bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acquired resistance to combined BET and CDK4/6 inhibition in triple-negative breast cancer
Authors: Ge Jennifer Y. , Shu Shaokun , Kwon Mijung , Jovanović Bojana , Murphy Katherine , Gulvady Anushree , Fassl Anne , Trinh Anne , Kuang Yanan , Heavey Grace A. , Luoma Adrienne , Paweletz Cloud , Thorner Aaron R. , Wucherpfennig Kai W. , Qi Jun , Brown Myles , Sicinski Piotr , McDonald Thomas O. , Pellman David , Michor Franziska , Polyak Kornelia 
Published: May 2020

AbstractBET inhibitors are promising therapeutic agents for the treatment of triple-negative breast cancer (TNBC), but the rapid emergence of resistance necessitates investigation of combination therapies and their effects on tumor evolution. Here, we show that palbociclib, a CDK4/6 inhibitor, and paclitaxel, a microtubule inhibitor, synergize with the BET inhibitor JQ1 in TNBC lines. High-complexity DNA barcoding and mathematical modeling indicate a high rate of de novo acquired resistance to these drugs relative to pre-existing resistance. We demonstrate that the combination of JQ1 and palbociclib induces cell division errors, which can increase the chance of developing aneuploidy. Characterizing acquired resistance to combination treatment at a single cell level shows heterogeneous mechanisms including activation of G1-S and senescence pathways. Our results establish a rationale for further investigation of combined BET and CDK4/6 inhibition in TNBC and suggest novel mechanisms of action for these drugs and new vulnerabilities in cells after emergence of resistance.
ORF Capture-Seq as a versatile method for targeted identification of full-length isoforms
Authors: Sheynkman Gloria M. , Tuttle Katharine S. , Laval Florent , Tseng Elizabeth , Underwood Jason G. , Yu Liang , Dong Da , Smith Melissa L. , Sebra Robert , Willems Luc , Hao Tong , Calderwood Michael A. , Hill David E. , Vidal Marc 
Published: May 2020

AbstractMost human protein-coding genes are expressed as multiple isoforms, which greatly expands the functional repertoire of the encoded proteome. While at least one reliable open reading frame (ORF) model has been assigned for every coding gene, the majority of alternative isoforms remains uncharacterized due to (i) vast differences of overall levels between different isoforms expressed from common genes, and (ii) the difficulty of obtaining full-length transcript sequences. Here, we present ORF Capture-Seq (OCS), a flexible method that addresses both challenges for targeted full-length isoform sequencing applications using collections of cloned ORFs as probes. As a proof-of-concept, we show that an OCS pipeline focused on genes coding for transcription factors increases isoform detection by an order of magnitude when compared to unenriched samples. In short, OCS enables rapid discovery of isoforms from custom-selected genes and will accelerate mapping of the human transcriptome.
Synergistic effect of fasting-mimicking diet and vitamin C against KRAS mutated cancers
Authors: Di Tano Maira , Raucci Franca , Vernieri Claudio , Caffa Irene , Buono Roberta , Fanti Maura , Brandhorst Sebastian , Curigliano Giuseppe , Nencioni Alessio , de Braud Filippo , Longo Valter D. 
Published: May 2020

AbstractFasting-mimicking diets delay tumor progression and sensitize a wide range of tumors to chemotherapy, but their therapeutic potential in combination with non-cytotoxic compounds is poorly understood. Here we show that vitamin C anticancer activity is limited by the up-regulation of the stress-inducible protein heme-oxygenase-1. The fasting-mimicking diet selectivity reverses vitamin C-induced up-regulation of heme-oxygenase-1 and ferritin in KRAS-mutant cancer cells, consequently increasing reactive iron, oxygen species, and cell death; an effect further potentiated by chemotherapy. In support of a potential role of ferritin in colorectal cancer progression, an analysis of The Cancer Genome Atlas Database indicates that KRAS mutated colorectal cancer patients with low intratumor ferritin mRNA levels display longer 3- and 5-year overall survival. Collectively, our data indicate that the combination of a fasting-mimicking diet and vitamin C represents a promising low toxicity intervention to be tested in randomized clinical trials against colorectal cancer and possibly other KRAS mutated tumors.
Interventions to improve medication adherence in tuberculosis patients: a systematic review of randomized controlled studies
Authors: Pradipta Ivan S. , Houtsma Daphne , van Boven Job F. M. , Alffenaar Jan-Willem C. , Hak Eelko 
Published: May 2020

AbstractNon-adherence to anti-tuberculosis (anti-TB) medication is a major risk factor for poor treatment outcomes. We therefore assessed the effectiveness of medication adherence enhancing interventions in TB patients. We report a systematic review of randomized controlled trials that included either latent tuberculosis infection (LTBI) or active TB patients. Outcomes of interest included adherence rate, completed treatment, defaulted treatment and treatment outcomes. We identified four LTBI and ten active TB studies. In active TB patients, directly observed treatment (DOT) by trained community workers, short messaging service combined with education, counselling, monthly TB vouchers, drug box reminders and combinations of those were found effective. In LTBI patients, shorter regimens and DOT effectively improved treatment completion. Interestingly, DOT showed variable effectiveness, highlighting that implementation, population and setting may play important roles. Since non-adherence factors are patient-specific, personalized interventions are required to enhance the impact of a programme to improve medication adherence in TB patients.
H7N9 influenza split vaccine with SWE oil-in-water adjuvant greatly enhances cross-reactive humoral immunity and protection against severe pneumonia in ferrets
Authors: de Jonge Jørgen , van Dijken Harry , de Heij Femke , Spijkers Sanne , Mouthaan Justin , de Jong Rineke , Roholl Paul , Adami Eduardo Alfredo , Akamatsu Milena Apetito , Ho Paulo Lee , Brunner Livia , Collin Nicolas , Friede Martin , Ferreira José A. , Luytjes Willem 
Published: May 2020

AbstractUntil universal influenza vaccines become available, pandemic preparedness should include developing classical vaccines against potential pandemic influenza subtypes. We here show that addition of SWE adjuvant, a squalene-in-water emulsion, to H7N9 split influenza vaccine clearly enhanced functional antibody responses in ferrets. These were cross-reactive against H7N9 strains from different lineages and newly emerged H7N9 variants. Both vaccine formulations protected in almost all cases against severe pneumonia induced by intratracheal infection of ferrets with H7N9 influenza; however, the SWE adjuvant enhanced protection against virus replication and disease. Correlation analysis and curve fitting showed that both VN- and NI-titers were better predictors for protection than HI-titers. Moreover, we show that novel algorithms can assist in better interpretation of large data sets generated in preclinical studies. Cluster analysis showed that the adjuvanted vaccine results in robust immunity and protection, whereas the response to the non-adjuvanted vaccine is heterogeneous, such that the protection balance may be more easily tipped toward severe disease. Finally, cluster analysis indicated that the dose-sparing capacity of the adjuvant is at least a factor six, which greatly increases vaccine availability in a pandemic situation.
CoryneRegNet 7, the reference database and analysis platform for corynebacterial gene regulatory networks
Authors: Parise Mariana Teixeira Dornelles , Parise Doglas , Kato Rodrigo Bentes , Pauling Josch Konstantin , Tauch Andreas , Azevedo Vasco Ariston de Carvalho , Baumbach Jan 
Published: May 2020

AbstractWe present the newest version of CoryneRegNet, the reference database for corynebacterial regulatory interactions, available at www.exbio.wzw.tum.de/coryneregnet/. The exponential growth of next-generation sequencing data in recent years has allowed a better understanding of bacterial molecular mechanisms. Transcriptional regulation is one of the most important mechanisms for bacterial adaptation and survival. These mechanisms may be understood via an organism’s network of regulatory interactions. Although the Corynebacterium genus is important in medical, veterinary and biotechnological research, little is known concerning the transcriptional regulation of these bacteria. Here, we unravel transcriptional regulatory networks (TRNs) for 224 corynebacterial strains by utilizing genome-scale transfer of TRNs from four model organisms and assigning statistical significance values to all predicted regulations. As a result, the number of corynebacterial strains with TRNs increased twenty times and the back-end and front-end were reimplemented to support new features as well as future database growth. CoryneRegNet 7 is the largest TRN database for the Corynebacterium genus and aids in elucidating transcriptional mechanisms enabling adaptation, survival and infection.
Pofatu, a curated and open-access database for geochemical sourcing of archaeological materials
Authors: Hermann Aymeric , Forkel Robert , McAlister Andrew , Cruickshank Arden , Golitko Mark , Kneebone Brendan , McCoy Mark , Reepmeyer Christian , Sheppard Peter , Sinton John , Weisler Marshall 
Published: May 2020

AbstractCompositional analyses have long been used to determine the geological sources of artefacts. Geochemical “fingerprinting” of artefacts and sources is the most effective way to reconstruct strategies of raw material and artefact procurement, exchange or interaction systems, and mobility patterns during prehistory. The efficacy and popularity of geochemical sourcing has led to many projects using various analytical techniques to produce independent datasets. In order to facilitate access to this growing body of data and to promote comparability and reproducibility in provenance studies, we designedPofatu, the first online and open-access database to present geochemical compositions and contextual information for archaeological sources and artefacts in a form that can be readily accessed by the scientific community. This relational database currently contains 7759 individual samples from archaeological sites and geological sources across the Pacific Islands. Each sample is comprehensively documented and includes elemental and isotopic compositions, detailed archaeological provenance, and supporting analytical metadata, such as sampling processes, analytical procedures, and quality control.
Functional culture and in vitro genetic and small-molecule manipulation of adult mouse cardiomyocytes
Authors: Callaghan Neal I. , Lee Shin-Haw , Hadipour-Lakmehsari Sina , Lee Xavier A. , Ahsan Siraj M. , Driouchi Amine , Yip Christopher M. , Husain Mansoor , Simmons Craig A. , Gramolini Anthony O. 
Published: May 2020

AbstractPrimary adult cardiomyocyte (aCM) represent the mature form of myocytes found in the adult heart. However, culture of aCMs in particular is challenged by poor survival and loss of phenotype, rendering extended in vitro experiments unfeasible. Here, we establish murine aCM culture methods that enhance survival and maintain sarcomeric structure and Ca2+ cycling to enable physiologically relevant contractile force measurements. We also demonstrate genetic and small-molecule manipulations that probe mechanisms underlying myocyte functional performance. Together, these refinements to aCM culture present a toolbox with which to advance our understanding of myocardial physiology.
Pd-catalyzed fluoro-carbonylation of aryl, vinyl, and heteroaryl iodides using 2-(difluoromethoxy)-5-nitropyridine
Authors: Liang Yumeng , Zhao Zhengyu , Shibata Norio 
Published: May 2020

AbstractAcyl fluorides have recently gained a lot of attention as robust and versatile synthetic tools in synthetic chemistry. While several synthetic routes to acyl fluorides have been reported, a procedure involving direct insertion of the “fluoro-carbonyl” moiety using a single reagent has not yet been realized. Here we report the preparation of acyl fluorides by palladium-catalyzed fluoro-carbonylation of aryl, vinyl, and heteroaryl iodides using 2-(difluoromethoxy)-5-nitropyridine under CO-free conditions. 2-(difluoromethoxy)-5-nitropyridine is a stable, colorless solid that can be used as an alternative to the toxic gaseous formyl fluoride, which is commonly used under fluoride catalysis conditions. A wide variety of acyl fluorides are efficiently and safely obtained in high yield (up to 99%). A broad range of functional groups is tolerated under the optimized reaction conditions and the method can be applied to the late-stage fluoro-carbonylation of structurally complex Csp2-iodides, including bioactive derivatives, such as Fenofibrate, Isoxepac, and Tocopherol. Furthermore, the one-pot transformation of aryl-iodides, including drug-like molecules, into the corresponding amides by successive fluoro-carbonylation/amidation reactions, demonstrates the potential synthetic utility of this strategy.
Diarylethene moiety as an enthalpy-entropy switch: photoisomerizable stapled peptides for modulating p53/MDM2 interaction
Authors: Strizhak Alexander V. , Babii Oleg , Afonin Sergii , Bakanovich Iuliia , Pantelejevs Teodors , Xu Wenshu , Fowler Elaine , Eapen Rohan , Sharma Krishna , Platonov Maxim O. , Hurmach Vasyl V. , Itzhaki Laura , Hyvönen Marko , Ulrich Anne S. , Spring David R. , Komarov Igor V. 
Published: May 2020

Photoisomerization of diarylethene-modified peptides changes the thermodynamics of their binding to MDM2: the “closed” photoisomers bind largely due to a high negative enthalpy, whereas the “open” forms bind better due to a more favourable entropy.
Whole exome sequencing identified a new compound heterozygous PRKN mutation in a Chinese family with early-onset Parkinson’s disease
Authors: Li Tianbai , Kou Daqing , Cui Yanhua , Le Weidong 
Published: May 2020

Abstract
Early-onset Parkinson’s disease (EOPD) is usually caused by genetic variants and patients with EOPD develop symptoms before the age of 50, accounting for 5% Parkinson’s disease (PD). Here we present a Chinese Han pedigree with clinical features of EOPD. To determine the diagnosis and pathogenic mutations of this pedigree, whole exome sequencing, Sanger sequencing and real-time quantitative PCR were performed to detect all the four family members. Our results showed that a new form of compound heterozygous mutation in the PRKN gene, consisting of heterozygous point mutation c.850G &gt; C (p.G284R) along with exon 4 deletion, is the causative genetic factor for EOPD in this pedigree. These discoveries may have implications for genetic counseling, clinical management and developing PRKN target gene therapy strategy.
Current status and possible extension of the global neutron monitor network
Authors: Mishev Alexander , Usoskin Ilya 
Published: May 2020

The global neutron monitor network has been successfully used over several decades to study cosmic ray variations and fluxes of energetic solar particles. Nowadays, it is used also for space weather purposes, e.g. alerts and assessment of the exposure to radiation. Here, we present the current status of the global neutron monitor network. We discuss the ability of the global neutron monitor network to study solar energetic particles, specifically during large ground level enhancements. We demonstrate as an example, the derived solar proton characteristics during ground level enhancements GLE #5 and the resulting effective dose over the globe at a typical commercial jet flight altitude of 40 kft (≈12,200 m) above sea level. We present a plan for improvement of space weather services and applications of the global neutron monitor network, specifically for studies related to solar energetic particles, namely an extension of the existing network with several new monitors. We discuss the ability of the optimized global neutron monitor network to study various populations of solar energetic particles and to provide reliable space weather services.
Facies leontina bei chronischer lymphatischer Leukämie
Authors: Kuske M. , Hering M. , Sergon M. , Beissert S. , Aschoff R. 
Published: May 2020

ZusammenfassungWir berichten über die seltene Entwicklung einer Leukaemia cutis, die sich als Facies leontina bei einem Patienten mit seit 4 Jahren bekannter chronischer lymphatischer Leukämie manifestierte. In Zusammenschau der Histomorphologie und des immunhistochemischen Phänotyps zeigte sich in der Dermis ein monomorphes Infiltrat von kleinen lymphatischen Zellen mit runden chromatindichten Zellkernen sowie Koexpression von CD20, CD5 und CD23. Dazwischen eingestreut waren einzelne CD3-positive T-Zellen. Obwohl die Facies leontina am häufigsten mit der lepromatösen Lepra oder einem kutanen T-Zell-Lymphom assoziiert ist, sollte insbesondere bei älteren Menschen auch an eine zugrundeliegende Leukämie gedacht werden.
Bildgebende Diagnostik des Multiplen Myeloms
Authors: Kosmala Aleksander , Bley Thorsten , Petritsch Bernhard 
Published: May 2020

Hintergrund Das Multiple Myelom ist eine maligne hämatologische Erkrankung, die sich durch die Proliferation von monoklonalen Plasmazellen vor allem im Knochenmark auszeichnet. Die Bildgebung spielt zur Diagnosestellung und Verlaufsbeurteilung eine wichtige Rolle.
Methode Dieser Übersichtsartikel informiert über das Krankheitsbild des Multiplen Myeloms samt Vorstufen und beschreibt die zur Verfügung stehenden bildgebenden Untersuchungstechniken. Diese werden samt Vor- und Nachteilen sowie möglichen prognostischen und therapeutischen Implikationen vor dem Hintergrund der aktuellen Literatur vorgestellt.
Ergebnisse und Schlussfolgerung Der konventionelle Röntgenstatus ist beim Multiplen Myelom mittlerweile vollständig von Schnittbildtechniken ersetzt worden. Die breit verfügbare Ganzkörper-Computertomografie wird routinemäßig verwendet, um Osteolysen nachzuweisen. Die Magnetresonanztomografie hat die höchste Sensitivität zur Detektion von Knochenmarkbefall und wird insbesondere bei den Vorstufen des symptomatischen Multiplen Myeloms empfohlen. Die Positronen-Emissions-Tomografie vereint morphologische und funktionelle Bildgebung. Sie kommt vor allem bei der Verlaufsbeurteilung und Evaluation von Therapieansprechen zum Einsatz.
Kernaussagen:
Checklist Focused on Patients for Making of Teaching Videos in Orthopedic Surgery
Authors: Meder Adrian , Ruesseler Miriam , Stefanescu Maria-Christina , Sakmen Dennis , Verboket Rene , Froehlich Susanne , Schulz Arndt Peter , Obertacke Udo , Houy Birgit , Sterz Jasmina 
Published: May 2020

Abstract
Introduction The focus of medical-didactic research is the improvement of clinical-practical training. One way to support practical skills training in a time- and resource-saving way is to provide instructional videos. Often the freely available instructional videos do not meet didactic or content requirements. Creating your own videos can therefore be a useful alternative for teachers. There are a variety of instructions on the Internet for shooting instruction videos. To date, this does not include any concrete instructions/assistance for the production of medical instructional videos. However, the presentation of medical learning content in particular can contain many hurdles. The aim of this work was to design a checklist for the creation of instructional videos, which can be used as a guide.
Methods As a first step, a systematic literature search was carried out to identify works that deal with the creation and not the use of medical instructional videos. To date, corresponding publications do not exist. In a workshop, the participants, who already gained experience in creating this type of video, exchanged ideas. These were critically discussed and analyzed. As a result, a checklist was created. In a subsequent multi-step review process, the checklist was reviewed with regard to applicability, comprehensibility, completeness and quality of the items.
Results Four phases in the creation of an instructional video could be differentiated: preliminary reflections, preparation, day of filming, post-production. The checklist is structured accordingly and should be actively processed phase by phase. The checklist is created in such a way that it can be used and edited without reading this text. Particular focus is placed on the patient and his needs.
Conclusion The checklist created provides useful help in the creation of medical instructional videos and can for the first time serve as a guide especially for orthopedic and accident surgical instructional videos.
Einfluss gutartiger Tumoren der Glandula parotis auf die Gesamtspeichelflussrate
Authors: Burghartz Marc , Sittel Christian , Fiz Ivana , Taxis Delf , Plecko Thomas , Kolkmeyer Carina Anna , Hagen Rudolf , Hackenberg Stephan 
Published: May 2020

Zusammenfassung
Hintergrund Der Einfluss von gutartigen Tumoren der Gl. parotis auf den Gesamtspeichelfluss oder die Zusammensetzung des Speichels ist weitestgehend unklar.
Material und Methoden 22 Patienten mit einem gutartigen Tumor der Gl. parotis und 18 Probanden einer gesunden Kontrollgruppe wurden im Hinblick auf den unstimulierten und stimulierten Gesamtspeichelfluss sowie die Speichelzusammensetzung (Natrium, Kalium, Kalzium, Amylase und pH) miteinander verglichen. Zudem wurden die Studienteilnehmer mittels visueller Analogskala (VAS) bzw. Lebensqualitätsfragebogen (QoL) zu einer möglichen Mundtrockenheit (Xerostomie) befragt.
Ergebnisse Der stimulierte Gesamtspeichelfluss in der Patientengruppe war im Vergleich zur Kontrollgruppe signifikant geringer (2,76 ± 0,96 ml/min vs. 3,85 ± 0,72 ml/min; p = 0,009). Jedoch ergab der Vergleich des unstimulierten Gesamtspeichelflusses, der Speichelzusammensetzung und der subjektiven Parameter (VAS, QoL) keinen signifikanten Unterschied zwischen der Patienten- und der Kontrollgruppe (0,73 ± 0,41 ml/min vs. 0,68 ± 0,39 ml/min; p = 1).
Schlussfolgerungen Die Ergebnisse der vorliegenden Studie könnten einen Hinweis darauf geben, dass gutartige Tumoren der Gl. parotis den stimulierten Gesamtspeichelfluss reduzieren, während sie den unstimulierten Gesamtspeichelfluss sowie die Speichelzusammensetzung unbeeinflusst lassen. Dennoch scheinen die Patienten unter keiner signifikanten Mundtrockenheit zu leiden.
The COVID-19 Pandemic and its Impact on Plastic Surgery in Europe – An ESPRAS Survey
Authors: Giunta Riccardo E. , Frank Konstantin , Costa Horacio , Demirdöver Cenk , di Benedetto Giovanni , Elander Anna , Henley Mark , Murray Dylan J. , Schaefer Dirk , Spendel Stephan , Vasar Olavi , Zic Rado 
Published: May 2020

AbstractThe present article provides an overview of the current and expected effects of plastic surgery in Europe. It presents the experience of departments for plastic and reconstructive surgery, as evaluated by interviews with members of the Executive Committee (ExCo) of the European Society of Plastic, Reconstructive and Aesthetic Surgery (ESPRAS). The objective of this overview is to summmarise current information in our area of work and to make this accessible to a broad group of readers. As our knowledge is rapidly increasing during the current pandemic, it is evident that we can only provide a snapshot and this will inevitably be incomplete.