down, fragile X, Prader–Willi, Rett, Smith–Magenis and Williams syndromes, mucopolysaccharidoses (MPS disorders), neurofibromatosis and tuberous sclerosis complex. Prevalence estimates were higher in genetic syndromes than published equivalents for typically developing individuals, with few exceptions. Between-syndrome differences for some disorders were evident; sleep-disordered breathing was most prevalent in MPS disorders (72–77%), while excessive daytime sleepiness was highest in Smith–Magenis syndrome (60%). Conversely, insomnia, which was reported at a higher rate than TD estimates in all syndromes except fragile X, was not associated with specific genetic risk. This suggests insomnia could emerge because of the individual’s environment or associated developmental delay, rather than any specific genetic syndromes.LimitationsDue to the broad scope of the meta-analysis, only syndromes previously identified as reporting preliminary sleep research were included. Other syndromes may also experience elevated prevalence rates of specific types of sleep disorder. Only English language papers were included.ConclusionsDiffering prevalence rates between types of sleep disorder suggest differing causal mechanisms, such as cranio-facial morphology in Down and Prader–Willi syndromes and the build-up of mucopolysaccharides in MPS disorders. Priorities for clinical assessment and intervention for sleep disorders are discussed.
15-Year-old with neglected recto-vestibular fistula in western Uganda: a case report
Authors: Oyania Felix , Kotagal Meera , Situma Martin 
Published: February 2021

Abstract
Background
Teenage and late presentation of anorectal malformations are not uncommon in developing world. Some of the reasons for late presentation include but not limited to illiteracy, poverty, lack of awareness, and limited trained pediatric surgeons. In rural areas, neonates with ARMs are considered cursed and are marginalized.

Case
15-Year-old African girl (a munyankole by tribe in Uganda) from western Uganda presented at 15 years of life with colostomy and uncorrected anorectal malformation. Never went to school due to social stigma.

Conclusion
Due to limited number of trained pediatric surgeons in most of African Countries, many children in addition to living with a colostomy or untreated malformation, may also be undiagnosed with chronic constipation. Improved awareness and advocacy would promote early presentation and treatment.
Inhibition of miR-199a-5p rejuvenates aged mesenchymal stem cells derived from patients with idiopathic pulmonary fibrosis and improves their therapeutic efficacy in experimental pulmonary fibrosis
Authors: Shi Linli , Han Qian , Hong Yimei , Li Weifeng , Gong Gencheng , Cui Jiangyu , Mao Mengmeng , Liang Xiaoting , Hu Bei , Li Xin , Luo Qun , Zhang Yuelin 
Published: February 2021

Abstract
Background
Idiopathic pulmonary fibrosis (IPF) is an age-related disease with no cure. Mesenchymal stem cell (MSC)-based therapy has emerged as a novel strategy for IPF treatment. Nevertheless, MSCs derived from patients with IPF (IPF-MSCs) become senescent, thereby reducing their beneficial effects in IPF. MicroRNAs (miRNAs) mediate the senescence of MSCs, but the underlying mechanisms are not fully understood. We investigated the mechanisms by which miR-199a-5p regulates IPF-MSC senescence and whether its inhibition could rejuvenate IPF-MSCs and enhance their therapeutic efficacy.

Methods
Control-MSCs and IPF-MSCs were isolated from the adipose tissue of age-matched healthy and IPF donors, respectively. Cell senescence was examined by senescence-associated β-galactosidase (SA-β-gal) staining. The level of miR-199a-5p was measured by RT-PCR. Autophagy was determined using a transmission electron microscope (TEM). The therapeutic efficacy of anti-miR-199a-5p-IPF-MSCs was assessed using a mouse model of bleomycin-induced lung fibrosis.

Results
Despite similar surface makers, IPF-MSCs exhibited increased cellular senescence and decreased proliferative capacity compared with control-MSCs. The expression of miR-199a-5p was significantly enhanced in the serum of IPF patients and IPF-MSCs compared with that of healthy donors and control-MSCs. The upregulation of miR-199a-5p induced senescence of control-MSCs, whereas the downregulation rescued IPF-MSC senescence. Mechanistically, miR-155-5p suppressed autophagy of MSCs via the AMPK signaling pathway by downregulating the expression of Sirtuin 1(Sirt1), resulting in cellular senescence. Accordingly, miR-155-5p inhibition promoted autophagy and ameliorated IPF-MSC senescence by activating the Sirt1/AMPK signaling pathway. Compared with IPF-MSCs, the transplantation of anti-miR-199a-5p-IPF-MSCs increased the ability to prevent progression of pulmonary fibrosis in bleomycin-treated mice.

Conclusions
Our study shows that miR-199a-5p regulates MSC senescence in patients with IPF by regulating the Sirt1/AMPK signaling pathway and miR-199a-5p is a novel target to rejuvenate IPF-MSCs and enhance their beneficial effects.