bluuebunny/crossref_metadata_2025_split huggingface dataset:
Data-driven design of targeted gene panels for estimating immunotherapy biomarkers
Authors: Bradley Jacob R. , Cannings Timothy I. 
Published: February 2022

AbstractTumour mutation burden and other exome-wide biomarkers are used to determine which patients will benefit from immunotherapy. However, the cost of whole exome sequencing limits the widespread use of such biomarkers. Here, we introduce a data-driven framework for the design of targeted gene panels for estimating a broad class of biomarkers including tumour mutation burden and tumour indel burden. Our first goal is to develop a generative model for the profile of mutation across the exome, which allows for gene- and variant type-dependent mutation rates. Based on this model, we then propose a procedure for constructing biomarker estimators. Our approach allows the practitioner to select a targeted gene panel of prespecified size and construct an estimator that only depends on the selected genes. Alternatively, our method may be applied to make predictions based on an existing gene panel, or to augment a gene panel to a given size. We demonstrate the excellent performance of our proposal using data from three non small-cell lung cancer studies, as well as data from six other cancer types.
Combination of antiviral drugs inhibits SARS-CoV-2 polymerase and exonuclease and demonstrates COVID-19 therapeutic potential in viral cell culture
Authors: Wang Xuanting , Sacramento Carolina Q. , Jockusch Steffen , Chaves Otávio Augusto , Tao Chuanjuan , Fintelman-Rodrigues Natalia , Chien Minchen , Temerozo Jairo R. , Li Xiaoxu , Kumar Shiv , Xie Wei , Patel Dinshaw J. , Meyer Cindy , Garzia Aitor , Tuschl Thomas , Bozza Patrícia T. , Russo James J. , Souza Thiago Moreno L. , Ju Jingyue 
Published: February 2022

AbstractSARS-CoV-2 has an exonuclease-based proofreader, which removes nucleotide inhibitors such as Remdesivir that are incorporated into the viral RNA during replication, reducing the efficacy of these drugs for treating COVID-19. Combinations of inhibitors of both the viral RNA-dependent RNA polymerase and the exonuclease could overcome this deficiency. Here we report the identification of hepatitis C virus NS5A inhibitors Pibrentasvir and Ombitasvir as SARS-CoV-2 exonuclease inhibitors. In the presence of Pibrentasvir, RNAs terminated with the active forms of the prodrugs Sofosbuvir, Remdesivir, Favipiravir, Molnupiravir and AT-527 were largely protected from excision by the exonuclease, while in the absence of Pibrentasvir, there was rapid excision. Due to its unique structure, Tenofovir-terminated RNA was highly resistant to exonuclease excision even in the absence of Pibrentasvir. Viral cell culture studies also demonstrate significant synergy using this combination strategy. This study supports the use of combination drugs that inhibit both the SARS-CoV-2 polymerase and exonuclease for effective COVID-19 treatment.
A comprehensive design approach for a three‐winding planar transformer
Authors: Zou Shenli , Singhabahu Chanaka , Chen Jianfei , Khaligh Alireza 
Published: February 2022

AbstractIn this paper, a new three‐winding planar transformer design with the integrated leakage inductor is proposed for a triple‐active‐bridge converter. It enables two output voltage levels: a high voltage (HV) output port and a low voltage (LV) output port. The primary and secondary windings are split unevenly in both side legs while the tertiary winding is connected in parallel. The unique winding configuration enables: (i) enhanced efficiency with low volume; and (ii) suppressed parasitic capacitances. Detailed transformer reluctance and loss models are developed in the design process. The core geometry is optimized using a reluctance‐model‐based mathematical computation. Moreover, comprehensive high‐fidelity simulations are conducted to analyse the trade‐offs among parasitic capacitances, losses, and inductances. The customized core and the non‐overlapping winding boards are assembled, characterized, and tested under various power flow conditions.
Responding trends of ionosphericF2-layer to weaker geomagnetic activities
Authors: Chen Yiding , Liu Libo , Le Huijun , Zhang Hui , Zhang Ruilong 
Published: February 2022

Geomagnetic activities frequently occur in varying degrees. Strong geomagnetic activities, which have been widely investigated, occur occasionally; they can cause distinguishable and significant disturbances in the ionosphere. Weaker geomagnetic activities frequently appear, whereas their effects are generally difficult to be distinguished from complex ionospheric variations. Weaker geomagnetic activities play important roles in ionospheric day-to-day variability thus should deserve further attention. In this study, long-term (longer than one solar cycle) measurements of theF2-layer critical frequency (foF2) were collected to statistically investigate ionospheric responses to weaker geomagnetic activities (Ap < 60). The responding trends of low- to high-latitudefoF2to increasing geomagnetic activity are presented for the first time; they are statistically evident. Both increasing and decreasing trends can occur, depending on latitudes and seasons. The trend gradually transits from high-latitude decreasing trends to equatorial increasing trends with decreasing latitude, and this transition is seasonally dependent. As a result, the trend has a seasonal difference at mid-latitudes. The responding trend is generally more distinct at higher latitudes and in the equatorial region than at mid-latitudes, and the responding intensity is largest at higher latitudes. Although theoretically, geomagnetic activities can disturb the ionosphere through multiple mechanisms, the morphology of the trend suggests that the frequent weaker geomagnetic activities modulate the high- to low-latitude ionosphere mainly through disturbing high-latitude thermospheric composition and further altering the thermospheric background circulation.
Akute Schwellung im Halsbereich nach iodhaltigem Kontrastmittel – der oft unerkannte Iodmumps anhand von drei Fallbeispielen
Authors: Bircher Andreas J. , Hofmeier Kathrin Scherer 
Published: February 2022

ZusammenfassungEs werden drei Patientinnen vorgestellt, die zur Abklärung einer akuten Halsschwellung nach einer Untersuchung mit iodierten Kontrastmitteln zugewiesen wurden. Bei allen drei war ein akutes Angioödem vermutet worden, das allerdings nicht ausreichend auf Antihistaminika und Kortikosteroide ansprach. Es wurde schließlich ein sog. „Iodmumps“ oder Iod-assoziierte Sialoadenopathie diagnostiziert. Sonografisch und histologisch finden sich lediglich ein Ödem der Speicheldrüsen, hingegen keine Hinweise für eine ausgeprägte entzündliche Reaktion. Diese Komplikation ist nicht so selten und wird von Iod selbst ausgelöst, wie mit einer Provokation mit Iod-Kaliumiodid (Lugolʼscher Lösung) nachgewiesen werden konnte. Die pathophysiologisch ungeklärte Iod-assoziierte Sialoadenopathie wird somit als idiosynkratische Reaktion klassifiziert.
An Update on Safe Anticoagulation
Authors: Mailer Reiner K. , Kuta Piotr , Renné Thomas 
Published: February 2022

AbstractBlood coagulation is essential to maintain the integrity of a closed circulatory system (hemostasis), but also contributes to thromboembolic occlusion of vessels (thrombosis). Thrombosis may cause deep vein thrombosis, pulmonary embolism, myocardial infarction, peripheral artery disease, and ischemic stroke, collectively the most common causes of death and disability in the developed world. Treatment for the prevention of thromboembolic diseases using anticoagulants such as heparin, coumarins, thrombin inhibitors, or antiplatelet drugs increase the risk of bleeding and are associated with an increase in potentially life-threatening hemorrhage, partially offsetting the benefits of reduced coagulation. Thus, drug development aiming at novel targets is needed to provide efficient and safe anticoagulation. Within the last decade, experimental and preclinical data have shown that some coagulation mechanisms principally differ in thrombosis and hemostasis. The plasma contact system protein factors XII and XI, high-molecular-weight kininogen, and plasma kallikrein specifically contribute to thrombosis, however, have minor, if any, role in hemostatic coagulation mechanisms. Inherited deficiency in contact system proteins is not associated with increased bleeding in humans and animal models. Therefore, targeting contact system proteins provides the exciting opportunity to interfere specifically with thromboembolic diseases without increasing the bleeding risk. Recent studies that investigated pharmacologic inhibition of contact system proteins have shown that this approach provides efficient and safe thrombo-protection that in contrast to classical anticoagulants is not associated with increased bleeding risk. This review summarizes therapeutic and conceptual developments for selective interference with pathological thrombus formation, while sparing physiologic hemostasis, that enables safe anticoagulation treatment.
Verkürzte Therapiekonzepte im Maßregelvollzug
gemäß §64 StGB: Ein maßgeschneiderter
Behandlungspfad?
Authors: Praus Peter , Biebinger Eva , Bepler Ralf , Kubath-Heimann Sylvia , Funk Beate , Dreßing Harald 
Published: February 2022

ZusammenfassungDie forensische Therapie gemäß §64 StGB zeichnet sich
aktuell durch hohe Abbruch- bzw. Erledigungsquoten aus. Das hier vorgestellte
verkürzte Therapiekonzept der Klinik für Forensische Psychiatrie
des Pfalzklinikums für Patienten mit günstigen Prognosemerkmalen
soll durch Förderung von Eigeninitiative, Verantwortung und Motivation
sowie eine möglichst individualisierte, störungsorientierte,
strafzeit- und tatangemessene Behandlung mit intensiver Erprobung unter
Alltagsbedingungen zu einer Verkürzung der stationären
Unterbringung führen. Empirische Belege hierfür fehlen jedoch
bislang. Erstmals werden hier Pilotdaten aus dem Zeitraum April 2016 bis Mai
2021 vorgestellt. Zusammenfassend hat sich das o.g. Konzept als umsetzbar
erwiesen. Die erhobenen Daten weisen darauf hin, dass die im verkürzten
Therapieprogramm behandelten Patienten eine geringere Erledigungsquote als der
Durchschnitt aller gemäß §64 StGB untergebrachter
Patienten aufweist. Eine deutliche Verkürzung der durchschnittlichen
Behandlungsdauer ließ sich demgegenüber jedoch nicht belegen.
Die vorliegende Arbeit will einen ersten Beitrag zur Diskussion und
Weiterentwicklung derartiger Behandlungsoptionen leisten. Mögliche
Nachteile derartiger Therapieangebote bei für ungeeignet befundenen
Patienten, z. B. eine Abnahme der Therapiemotivation, werden
diskutiert.
Rescue Extracranial–Intracranial Bypass for Ischemic Stroke Secondary to Progressive Human Immunodeficiency Virus–Associated Vasculopathy
Authors: Mizushima Makoto , Sugiyama Taku , Eguchi Katsuki , Tarisawa Monami , Tokairin Kikutaro , Ito Masaki , Hashimoto Daigo , Yabe Ichiro , Fujimura Miki 
Published: February 2022

Abstract
Background Human immunodeficiency virus (HIV) associated vasculopathy can cause ischemic cerebral stroke; however, there is limited evidence on optimal management. Herein, we report a case of acute ischemic stroke due to progressive internal carotid artery (ICA) stenosis in an HIV-positive patient. Superficial temporal artery to middle cerebral artery (STA-MCA) bypass, in addition to the best medical treatments, prevented stroke progression.
Clinical Description A 39-year-old man with HIV infection presented with a sudden onset of aphasia and right hemiparesis. Magnetic resonance imaging revealed an ischemic lesion in the left basal ganglia and concentric thickening of the vessel wall in the terminal portion of the bilateral ICAs. Despite maximal medical treatments for HIV-associated vasculopathy and possible opportunistic infections, bilateral ICA stenoses progressed, leading to a second hemodynamic stroke event. Because tissue plasminogen activator treatment failed, we performed STA-MCA bypass. A significant improvement in neurologic symptoms and cerebral blood flow was observed after surgery. No further stroke events occurred during the continuation of medical treatments.
Conclusion This is the first case of STA-MCA bypass performed in a patient with recurrent ischemic stroke caused by HIV-associated vasculopathy. Although further evidence is needed, such treatment options can shed new light on the management of progressive HIV-associated vasculopathy, which is refractory to maximal medical treatment.
Catalytic Enantioselective Synthesis of C–N Atropisomeric Heterobiaryls
Authors: Knipe Peter C. , Sweet Jamie S. 
Published: February 2022

AbstractMolecules containing an atropisomeric C–N biaryl axis are gaining increasing attention in catalytic and medicinal chemistry. Despite this rising interest, relatively few approaches towards their catalytic enantioselective synthesis have been reported. Here we review these approaches, with a focus on the mechanism of asymmetric induction. Some common themes emerge: Brønsted acid catalysed cyclo-condensation and palladium-catalysed ring-closure are the most common and successful approaches. Meanwhile, the more direct but challenging axial C–N bond formation strategy remains in its infancy, with just two reports to-date. We hope this review will inform and inspire other researchers to develop new creative approaches to this important chemical motif.1	Introduction2	Cyclo-Condensation3	Proximal C–N Bond Formation4	Desymmetrisation of Intact Axes5	ortho-C–H Functionalisation6	Cycloaddition7	Axial C–N Bond Formation8	Atropisomeric N–N Axes: An Emerging Class of Heterobiaryls9	Conclusion and Outlook
Cross-Cultural Adaptation, Validation, and Arabic Translation of the Eustachian Tube Dysfunction Questionnaire (ETDQ-7)
Authors: Alkholaiwi Feras , Alnatheer Abdullah M. , Theyab Rami Saud , Alyousef Meshal , Aldrees Turki , Dahmash Abdulmajeed Bin , Alghonaim Yazeed 
Published: February 2022

Abstract
Introduction The Eustachian Tube Dysfunction Patient Questionnaire (ETDQ-7) scale is used to assess the effectiveness of the treatment and to determine the severity of the eustachian tube dysfunction (ETD). There is currently no validated Arabic version of the ETDQ-7.
Objectives The aim of the present study is to test the validity and the reliability of a translated Arabic version of the ETDQ-7.
Methods A multicenter prospective validation study was conducted in Riyadh, Saudi Arabia. The ETDQ-7 was adapted and translated into Arabic using a standard validation methodology. Fifty-one patients diagnosed with Eustachian tube dysfunction and 45 healthy individuals were enrolled in the study. The known-groups method was used in the validity analysis. The test-retest method, item-total score correlation, and internal consistency analysis were used for the reliability analyses.
Result The overall internal consistency of the Arabic ETDQ items was measured using Cronbach α (Cronbach α = 0.803). The average and total ETDQ scores were significantly higher in the ETD group (17.6) than in the control group (9.87) (p < 0.001). The results indicate a good to excellent correlation (> 0.7). The area under the curve for the total ETDQ score was 88.6% (95% confidence interval [CI]: 80.3–96.8%)
Conclusion The Arabic version of the ETDQ-7 scale is a valid instrument for evaluating ETD. It can also be used as an important tool for diagnosis, patient follow-up, and treatment management.
Molecular Characterization of High-Level Aminoglycoside Resistance among Enterococcus Species
Authors: Manoharan Harish , Lalitha Aishwarya K.V. , Mariappan Shanthi , Sekar Uma , Venkataramana Geetha P. 
Published: February 2022

Abstract
Background Enterococci are nosocomial pathogen. They can develop high-level resistance to aminoglycoside by producing aminoglycoside modifying enzymes (AMEs). In enterococci, high level resistance to aminoglycosides is mediated by acquisition of plasmid mediated genes encoding for aminoglycoside modifying enzymes (AMEs). High level gentamicin resistance (MIC ≥ 500μg /mL) is predominantly mediated by aac(6′)-Ie-aph(2″)-Ia, encoding the bifunctional aminoglycoside modifying enzyme AAC(6′)-APH(2″). This enzyme eliminates the synergistic activity of gentamicin when combined with a cell wall active agent. Other AME genes such as aph(2″)-Ib, aph(2″)-Ic, aph(2″)-Id and ant(4′)-1a have also been detected in enterococci.
Objective This study was carried out to determine the diverse prevalence of AME and their pattern of occurrence in the clinical isolates of Enterococci.
Materials and Methods A total number of 150 clinical isolates were included in this study. Susceptibility to various antibiotics was determined by disc diffusion. Minimum Inhibitory Concentration (MIC) was ascertained by agar dilution method. Polymerase chain reaction was done to screen the following AMEs (aac(6′)-Ie-aph(2″)-Ia; aph(2″)-Ib; aph(2″)-Ic; aph(2″)-Id and aph(3′)- IIIa genes).
Results 51.3% of the study isolates exhibited high level gentamicin resistance. Polymerase chain reaction revealed that aph(3′)-111a is the most prevalent AME, followed by aac(6′)-1e-aph(2″)-1a. The combination of both the genes were detected in 44.1% of the study isolates. The rest of the AMEs and their combinations were not encountered in this study. 8.6% of the study isolates did not harbour any AME genes screened for, but was phenotypically resistant to gentamicin. In contrast 31.3% anchored the AME genes but phenotypically appeared susceptible to gentamicin.
Conclusion This study indicates the high- level aminoglycoside resistance disseminated among Enterococci in our geographical region. It also emphasizes the detection of AMEs by PCR is mandatory because strains that appear susceptible by disc diffusion and/or MIC method may harbour one or more AMEs genes leading to therapeutic failure.
Elevated shear rate‐induced by exercise increases eNOS ser1177 but not PECAM‐1 Tyr713 phosphorylation in human conduit artery endothelial cells
Authors: Tryfonos Andrea , Rasoul Debar , Sadler Daniel , Shelley James , Mills Joseph , Green Daniel J. , Dawson Ellen A. , Cocks Matthew 
Published: February 2022

ABSTRACTAlthough evidence demonstrates the fundamental role of shear stress in vascular health, predominantly through the release of nitric oxide (NO), the mechanisms by which endothelial cells (EC)s sense and transduce shear are poorly understood. In cultured ECs tyrosine phosphorylation of PECAM‐1 has been shown to activate eNOS in response to shear stress. However, in the human skeletal muscle microcirculation PECAM‐1 was not activated in response to exercise or passive leg movement. Given this contradiction, this study aimed to assess the effect of exercise on conduit artery PECAM‐1 and eNOS activation in humans. Eleven males were randomised to two groups; 30 min of handgrip exercise (n = 6), or a time‐control group (n = 5). Protein content of eNOS and PECAM‐1, alongside eNOS Ser1177 and PECAM‐1 Tyr713 phosphorylation were assessed in ECs obtained from the radial artery pre‐ and post‐intervention. Handgrip exercise resulted in a 5‐fold increase in mean shear rate in the exercise group, with no change in the control group (group*time, P < 0.001). There was a 54% increase in eNOS Ser1177 phosphorylation in the exercise group, when compared to control group (group*time, P = 0.016), but no change was reported in PECAM‐1 Tyr713 phosphorylation in either group (group*time, P > 0.05). eNOS and PECAM‐1 protein content were unchanged (group*time, P > 0.05). Our data show that exercise‐induced elevations in conduit artery shear rate increase eNOS Ser1177 phosphorylation but not PECAM‐1 Tyr713 phosphorylation. This suggests PECAM‐1 phosphorylation may not be involved in the vascular response to acute but prolonged elevations in exercise‐induced shear rate in conduit arteries of healthy, active men.
Analysis of correlations in strong field ionization
Authors: Ivanov I A , Kim Kyung Taec 
Published: February 2022

Abstract
We propose to use correlation function analysis as a tool for the study of strong field ionization. We show, in particular, that study of the correlations of electron’s coordinate and velocity reveals patterns which can be naturally interpreted as manifestations of the electron’s exit point (the spatial point where the electron exits the tunneling barrier). This analysis provides an unambiguous definition of the exit point. The location of the exit point thus determined agrees well with the estimates used in the semiclassical simulations.
Chemically imaging nanostructures formed by the covalent assembly of molecular building blocks on a surface with ultrahigh vacuum tip-enhanced Raman spectroscopy
Authors: Schultz Jeremy F , Li Linfei , Mahapatra Sayantan , Jiang Nan 
Published: February 2022

Abstract
Surface-bound reactions have become a viable method to develop nanoarchitectures through bottom-up assembly with near atomic precision. However, the bottom-up fabrication of nanostructures on surfaces requires careful consideration of the intrinsic properties of the precursors and substrate as well as the complex interplay of any interactions that arise in the heterogeneous two-dimensional (2D) system. Therefore, it becomes necessary to consider these systems with characterization methods sensitive to such properties with suitable spatial resolution. Here, low temperature ultrahigh vacuum scanning tunneling microscopy (STM) and tip-enhanced Raman spectroscopy (TERS) were used to investigate the formation of 2D covalent networks via coupling reactions of tetra(4-bromophenyl)porphyrin (Br4TPP) molecules on a Ag(100) substrate. Through the combination of STM topographic imaging and TERS vibrational fingerprints, the conformation of molecular precursors on the substrate was understood. Following the thermally activated coupling reaction, STM and TERS imaging confirm the covalent nature of the 2D networks and suggest that the apparent disorder arises from molecular flexibility.
Liquid film characteristics measurement based on NIR in gas–liquid vertical annular upward flow
Authors: Zhao Zhiyue , Wang Baohui , Wang Jing , Fang Lide , Li Xiaoting , Wang Fan , Zhao Ning 
Published: February 2022

Abstract
Liquid film plays a crucial role in void fraction, friction pressure drops, momentum and heat transfer in the two-phase flow. The film thickness measurement experiments of annular flow at four pressure conditions have been conducted using near-infrared sensor. The signal is processed by variational mode decomposition, whose parameters are optimized using the sparrow search algorithm. The envelope spectrum and Pearson correlation coefficient judgment criteria were adopted for signal reconstruction, and the value of the liquid film thickness is obtained. The effect (such as flow rate, pressure, entrainment, etc) of the liquid film thickness are analyzed theoretically. The characterization parameters Weg″, Wel, Nμl
and X
mod have been extracted and optimized, and a new average liquid film thickness correlation is proposed. The laboratory results indicate that the mean absolute percentage error of the predictive correlation is 4.35% (current data) and 12.02% (literatures data) respectively.