bluuebunny/crossref_metadata_2025_split huggingface dataset:
Site-specific N-glycosylation analysis of animal cell culture-derived Zika virus proteins
Authors: Pralow Alexander , Nikolay Alexander , Leon Arnaud , Genzel Yvonne , Rapp Erdmann , Reichl Udo 
Published: March 2021

AbstractHere, we present for the first time, a site-specific N-glycosylation analysis of proteins from a Brazilian Zika virus (ZIKV) strain. The virus was propagated with high yield in an embryo-derived stem cell line (EB66, Valneva SE), and concentrated by g-force step-gradient centrifugation. Subsequently, the sample was proteolytically digested with different enzymes, measured via a LC–MS/MS-based workflow, and analyzed in a semi-automated way using the in-house developed glyXtoolMS software. The viral non-structural protein 1 (NS1) was glycosylated exclusively with high-mannose structures on both potential N-glycosylation sites. In case of the viral envelope (E) protein, no specific N-glycans could be identified with this method. Nevertheless, N-glycosylation could be proved by enzymatic de-N-glycosylation with PNGase F, resulting in a strong MS-signal of the former glycopeptide with deamidated asparagine at the potential N-glycosylation site N444. This confirmed that this site of the ZIKV E protein is highly N-glycosylated but with very high micro-heterogeneity. Our study clearly demonstrates the progress made towards site-specific N-glycosylation analysis of viral proteins, i.e. for Brazilian ZIKV. It allows to better characterize viral isolates, and to monitor glycosylation of major antigens. The method established can be applied for detailed studies regarding the impact of protein glycosylation on antigenicity and human pathogenicity of many viruses including influenza virus, HIV and corona virus.
Gene expression for secondary metabolite biosynthesis in hop (Humulus lupulus L.) leaf lupulin glands exposed to heat and low-water stress
Authors: Eriksen Renée L. , Padgitt-Cobb Lillian K. , Townsend M. Shaun , Henning John A. 
Published: March 2021

AbstractHops are valued for their secondary metabolites, including bitter acids, flavonoids, oils, and polyphenols, that impart flavor in beer. Previous studies have shown that hop yield and bitter acid content decline with increased temperatures and low-water stress. We looked at physiological traits and differential gene expression in leaf, stem, and root tissue from hop (Humulus lupulus) cv. USDA Cascade in plants exposed to high temperature stress, low-water stress, and a compound treatment of both high temperature and low-water stress for six weeks. The stress conditions imposed in these experiments caused substantial changes to the transcriptome, with significant reductions in the expression of numerous genes involved in secondary metabolite biosynthesis. Of the genes involved in bitter acid production, the critical gene valerophenone synthase (VPS) experienced significant reductions in expression levels across stress treatments, suggesting stress-induced lability in this gene and/or its regulatory elements may be at least partially responsible for previously reported declines in bitter acid content. We also identified a number of transcripts with homology to genes shown to affect abiotic stress tolerance in other plants that may be useful as markers for breeding improved abiotic stress tolerance in hop. Lastly, we provide the first transcriptome from hop root tissue.
An association between body image dissatisfaction and digit ratio among Chinese children and adolescents
Authors: Yuan Yongting , Hu Jingyao , Sun Lili , Zhang Yifei , Wang Bangxuan , Yao Rongying , Han Hui , Fu Lianguo 
Published: March 2021

AbstractBody image dissatisfaction (BID) is a negative evaluation of personal physical characteristics, including dissatisfaction with body shape, gender, sexual organs, appearance and so forth, and it plays an important role in growth and development. The second-to-fourth digit ratio (2D:4D) is recognized as a putative indicator of intra-uterine testosterone to estrogen ratio exposure, and it has been observed that higher levels of fetal testosterone exposure are associated with a lower 2D:4D. The present paper contributes to a better understanding of the biological underpinnings of BID by analyzing BID and the digit ratio (2D:4D). We found that the 2D:4D was positively related to appearance dissatisfaction in boys with first spermatorrhea, which means that low prenatal androgen exposure may increase boys’ dissatisfaction with their appearance. In girls with breast development being lower than Tanner stage II, their 2D:4D was negatively related to their body shape dissatisfaction, which means that high prenatal androgen exposure may increase girls’ dissatisfaction with their body shape. These results suggest that the prenatal androgen exposure level might play an important role in the body image dissatisfaction of the offspring.
Factors associated with physician decision making on withholding cardiopulmonary resuscitation in prehospital medicine
Authors: Zajic Paul , Zoidl Philipp , Deininger Marlene , Heschl Stefan , Fellinger Tobias , Posch Martin , Metnitz Philipp , Prause Gerhard 
Published: March 2021

AbstractThis study seeks to identify factors that are associated with decisions of prehospital physicians to start (continue, if ongoing) or withhold (terminate, if ongoing) CPR in patients with OHCA. We conducted a retrospective study using anonymised data from a prehospital physician response system. Data on patients attended for cardiac arrest between January 1st, 2010 and December 31st, 2018 except babies at birth were included. Logistic regression analysis with start of CPR by physicians as the dependent variable and possible associated factors as independent variables adjusted for anonymised physician identifiers was conducted. 1525 patient data sets were analysed. Obvious signs of death were present in 278 cases; in the remaining 1247, resuscitation was attempted in 920 (74%) and were withheld in 327 (26%). Factors significantly associated with higher likelihood of CPR by physicians (OR 95% CI) were resuscitation efforts by EMS before physician arrival (60.45, 19.89–184.29), first monitored heart rhythm (3.07, 1.21–7.79 for PEA; 29.25, 1.93–442. 51 for VF / pVT compared to asystole); advanced patient age (modelled using cubic splines), physician response time (0.92, 0.87–0.97 per minute) and malignancy (0.22, 0.05–0.92) were significantly associated with lower odds of CPR. We thus conclude that prehospital physicians make decisions to start or withhold resuscitation routinely and base those mostly on situational information and immediately available patient information known to impact outcomes.
Telomeres and replicative cellular aging of the human placenta and chorioamniotic membranes
Authors: Lai Tsung-Po , Simpson Mark , Patel Krunal , Verhulst Simon , Noh Jungsik , Roche Natalie , Heller Debra , Guirguis George , Shay Jerry W. , Herbig Utz , Aviv Abraham 
Published: March 2021

AbstractRecent hypotheses propose that the human placenta and chorioamniotic membranes (CAMs) experience telomere length (TL)-mediated senescence. These hypotheses are based on mean TL (mTL) measurements, but replicative senescence is triggered by short and dysfunctional telomeres, not mTL. We measured short telomeres by a vanguard method, the Telomere shortest length assay, and telomere-dysfunction-induced DNA damage foci (TIF) in placentas and CAMs between 18-week gestation and at full-term. Both the placenta and CAMs showed a buildup of short telomeres and TIFs, but not shortening of mTL from 18-weeks to full-term. In the placenta, TIFs correlated with short telomeres but not mTL. CAMs of preterm birth pregnancies with intra-amniotic infection showed shorter mTL and increased proportions of short telomeres. We conclude that the placenta and probably the CAMs undergo TL-mediated replicative aging. Further research is warranted whether TL-mediated replicative aging plays a role in all preterm births.
COVID-19 engages clinical markers for the management of cancer and cancer-relevant regulators of cell proliferation, death, migration, and immune response
Authors: Souchelnytskyi Serhiy , Nera Andriy , Souchelnytskyi Nazariy 
Published: March 2021

AbstractClinical reports show that the management of cancer patients infected with SARS-CoV-2 requires modifications. Understanding of cancer-relevant mechanisms engaged by the virus is essential for the evidence-based management of cancer. The network of SARS-CoV-2 regulatory mechanisms was used to study potential engagement of oncogenes, tumor suppressors, other regulators of tumorigenesis and clinical markers used in the management of cancer patients. Our network analysis confirms links between COVID-19 and tumorigenesis that were predicted in epidemiological reports. The COVID-19 network shows the involvement of tumorigenesis regulators and clinical markers. Regulators of cell proliferation, death, migration, and the immune system were retrieved. Examples are pathways initiated by EGF, VEGF, TGFβ and FGF. The SARS-CoV-2 network engages markers for diagnosis, prognosis and selection of treatment. Intersection with cancer diagnostic signatures supports a potential impact of the virus on tumorigenesis. Clinical observations show the diversity of symptoms correlating with biological processes and types of cells engaged by the virus, e.g. epithelial, endothelial, smooth muscle, glial and immune system cells. Our results describe an extensive engagement of cancer-relevant mechanisms and clinical markers by COVID-19. Engagement by the virus of clinical markers provides a rationale for clinical decisions based on these markers.
Polyunsaturated ω-3 fatty acids inhibit ACE2-controlled SARS-CoV-2 binding and cellular entry
Authors: Goc Anna , Niedzwiecki Aleksandra , Rath Matthias 
Published: March 2021

AbstractThe strain SARS-CoV-2, newly emerged in late 2019, has been identified as the cause of COVID-19 and the pandemic declared by WHO in early 2020. Although lipids have been shown to possess antiviral efficacy, little is currently known about lipid compounds with anti-SARS-CoV-2 binding and entry properties. To address this issue, we screened, overall, 17 polyunsaturated fatty acids, monounsaturated fatty acids and saturated fatty acids, as wells as lipid-soluble vitamins. In performing target-based ligand screening utilizing the RBD-SARS-CoV-2 sequence, we observed that polyunsaturated fatty acids most effectively interfere with binding to hACE2, the receptor for SARS-CoV-2. Using a spike protein pseudo-virus, we also found that linolenic acid and eicosapentaenoic acid significantly block the entry of SARS-CoV-2. In addition, eicosapentaenoic acid showed higher efficacy than linolenic acid in reducing activity of TMPRSS2 and cathepsin L proteases, but neither of the fatty acids affected their expression at the protein level. Also, neither reduction of hACE2 activity nor binding to the hACE2 receptor upon treatment with these two fatty acids was observed. Although further in vivo experiments are warranted to validate the current findings, our study provides a new insight into the role of lipids as antiviral compounds against the SARS-CoV-2 strain.
Genetik und Diagnostik des primären Lymphödems
Authors: Kemper Charlotte , Danyel Magdalena , Ott Claus-Eric , Hägerling René 
Published: March 2021

Zusammenfassung
Einleitung Das primäre Lymphödem ist eine genetisch bedingte, angeborene Erkrankung, die durch einen unzureichenden Abtransport von Lymphflüssigkeit aufgrund einer Fehlbildung oder Fehlfunktion des Lymphgefäßsystems entsteht. Dabei tragen periphere und systemische Manifestationen zum letztendlichen Phänotyp bei. Neben peripheren Manifestationen des primären Lymphödems, v. a. Schwellungen der unteren Extremität, können auch systemische Manifestationen, wie z. B. Aszites, intestinale und pleurale Lymphangiektasien, Chylothorax, Pleura- und Perikarderguss oder auch der Hydrops fetalis, auftreten. In Abhängigkeit vom ursächlichen Gen und der zugrunde liegenden genetischen Veränderung unterscheiden sich sowohl die klinischen Manifestationen als auch der Ausprägungsgrad des Lymphödems.
Klassifikation Die Krankheitsbilder, die mit einem primären Lymphödem einhergehen, lassen sich in 5 Kategorien aufteilen: (1) Erkrankungen, die mit einer segmentalen Wachstumsstörung assoziiert sind und auf einem somatischen Mosaik beruhen, (2) syndromale Erkrankungen, (3) Erkrankungen, bei denen das primäre Lymphödem eine systemische Beteiligung aufweist, (4) kongenitale Krankheitsbilder und (5) nach dem ersten Lebensjahr auftretende (Late Onset) Krankheitsbilder.
Genetische Diagnostik Basierend auf der Klinik des Patienten und der Zuordnung zu einer der 5 Kategorien kann eine zielgerichtete genetische Diagnostik erfolgen, zunächst beginnend mit einer konventionellen zytogenetischen Untersuchung (Chromosomenanalyse) sowie einer molekularzytogenetischen Methode (Array-CGH). Anschließend kann eine molekulargenetische Untersuchung im Rahmen von Einzelgenanalysen, Panel-Untersuchungen oder Exom- sowie Ganzgenomsequenzierung durchgeführt werden, durch die genetische Varianten oder Mutationen aufgedeckt werden können, die als kausal für die Symptomatik identifiziert werden können.
Fazit Betroffene eines primären Lymphödems profitieren von einer gezielten genetischen Diagnostik, da die verschiedenen Krankheitsbilder meistens nur durch die Detektion einer assoziierten genetischen Veränderung diagnostiziert werden können und somit eine Aussage über Vererbung und Wiederholungsrisiko möglich ist.
Tryptophan N
1-Alkylation: Quick and Simple Access to Diversely Substituted Tryptophans
Authors: Junk Lukas , Papadopoulos Emanuel , Kazmaier Uli 
Published: March 2021

AbstractThe diversification of amino acid sidechains is a major challenge in the synthesis and derivatization of peptides for pharmaceutical applications. We herein present a new protocol to alkylate the indole-nitrogen (N1) of N
α-protected tryptophans. This method provides quick and epimerization-free access to tryptophan derivatives, which can directly be incorporated into peptides. Depending on the functionalities introduced in the side chain, different options for the late-stage modification of peptides are possible.
Loop Ileostomy in Europe's Tiniest Male Newborn for Meconium-Related Ileus
Authors: Till Holger , Singer Georg , Castellani Christoph , Urlesberger Berndt 
Published: March 2021

AbstractWith the advances of neonatology, the survival rate for “live-born periviable fetuses” weighing < 300 g, a subgroup of extremely low birth weight (BW) infants, has improved over the past 10 years. Meconium-related ileus (MRI) represents an early postnatal hazard, and, if medical evacuation fails, a surgical challenge in such immature babies. We report the interdisciplinary management of surgically treated MRI in a newborn with a BW of 273 g. According to the worldwide database held by the University of Iowa, he is registered as the tiniest male newborn in Europe. The boy was born in the 25th gestational week by cesarean section after a triplet pregnancy with twin–twin transfusion syndrome, him being the donor. He had a BW of 273 g, whereas his brothers had a BW of 740 g and 722 g. Cardiopulmonary stabilization and ventilation were successful. He developed MRI unresponsive to medical treatment. On day 14 of life, a minilaparotomy was performed in the right lower quadrant to externalize a loop of the distal ileum in a no-touch technique. Despite the small diameter of only 2 mm, a standard loop ileostomy could be fashioned. There were no intra- or postoperative abdominal complications. Bowel function and weight gain were adequate and the ileostomy was closed electively 5 months later at a body weight of 3.5 kg.In summary, minilaparotomy and loop ileostomy placement were effective to treat surgical MRI in Europe's tiniest male newborn. With the advances of neonatology, pediatric surgery reaches new frontiers as well.
In Vitro Assessment of Cytoprotective Effects of CANOVA against Cell Death Induced by the Anti-malarial Artesunate – A Preliminary Experiment
Authors: Bonfim Laís Teixeira , Bahia Marcelo de Oliveira 
Published: March 2021

Abstract
Background Artesunate (ATS) is a semi-synthetic compound derived from artemisinin, which is widely accepted in the treatment of malaria. However, there is evidence that ATS, under certain in vitro conditions, induces several impairments to normal cell functions. Canova (CA) is a Brazilian homeopathic formulation indicated for patients with depressed immune system. CA shows both in vitro and in vivo protective effects against mutagenic/carcinogenic compounds. Therefore, we aimed to assess in vitro the cytoprotective effects of CA against the cytotoxicity of ATS in Vero cells.
Methods Viability of Vero cells exposed to ATS was assessed by MTT assay, whereas the anti-cytotoxic effect of CA was evaluated by apoptosis and necrosis quantification with fluorescent dyes.
Results After 24 hours of ATS treatment, a reduction in cell viability was observed at 32 and 64 µg/mL, the latter being statistically significant (p < 0.05) in relation to the negative control. The concentration of 64 µg/mL was chosen for the subsequent experiments. ATS significantly induced both apoptosis and necrosis in Vero cells in relation to controls (p < 0.01). We also observed a statistically significant decrease in the number of apoptotic cells observed in the CA 16% + ATS co-treatment compared with ATS treatment (p < 0.01). Treatment with CA alone also had no influence on either type of cell death.
Conclusion Our results demonstrated that ATS is cytotoxic in the assessed conditions. However, such cytotoxicity was attenuated when the cells were treated simultaneously with ATS and CA.
The Development and Piloting of the Ambulatory Electronic Health Record Evaluation Tool: Lessons Learned
Authors: Co Zoe , Holmgren A. Jay , Classen David C. , Newmark Lisa P. , Seger Diane L. , Cole Jessica M. , Pon Barbara , Zimmer Karen P. , Bates David W. 
Published: March 2021

Abstract
Background Substantial research has been performed about the impact of computerized physician order entry on medication safety in the inpatient setting; however, relatively little has been done in ambulatory care, where most medications are prescribed.
Objective To outline the development and piloting process of the Ambulatory Electronic Health Record (EHR) Evaluation Tool and to report the quantitative and qualitative results from the pilot.
Methods The Ambulatory EHR Evaluation Tool closely mirrors the inpatient version of the tool, which is administered by The Leapfrog Group. The tool was piloted with seven clinics in the United States, each using a different EHR. The tool consists of a medication safety test and a medication reconciliation module. For the medication test, clinics entered test patients and associated test orders into their EHR and recorded any decision support they received. An overall percentage score of unsafe orders detected, and order category scores were provided to clinics. For the medication reconciliation module, clinics demonstrated how their EHR electronically detected discrepancies between two medication lists.
Results For the medication safety test, the clinics correctly alerted on 54.6% of unsafe medication orders. Clinics scored highest in the drug allergy (100%) and drug–drug interaction (89.3%) categories. Lower scoring categories included drug age (39.3%) and therapeutic duplication (39.3%). None of the clinics alerted for the drug laboratory or drug monitoring orders. In the medication reconciliation module, three (42.8%) clinics had an EHR-based medication reconciliation function; however, only one of those clinics could demonstrate it during the pilot.
Conclusion Clinics struggled in areas of advanced decision support such as drug age, drug laboratory, and drub monitoring. Most clinics did not have an EHR-based medication reconciliation function and this process was dependent on accessing patients' medication lists. Wider use of this tool could improve outpatient medication safety and can inform vendors about areas of improvement.
Delayed Diagnosis of a Pyloric Web Causing Gastric Outlet Obstruction in a 13-Month-Old Girl
Authors: Elifranji Mohammed , Sankar Jisha , Abdelrasool Israa , Brisseau Guy 
Published: March 2021

AbstractPyloric web is a rare cause of gastric outlet obstruction. Classical pyloric web can be diagnosed by obtaining a patient history, physical examination, and plain abdominal X-ray, whereas a perforated web leads to incomplete intestinal obstruction. Delayed diagnosis is rare, and the definite diagnosis is made by upper endoscopy. In this report, we report a case of a girl in whom a pyloric web was diagnosed at the age of 13 months.
Centralization of Biliary Atresia: Has Germany Learned Its Lessons?
Authors: Madadi-Sanjani Omid , Fortmann David , Rolle Udo , Rodeck Burkhard , Sturm Ekkehard , Pfister Eva-Doreen , Kuebler Joachim F. , Baumann Ulrich , Schmittenbecher Peter , Petersen Claus 
Published: March 2021

AbstractIntroduction The majority of pediatric surgeons and hepatologists recommend the centralization of biliary atresia (BA) treatment within experienced liver units. We aimed to investigate whether voluntary self-restriction and acceptance of the need for this change in practice changed the BA referral policy in Germany during the last decade.Materials and Methods In cooperation with pediatric surgeons, gastroenterologists or hepatologists, and pediatric liver transplant units, the 2-year follow-up data of infants with BA born in Germany between 2010 and 2014 were collected using www.bard-online.com or pseudonymized data transfer. Results were compared with our previous analysis of the outcome data of infants with BA born between 2001 and 2005 in Germany.Result Overall, 173 infants with BA were identified, of whom 160 underwent Kasai portoenterostomy (KPE; 92.5%) and 13 (7.5%) underwent primary liver transplantation at 21 German centers. At 2-year follow-up, overall survival was 87.7% (vs. 81.9% in 2001–2005 [p = 0.19]), survival with native liver post-KPE was 29.2% (vs. 22.8% in 2001–2005 [p = 0.24]), and jaundice-free survival with native liver post-KPE was 24.0% (vs. 20.1% in 2001–2005 [p = 0.5]). Compared with the 2001–2005 analysis, all criteria showed improvement but the differences are statistically not significant.Conclusion Our observation shows that KPE management requires improvement in Germany. Centralization of BA patients to German reference liver units is not yet mandatory. However, European and national efforts with regard to the centralization of rare diseases support our common endeavor in this direction.