bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microsecond-timescale MD simulation of EGFR minor mutation predicts the structural flexibility of EGFR kinase core that reflects EGFR inhibitor sensitivity
Authors: Yoshizawa Takahiro , Uchibori Ken , Araki Mitsugu , Matsumoto Shigeyuki , Ma Biao , Kanada Ryo , Seto Yosuke , Oh-hara Tomoko , Koike Sumie , Ariyasu Ryo , Kitazono Satoru , Ninomiya Hironori , Takeuchi Kengo , Yanagitani Noriko , Takagi Satoshi , Kishi Kazuma , Fujita Naoya , Okuno Yasushi , Nishio Makoto , Katayama Ryohei 
Published: April 2021

AbstractApproximately 15–30% of patients with lung cancer harbor mutations in the EGFR gene. Major EGFR mutations (>90% of EGFR-mutated lung cancer) are highly sensitive to EGFR tyrosine kinase inhibitors (TKIs). Many uncommon EGFR mutations have been identified, but little is known regarding their characteristics, activation, and sensitivity to various EGFR-TKIs, including allosteric inhibitors. We encountered a case harboring an EGFR-L747P mutation, originally misdiagnosed with EGFR-del19 mutation using a routine diagnostic EGFR mutation test, which was resistant to EGFR-TKI gefitinib. Using this minor mutation and common EGFR-activating mutations, we performed the binding free energy calculations and microsecond-timescale molecular dynamic (MD) simulations, revealing that the L747P mutation considerably stabilizes the active conformation through a salt-bridge formation between K745 and E762. We further revealed why several EGFR inhibitors, including the allosteric inhibitor, were ineffective. Our computational structural analysis strategy would be beneficial for future drug development targeting the EGFR minor mutations.
1D metallic states at 2D transition metal dichalcogenide semiconductor heterojunctions
Authors: Krishnamurthi Sridevi , Brocks Geert 
Published: April 2021

AbstractTwo-dimensional (2D) lateral heterojunctions between different transition metal dichalcogenides (TMDCs) have been realized in recent years. Homogeneous semiconducting TMDC layers are characterized by a topological invariant, their in-plane electric polarization. It suggests the possibility of one-dimensional (1D) metallic states at heterojunctions where the value of the invariant changes. We study such lateral 2D TMDC junctions by means of first-principles calculations and show that 1D metallic states emerge even in cases where the different materials are joined epitaxially. We find that the metallicity does not depend on structural details, but, as the invariant is protected by spatial symmetry only, it can be upset by breaking the symmetry. Indeed, 1D charge- and spin-density wave instabilities appear spontaneously, making 2D TMDC heterojunctions ideal systems for studying 1D systems.
Superlubricity under ultrahigh contact pressure enabled by partially oxidized black phosphorus nanosheets
Authors: Ren Xiaoyong , Yang Xiao , Xie Guoxin , He Feng , Wang Rong , Zhang Chenhui , Guo Dan , Luo Jianbin 
Published: April 2021

AbstractSuperlubricity has recently raised an increasing interest owing to its great potential in energy saving and environmental benefits. Yet how to obtain stable superlubricity under an ultrahigh contact pressure (>1 GPa) still remains a challenge. Here, we demonstrate that robust liquid superlubricity can be realized even under a contact pressure of 1193 MPa by lubrication with partially oxidized black phosphorus (oBP) nanosheets. The analysis indicates that the oBP nanosheets that absorb large amounts of water molecules are retained at the friction interface and transform the friction pairs interface to that between the oBP nanosheets. Molecular dynamics simulation demonstrates that water molecules could be retained at the friction interface even under the ultrahigh contact pressure owing to the abundant P=O and P–OH bonds formed on the oBP nanosheet surfaces, contributing to the achievement of stable superlubricity under the ultrahigh contact pressure. This work has the potential of introducing the liquid superlubricity concept in diverse industrial applications involving high-contact-pressure operating conditions.
Using digital surveillance tools for near real-time mapping of the risk of infectious disease spread
Authors: Bhatia Sangeeta , Lassmann Britta , Cohn Emily , Desai Angel N. , Carrion Malwina , Kraemer Moritz U. G. , Herringer Mark , Brownstein John , Madoff Larry , Cori Anne , Nouvellet Pierre 
Published: April 2021

AbstractData from digital disease surveillance tools such as ProMED and HealthMap can complement the field surveillance during ongoing outbreaks. Our aim was to investigate the use of data collected through ProMED and HealthMap in real-time outbreak analysis. We developed a flexible statistical model to quantify spatial heterogeneity in the risk of spread of an outbreak and to forecast short term incidence trends. The model was applied retrospectively to data collected by ProMED and HealthMap during the 2013–2016 West African Ebola epidemic and for comparison, to WHO data. Using ProMED and HealthMap data, the model was able to robustly quantify the risk of disease spread 1–4 weeks in advance and for countries at risk of case importations, quantify where this risk comes from. Our study highlights that ProMED and HealthMap data could be used in real-time to quantify the spatial heterogeneity in risk of spread of an outbreak.
CryoET structures of immature HIV Gag reveal six-helix bundle
Authors: Mendonça Luiza , Sun Dapeng , Ning Jiying , Liu Jiwei , Kotecha Abhay , Olek Mateusz , Frosio Thomas , Fu Xiaofeng , Himes Benjamin A. , Kleinpeter Alex B. , Freed Eric O. , Zhou Jing , Aiken Christopher , Zhang Peijun 
Published: April 2021

AbstractGag is the HIV structural precursor protein which is cleaved by viral protease to produce mature infectious viruses. Gag is a polyprotein composed of MA (matrix), CA (capsid), SP1, NC (nucleocapsid), SP2 and p6 domains. SP1, together with the last eight residues of CA, have been hypothesized to form a six-helix bundle responsible for the higher-order multimerization of Gag necessary for HIV particle assembly. However, the structure of the complete six-helix bundle has been elusive. Here, we determined the structures of both Gag in vitro assemblies and Gag viral-like particles (VLPs) to 4.2 Å and 4.5 Å resolutions using cryo-electron tomography and subtomogram averaging by emClarity. A single amino acid mutation (T8I) in SP1 stabilizes the six-helix bundle, allowing to discern the entire CA-SP1 helix connecting to the NC domain. These structures provide a blueprint for future development of small molecule inhibitors that can lock SP1 in a stable helical conformation, interfere with virus maturation, and thus block HIV-1 infection.
Hydrogenation of benzoic acid derivatives over Pt/TiO2 under mild conditions
Authors: Guo Miao , Kong Xiangtao , Li Chunzhi , Yang Qihua 
Published: April 2021

AbstractHydrogenation of benzoic acid (BA) to cyclohexanecarboxylic acid (CCA) has important industrial and academic significance, however, the electron deficient aromatic ring and catalyst poisoning by carboxyl groups make BA hydrogenation a challenging transformation. Herein, we report that Pt/TiO2 is very effective for BA hydrogenation with, to our knowledge, a record TOF of 4490 h−1 at 80 °C and 50 bar H2, one order higher than previously reported results. Pt/TiO2 catalysts with electron-deficient and electron-enriched Pt sites are obtained by modifying the electron transfer direction between Pt and TiO2. Electron-deficient Pt sites interact with BA more strongly than electron-rich Pt sites, helping the dissociated H of the carboxyl group to participate in BA hydrogenation, thus enhancing its activity. The wide substrate scope, including bi- and tri-benzoic acids, further demonstrates the high efficiency of Pt/TiO2 for hydrogenation of BA derivatives.
Chronisch-venöse Insuffizienz
Authors: Stern Apothekerin Cornelia , Vigl Sebastian , Heilmann-Wagner Krankenpflegerin Elke , Corts Magga 
Published: April 2021

SummaryVier Experten stellen die Behandlung von chronisch-venöser Insuffizient mithilfe von Gemmotherapie, Wickel/Auflagen/Kneipp-Anwendungen und Osteopathie vor.
Update: Bareinnahmen in der Heilpraktikerpraxis
Authors: Geweke Uwe 
Published: April 2021

SummaryAufgrund steuerrechtlicher Änderungen in den Jahren 2017 und 2020 gelten bei der Erfassung von Bareinnahmen und der Kassenführung neue Vorschriften. Sie betreffen insbesondere die Einzelaufzeichnungspflicht für Bareinnahmen, die Kassen-Nachschau und technische Sicherheitseinrichtungen für elektronische beziehungsweise digitale Kassensysteme. Viele Heilpraktiker nutzen die sogenannte offene Ladenkasse. Hier empfiehlt sich zusätzlich zur Einzelaufzeichnung ein Kassenbericht.
Rotes-Skrotum-Syndrom – Übersicht und Fallbeispiel
Authors: Moll I. 
Published: April 2021

ZusammenfassungDas Rote-Skrotum-Syndrom (RSS) ist ein chronisches Erythem der Ventralseite des Skrotums, das scharf umschrieben ist und typischerweise weder Exkoriationen noch Lichenifizierung oder Schuppung aufweist. Es verursacht rezidivierend brennende und ziehende Schmerzen, aber keinen Juckreiz. Es ist selten und betrifft meist ältere Männer. Die Ursachen des RSS sind unklar. Diskutiert werden neurogene Entzündungen, Formen der Erythromelalgie, Rosacea erythematosa oder eine Hypervaskularisation. Ebenso existiert keine etablierte Therapie. Verschiedene topische Therapien, insbesondere Steroide, führen häufig zu Verschlechterungen. Vorsichtig können PEA, Calcineurin-Inhibitoren und pflegende wasserreiche Cremes versucht werden. An systemischen Therapien kommen NSAIDs zur Linderung der Schmerzen, Doxycyclin, Metronidazol, Steroide, Penicillin oder Antihistaminika in Betracht, bei ausbleibender Besserung daneben Gabapentin, Pregabalin, Amitryptilin oder Carvediol. Die Differenzialdiagnosen umfassen generalisierte und lokalisierte Dermatosen.
Hochbelastete Gruppen pflegender Angehöriger – Ergebnisse einer Clusteranalyse
Authors: Bohnet-Joschko Sabine , Bidenko Katharina 
Published: April 2021

Abstract
Ziel Ziel der vorliegenden Studie ist die Untersuchung von unterschiedlichen häuslichen Pflegesituationen und die Identifizierung von Gruppen pflegender Angehöriger mit erhöhten gesundheitlichen und finanziellen Belastungen.
Methodik Die Datenerhebung erfolgte mittels einer schriftlichen Befragung von 1429 pflegenden Angehörigen. Als pflegende Angehörige wurden Familienangehörige, Freunde oder Nachbarn definiert, die eine hilfebedürftige Person versorgen. Die Gruppenbildung erfolgte mittels Clusteranalyse. Gruppenunterschiede wurden auf statistische Signifikanz mittels Chi-Quadrat-Test und Varianzanalyse geprüft.
Ergebnisse Es konnten fünf Gruppen von pflegenden Angehörigen anhand ihrer Tätigkeiten in der Pflege identifiziert werden. Die Gruppen sind sowohl durch die Pflegesituation (Verhältnis zu Hilfebedürftigen, zeitlicher Aufwand und Dauer der Pflege) als auch durch soziodemografische Faktoren (Geschlecht, Alter und Erwerbstätigkeit) charakterisiert. Die Gruppen unterscheiden sich bei der Wahrnehmung von mit der Pflegesituation verbundenen Belastungen. Während emotionale Belastung in nahezu allen Gruppen hoch ist, berichteten Angehörige, die täglich grundpflegerische Versorgung leisten, von hoher physischer Belastung und Angehörige, die durchgehend Langzeitpflege erbringen, von hoher finanzieller Belastung.
Schlussfolgerung Pflegende Angehörige sind keine homogene Gruppe. Sie übernehmen unterschiedliche Rollen und sind verschiedenen gesundheitlichen und finanziellen Belastungen ausgesetzt. Die vorgestellte Typologie unterstützt Kassen und Gebietskörperschaften bei der Entwicklung und Vermittlung wirksamer Unterstützungsangebote für hochbelastete Gruppen pflegender Angehöriger.
COVID-19-bedingte Kontaktbeschränkungen in Deutschland und Veränderungen der körperlichen Aktivität
Authors: Tschuschke Lara , Schröder Jan 
Published: April 2021

Zusammenfassung
Hintergrund und Ziel der Arbeit Internationale Befunde berichten über die Abnahme der körperlichen Aktivität durch die häuslichen COVID-19-Isolationen. Eine Übertragung auf die deutsche Bevölkerung ist bei weltweit unterschiedlichen Beschränkungen nur bedingt möglich. Ziel der vorliegenden Arbeit war es, mögliche Veränderungen der körperlichen Aktivität in der deutschen Bevölkerung aufgrund der ersten Phase der deutschlandweiten Kontaktbeschränkungen im Frühjahr 2020 während der COVID-19-Pandemie zu ermitteln.
Methodik Die körperliche Aktivität wurde mithilfe des Global Physical Activity Questionnaire erfasst (April bis Mai 2020). 282 Fragebögen wurden Chi²-basiert ausgewertet (65,2 % weiblich; Alter 18 – 64 [33 ± 14] Jahre; BMI 16,9-42,8 [23,5 ± 3,9] kg / m²) und mit Daten einer deutschen Referenzpopulation (n = 2.248, 52 % Frauen) aus dem Jahr 2012 retrospektiv verglichen.
Ergebnisse Während der Kontaktbeschränkungen im Frühjahr 2020 waren adipöse Personen überproportional inaktiv (Chi²[4; 282] = 15,58; p = 0,004). Im Vergleich mit Daten aus 2012 erwiesen sich die Adipösen (BMI ≥ 30, n = 19) während der Kontaktbeschränkungen als noch weniger aktiv als ohne Kontaktbeschränkungen (Chi²[2, 317] = 7,51; p = 0,02), während weder für die Gesamtkohorten (Chi²[2, 2512] = 2,95; p = 0,23), noch für weitere BMI- oder Altersgruppen signifikante Unterschiede vorlagen (p > 0,05).
Schlussfolgerungen Die vorliegenden Daten legen trotz geringer Fallzahlen nahe, dass insbesondere übergewichtige Personen mit ohnehin vermehrten inaktivitätsassoziierten gesundheitlichen Risiken durch die COVID-19-Kontaktbeschränkungen häufiger als zuvor eine geringe körperliche Aktivität aufwiesen. Weiterführende Untersuchungen sollten mit größeren repräsentativ erhobenen Fallzahlen detailliert die tatsächlich durchgeführte körperliche Aktivität erfassen.
Perforation and post-polypectomy bleeding complicating colonoscopy in a population-based screening program
Authors: Paszat Lawrence F. , Sutradhar Rinku , Luo Jin , Rabeneck Linda , Tinmouth Jill 
Published: April 2021

Abstract
Background and study aims We aimed to estimate the rate of hospital admissions for perforation and for post-polypectomy bleeding, after outpatient colonoscopy following a first positive fecal occult blood test screen through the population-based ColonCancerCheck program in Ontario, Canada.
Patients and methods We identified all individuals aged 50 to 74 years with a first positive CCC gFOBT screening result from 2008 to 2017 who underwent outpatient colonoscopy ≤ 6 months later and who did not receive a diagnosis of CRC ≤ 24 months later. We identified inpatient hospital admissions for colonic perforation ≤ 7 days after and for post-polypectomy bleeding ≤ 14 days following colonoscopy.
Results Among 121,626 individuals who underwent colonoscopy, the rate of perforation was 0.6 per 1000 from 2008 to 2012 and 0.4 per 1000 from 2013 to 2017. The rate was elevated among those aged 70 to 74 years; those with comorbidities; when colonoscopy was performed by endoscopists other than gastroenterologists or endoscopists with low prior year volume; and when polypectomy was performed during colonoscopy. The rate of bleeding was 4.3 per 1000 and was elevated among those aged 70 to 74 years, those with comorbidity, and with complex polypectomy. Both outcomes were more common among those aged 70 to 74 years, those with a 5-year cumulative Charlson score ≥ 1, those with prior hospitalization for ischemic heart disease, and those with endoscopists whose prior year colonoscopy volume was in the three lower quartiles.
Conclusions Colonic perforation and post-polypectomy bleeding, among participants of population-based colorectal screening programs who test positive in the absence of colorectal cancer, are infrequent but serious complications, which increase with participant age and comorbidity, and with endoscopist characteristics.
Platelets and Matrix Metalloproteinases: A Bidirectional Interaction with Multiple Pathophysiologic Implications
Authors: Gresele P. , Falcinelli E. , Momi S. , Petito E. , Sebastiano M. 
Published: April 2021

AbstractPlatelets contain and release several matrix metalloproteinases (MMPs), a highly conserved protein family with multiple functions in organism defense and repair. Platelet-released MMPs as well as MMPs generated by other cells within the cardiovascular system modulate platelet function in health and disease. In particular, a normal hemostatic platelet response to vessel wall injury may be transformed into pathological thrombus formation by platelet-released and/or by locally generated MMPs. However, it is becoming increasingly clear that platelets play a role not only in hemostasis but also in immune response, inflammation and allergy, atherosclerosis, and cancer development, and MMPs seem to contribute importantly to this role. A deeper understanding of these mechanisms may open the way to novel therapeutic approaches to the inhibition of their pathogenic effects and lead to significant advances in the treatment of cardiovascular, inflammatory, and neoplastic disorders.
Operieren in der Schwangerschaft – ein Tabu?
Authors: Necknig Ulrike Hendrika , Arnold Hannah , von Ostau Nicola 
Published: April 2021

ZusammenfassungMit Bekanntgabe einer Schwangerschaft ändert sich der Berufsalltag für betroffene Urologinnen erheblich. Aus Sorge vor rechtlichen Konsequenzen dürfen schwangere Mitarbeiter nach wie vor kaum operieren. Dabei schließt die Neuregelung des Mutterschutzgesetzes das Arbeiten und Operieren von schwangeren Urologinnen nicht grundsätzlich aus. Wieso leisten sich Kliniken dennoch einen solchen Missstand, der den Arbeitsalltag gefährdet und die Weiterbildung von schwangeren Urologinnen erschwert?
Recent Trends in Patient Registries for Health Services Research
Authors: Stausberg Jürgen , Harkener Sonja , Semler Sebastian C. 
Published: April 2021

Abstract
Background Patient registries are an established methodology in health services research. Since more than 150 years, registries collect information concerning groups of similar patients to answer research questions. Elaborated recommendations about an appropriate development and an efficient operation of registries are available. However, the scene changes rapidly.
Objectives The aim of the study is to describe current trends in registry research for health services research.
Methods Registries developed within a German funding scheme for model registries in health services research were analyzed. The observations were compared with recent recommendations of the Agency for Healthcare Research and Quality (AHRQ) on registries in the 21st century.
Results Analyzing six registries from the funding scheme revealed the following trends: recruiting healthy individuals, representing familial or other interpersonal relationships, recording of patient-reported experiences or outcomes, accepting participants as study sites, active informing of participants, integrating the registry with other data collections, and transferring data from the registry to electronic patient records. This list partly complies with the issues discussed by the AHRQ. The AHRQ structured its ideas in five chapters, increasing focus on the patient, engaging patients as partners, digital health and patient registries, direct-to-patient registry, and registry networks.
Conclusion For the near future, it can be said that the concept and the design of a registry should place the patient in the center. Registries will be increasingly linked together and interconnected with other data collections. New challenges arise regarding the management of data quality and the interpretation of results from less controlled settings. Here, further research related to the methodology of registries is needed.
Self-Report Hearing and Injury or Falls in Older Adults from the National Health and Information Survey
Authors: Powell Danielle S. , Morales Emmanuel E. Garcia , Pletnikova Sasha , Deal Jennifer A. , Reed Nicholas S. 
Published: April 2021

AbstractThis article aims to investigate the association between hearing and nonfatal injury or falls in a nationally representative sample of adults from the National Health Interview Survey (NHIS) utilizing over 20 years of participant surveys. We conducted a pooled cross-sectional analysis of participant surveys (aged 50 years and older) from 1997 to 2017. Self-report hearing difficulty, history of injury over the last 3 months, reported injury from fall over the last 3 months, and reported reason for fall (including due to balance/dizziness) were collected. Using logistic regression, we investigated the odds of injury, injury from fall, and fall due to balance/dizziness by self-report hearing status. In secondary analysis, we investigated the odds of each outcome by reported hearing aid use. Models were adjusted for demographics, year of study, vision difficulty, diabetes, employment, and cardiovascular disease. Reported moderate or greater difficulty hearing demonstrated a significantly greater odds of injury (odds ratio [OR]: 1.29; 95% confidence interval [CI]: 1.18, 1.42) or fall due to balance/dizziness (OR: 1.26; 95% CI: 1.00, 1.60) compared with reported excellent/good hearing. A dose–response association was seen across levels of reported difficulty hearing for all outcomes. In this nationally representative study of adults aged 50 years and older, greater reported difficulty hearing was significantly associated with increased odds of injury and suggests greater odds of falls or fall due to balance/dizziness compared with reported good hearing. Results suggest hearing loss should be considered as a possible risk factor for both injury and fall prevention studies and programming in older adults.
Processing variables of direct-write, near-field electrospinning impact size and morphology of gelatin fibers
Authors: Davis Zachary G , Hussain Aasim F , Fisher Matthew B 
Published: April 2021

AbstractSeveral biofabrication methods are being investigated to produce scaffolds that can replicate the structure of the extracellular matrix. Direct-write, near-field electrospinning of polymer solutions and electrowriting of polymer melts are methods which combine fine fiber formation with computer-guided control. Research with such systems has focused primarily on synthetic polymers. To better understand the behavior of biopolymers used for direct-writing, this project investigated changes in fiber morphology, size, and variability caused by varying gelatin and acetic acid concentration, as well as process parameters such as needle gauge and height, stage speed, and interfiber spacing. Increasing gelatin concentration at a constant acetic acid concentration improved fiber morphology from large, planar structures to small, linear fibers with a median of 2.3 µm. Further varying the acetic acid concentration at a constant gelatin concentration did not alter fiber morphology and diameter throughout the range tested. Varying needle gauge and height further improved the median fiber diameter to below 2 µm and variability of the first and third quartiles to within ±1 µm of the median. Additional adjustment of stage speed did not impact the fiber morphology or diameter. Repeatable interfiber spacings down to 250 µm were shown to be capable with the system. In summary, this study illustrates the optimization of processing parameters for direct-writing of gelatin to produce fibers on the scale of collagen fibers. This system is thus capable of replicating the fibrous structure of musculoskeletal tissues with biologically relevant materials which will provide a durable platform for the analysis of single cell-fiber interactions to help better understand the impact scaffold materials and dimensions have on cell behavior.