bluuebunny/crossref_metadata_2025_split huggingface dataset:
A benchmark of hemoglobin blocking during library preparation for mRNA-Sequencing of human blood samples
Authors: Uellendahl-Werth Florian , Wolfien Markus , Franke Andre , Wolkenhauer Olaf , Ellinghaus David 
Published: March 2020

AbstractRNA-Sequencing (RNA-Seq) of peripheral blood can be a valuable source of information for investigating the status and mechanism of diseases. However, blood contains 50–80% unwanted hemoglobin (Hb) transcripts. Lexogen’s QuantSeq mRNA-Seq-Kit for Illumina RNA-Seq features a ‘Globin Block’ (GB) module that depletes Hb cDNAs during library preparation. Here, we aimed to assess GB’s effectiveness and checked for technical biases attributable to GB. Using whole blood total RNA samples of 91 healthy individuals, we sequenced 91 pairs of GB and non-blocked samples (noGB) on Illumina HiSeq2500 and 8 pairs of GB/noGB technical replicates on HiSeq4000. GB reduced the fraction of Hb transcripts from 43% (s.d. 14%) to 8.0% (s.d. 4.3%). From GB samples we detected 1,397 more expressed genes at approximately 11 million reads per RNA-isolate. Enrichment and differential expression analyses did not reveal significant differences for GB and noGB samples with respect to molecular function. In contrast to results from studies that have examined the performance of GB during RNA isolation, we were able to assign GB to corresponding noGB samples (from multiple sequencing runs on HiSeq2500) with at least 89.8% accuracy from the complete correlation matrix of all GB/GB, noGB/noGB and GB/noGB pairs. However, the use of different sequencers (HiSeq2500 vs HiSeq4000) impaired assignment of technical replicates, whereas assignment of GB to corresponding noGB samples worked perfectly when sequencing on one lane on HiSeq4000. Lexogen’s GB RNA-Seq module is a valuable addition during mRNA-Seq library preparation which works even with low amounts of input total RNA (50 ng per sample). GB facilitated the detection of low abundant transcripts and yielded more non-hemoglobin reads, while preserving biological information. We observed that differences in sequencing run and platform have a far greater effect on technical variation than the use of GB.
Investigation of auranofin and gold-containing analogues antibacterial activity against multidrug-resistant Neisseria gonorrhoeae
Authors: Elkashif Ahmed , Seleem Mohamed N. 
Published: March 2020

AbstractNeisseria gonorrhoeae represents an urgent public health threat due to the rapid emergence of resistance to current antibiotics and the limited number of anti-gonococcal agents currently in clinical trials. This study utilized a drug repositioning strategy to investigate FDA-approved gold-containing drugs against N. gonorrhoeae. Auranofin, sodium aurothiomalate and aurothioglucose inhibited 48 clinical isolates of N. gonorrhoeae including multidrug-resistant strains at a concentration as low as 0.03 µg/mL. A time-kill assay revealed that auranofin exhibited rapid bactericidal activity against N. gonorrhoeae. Moreover, both sodium aurothiomalate and aurothioglucose did not inhibit growth of vaginal protective commensal lactobacilli. Auranofin, in combination with azithromycin, ceftriaxone, cefixime or tetracycline showed an additive effect against four N. gonorrhoeae strains, suggesting the possibility of using auranofin in dual therapy. Moreover, auranofin reduced the burden of intracellular N. gonorrhoeae by over 99% outperforming the drug of choice ceftriaxone. Auranofin was found superior to ceftriaxone in reducing the secretion of the pro-inflammatory cytokine IL-8 by endocervical cells infected with N. gonorrhoeae. Furthermore, auranofin exhibited a prolonged post-antibiotic effect over 10 h, as well as inability to generate resistant mutants. Overall, the current study suggests that repurposing gold-containing drugs, like auranofin, for treatment of gonorrhea warrants further investigation.
Bufalin down-regulates Axl expression to inhibit cell proliferation and induce apoptosis in non-small-cell lung cancer cells
Authors: Kim Nam-Yi , Suh Young-Ah , Kim Soyoung , Lee ChuHee 
Published: March 2020

Abstract
Axl, a member of the TAM (Tyro3, AXL, Mer) receptor tyrosine kinase family, plays critical roles in cell growth, proliferation, apoptosis, and migration. In the present study, we demonstrated that the anti-cancer activity of bufalin, a major bioactive component of the Chinese traditional medicine Chan Su, is mediated by the down-regulation of Axl in non-small-cell lung cancer (NSCLC) cells. We observed the inhibitory effect of bufalin on the proliferation of A549 and H460 NSCLC cells and the clonogenicity of these cells was reduced by bufalin treatment in a dose-dependent manner. Next, we found that the protein level of Axl was decreased in proportion to the concentration of bufalin in both A549 and H460 cells. Moreover, the promoter activity of the Axl gene was decreased by bufalin in a dose- and time-dependent manner, indicating that bufalin down-regulates Axl gene expression at the transcriptional level. We further examined if the anti-proliferative property of bufalin is influenced by Axl at the protein level. Axl overexpression attenuated the effect of bufalin in inhibiting cell proliferation and colony formation and inducing apoptosis in H460 cells, while knockdown of Axl gene expression induced the opposite effect. Taken together, our data indicate that the anti-proliferative and pro-apoptotic effects of bufalin were associated with the protein level of Axl, suggesting that Axl is a potent therapeutic target of bufalin in suppressing proliferation and inducing apoptosis in NSCLC cells.
Role of the renin–angiotensin system in kidney development and programming of adult blood pressure
Authors: Almeida Lucas F. , Tofteng Signe S. , Madsen Kirsten , Jensen Boye L. 
Published: March 2020

Abstract
Adverse events during fetal life such as insufficient protein intake or elevated transfer of glucocorticoid to the fetus may impact cardiovascular and metabolic health later in adult life and are associated with increased incidence of type 2 diabetes, ischemic heart disease and hypertension. Several adverse factors converge and suppress the fetal renin–angiotensin–aldosterone system (RAAS). The aim of this review is to summarize data on the significance of RAAS for kidney development and adult hypertension. Genetic inactivation of RAAS in rodents at any step from angiotensinogen to angiotensin II (ANGII) type 1 receptor (AT1) receptors or pharmacologic inhibition leads to complex developmental injury to the kidneys that has also been observed in human case reports. Deletion of the ‘protective’ arm of RAAS, angiotensin converting enzyme (ACE) 2 (ACE-2) and G-protein coupled receptor for Angiotensin 1–7 (Mas) receptor does not reproduce the AT1 phenotype. The changes comprise fewer glomeruli, thinner cortex, dilated tubules, thicker arterioles and arteries, lack of vascular bundles, papillary atrophy, shorter capillary length and volume in cortex and medulla. Altered activity of systemic and local regulators of fetal-perinatal RAAS such as vitamin D and cyclooxygenase (COX)/prostaglandins are associated with similar injuries. ANGII–AT1 interaction drives podocyte and epithelial cell formation of vascular growth factors, notably vascular endothelial growth factor (VEGF) and angiopoietins (Angpts), which support late stages of glomerular and cortical capillary growth and medullary vascular bundle formation and patterning. RAAS-induced injury is associated with lower glomerular filtration rate (GFR), lower renal plasma flow, kidney fibrosis, up-regulation of sodium transporters, impaired sodium excretion and salt-sensitive hypertension. The renal component and salt sensitivity of programmed hypertension may impact dietary counseling and choice of pharmacological intervention to treat hypertension.
A Program Review of Head Start and Elementary School Hearing Screenings
Authors: Hurley Annette , Willis Michelle , Guidry Megan , Bode Dan , Corneille Marissa L. , Mills Sara 
Published: March 2020

Purpose
The purpose of this study was to review quality benchmarks from hearing screening programs conducted at local Head Start centers and preschool and elementary schools associated with our university training programs.

Method
Hearing screening results from 6,043 children were reviewed. Hearing screening was accomplished using either distortion product otoacoustic emissions (DPOAEs) at Head Start centers, pure-tone audiometry at preschool and elementary schools, and tympanometry at all settings. All children who did not pass the initial screening were screened a second time. Referrals were made if a child did not pass the automated DPOAE pass criteria for one ear, failed at least one pure-tone frequency for one ear, or had abnormal tympanometry in one ear.

Results
Refer rates were 10.9% for DPOAEs and 11.4% for pure-tone audiometry and tympanometry, with an overall refer rate of 11%.

Conclusions
Our hearing screening program review yielded refer rates that are similar to other published reports for this population. Presently, there are no published target refer rates for hearing screening programs in preschool and elementary schools. Although we were not able to complete other program quality benchmark indicators including sensitivity and specificity, these data may support benchmarks for other hearing screening programs.
Discovery of new members of the nearby young stellar association in Cepheus
Authors: Klutsch A. , Frasca A. , Guillout P. , Montes D. , Pineau F.-X. , Grosso N. , Stelzer B. 
Published: March 2020

Context. Young field stars are hardly distinguishable from older ones because their space motion rapidly mixes them with the stellar population of the Galactic plane. Nevertheless, a careful target selection allows for young stars to be spotted throughout the sky.
Aims. We aim to identify additional sources associated with the four young comoving stars that we discovered towards the CO Cepheus void and to provide a comprehensive view of the Cepheus association.
Methods. Based on multivariate analysis methods, we have built an extended sample of 193 young star candidates, which are the optical and infrared counterparts of ROSAT All-Sky Survey and XMM-Newton X-ray sources. From optical spectroscopic observations, we measured their radial velocity with the cross-correlation technique. We derived their atmospheric parameters and projected rotational velocity with the code ROTFIT. We applied the subtraction of inactive templates to measure the lithium equivalent width, from which we infer their lithium abundance and age. Finally, we studied their kinematics using the second Gaia data release.
Results. Our sample is mainly composed of young or active stars and multiple systems. We identify two distinct populations of young stars that are spatially and kinematically separated. Those with an age between 100 and 300 Myr are mostly projected towards the Galactic plane. In contrast, 23 of the 37 sources younger than 30 Myr are located in the CO Cepheus void, and 21 of them belong to the stellar kinematic group that we previously reported in this sky area. We report a total of 32 bona fide members and nine candidates for this nearby (distance = 157 ± 10 pc) young (age = 10–20 Myr) stellar association. According to the spatial distribution of its members, the original cluster is already dispersed and partially mixed with the local population of the Galactic plane.
Mapping large-scale diffuse γ-ray emission in the 10−100 TeV band with Cherenkov telescopes
Authors: Neronov A. , Semikoz D. 
Published: March 2020

Context. Measurement of diffuse γ-ray emission from the Milky Way with Imaging Atmospheric Cherenkov Telescopes (IACT) is difficult because of the high level of charged cosmic ray background and the small field of view.
Aims. We show that such a measurement is nevertheless possible in the energy band 10−100 TeV.
Methods. The minimal charged particle background for IACTs is achieved by selecting the events to be used for the analyses of the cosmic ray electrons. Tight cuts on the event quality in these event selections allow us to obtain a sufficiently low background level to allow measurement of the diffuse Galactic γ-ray flux above 10 TeV. We calculated the sensitivities of different types of IACT arrays for the Galactic diffuse emission measurements and compared them with the diffuse γ-ray flux from different parts of the sky measured by the Fermi Large Area Telescope below 3 TeV and with the astrophysical neutrino signal measured by IceCube telescope.
Results. We show that deep exposure of existing IACT systems is sufficient for detection of the diffuse flux from all the Galactic Plane up to Galactic latitude |b| ∼ 5°. The Medium Size Telescope array of the CTA will be able to detect the diffuse flux up 30° Galactic latitude. Its sensitivity will be sufficient for detection of the γ-ray counterpart of the Galactic component of the IceCube astrophysical neutrino signal above 10 TeV. We also propose that a dedicated IACT system composed of small but wide-field-of-view telescopes could be used to map the 10−100 TeV diffuse γ-ray emission from across the whole sky.
Conclusions. Detection and detailed study of diffuse Galactic γ-ray emission in the previously unexplored 10−100 TeV energy range is possible with the IACT technique. This is important for identification of the Galactic component of the astrophysical neutrino signal and for understanding the propagation of cosmic rays in the interstellar medium.
Zugang erleichtern
Authors: Tasser Isabella , Schneiderwind Randolf 
Published: March 2020

ZusammenfassungImmer mehr Kliniken müssen auf ausländische Pflegekräfte zurückgreifen, um ihren Personalbedarf zu decken. Deshalb wäre es wichtig, die Zuwanderungsverfahren der deutschen Behörden zu beschleunigen.
Am Ende profitiert der Patient
Authors: Kurmann Jörg 
Published: March 2020

ZusammenfassungIn Kliniken ist die interprofessionelle Kooperation oft schwierig. Aus diesem Grund hat das Johanna Etienne Krankenhaus ein Programm für Assistenzärzte und Pflegende aufgelegt, das die Berufsgruppen zusammenrücken lässt.
A novel method of biopsy for indeterminate pancreaticobiliary strictures: tube-assisted biopsy
Authors: Ko Sung Woo , Lee Sang Soo , So Hoonsub , Hwang Jun Seong , Song Tae Jun , Lee Sung Koo , Kim Myung-Hwan 
Published: March 2020

Abstract
Background Single-operator cholangioscopy (SOC) provides an accurate diagnosis of indeterminate pancreaticobiliary strictures. However, the procedure is expensive and can be performed using only limited accessories. Therefore, we devised a novel tube-assisted biopsy (TAB) technique and evaluated its feasibility, diagnostic yield, and safety for indeterminate pancreaticobiliary strictures.
Methods The medical records of patients with indeterminate pancreaticobiliary strictures who underwent TAB between September 2018 and July 2019 were reviewed. We assessed the technical success rate, adverse event rate, sensitivity, specificity, and overall accuracy of TAB in differentiating malignant from benign lesions.
Results TABs were performed in 16 patients: 12 had biliary strictures; four had pancreatic strictures. The technical success rate was 93.7 % (15/16), and the sensitivity, specificity, and overall accuracy of TAB were 87.5 %, 100 %, and 93.7 %, respectively. No serious adverse events occurred either during or after the procedure in any of the patients.
Conclusions TAB has an acceptable accuracy for the diagnosis of indeterminate pancreaticobiliary strictures and may represent a useful diagnostic method in patients where SOC cannot be implemented.
Evaluation of the hepatotoxic potential of Tinospora crispa and its isolated borapetosides B, C and F in a murine model
Authors: Parveen Abidah , Maqbool Mir Tahir , Wang Yan-Hong , Ali Zulfiqar , Khan Ikhlas A. , Ashfaq M. Khalid 
Published: March 2020

AbstractThe hepatotoxic potential of the methanolic extract of the stems of Tinospora crispa and of its furano-diterpenoid–borapetosides B, C, and F–was investigated in normal and health-compromised mice. Health-compromised condition was established by a single intraperitoneal injection of LPS (6 mg/kg). Two different sets of experiments were conducted to evaluate the hepatotoxic potential. A 21-day study where the mice were dosed with the extract of T. crispa (1 gm/kg b. wt./day) or standardized combination of borapetosides B, C and F (500 mg/kg b. wt.) with or without a single dose of LPS (1 gm/kg b. wt./day). In the acute toxicity study, mice were dosed with borapetosides B, C, and F (500 mg/kg b. wt.). Results showed that the ALT levels were normal and liver histopathology unaltered. No conclusive hepatotoxicity was observed in the methanolic extract or pure compounds tested under the given experimental conditions.
Salvage-Lymphadenektomie des lymphogenen Prostatakarzinomrezidivs
Authors: Stolzenbach Lara Franziska , Knipper Sophie , Maurer Tobias 
Published: March 2020

ZusammenfassungDas lymphogene Prostatakarzinomrezidiv kann seit der Einführung funktioneller Bildgebung wie der PSMA PET/CT oft frühzeitig diagnostiziert werden. Aktuelle Studien zur lokalen Behandlung der Lymphknotenmetastasen legen einen positiven Einfluss auf die Prognose bei ausgewählten Patienten nahe. Dennoch ist die Mehrzahl der Studien retrospektiv und aus Mangel an höhergradiger Evidenz gilt die Salvage-Lymphadenektomie (LA) als nicht-leitlinienkonform.Ziel dieser Arbeit ist die kritische Zusammenfassung der aktuellen Datenlage zur Salvage-LA des lymphogenen Prostatakarzinomrezidivs mit dem Fokus auf die bildgebenden Verfahren, die Ausdehnung der LA und den onkologischen Verlauf.Die europäischen Leitlinien empfehlen die Durchführung der Cholin- oder PSMA PET/CT-Bildgebung bei einem Verdacht auf ein Prostatakarzinomrezidiv. Die PSMA-PET/CT ist der Cholin-PET/CT in Sensitivität und Spezifität überlegen und sollte dabei favorisiert werden.Wird eine Salvage-LA dennoch durchgeführt, ist die gängige Praxis eine bilaterale LA – auch bei einem im PSMA-PET/CT nachgewiesenen einseitigen Lymphknotenbefall. Allerdings kann ebenfalls die unilaterale LA in Erwägung gezogen werden. Eine aktuell eingeleitete randomisierte prospektive Studie (ProSTone) soll diese Fragestellung beantworten.Ein neuer vielversprechender chirurgischer Ansatz scheint die PSMA-radioguided surgery zu sein. Sie erleichtert das intraoperative Auffinden von Lymphknotenmetastasen. Langzeitdaten sind aber noch abzuwarten.Insgesamt erreicht die Salvage-LA bei sorgfältig ausgewählten Patienten eine respektable biochemische Ansprechrate. Dennoch sind für die Zukunft prospektive Studien notwendig, um den Stellenwert genauer definieren zu können.
Primary Aldosteronism and Obstructive Sleep Apnea: Casual Association or Pathophysiological Link?
Authors: Pecori Alessio , Buffolo Fabrizio , Pieroni Jacopo , Forestiero Vittorio , Sconfienza Elisa , Veglio Franco , Mulatero Paolo , Monticone Silvia 
Published: March 2020

AbstractThe coexistence of aldosterone oversecretion and obstructive sleep apnea is frequently observed, especially in patients with resistant hypertension, obesity, and metabolic syndrome. Since aldosterone excess and sleep apnea are both independently associated with an increased risk of cardiovascular disease, to investigate whether their coexistence might be attributed to common predisposing conditions, such as metabolic disorders, or to an actual pathophysiological interconnection appears of great importance. Fluid overload and metabolic abnormalities relating to aldosterone oversecretion may be implicated in obstructive sleep apnea development. Nocturnal intermittent hypoxia may in turn exacerbate renin-angiotensin-aldosterone system activity, thus leading to hyperaldosteronism. Furthermore, fat tissue excess and adipocyte secretory products might predispose to both sleep apnea and aldosterone oversecretion in subjects with obesity. Consistent with these evidences, obstructive sleep apnea frequently affects patients with primary aldosteronism. Conversely, whether primary aldosteronism is more prevalent in individuals affected by obstructive sleep apnea compared to the general population remains controversial.
Effects of ACE Inhibitors and Angiotensin Receptor Blockers in
Normotensive Patients with Diabetic Kidney Disease
Authors: He Dandan , Zhang Yaru , Zhang Wei , Xing Yue , Guo Yipeng , Wang Fuzhen , Jia Junya , Yan Tiekun , Liu Youxia , Lin Shan 
Published: March 2020

AbstractThe role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin
receptor blockers (ARBs) in reducing the progression of albuminuria and risk of
cardiovascular events in hypertensive patients with diabetic kidney disease
(DKD) is well-documented. However, the efficacy and safety of these agents in
normotensive patients with DKD are still controversial. MEDLINE, Embase, and
Cochrane Library were searched for relevant random controlled trials. The odd
risk (OR) reductions were calculated with a random-effects model. Decrease in
albuminuria, changes in eGFR, major cardiovascular events, and drug-related
adverse events were analyzed. Thirteen RCTs including 1282 patients were
retrieved. Compared with placebo or other active agent groups, ACEIs or ARBs
significantly decreased albuminuria (MD –80.28 mg/d,
95% CI –104.79 mg/d to
–55.77 mg/d), and the efficacy is independent of changes
in blood pressure and systolic blood pressure at baseline. The result of
subanalysis showed the declining of albuminuria was more significantly in
normotensive DKD patients with 2DM (p=0.005). No significant differences
were found with regard to the declining of evaluated glomerular filtration rate
(eGFR) (MD
–0.29 ml/min/1.73 m2,
95% CI –2.99 to
2.41 ml/min/1.73 m2). There were
no significant differences in the side effect of the drugs such as hypotension
and hyperkalemia. This meta-analysis demonstrated that ACEIs or ARBs can
decrease albuminuria to varying degree in normotensive patients with DKD, and
better response occurred in patients with 2DM.
Myosin filament-based regulation of the dynamics of contraction in heart muscle
Authors: Brunello Elisabetta , Fusi Luca , Ghisleni Andrea , Park-Holohan So-Jin , Ovejero Jesus G. , Narayanan Theyencheri , Irving Malcolm 
Published: March 2020

Significance
Cardiovascular disease continues to be the leading cause of death worldwide, and is frequently associated with heart failure. Efforts to develop better therapeutics for heart failure have been held back by limited understanding of the normal control of contraction on the timescale of the heartbeat. We used synchrotron X-ray diffraction to determine the dynamic structural changes in the myosin motors that drive contraction in the heart muscle, and show that myosin filament-based control mechanisms determine the time course and strength of contraction, allowing those mechanisms to be targeted for developing new therapies for heart disease.
Hanging droplets from liquid surfaces
Authors: Xie Ganhua , Forth Joe , Zhu Shipei , Helms Brett A. , Ashby Paul D. , Shum Ho Cheung , Russell Thomas P. 
Published: March 2020

Significance
Heavier objects usually sink in a less dense fluid. Water-walking anthropods and biomimetic water-walking robots harness surface tension in order to overcome this tendency, floating on top of liquids. By hanging a coacervate-encased droplet of a denser aqueous dextran solution from the surface of an aqueous solution of poly(ethylene glycol) (PEG), we harness the binding of dense droplets to interfaces by surface tension to build two-dimensional ensembles of structurally complex droplets. Applications ranging from reaction vessels with selective transport to motors and robotics are enabled by our findings.