bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA unchained: two assays to discover and study inhibitors of the DNA clustering function of barrier-to-autointegration factor
Authors: Burger Michael , Schmitt-Koopmann Caroline , Leroux Jean-Christophe 
Published: July 2020

AbstractThe protein barrier-to-autointegration factor (BAF) and its interaction partners, the LEM (LAP2B, emerin, MAN1)-domain proteins, constitute a powerful cytoplasmic DNA defense mechanism. Invading DNA molecules are quickly bound by the BAF system and trapped in membrane compartments. This decreases the nuclear uptake of DNA from the cytoplasm. Inhibition of the BAF system is therefore expected to enhance the efficacy of non-viral DNA transfection agents. In this study, we introduced a protocol for the recombinant expression of soluble BAF and developed two ELISA-type assays to discover small molecule inhibitors of BAF-dependent DNA retention by high throughput screening (HTS). The proton pump inhibitor rabeprazole as well as three compounds of the Maybridge library were identified as inhibitors of the LEM-BAF-DNA interaction chain. The inhibition was based on adduct formation with BAF cysteine residues. An enhancing effect of the compounds on cell culture transfection, however, was not observed, which may be attributed to the reducing environment of the cytoplasm that prevents the adduct formation with BAF cysteine residues. The novel assays developed here can provide new tools to further study the biological functions of the BAF system, and may lead to the identification of suitable BAF inhibitors in future HTS campaigns.
Identification of potential biomarkers for predicting the early onset of diabetic cardiomyopathy in a mouse model
Authors: Johnson Rabia , Nxele Xolisa , Cour Martin , Sangweni Nonhlakanipho , Jooste Tracey , Hadebe Nkanyiso , Samodien Ebrahim , Benjeddou Mongi , Mazino Mikateko , Louw Johan , Lecour Sandrine 
Published: July 2020

AbstractType 2 diabetes (T2D) is characterized by metabolic derangements that cause a shift in substrate preference, inducing cardiac interstitial fibrosis. Interstitial fibrosis plays a key role in aggravating left ventricular diastolic dysfunction (LVDD), which has previously been associated with the asymptomatic onset of heart failure. The latter is responsible for 80% of deaths among diabetic patients and has been termed diabetic cardiomyopathy (DCM). Through in silico prediction and subsequent detection in a leptin receptor-deficient db/db mice model (db/db), we confirmed the presence of previously identified potential biomarkers to detect the early onset of DCM. Differential expression of Lysyl Oxidase Like 2 (LOXL2) and Electron Transfer Flavoprotein Beta Subunit (ETFβ), in both serum and heart tissue of 6–16-week-old db/db mice, correlated with a reduced left-ventricular diastolic dysfunction as assessed by high-resolution Doppler echocardiography. Principal component analysis of the combined biomarkers, LOXL2 and ETFβ, further displayed a significant difference between wild type and db/db mice from as early as 9 weeks of age. Knockdown in H9c2 cells, utilising siRNA of either LOXL2 or ETFβ, revealed a decrease in the expression of Collagen Type I Alpha1 (COL1A1), a marker known to contribute to enhanced myocardial fibrosis. Additionally, receiver-operating curve (ROC) analysis of the proposed diagnostic profile showed that the combination of LOXL2 and ETFβ resulted in an area under the curve (AUC) of 0.813, with a cut-off point of 0.824, thus suggesting the favorable positive predictive power of the model and further supporting the use of LOXL2 and ETFβ as possible early predictive DCM biomarkers.
Molecular malaria surveillance using a novel protocol for extraction and analysis of nucleic acids retained on used rapid diagnostic tests
Authors: Guirou Etienne A. , Schindler Tobias , Hosch Salome , Donfack Olivier Tresor , Yoboue Charlene Aya , Krähenbühl Silvan , Deal Anna , Cosi Glenda , Gondwe Linda , Mwangoka Grace , Masuki Heavenlight , Salim Nahya , Mpina Maxmillian , Said Jongo , Abdulla Salim , Hoffman Stephen L. , Nlavo Bonifacio Manguire , Maas Carl , Falla Carlos Cortes , Phiri Wonder P. , Garcia Guillermo A. , Tanner Marcel , Daubenberger Claudia 
Published: July 2020

AbstractThe use of malaria rapid diagnostic tests (RDTs) as a source for nucleic acids that can be analyzed via nucleic acid amplification techniques has several advantages, including minimal amounts of blood, sample collection, simplified storage and shipping conditions at room temperature. We have systematically developed and extensively evaluated a procedure to extract total nucleic acids from used malaria RDTs. The co-extraction of DNA and RNA molecules from small volumes of dried blood retained on the RDTs allows detection and quantification of P. falciparum parasites from asymptomatic patients with parasite densities as low as 1 Pf/µL blood using reverse transcription quantitative PCR. Based on the extraction protocol we have developed the ENAR (Extraction of Nucleic Acids from RDTs) approach; a complete workflow for large-scale molecular malaria surveillance. Using RDTs collected during a malaria indicator survey we demonstrated that ENAR provides a powerful tool to analyze nucleic acids from thousands of RDTs in a standardized and high-throughput manner. We found several, known and new, non-synonymous single nucleotide polymorphisms in the propeller region of the kelch 13 gene among isolates circulating on Bioko Island, Equatorial Guinea.
Serum proteome profiles revealed dysregulated proteins and mechanisms associated with fibromyalgia syndrome in women
Authors: Han Chia-Li , Sheng Yung-Ching , Wang San-Yuan , Chen Yi-Hsuan , Kang Jiunn-Horng 
Published: July 2020

AbstractFibromyalgia syndrome (FM) is a multifactorial disorder whose pathogenesis and diagnosis are poorly understood. This study investigated differential serum proteome profiles in patients with FM and healthy pain-free controls and explored the association between serum proteome and clinical profiles in patients with FM. Twenty patients with FM (according to the American College of Rheumatology criteria, 2010) and 20 healthy pain-free controls were recruited for optimized quantitative serum proteomics analysis. The levels of pain, pressure pain threshold, sleep, anxiety, depression, and functional status were evaluated for patients with FM. We identified 22 proteins differentially expressed in FM when compared with healthy pain-free controls and propose a panel of methyltransferase-like 18 (METTL18), immunoglobulin lambda variable 3–25 (IGLV3–25), interleukin-1 receptor accessory protein (IL1RAP), and IGHV1OR21-1 for differentiating FM from controls by using a decision tree model (accuracy: 0.97). In addition, we noted several proteins involved in coagulation and inflammation pathways with distinct expression patterns in patients with FM. Novel proteins were also observed to be correlated with the levels of pain, depression, and dysautonomia in patients with FM. We suggest that upregulated inflammation can play a major role in the pathomechanism of FM. The differentially expressed proteins identified may serve as useful biomarkers for diagnosis and evaluation of FM in the future.
Prophylactic treatment with transdermal deferoxamine mitigates radiation-induced skin fibrosis
Authors: Shen Abra H. , Borrelli Mimi R. , Adem Sandeep , Deleon Nestor M. Diaz , Patel Ronak A. , Mascharak Shamik , Yen Sara J. , Sun Blake Y. , Taylor Walter L. , Januszyk Michael , Nguyen Dung H. , Momeni Arash , Gurtner Geoffrey C. , Longaker Michael T. , Wan Derrick C. 
Published: July 2020

AbstractRadiation therapy can result in pathological fibrosis of healthy soft tissue. The iron chelator deferoxamine (DFO) has been shown to improve skin vascularization when injected into radiated tissue prior to fat grafting. Here, we evaluated whether topical DFO administration using a transdermal drug delivery system prior to and immediately following irradiation (IR) can mitigate the chronic effects of radiation damage to the skin. CD-1 nude immunodeficient mice were split into four experimental groups: (1) IR alone (IR only), (2) DFO treatment for two weeks after recovery from IR (DFO post-IR), (3) DFO prophylaxis with treatment through and post-IR (DFO ppx), or (4) no irradiation or DFO (No IR). Immediately following IR, reactive oxygen species and apoptotic markers were significantly decreased and laser doppler analysis revealed significantly improved skin perfusion in mice receiving prophylactic DFO. Six weeks following IR, mice in the DFO post-IR and DFO ppx groups had improved skin perfusion and increased vascularization. DFO-treated groups also had evidence of reduced dermal thickness and collagen fiber network organization akin to non-irradiated skin. Thus, transdermal delivery of DFO improves tissue perfusion and mitigates chronic radiation-induced skin fibrosis, highlighting a potential role for DFO in the treatment of oncological patients.
Impact of admission serum ionized calcium levels on risk of acute kidney injury in hospitalized patients
Authors: Thongprayoon Charat , Cheungpasitporn Wisit , Chewcharat Api , Mao Michael A. , Bathini Tarun , Vallabhajosyula Saraschandra , Thirunavukkarasu Sorkko , Kashani Kianoush B. 
Published: July 2020

AbstractThis study aimed to investigate the risk of acute kidney injury (AKI) in hospitalized patients based on admission serum ionized calcium levels. This is a cohort study of all hospitalized adult patients, from January 2009 to December 2013 at a tertiary referral hospital, who had available serum ionized calcium at the time of admission. We excluded patients who had end-stage kidney disease or AKI at admission. We stratified admission serum ionized calcium into 6 groups; ≤ 4.39, 4.40–4.59, 4.60–4.79, 4.80–4.99, 5.00–5.19, and ≥ 5.20 mg/dL. We used serum creatinine criterion of KDIGO definition for diagnosis of AKI. We performed logistic regression analysis to assess the risk of in-hospital AKI occurrence based on admission serum ionized calcium, using serum ionized calcium of 5.00–5.19 mg/dL as the reference group. We studied a total of 25,844 hospitalized patients. Of these, 3,294 (12.7%) developed AKI in hospital, and 622 (2.4%) had AKI stage 2 or 3. We observed a U-shaped association between admission serum ionized calcium and in-hospital AKI, with nadir in-hospital AKI was in serum ionized calcium of 5.00–5.19 mg/dL. After adjustment for confounders, low serum ionized calcium of 4.40–4.59, ≤ 4.39 mg/dL and elevated serum ionized calcium ≥ 5.20 mg/dL were associated with increased risk of AKI with odds ratio of 1.33 (95% CI 1.14–1.56), 1.45 (95% CI 1.21–1.74), and 1.26 (95% CI 1.04–1.54), respectively. Both hypocalcemia, and hypercalcemia at the time of admission were associated with an increased risk of hospital-acquired AKI.
Body weight-dependent foot loads, assessed in terms of BMI and adiposity, in school-aged children: a cross sectional study
Authors: Szczepanowska-Wolowiec Beata , Sztandera Paulina , Kotela Ireneusz , Zak Marek 
Published: July 2020

AbstractWhereas inherently vulnerable structure of both a child's and an adolescent's foot, characteristic for its dynamic, developmental stage, is particularly exposed to numerous environmental factors, excessive body weight gain may potentially become a crucial causal factor, bringing on a cascade of adverse effects throughout the body, e.g. disorders of the skeletal-articular system, gait alterations, abnormally excessive loading of the plantar zones of the foot, and consequently serious postural defects, especially in later life. Since obesity, aptly dubbed the scourge of the 21st c., directly impacts the way the foot biomechanics are developed, whereupon the actual paradigm of foot loading becomes subject to numerous, adverse modifications, the present study focused on gaining an in-depth insight into prevalent association of BMI, adipose tissue content in body composition, and the actual distribution of foot loads in the school-aged children. Since body weight, the simplest anthropometric indicator, is actually non-indicative of the proportion of adipose tissue within body composition, a number of modern, non-invasive diagnostic methods were applied by the investigators to have this deficit effectively addressed, inclusive of comprehensively mapping out the actual load distribution in the plantar zones of the foot.
Identification of long non-coding RNAs in advanced prostate cancer associated with androgen receptor splicing factors
Authors: Takayama Ken-ichi , Fujimura Tetsuya , Suzuki Yutaka , Inoue Satoshi 
Published: July 2020

AbstractThe molecular and cellular mechanisms of development of castration-resistant prostate cancer (CRPC) remain elusive. Here, we analyzed the comprehensive and unbiased expression profiles of both protein-coding and long non-coding RNAs (lncRNAs) using RNA-sequencing to reveal the clinically relevant molecular signatures in CRPC tissues. For protein-coding genes upregulated in CRPC, we found that mitochondria-associated pathway, androgen receptor (AR), and spliceosome associated genes were enriched. Moreover, we discovered AR-regulated lncRNAs, CRPC-Lncs, that are highly expressed in CRPC tissues. Notably, silencing of two lncRNAs (CRPC-Lnc #6: PRKAG2-AS1 and #9: HOXC-AS1) alleviated CRPC tumor growth, showing repression of AR and AR variant expression. Mechanistically, subcellular localization of the splicing factor, U2AF2, with an essential role in AR splicing machinery was modulated dependent on the expression level of CRPC-Lnc #6. Thus, our investigation highlights a cluster of lncRNAs which could serve as AR regulators as well as potential biomarkers in CRPC.
High-resolution X-ray spectroscopy of the stellar wind in Vela X-1 during a flare
Authors: Lomaeva M. , Grinberg V. , Guainazzi M. , Hell N. , Bianchi S. , Bissinger né Kühnel M. , Fürst F. , Kretschmar P. , Martínez-Chicharro M. , Martínez-Núñez S. , Torrejón J. M. 
Published: July 2020

Context. We present a ~130 ks observation of the prototypical wind-accreting, high-mass X-ray binary Vela X-1 collected with XMM-Newton at orbital phases between 0.12 and 0.28. A strong flare took place during the observation that allows us to investigate the reaction of the clumpy stellar wind to the increased X-ray irradiation.
Aims. To examine the wind’s reaction to the flare, we performed both time-averaged and time-resolved analyses of the RGS spectrum and examined potential spectral changes.
Methods. We focused on the high-resolution XMM-Newton RGS spectra and divided the observation into pre-flare, flare, and post-flare phases. We modeled the time-averaged and time-resolved spectra with phenomenological components and with the self-consistent photoionization models calculated via CLOUDY and XSTAR in the pre-flare phase, where strong emission lines due to resonant transitions of highly ionized ions are seen.
Results. In the spectra, we find emission lines corresponding to K-shell transitions in highly charged ions of oxygen, neon, magnesium, and silicon as well as radiative recombination continua (RRC) of oxygen. Additionally, we observe potential absorption lines of magnesium at a lower ionization stage and features identified as iron L lines. The CLOUDY and XSTAR photoionization models provide contradictory results, either pointing towards uncertainties in theory or possibly a more complex multi-phase plasma, or both.
Conclusions. We are able to demonstrate the existence of a plethora of variable narrow features, including the firm detection of oxygen lines and RRC that RGS enables to observe in this source for the first time. We show that Vela X-1 is an ideal source for future high-resolution missions, such as XRISM and Athena.
EEG als Steuersignal: Gehirnaktivität entschlüsseln
und effizient als Kommunikationsmittel für Patienten mit motorischen
Defiziten nutzen
Authors: Reichert Christoph , Dürschmid Stefan , Hinrichs Hermann 
Published: July 2020

Zusammenfassung
Ziel der Studie Ereignis-korrelierte Potenziale werden in der Regel in
einzelnen EEG-Kanälen ermittelt. Mit einem einzelnen Kanal wird jedoch
nur ein Teil des gesamten Hirnprozesses erfasst. Für eine
Gehirn-Computer Schnittstelle, die in kurzer Zeit eine Entscheidung treffen
muss, ist diese singuläre Gehirnantwort häufig unzureichend
wogegen die Information aus mehreren Kanälen häufig redundant
ist. Beide Vorgehensweisen sind nicht optimal. Daher ist es unser Ziel, die
Kanäle zu wenigen Komponenten zu kombinieren, die die relevantesten
Modulationen eines Hirnprozesses erfassen.
Methodik Wir nutzen die kanonische Korrelationsanalyse, um datengetrieben
räumliche Filter aus dem EEG zu bestimmen. Mit der Produkt-Moment
Korrelation ermitteln wir, auf welche von 12 verschiedenen Stimulussequenzen die
Studienteilnehmer geachtet haben.
Ergebnisse Die verdeckte Aufmerksamkeit der Studienteilnehmer konnte mit
hoher Genauigkeit (89,3±9,2%) aus dem räumlich
gefilterten EEG und signifikant besser als aus einzelnen Kanälen
dekodiert werden.
Schlussfolgerung Die aus dem EEG erlernten räumlichen Filter
ermöglichen die Extraktion von Komponenten, die einen event-korrelierten
Gehirnprozess charakterisieren und eine Gehirn-Computer Schnittstelle effektiv
steuern können, was von hoher Relevanz für Patienten ist, die
nicht mehr anderweitig kommunizieren können.
Impact of Long-term, High-fat, and High-calorie Diet on Murine Vertebrae Bones
Authors: Schildberg Frank Alexander , Kabir Koroush , Bojko Jessica , Khoury Mona , Masson Werner , Weber Anna , Hilgers Cäcilia , Bourauel Christoph , Steinmetz Martin , Welle Kristian 
Published: July 2020

AbstractAs the percentage of overweight individuals in the population rises, diseases associated with excess weight resulting from poor nutrition are becoming more and more widespread. So
far, the influence of weight or nutrition on bone health has shown conflicting results. In the literature, the existing studies disagree about the effect of diet on bones.
Therefore, this study investigated the impact of a long-term, high-fat, and high-calorie diet on the spine in a mouse model. Wild-type mice were randomly separated into two groups;
one group received a high-fat and high-calorie diet, and a control group was fed with a regular diet for a duration of 24 weeks. The first to fifth thoracic vertebrae were
extracted and investigated using histology and micro-CT. Samples were analyzed regarding different parameters: percentage of bone structure compared to the whole vertebra and the
amount and thickness of the trabeculae. Both methods of the analysis showed similar results. Diet did not have a significant impact on the bone density of the vertebrae. The
micro-CT examination showed that the average bone percentage of the examined vertebra was 6% (p = 0.2330) higher in the control group compared to the diet group. The same tendency
was demonstrated in histology even though with a smaller difference of only 5%. The results of both methods were comparable and showed trends for the influence of different diets
but not significant impacts. In summary, this study showed that a high-fat and high-calorie diet has a slightly negative impact on bone density. In order to further analyze the
effects of different diets on bone composition, structure, and density, additional long-term studies should be carried out, and more parameters such as movement and genetic factors
should be analyzed. Furthermore, other parameters such as exercise and genetic factors that could have a secondary influence on obesity should be investigated.
Sozialbedingte Ungleichheiten von Gesundheit und Gesundheitsverhalten
bei Studierenden
Authors: Diehl Katharina , Hilger-Kolb Jennifer , Herr Raphael M. 
Published: July 2020

Zusammenfassung
Ziel der Studie Studierende sind in den letzten Jahren immer mehr in den
Fokus von Prävention und gesundheitswissenschaftlicher Forschung
gerückt. Allerdings werden sie meist als homogene Gruppe wahrgenommen.
Ziel des vorliegenden Beitrags war es, zu prüfen, ob in der Gruppe
Studierender gesundheitliche Ungleichheit existiert.
Methodik Zur Beantwortung der Frage wurde ein bundesweiter
Studierendensurvey, die sogenannte NuPhA-Studie, herangezogen (n=689,
69,5% weiblich, Altersdurchschnitt: 22,69 Jahre).
Ergebnisse und Schlussfolgerung Tatsächlich zeigten sich
Zusammenhänge zwischen sozioökonomischen Indikatoren und
Gesundheit sowie Gesundheitsverhalten. Beispielsweise war die
Studienfinanzierung über ein Stipendium mit einer besseren allgemeinen,
psychischen und physischen Gesundheit verbunden. Insbesondere der subjektive
Sozialstatus war positiv mit einer besseren allgemeinen, psychischen und
körperlichen Gesundheit sowie einer höheren
Sportaktivität verknüpft. Die Ergebnisse sprechen für
ein Vorliegen von gesundheitlicher Ungleichheit in der zunächst homogen
erscheinenden Gruppe Studierender. Dies unterstreicht die Notwendigkeit einer
differenzierten Betrachtung der Gruppe Studierender und die Wichtigkeit,
gesundheitliche Ungleichheit unter Studierenden tiefergehend zu untersuchen, zu
erklären und schließlich zu reduzieren.
Review of Clinical Trials in COVID-19: Trying to Solve the Clinicians’ Conundrum
Authors: Athavale Amita , Khatri Vijay , Athavale Tanya , Deshmukh Hemant , Nataraj Gita , Bahot Rahul 
Published: July 2020

AbstractSARS-CoV-2 and the resulting “COVID-19” has escalated into a pandemic and has resulted in significant morbidity and mortality. Currently, there is no approved antiviral treatment available. Few antiviral agents are undergoing clinical trials for their safety and efficacy against COVID-19. With various repurposed drugs under evaluation, treatment approaches range from search for an effective antiviral, immunomodulation and anticoagulation, use of point-of-care ultrasound to novel ventilatory strategies. Newer agents targeting the inflammatory pathway are also under investigation. There are more than 1955 ongoing clinical trials of repurposed and novel agents. Here we review some of the ongoing trials that have published, at least, interim results of treating patients with COVID-19.
The Compliance of Prescribed Activity Restriction in Women at High Risk for Preterm Birth
Authors: Bitar Ghamar , Sciscione Anthony 
Published: July 2020

Objective Despite lack of evidence to support efficacy, activity restriction is one of the most commonly prescribed interventions used for the prevention of preterm birth. We have a departmental policy against the use of activity restriction but many practitioners still prescribe it in an effort to prevent preterm birth. We sought to evaluate the rate and compliance of women who are prescribed activity restriction during pregnancy to prevent preterm birth.
Study Design This was a single-site retrospective questionnaire study at a tertiary care, academic affiliated medical center. Women with a history of preterm delivery or short cervix were included. Once patients were identified, each patient was contacted and administered a questionnaire. We assessed the rates of activity restriction prescription and compliance. Secondary outcomes included details regarding activity restriction and treatment in pregnancy. Continuous variables were compared with t-test and categorical variables with Chi-square test. The value p < 0.05 was considered significant.
Results Among the 52 women who responded to the questionnaire, 18 reported being placed on activity restriction by a physician, with 1 self-prescribing activity restriction, giving a rate of our primary outcome of 19 of 52 (36.5%). All women reported compliance with prescribed activity restriction (100%). Gestational age at delivery was not different in women placed on activity restriction.
Conclusion This questionnaire suggests that approximately one in three high-risk women were placed on activity restriction during their pregnancy despite a departmental policy against its use. The 100% compliance rate in patients placed on activity restriction is a strong reminder of the impact prescribing patterns of physicians can have on patients.
Key Points