bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of enhanced innate immune evasion by SARS-CoV-2
Authors: Thorne Lucy G. , Bouhaddou Mehdi , Reuschl Ann-Kathrin , Zuliani-Alvarez Lorena , Polacco Ben , Pelin Adrian , Batra Jyoti , Whelan Matthew V. X. , Hosmillo Myra , Fossati Andrea , Ragazzini Roberta , Jungreis Irwin , Ummadi Manisha , Rojc Ajda , Turner Jane , Bischof Marie L. , Obernier Kirsten , Braberg Hannes , Soucheray Margaret , Richards Alicia , Chen Kuei-Ho , Harjai Bhavya , Memon Danish , Hiatt Joseph , Rosales Romel , McGovern Briana L. , Jahun Aminu , Fabius Jacqueline M. , White Kris , Goodfellow Ian G. , Takeuchi Yasu , Bonfanti Paola , Shokat Kevan , Jura Natalia , Verba Klim , Noursadeghi Mahdad , Beltrao Pedro , Kellis Manolis , Swaney Danielle L. , García-Sastre Adolfo , Jolly Clare , Towers Greg J. , Krogan Nevan J. 
Published: December 2021

AbstractThe emergence of SARS-CoV-2 variants of concern suggests viral adaptation to enhance human-to-human transmission1,2. Although much effort has focused on the characterization of changes in the spike protein in variants of concern, mutations outside of spike are likely to contribute to adaptation. Here, using unbiased abundance proteomics, phosphoproteomics, RNA sequencing and viral replication assays, we show that isolates of the Alpha (B.1.1.7) variant3suppress innate immune responses in airway epithelial cells more effectively than first-wave isolates. We found that the Alpha variant has markedly increased subgenomic RNA and protein levels of the nucleocapsid protein (N), Orf9b and Orf6—all known innate immune antagonists. Expression of Orf9b alone suppressed the innate immune response through interaction with TOM70, a mitochondrial protein that is required for activation of the RNA-sensing adaptor MAVS. Moreover, the activity of Orf9b and its association with TOM70 was regulated by phosphorylation. We propose that more effective innate immune suppression, through enhanced expression of specific viral antagonist proteins, increases the likelihood of successful transmission of the Alpha variant, and may increase in vivo replication and duration of infection4. The importance of mutations outside the spike coding region in the adaptation of SARS-CoV-2 to humans is underscored by the observation that similar mutations exist in the N and Orf9b regulatory regions of the Delta and Omicron variants.
Pan-AMPK activator O304 prevents gene expression changes and remobilisation of histone marks in islets of diet-induced obese mice
Authors: López-Pérez Ana , Norlin Stefan , Steneberg Pär , Remeseiro Silvia , Edlund Helena , Hörnblad Andreas 
Published: December 2021

AbstractAMP-activated protein kinase (AMPK) has an important role in cellular energy homeostasis and has emerged as a promising target for treatment of Type 2 Diabetes (T2D) due to its beneficial effects on insulin sensitivity and glucose homeostasis. O304 is a pan-AMPK activator that has been shown to improve glucose homeostasis in both mouse models of diabetes and in human T2D subjects. Here, we describe the genome-wide transcriptional profile and chromatin landscape of pancreatic islets following O304 treatment of mice fed high-fat diet (HFD). O304 largely prevented genome-wide gene expression changes associated with HFD feeding in CBA mice and these changes were associated with remodelling of active and repressive chromatin marks. In particular, the increased expression of the β-cell stress marker Aldh1a3 in islets from HFD-mice is completely abrogated following O304 treatment, which is accompanied by loss of active chromatin marks in the promoter as well as distant non-coding regions upstream of the Aldh1a3 gene. Moreover, O304 treatment restored dysfunctional glucose homeostasis as well as expression of key markers associated with β-cell function in mice with already established obesity. Our findings provide preclinical evidence that O304 is a promising therapeutic compound not only for T2D remission but also for restoration of β-cell function following remission of T2D diabetes.
Fabrication and characterization of 3D printing scaffold technology by extract oils from plant and its applications in the cardiovascular blood
Authors: Naderi Soheila , Esmaeili Akbar 
Published: December 2021

AbstractExtract oils from plants used in 3D polysaccharides modified with natural protein polymer modified polymer scaffolds can help to reduce blood pressure. This study aimed to use extract oils from plant (EOP)as blood pressure-reducing, bind them to magnetic iron nanoparticles (Fe3O4@NPs), then bind them to polymeric 3D print scaffolds [chitosan, polylactic acid, and polyurethane (CS/PLA/PU), modified with natural protein and finally separate them. This method made it possible to investigate different variables for nanoparticles. In this project, synthesis polymer, modified gelatin (Mo-Ge), PEGylation, extract oils from plant loading and release process in nanocarrier with different concentrations were examined and cell proliferation was optimized. The results show that 75% of the extract oils from plant loaded on iron magnetic nanoparticles containing PEGylated polymer scaffolds was released. Cell proliferation was performed for the sample. In this process, modification of scaffolding with polysaccharides modified with natural protein and extract oils from plant increased the efficiency of nanoparticles among the studied Allium sativum and Zingiber officinale. The size of A. sativum and Z. officinale were 29.833 nm and 150.02 nm size, respectively. These behaved very similarly to each other and A. sativum had the biggest effect in lowering blood pressure. The application of extract oils from plant in 3D mode scaffolding has not been studied before and this is the first analysis to do so, using nanoparticles.
Global maps of cropland extent and change show accelerated cropland expansion in the twenty-first century
Authors: Potapov Peter , Turubanova Svetlana , Hansen Matthew C. , Tyukavina Alexandra , Zalles Viviana , Khan Ahmad , Song Xiao-Peng , Pickens Amy , Shen Quan , Cortez Jocelyn 
Published: December 2021

AbstractSpatiotemporally consistent data on global cropland extent is essential for tracking progress towards sustainable food production. In the present study, we present an analysis of global cropland area change for the first two decades of the twenty-first century derived from satellite data time-series. We estimate that, in 2019, the cropland area was 1,244 Mha with a corresponding total annual net primary production (NPP) of 5.5 Pg C year−1. From 2003 to 2019, cropland area increased by 9% and cropland NPP by 25%, primarily due to agricultural expansion in Africa and South America. Global cropland expansion accelerated over the past two decades, with a near doubling of the annual expansion rate, most notably in Africa. Half of the new cropland area (49%) replaced natural vegetation and tree cover, indicating a conflict with the sustainability goal of protecting terrestrial ecosystems. From 2003 to 2019, global per-capita cropland area decreased by 10% due to population growth. However, the per-capita annual cropland NPP increased by 3.5% as a result of intensified agricultural land use. The presented global, high-resolution, cropland map time-series supports monitoring of natural land appropriation at the local, national and international levels.
Bone marrow endothelial dysfunction promotes myeloid cell expansion in cardiovascular disease
Authors: Rohde David , Vandoorne Katrien , Lee I-Hsiu , Grune Jana , Zhang Shuang , McAlpine Cameron S. , Schloss Maximilian J. , Nayar Ribhu , Courties Gabriel , Frodermann Vanessa , Wojtkiewicz Gregory , Honold Lisa , Chen Qi , Schmidt Stephen , Iwamoto Yoshiko , Sun Yuan , Cremer Sebastian , Hoyer Friedrich F. , Iborra-Egea Oriol , Muñoz-Guijosa Christian , Ji Fei , Zhou Bin , Adams Ralf H. , Wythe Joshua D. , Hidalgo Juan , Watanabe Hideto , Jung Yookyung , van der Laan Anja M. , Piek Jan J. , Kfoury Youmna , Désogère Pauline A. , Vinegoni Claudio , Dutta Partha , Sadreyev Ruslan I. , Caravan Peter , Bayes-Genis Antoni , Libby Peter , Scadden David T. , Lin Charles P. , Naxerova Kamila , Swirski Filip K. , Nahrendorf Matthias 
Published: December 2021

AbstractAbnormal hematopoiesis advances cardiovascular disease by generating excess inflammatory leukocytes that attack the arteries and the heart. The bone marrow niche regulates hematopoietic stem cell proliferation and hence the systemic leukocyte pool, but whether cardiovascular disease affects the hematopoietic organ’s microvasculature is unknown. Here we show that hypertension, atherosclerosis and myocardial infarction (MI) instigate endothelial dysfunction, leakage, vascular fibrosis and angiogenesis in the bone marrow, altogether leading to overproduction of inflammatory myeloid cells and systemic leukocytosis. Limiting angiogenesis with endothelial deletion of Vegfr2 (encoding vascular endothelial growth factor (VEGF) receptor 2) curbed emergency hematopoiesis after MI. We noted that bone marrow endothelial cells assumed inflammatory transcriptional phenotypes in all examined stages of cardiovascular disease. Endothelial deletion of Il6 or Vcan (encoding versican), genes shown to be highly expressed in mice with atherosclerosis or MI, reduced hematopoiesis and systemic myeloid cell numbers in these conditions. Our findings establish that cardiovascular disease remodels the vascular bone marrow niche, stimulating hematopoiesis and production of inflammatory leukocytes.
Strategies for Teachers to Support Children Who Stutter: Perspectives of Speech-Language Pathologists
Authors: Cozart Gabrielle , Wilson Laura 
Published: December 2021

Purpose:
This study assessed how speech-language pathologists (SLPs) believe teachers can best support school-age children who stutter (CWS) in the classroom.

Method:

An online survey adapted from the Personal Appraisal of Support for Stuttering–Parent was given to 122 SLPs licensed in the State of Oklahoma. The median age of the participants was 43 years (interquartile range [IQR] = 16), and the average number of CWS the participants reported treating was 14 (IQR = 14). The participants rated the helpfulness of supports teachers can use as they interact with CWS (e.g., “Tell the child to slow down”). The participants rated 41 items on a 1–5 Likert scale, with 1 indicating
unhelpful
and 5 indicating
very helpful
, followed by a “not sure” category.

Results:
The three items rated most helpful were for teachers to collaborate with the child's SLP, to be patient when the child talks, and to know how to react when the child stutters. The three items rated least helpful were for teachers to be bothered by the child's stuttering, to laugh at the child because of the child's stuttering, and to use a fast rate of speech. The two items with the greatest response variability were for teachers to tell the child to think about what to say before speaking and to tell the child what to do when stuttering. The variability suggests inconsistency in the SLPs' beliefs about the helpfulness of those actions.

Conclusion:
Findings from this study contribute to the literature on supporting CWS and the development of educational materials for classroom teachers.
Aktuelles Management des Basalzellkarzinoms
Authors: Krieter Manuel , Schultz Erwin S. 
Published: December 2021

ZusammenfassungZiel der Studie Der aktuelle Standard von Diagnostik und Therapie des Basalzellkarzinoms soll dargestellt werden. Hieraus sollen sinnvolle Vorgehensweisen für das klinische Management abgeleitet werden.Methodik Es erfolgte eine systematische Literaturrecherche in der Online-Datenbank PubMed. Die gesammelten Informationen wurden analysiert und bewertet. Aus den gewonnenen Erkenntnissen wurde ein Gesamtkonzept erstellt.Ergebnisse Das Basalzellkarzinom ist der häufigste Tumor des Menschen und die Inzidenz wird voraussichtlich künftig weiter zunehmen. Beim Management der Erkrankung wird eine eindimensionale Orientierung am klinischen bzw. histologischen Basalzellkarzinom-Subtyp der Heterogenität des Tumors nicht gerecht. Zunehmende Bedeutung gewinnt die primäre Durchführung einer Risikostratifizierung, die für die weiteren diagnostischen und therapeutischen Schritte maßgeblich ist. Goldstandard in der Behandlung bleibt weiterhin das operative Vorgehen, welches möglichst mittels mikrografisch kontrollierter Chirurgie erfolgen sollte. Daneben existieren weitere Therapieverfahren wie die Radiotherapie oder eine Reihe an topischen Therapieoptionen (photodynamische Therapie, Kryotherapie oder Applikation von 5-Fluoruracil bzw. Imiquimod), die in bestimmten Fällen zur Anwendung kommen können. Auch für fortgeschrittene oder metastasierte Basalzellkarzinome stehen mit den Hedgehog-Inhibitoren wirksame Medikamente zur Verfügung, für die inzwischen eine mehrjährige Anwendungserfahrung hinsichtlich Wirksamkeit und Umgang mit unerwünschten Ereignissen vorliegt. Mit den PD-1-Inhibitoren steht eine weitere systemische Therapieoption in Aussicht, deren Nutzen aktuell noch in klinischen Studien überprüft wird.Schlussfolgerung Das Basalzellkarzinom wird in den kommenden Jahren weiter an Relevanz in der täglichen dermatologischen Praxis gewinnen. Eine strukturierte Herangehensweise zur Einschätzung der vorliegenden Risikokategorie des Tumors und die anschließende Festlegung des optimalen Therapieregimes sind von zentraler Bedeutung. Fortgeschrittene oder metastasierte Tumoren stellen keine aussichtslose Situation für den Patienten mehr dar. Durch adaptierte Dosierschemata kann ein nebenwirkungsbedingter Therapieabbruch unter langfristiger Hedgehog-Therapie vermieden werden. Das therapeutische Potenzial von PD-1-Inhibitoren könnte bald auch beim Basalzellkarzinom genutzt werden.
Serum NT-pro-BNP Levels Predict Cardiovascular Events in Acromegaly
Patients
Authors: Ragonese Marta , Di Bella Gianluca , Spagnolo Federica , Grasso Loredana , Alibrandi Angela , Giuffrida Guiseppe , Moleti Mariacarla , Ferraù Francesco , Cannavò Salvatore 
Published: December 2021

Abstract
Background Acromegaly is associated with an increased risk of fatal and
non-fatal cardiovascular (CV) events. Controlling acromegaly decreases, but does
not normalize this risk. Brain natriuretic peptide (BNP) assessment is used in
the general population for the diagnosis of heart failure and to predict
ischemic recurrences and mortality. This is a retrospective, longitudinal,
monocenter study that evaluates the role of serum N-terminal fragment of BNP
(NT-pro-BNP) for predicting CV events in acromegaly patients.
Methods Serum NT-pro-BNP levels were measured in 76 patients with
acromegaly (23 males, 57.7±1.5 years), and compared with other
predictors of CV events. NT-pro-BNP cut-off value discriminating the occurrence
of CV events was determined by ROC analysis. CV events were recorded during a
follow-up of 78.6±6.4 months.
Results CV events occurred in 9.2% of patients. Mean
log(NT-pro-BNP) concentration was higher in patients who experienced CV events
than in those who did not (p<0.01) and in patients who died due to CV
events than in those who died due to other causes (p<0.01). Based on the
ROC curve, a cut-off value of 91.55 pg/mL could predict CV
events (OR 19.06). Log(NT-pro-BNP) was lower in surgically treated patients by
surgery (p<0.05), and in those cured by neurosurgery
(p<0.02).
Conclusions High NT-pro-BNP value is an independent middle-term predictor
of fatal or non-fatal CV events in patients with acromegaly. According to this
parameter, surgically treated patients show lower CV risk than those managed
with medical therapy, especially if the disease is cured.
A Vicious Circle of Clonal Haematopoiesis of Indeterminate Potential and Cardiovascular Disease
Authors: Ehlert Carolin A. , Hilgendorf Ingo 
Published: December 2021

AbstractClonal haematopoiesis of indeterminate potential (CHIP) represents a recently identified overlap between cancer and cardiovascular disease (CVD). CHIP develops as a result of certain acquired somatic mutations that predispose to leukaemia, but clinically even more prevalent, associate with increased risk for CVD and CVD-related death. Experimental studies suggest a causal role for CHIP aggravating inflammatory processes in CVD, and recent epidemiologic and genetic studies indicate that classical CVD risk factors may increase the risk of acquiring CHIP driver mutations, thus fuelling a vicious circle. The potential mechanism underlying the associative link between CHIP and CVD and mortality has been the focus of a few recent excellent experimental and observational studies which are summarized and discussed in this concise non-systematic review article. These data support a pathomechanistic view of a spiralling vicious circle in which CHIP aggravates the inflammatory immune response in CVD, and CVD-driven elevated haematopoietic activity promotes CHIP development.
Zertifizierung: „Patientensicherheit in der Dermatologie (DDA)“
Authors: Elsner Peter , Fritz Klaus 
Published: December 2021

ZusammenfassungBehandlungsfehler oder „Patienten schadende Vorkommnisse, die eher auf der Behandlung als auf der Erkrankung selbst beruhen und die durch einen Fehler verursacht sind“, kommen auch im Fachgebiet der Dermatologie vor, wenn auch vermutlich seltener als in anderen, noch mehr operativ ausgerichteten Disziplinen. Patientensicherheit ist mehr als die bloße Abwesenheit von Behandlungsfehlern; sie beschreibt vielmehr ein aktives Bemühen um eine Beherrschung von jeder ärztlichen Behandlung inhärenten Risiken im Sinne einer „Sicherheitskultur“.Das Bemühen um die Patientensicherheit ist eine Priorität der Gesundheitspolitik, aber insbesondere genuine ethische Aufgabe der Ärzteschaft und so auch der Dermatologen. In der reformierten studentischen Lehre des Medizinstudiums nach dem „Nationalen Kompetenzbasierten Lernzielkatalog Medizin” nimmt die Patientensicherheit eine wichtige Stellung ein.Die Deutsche Dermatologische Akademie (DDA) hat daher mit dem Zertifikat „Patientensicherheit in der Dermatologie (DDA)“ ein wichtiges Fortbildungsangebot für diese auch in der Dermatologie in Klinik und Praxis zunehmend wichtiger werdenden Aspekte der Medizin geschaffen.Die Fortbildungsinhalte für die Zertifizierung „Patientensicherheit in der Dermatologie (DDA)“ werden in einem ganztägigen Modul (8 Stunden) vermittelt; auch eine Aufteilung in Halbtage im Rahmen größerer Fortbildungsveranstaltungen ist möglich.Das Seminare sind interaktiv; bestimmend ist die praxisorientierte Präsentation des Wissens und die kollegiale Diskussion mit ausgewiesenen Experten. Zum Erhalt des Zertifikats ist einmal alle 5 Jahre die Teilnahme an einem Qualitätszirkel (2 Stunden) vorgesehen, in dem aktuelle Entwicklungen komprimiert dargestellt und anhand von Falldiskussionen thematisiert werden. Das Zertifikat steht sowohl Dermatologen als auch Medizinischen Fachangestellten und Pflegekräften offen.
Dispensation Patterns of Glucose-Lowering Drugs in Newly Diagnosed
Type 2 Diabetes: Routine Data Analysis of Insurance Claims in
Germany
Authors: Bongaerts Brenda , Kollhorst Bianca , Kuss Oliver , Pigeot Iris , Rathmann Wolfgang 
Published: December 2021

Abstract
Aims To describe dispensation patterns of glucose-lowering drugs in newly
diagnosed type 2 diabetes in Germany.
Materials and methods Based on claims data from four statutory health
insurances (German Pharmacoepidemiological Research Database,>25 million
insurants), all individuals with newly diagnosed type 2 diabetes were
identified. Eligible patients had a first diagnosis for type 2 diabetes between
January 2012 and December 2016. We analyzed the dispensation patterns of
first-line glucose-lowering therapies initiated in the year after diabetes
diagnosis and patterns of second-line therapies dispensed one year after
first-line treatment.
Results A total of 356,647 individuals with newly diagnosed type 2
diabetes were included (average age [SD]: 63.5 [13.4] years; 49.3%
males). Of the 31.6% of individuals who were pharmacologically treated
in the year after diagnosis, metformin monotherapy was most frequently dispensed
(73.1%), followed by dual therapy of metformin and dipeptidyl
peptidase-4 inhibitors (DPP-4is) (6.4%), and monotherapy with DPP-4is
(2.9%). From 2012 through 2016, sulfonylurea dispensations were reduced
by more than 50%. Dispensations for combination therapies with DPP-4is
increased up to 10.6%. Glucagon-like peptide-1 receptor agonists and
sodium-glucose co-transporter-2 inhibitors contributed to 2% of all
treatments. After a median of 5 months, 20.0% of individuals on
pharmacological therapy initiated second-line glucose-lowering treatment.
Conclusions Data from German statutory health insurances (2012 to 2016)
showed that most individuals with newly diagnosed type 2 diabetes were dispensed
metformin monotherapy in line with diabetes care guidelines. A substantial
decrease in the use of sulfonylureas was observed after the introduction of
DPP-4i and GLP-1 receptor agonists.
A Review of Coagulation Abnormalities of Autoimmune Acquired Factor V Deficiency with a Focus on Japan
Authors: Ichinose Akitada , Osaki Tsukasa , Souri Masayoshi 
Published: December 2021

AbstractCoagulation factor V (or FV for the purpose of medical safety) is an essential cofactor of coagulation factor X in the common pathway of coagulation; severe FV deficiency leads to a bleeding tendency. Although both congenital and acquired FV deficiencies are widely recognized, FV deficiency also presents as an autoimmune disorder. A nationwide survey on autoimmune coagulation factor deficiencies (AiCFDs) conducted in Japan by our Japanese Collaborative Research Group identified 24 new patients with autoimmune FV deficiency (AiFVD) in the past 5 years. Furthermore, our extensive literature search confirmed that 177 AiFVD cases have been reported in previous articles published from Japan. Patients with AiFVD in Japan were predominantly men, with age similar to those with other AiCFDs. AiFVD was confirmed as a relatively mild type of bleeding diathesis, associated with lower mortality rate than that for AiFVD and other AiCFDs reported in previous studies. Patients with AiFVD had variable FV inhibitor titers and both neutralizing anti-FV autoantibodies and nonneutralizing counterparts. Although spontaneous resolution occurs in some patients, timely initiation of hemostatic and immunosuppressive therapies helps arrest the bleeding and eliminate anti-FV antibodies, resulting in a high cumulative recovery rate. Immunological anti-FV antibody detection is recommended to avoid missing AiFVD cases for the presence of nonneutralizing anti-FV autoantibodies. Further investigation is necessary to clarify the long-term prognosis and optimal management of AiFVD.