bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of active surveillance for prostate cancer on the risk of depression and anxiety
Authors: Sypre Davidson , Pignot Géraldine , Touzani Rajae , Marino Patricia , Walz Jochen , Rybikowski Stanislas , Maubon Thomas , Branger Nicolas , Salem Naji , Mancini Julien , Gravis Gwenaelle , Bendiane Marc-Karim , Bouhnik Anne-Deborah 
Published: July 2022

AbstractActive surveillance (AS) is a standard treatment option for low risk localized prostate cancer. However, the risk of anxiety and depression compared to other curative strategies, namely radical prostatectomy (RP) and radiotherapy (RT), is controversial. This study consisted in a French representative sample of 4174 5-years cancer survivors. Self-reported data, including quality-of-life assessment, were prospectively collected through telephone interviews. Among the 447 survivors with PC, we selected 292 patients with localized prostate cancer, T1–T2 stage, Gleason score ≤ 7 and we compared anxiety and depressive symptoms according to treatment strategy. Among patients on AS, 14.9% received curative treatment during the 5 years of follow-up. Anxiety was reported in 34.3% of cases in the AS group versus 28.6% in the RP group and 31.6% in the RT group (p = 0.400), while depressive symptoms were reported in 14.9% of cases in the AS group versus 10.7% in the RP group and 22.8% in the RT group (p = 0.770). Consumption of anxiolytics reported did not vary significantly between the 3 groups (p = 0.330). In conclusion, patients managed with AS for localized prostate cancer do not report more anxiety or depressive symptoms than patients managed with curative treatment, encouraging the extended use of active surveillance.
Convergence of virulence and antimicrobial resistance in increasingly prevalent Escherichia coli ST131 papGII+ sublineages
Authors: Biggel Michael , Moons Pieter , Nguyen Minh Ngoc , Goossens Herman , Van Puyvelde Sandra 
Published: July 2022

AbstractEscherichia coli lineage ST131 is an important cause of urinary tract and bloodstream infections worldwide and is highly resistant to antimicrobials. Specific ST131 lineages carrying invasiveness-associated papGII pathogenicity islands (PAIs) were previously described, but it is unknown how invasiveness relates to the acquisition of antimicrobial resistance (AMR). In this study, we analysed 1638 ST131 genomes and found that papGII+ isolates carry significantly more AMR genes than papGII-negative isolates, suggesting a convergence of virulence and AMR. The prevalence of papGII+ isolates among human clinical ST131 isolates increased dramatically since 2005, accounting for half of the recent E. coli bloodstream isolates. Emerging papGII+ lineages within clade C2 were characterized by a chromosomally integrated blaCTX-M-15 and the loss and replacement of F2:A1:B- plasmids. Convergence of virulence and AMR is worrying, and further dissemination of papGII+ ST131 lineages may lead to a rise in severe and difficult-to-treat extraintestinal infections.
The 1, 2-ethylenediamine SQ109 protects against tuberculosis by promoting M1 macrophage polarization through the p38 MAPK pathway
Authors: Singh Mona , Kumar Santosh , Singh Baldeep , Jain Preeti , Kumari Anjna , Pahuja Isha , Chaturvedi Shivam , Prasad Durbaka Vijay Raghava , Dwivedi Ved Prakash , Das Gobardhan 
Published: July 2022

AbstractDirectly Observed Treatment Short-course (DOTs), is an effective and widely recommended treatment for tuberculosis (TB). The antibiotics used in DOTs, are immunotoxic and impair effector T cells, increasing the risk of re-infections and reactivation. Multiple reports suggest that addition of immune-modulators along with antibiotics improves the effectiveness of TB treatment. Therefore, drugs with both antimicrobial and immunomodulatory properties are desirable. N1-(Adamantan-2-yl)-N2-[(2E)-3,7-dimethylocta-2,6-dien-1-yl]ethane-1,2-diamine (SQ109) is an asymmetric diamine derivative of adamantane, that targets Mycobacterial membrane protein Large 3 (MmpL3). SQ109 dissipates the transmembrane electrochemical proton-gradient necessary for cell-wall biosynthesis and bacterial activity. Here, we examined the effects of SQ109 on host-immune responses using a murine TB model. Our results suggest the pro-inflammatory nature of SQ109, which instigates M1-macrophage polarization and induces protective pro-inflammatory cytokines through the p38-MAPK pathway. SQ109 also promotes Th1 and Th17-immune responses that inhibit the bacillary burden in a murine model of TB. These findings put forth SQ109 as a potential-adjunct to TB antibiotic therapy.
Whole genome sequence association analysis of fasting glucose and fasting insulin levels in diverse cohorts from the NHLBI TOPMed program
Authors: DiCorpo Daniel , Gaynor Sheila M. , Russell Emily M. , Westerman Kenneth E. , Raffield Laura M. , Majarian Timothy D. , Wu Peitao , Sarnowski Chloé , Highland Heather M. , Jackson Anne , Hasbani Natalie R. , de Vries Paul S. , Brody Jennifer A. , Hidalgo Bertha , Guo Xiuqing , Perry James A. , O’Connell Jeffrey R. , Lent Samantha , Montasser May E. , Cade Brian E. , Jain Deepti , Wang Heming , D’Oliveira Albanus Ricardo , Varshney Arushi , Yanek Lisa R. , Lange Leslie , Palmer Nicholette D. , Almeida Marcio , Peralta Juan M. , Aslibekyan Stella , Baldridge Abigail S. , Bertoni Alain G. , Bielak Lawrence F. , Chen Chung-Shiuan , Chen Yii-Der Ida , Choi Won Jung , Goodarzi Mark O. , Floyd James S. , Irvin Marguerite R. , Kalyani Rita R. , Kelly Tanika N. , Lee Seonwook , Liu Ching-Ti , Loesch Douglas , Manson JoAnn E. , Minster Ryan L. , Naseri Take , Pankow James S. , Rasmussen-Torvik Laura J. , Reiner Alexander P. , Reupena Muagututi’a Sefuiva , Selvin Elizabeth , Smith Jennifer A. , Weeks Daniel E. , Xu Huichun , Yao Jie , Zhao Wei , Parker Stephen , Alonso Alvaro , Arnett Donna K. , Blangero John , Boerwinkle Eric , Correa Adolfo , Cupples L. Adrienne , Curran Joanne E. , Duggirala Ravindranath , He Jiang , Heckbert Susan R. , Kardia Sharon L. R. , Kim Ryan W. , Kooperberg Charles , Liu Simin , Mathias Rasika A. , McGarvey Stephen T. , Mitchell Braxton D. , Morrison Alanna C. , Peyser Patricia A. , Psaty Bruce M. , Redline Susan , Shuldiner Alan R. , Taylor Kent D. , Vasan Ramachandran S. , Viaud-Martinez Karine A. , Florez Jose C. , Wilson James G. , Sladek Robert , Rich Stephen S. , Rotter Jerome I. , Lin Xihong , Dupuis Josée , Meigs James B. , Wessel Jennifer , Manning Alisa K. 
Published: July 2022

AbstractThe genetic determinants of fasting glucose (FG) and fasting insulin (FI) have been studied mostly through genome arrays, resulting in over 100 associated variants. We extended this work with high-coverage whole genome sequencing analyses from fifteen cohorts in NHLBI’s Trans-Omics for Precision Medicine (TOPMed) program. Over 23,000 non-diabetic individuals from five race-ethnicities/populations (African, Asian, European, Hispanic and Samoan) were included. Eight variants were significantly associated with FG or FI across previously identified regions MTNR1B, G6PC2, GCK, GCKR and FOXA2. We additionally characterize suggestive associations with FG or FI near previously identified SLC30A8, TCF7L2, and ADCY5 regions as well as APOB, PTPRT, and ROBO1. Functional annotation resources including the Diabetes Epigenome Atlas were compiled for each signal (chromatin states, annotation principal components, and others) to elucidate variant-to-function hypotheses. We provide a catalog of nucleotide-resolution genomic variation spanning intergenic and intronic regions creating a foundation for future sequencing-based investigations of glycemic traits.
A native IgE in complex with profilin provides insights into allergen recognition and cross-reactivity
Authors: García-Ramírez Benjamín , Mares-Mejía Israel , Rodríguez-Hernández Annia , Cano-Sánchez Patricia , Torres-Larios Alfredo , Ortega Enrique , Rodríguez-Romero Adela 
Published: July 2022

AbstractAllergies have become a rising health problem, where plentiful substances can trigger IgE-mediated allergies in humans. While profilins are considered minor allergens, these ubiquitous proteins are primary molecules involved in cross-reactivity and pollen-food allergy syndrome. Here we report the first crystal structures of murine Fab/IgE, with its chains naturally paired, in complex with the allergen profilin fromHevea brasiliensis(Hev b 8). The crystallographic models revealed that the IgE’s six complementarity-determining regions (CDRs) interact with the allergen, comprising a rigid paratope-epitope surface of 926 Å2, which includes an extensive network of interactions. Interestingly, we also observed previously unreported flexibility at Fab/IgE’s elbow angle, which did not influence the shape of the paratope. The Fab/IgE exhibits a high affinity for Hev b 8, even when using 1 M NaCl in BLI experiments. Finally, based on the encouraging cross-reactivity assays using two mutants of the maize profilin (Zea m 12), this antibody could be a promising tool in IgE engineering for diagnosis and research applications.
ISX-9 potentiates CaMKIIδ-mediated BMAL1 activation to enhance circadian amplitude
Authors: Li Huilin , Ou Jiali , Li Yaqun , Xu Niannian , Li Qing , Wu Ping , Peng Chao , Tang Yun-Chi , Chang Hung-Chun 
Published: July 2022

AbstractCircadian dysregulation associates with numerous diseases including metabolic dysfunction, sleep disorder, depression and aging. Given that declined circadian amplitude is a trait commonly found with compromised health, interventions that design in precluding circadian amplitude from dampening will aid to mitigate complex, circadian-related diseases. Here we identify a neurogenic small molecule ISX-9 that is able to support persistent and higher amplitude of circadian oscillations. ISX-9 improves diurnal metabolic rhythms in middle-aged mice. Moreover, the ISX-9-treated mice show better sleep homeostasis with increased delta power during the day time and higher locomotive activity in the dark period. ISX-9 augments CaMKIIδ expression and increases BMAL1 activity via eliciting CaMKIIδ-mediated phosphorylation on BMAL1 residues S513/S515/S516, accordingly composes a positive feedback effect on enhancing circadian amplitude. CaMKIIδ-targeting, and the use of ISX-9 may serve as decent choices for treating circadian-related disorders.
Anaerobic oxidation has a minor effect on mitigating seafloor methane emissions from gas hydrate dissociation
Authors: Stranne Christian , O’Regan Matt , Hong Wei-Li , Brüchert Volker , Ketzer Marcelo , Thornton Brett F. , Jakobsson Martin 
Published: July 2022

AbstractContinental margin sediments contain large reservoirs of methane stored as gas hydrate. Ocean warming will partly destabilize these reservoirs which may lead to the release of substantial, yet unconstrained, amounts of methane. Anaerobic oxidation of methane is the dominant biogeochemical process to reduce methane flux, estimated to consume 90% of the methane produced in marine sediments today. This process is however neglected in the current projections of seafloor methane release from gas hydrate dissociation. Here, we introduce a fully coupled oxidation module to a hydraulic-thermodynamic-geomechanical hydrate model. Our results show that for seafloor warming rates > 1 °C century−1, the efficiency of anaerobic oxidation of methane in low permeability sediments is poor, reducing the seafloor methane emissions by <5%. The results imply an extremely low mitigating effect of anaerobic oxidation of methane on climate warming-induced seafloor methane emissions.
Photosynthetic microorganisms effectively contribute to bryophyte CO2 fixation in boreal and tropical regions
Authors: Jassey Vincent E J , Hamard Samuel , Lepère Cécile , Céréghino Régis , Corbara Bruno , Küttim Martin , Leflaive Joséphine , Leroy Céline , Carrias Jean-François 
Published: July 2022

Abstract
Photosynthetic microbes are omnipresent in land and water. While they critically influence primary productivity in aquatic systems, their importance in terrestrial ecosystems remains largely overlooked. In terrestrial systems, photoautotrophs occur in a variety of habitats, such as sub-surface soils, exposed rocks, and bryophytes. Here, we study photosynthetic microbial communities associated with bryophytes from a boreal peatland and a tropical rainforest. We interrogate their contribution to bryophyte C uptake and identify the main drivers of that contribution. We found that photosynthetic microbes take up twice more C in the boreal peatland (~4.4 mg CO2.h−1.m−2) than in the tropical rainforest (~2.4 mg CO2.h−1.m−2), which corresponded to an average contribution of 4% and 2% of the bryophyte C uptake, respectively. Our findings revealed that such patterns were driven by the proportion of photosynthetic protists in the moss microbiomes. Low moss water content and light conditions were not favourable to the development of photosynthetic protists in the tropical rainforest, which indirectly reduced the overall photosynthetic microbial C uptake. Our investigations clearly show that photosynthetic microbes associated with bryophyte effectively contribute to moss C uptake despite species turnover. Terrestrial photosynthetic microbes clearly have the capacity to take up atmospheric C in bryophytes living under various environmental conditions, and therefore potentially support rates of ecosystem-level net C exchanges with the atmosphere.
Kalman and Cauchy clustering for anomaly detection based authentication of IoMTs using extreme learning machine
Authors: Mohamed Tamara Saad , Aydin Sezgin , Alkhayyat Ahmed , Malik Rami Q. 
Published: July 2022

AbstractThe vulnerabilities of the Internet of Things (IoTs) in general and the Internet of Mobile Things (IoMTs) in particular motivate researchers to equip them with security systems against intruders and attacks. The integration of anomaly detection with intrusion detection for IoMTs has not been addressed adequately. This paper tackles this issue through building a Kalman filter and Cauchy clustering algorithm for anomaly detection and using them for authentication nodes within IoMTs using the Extreme Learning Machine classifier. The algorithm of this proposed work is composed of various components; first, the Kalman filter‐based model for estimating the trajectory of pedestrians within an indoor environment based on fusing WiFi with IMU data. Second, trustworthiness assessment for detecting anomaly behaviour in IoMT based on the estimated trajectory using the Kalman filter. Third, the trust IDS model for IoMT systems by integrating anomaly detection with online learning for attacks identification using an online sequential extreme learning machine. The algorithm has been implemented and evaluated using TamperU dataset for WiFi fingerprinting and KDD99 for intrusion detection. Furthermore, a comparison with benchmarks (the algorithms which used in other studies) for intrusion and anomaly detection proves the superiority of this proposed approach in terms of all the considered classification metrics.
Die Zusatzweiterbildung Klinische Akut- und Notfallmedizin
Authors: Schunk Domagoj , Malsy Manuela , Zimmermann Markus 
Published: July 2022

AbstractGerman emergency departments have experienced significant development in recent years due to changes in health care policy as well as continued professionalism in emergency department
medical care. The German Medical Association has taken this development into account and included an additional post residency fellowship training program in emergency medicine into their
2018 model training regulation guidelines. The specialized training in emergency medicine covers the initial diagnosis and treatment of patients in the emergency department as well as
medical decision making and coordination of further specialist medical care in interdisciplinary cooperation. The following article provides information about requirements, content, and
duration of the fellowship training program in emergency medicine, which has now been introduced in emergency departments throughout Germany.
Leitliniengerechte Synkopenabklärung
Authors: Diehl Rolf R. 
Published: July 2022

ZUSAMMENFASSUNGSynkopen bilden bei älteren Menschen häufige Sturzursachen. Die beste Sturzprophylaxe besteht in der ätiologischen Abklärung und Behandlung des Synkopenleidens. Die aktuellen Synkopenleitlinien der Deutschen Gesellschaft für Neurologie empfehlen bei Synkopenverdacht zunächst eine hypothesenorientierte Basisdiagnostik, in deren Zentrum die Anamnese mit einer sorgfältigen Exploration der verschiedenen Phasen des Ablaufes einer vorübergehenden Bewusstlosigkeit steht. Zur Basisdiagnostik gehören ferner ein 12-Kanal-EKG und Blutdruckmessungen im Liegen und im Stehen (aktiver Stehtest). Vasovagale Synkopen können bereits nach Anamnese und ohne weitere Zusatzdiagnostik diagnostiziert werden, wenn die Ohnmachten in typischen Situationen (z. B. Verletzungskontext) auftreten und ihnen Prodromi wie Wärmegefühl oder Schwitzen vorausgehen. Bei älteren Patienten bilden orthostatische Blutdruckabfälle durch eine zentrale oder periphere Schädigung des autonomen Nervensystems einen häufigen Synkopenmechanismus, weshalb der aktive Stehtest besonders beim älteren Menschen oft weitere Zusatzdiagnostik überflüssig macht.
Evaluation der langfristigen klinischen und ökonomischen Auswirkungen einer Behandlung mit Ofatumumab gegenüber Dimethylfumarat und Glatirameracetat bei Patienten mit schubförmiger Multipler Sklerose aus gesellschaftlicher Sicht in Deutschland
Authors: Koeditz Dominik , Frensch Jürgen , Bierbaum Martin , Ness Nils-Henning , Ettle Benjamin , Ziemssen Tjalf 
Published: July 2022

ZUSAMMENFASSUNG
Hintergrund Es gibt Hinweise darauf, dass bei schubförmiger Multipler Sklerose (Relapsing Multiple Sclerosis; RMS) ein früher Beginn einer hochwirksamen Therapie einer Eskalationsstrategie überlegen sein könnte.
Ziel Mit Hilfe einer Kosten-Folgen-Analyse sollen die klinischen und gesundheitsökonomischen Auswirkungen verschiedener Behandlungsszenarien mit Ofatumumab (OMB), Dimethylfumarat (DMF) bzw. Glatirameracetat (GA) simuliert werden: ein sofortiger Behandlungsbeginn mit OMB als Ersttherapie, ein früher Wechsel auf OMB nach einem Jahr unter Behandlung mit DMF oder GA, ein später Wechsel nach 5 Jahren bzw. kein Wechsel.
Methodik Der Simulation wurde ein EDSS-basiertes Markov-Modell mit einem Zeithorizont von 10 Jahren zugrunde gelegt. Bei jedem Zyklusübergang waren eine Progression, eine Verbesserung bzw. eine Stabilisierung des EDSS, ein Behandlungsabbruch, Schub oder Tod möglich. Inputdaten für das Modell stammten aus OMB-Studien, einer Netzwerk-Metaanalyse, aus Fachveröffentlichungen und öffentlich verfügbaren Quellen.
Ergebnisse Ein später Wechsel auf OMB resultierte im Vergleich mit der sofortigen OMB-Behandlung in einem geringeren Anteil an Patienten mit einem EDSS von 0 bis 3 nach 10 Jahren (∆ –7,5 % DMF; ∆ –10,3 % GA), in mehr Schüben (∆ + 0,72 DMF; ∆ + 1,23 GA) und in geringeren Beschäftigungsquoten (∆ –4,0 % DMF; ∆ –5,6 % GA). Dies gilt ebenso für den Vergleich eines späten mit einem frühen Wechsel. Das Szenario ohne Therapieumstellung führte zu schlechteren Ergebnissen. Die Arzneimittelkosten waren bei sofortiger bzw. früher OMB-Behandlung höher, wurden aber nahezu ausgeglichen durch niedrigere Kosten für die Patientenversorgung (u. a. stationäre bzw. informelle Pflege, gemeinschaftliche und soziale Dienstleistungen) und geringere Produktivitätsverluste.
Schlussfolgerung Eine sofortige Behandlung mit OMB bzw. ein früher Wechsel auf OMB führen zu besseren Ergebnissen hinsichtlich Klinik und Produktivität im Vergleich zu spätem oder keinem Wechsel auf OMB. Dabei bleiben die sofortige bzw. frühe OMB-Behandlung nahezu kostenneutral.
Choroidal Manifestation of Smoldering Myeloma: Case Report
Authors: Sokolenko Ekaterina , Johansson Patricia , Ting Saskia , Bechrakis Nikolaos E. , Fiorentzis Miltiadis 
Published: July 2022

AbstractThis case illustrates clinical, histopathological, immunohistochemical, and molecular pathological diagnostic testing of smoldering myeloma with atypical ophthalmic manifestations. In our
case, the choroidal lesion presented as a solitary manifestation of a systemic disease. Choroidal lesions of monoclonal plasma cells are extremely rare and should be included in the
differential diagnosis of amelanotic choroidal lesions, even if the histopathological examination of the primary lesion is not informative. Clinical course, immunohistochemistry, and
molecular pathology are essential components of the diagnostic pathway.
Oft übersehen – Ohnmacht und Kreislaufstörungen im Alter
Authors: Haubrich Christina 
Published: July 2022

ZUSAMMENFASSUNGBei älteren Patienten ist davon auszugehen, dass etwa die Hälfte aller Stürze unklarer Ursache auf Synkopen zurückzuführen ist. Gründe hierfür sind unter anderem die fehlende Erinnerung an Beschwerden wie Schwindel oder Benommenheit im Vorfeld des Sturzes und die oft atypischen Beschwerden. Dies trifft insbesondere auf ältere Patienten mit neurologischen bzw. neurodegenerativen Erkrankungen zu. Begünstigend hierfür sind zentrale und periphere neurovegetative Störungen, aber auch Vorerkrankungen des Herzens, Polypharmazie und Veränderungen des Salz-Wasserhaushaltes. In der Behandlung von Stürzen unklarer Ursache sollten Synkopen deshalb besonders berücksichtigt werden. Das beinhaltet die Anamnese neurologischer und kardiologisch-internistischer Risikofaktoren, die orientierende Untersuchung der Kreislaufregulation mittels verkürztem Schellong-Test sowie ggf. die Diagnostik neurovegetativer Kreislaufregulation bzw. autonome Funktionsdiagnostik. Der Behandlungserfolg hängt davon ab, ob medikamentöse und nicht medikamentöse Behandlungsempfehlungen interdisziplinär abgestimmt sind. Um erfolgreich vorbeugen zu können, sollten Patienten und Angehörige über das Risiko von Stürzen und Synkopen aufgeklärt werden.
Natural Dibenzo[b,f]oxepines, Pacharin and Bauhiniastatin-1, Isolated from Bauhinia acuruana Induce Apoptosis on Breast Cancer Cells via MCL-1 Protein
Reduction
Authors: Souza Silvia de Maria , Souza Luciano Santos de , Silva Valdenizia Rodrigues , Soares Milena Botelho Pereira , Bezerra Daniel Pereira , Gois Roberto Wagner da Silva , Silva Horlando Carlota da , Santiago Gilvandete Maria Pinheiro , Militao Gardenia Carmen Gadelha 
Published: July 2022

AbstractHerein, we describe the antiproliferative effects of two natural dibenzo [b,f]oxepines, pacharin and bauhiniastatin-1, isolated from Bauhinia acuruana on a breast cancer cell
line and the mode of action underlying the cytotoxicity. Both compounds were cytotoxic in a panel of six tumor lines analyzed by the MTT assay, and IC50 values ranged from 7.8 to
45.1 µM, including human breast adenocarcinoma (MCF-7) cells. In contrast, none of the compounds were cytotoxic on normal human peripheral blood mononuclear cells (IC50
> 100 µM). Human breast adenocarcinoma (MCF-7) cells treated with pacharin or bauhiniastatin-1 20 µM for 24 h presented a reduction in cell volume and intensification of chromatin
condensation, DNA fragmentation, and apoptotic cells. These findings became more evident after 48 h of exposure. Antiapoptotic B-cell lymphoma-2 family members, such as myeloid cell
leukemia-1 and B-cell lymphoma-extra large, are important targets in cancer cells since their overexpression confers resistance to cancer treatments. A significant reduction of the myeloid
cell leukemia-1 protein levels in human breast adenocarcinoma (MCF-7) cells after 24 h of treatment with pacharin or bauhiniastatin-1 at 20 µM was observed, while the B-cell lymphoma-extra
large protein content was reduced in bauhiniastatin-1-treated cells at 40 µM only. The cytotoxic effects of pacharin and bauhiniastatin-1 are likely linked to myeloid cell leukemia-1
inhibition, which leads to the apoptosis of breast adenocarcinoma cells.