bluuebunny/crossref_metadata_2025_split huggingface dataset:
Controlling gene expression with deep generative design of regulatory DNA
Authors: Zrimec Jan , Fu Xiaozhi , Muhammad Azam Sheikh , Skrekas Christos , Jauniskis Vykintas , Speicher Nora K. , Börlin Christoph S. , Verendel Vilhelm , Chehreghani Morteza Haghir , Dubhashi Devdatt , Siewers Verena , David Florian , Nielsen Jens , Zelezniak Aleksej 
Published: August 2022

AbstractDesign of de novo synthetic regulatory DNA is a promising avenue to control gene expression in biotechnology and medicine. Using mutagenesis typically requires screening sizable random DNA libraries, which limits the designs to span merely a short section of the promoter and restricts their control of gene expression. Here, we prototype a deep learning strategy based on generative adversarial networks (GAN) by learning directly from genomic and transcriptomic data. Our ExpressionGAN can traverse the entire regulatory sequence-expression landscape in a gene-specific manner, generating regulatory DNA with prespecified target mRNA levels spanning the whole gene regulatory structure including coding and adjacent non-coding regions. Despite high sequence divergence from natural DNA, in vivo measurements show that 57% of the highly-expressed synthetic sequences surpass the expression levels of highly-expressed natural controls. This demonstrates the applicability and relevance of deep generative design to expand our knowledge and control of gene expression regulation in any desired organism, condition or tissue.
Tackling recalcitrant Pseudomonas aeruginosa infections in critical illness via anti-virulence monotherapy
Authors: Singh Vijay K. , Almpani Marianna , Maura Damien , Kitao Tomoe , Ferrari Livia , Fontana Stefano , Bergamini Gabriella , Calcaterra Elisa , Pignaffo Chiara , Negri Michele , de Oliveira Pereira Thays , Skinner Frances , Gkikas Manos , Andreotti Danielle , Felici Antonio , Déziel Eric , Lépine Francois , Rahme Laurence G. 
Published: August 2022

AbstractIntestinal barrier derangement allows intestinal bacteria and their products to translocate to the systemic circulation. Pseudomonas aeruginosa (PA) superimposed infection in critically ill patients increases gut permeability and leads to gut-driven sepsis. PA infections are challenging due to multi-drug resistance (MDR), biofilms, and/or antibiotic tolerance. Inhibition of the quorum-sensing transcriptional regulator MvfR(PqsR) is a desirable anti-PA anti-virulence strategy as MvfR controls multiple acute and chronic virulence functions. Here we show that MvfR promotes intestinal permeability and report potent anti-MvfR compounds, the N-Aryl Malonamides (NAMs), resulting from extensive structure-activity-relationship studies and thorough assessment of the inhibition of MvfR-controlled virulence functions. This class of anti-virulence non-native ligand-based agents has a half-maximal inhibitory concentration in the nanomolar range and strong target engagement. Using a NAM lead in monotherapy protects murine intestinal barrier function, abolishes MvfR-regulated small molecules, ameliorates bacterial dissemination, and lowers inflammatory cytokines. This study demonstrates the importance of MvfR in PA-driven intestinal permeability. It underscores the utility of anti-MvfR agents in maintaining gut mucosal integrity, which should be part of any successful strategy to prevent/treat PA infections and associated gut-derived sepsis in critical illness settings. NAMs provide for the development of crucial preventive/therapeutic monotherapy options against untreatable MDR PA infections.
Antipsychotic-induced weight gain and metabolic effects show diurnal dependence and are reversible with time restricted feeding
Authors: Zapata Rizaldy C. , Silver Allison , Yoon Dongmin , Chaudry Besma , Libster Avraham , McCarthy Michael J. , Osborn Olivia 
Published: August 2022

AbstractAntipsychotic drugs (AP) are highly efficacious treatments for psychiatric disorders but are associated with significant metabolic side-effects. The circadian clock maintains metabolic homeostasis by sustaining daily rhythms in feeding, fasting and hormone regulation but how circadian rhythms interact with AP and its associated metabolic side-effects is not well-known. We hypothesized that time of AP dosing impacts the development of metabolic side-effects. Weight gain and metabolic side-effects were compared in C57Bl/6 mice and humans dosed with APs in either the morning or evening. In mice, AP dosing at the start of the light cycle/rest period (AM) resulted in significant increase in food intake and weight gain compared with equivalent dose before the onset of darkness/active period (PM). Time of AP dosing also impacted circadian gene expression, metabolic hormones and inflammatory pathways and their diurnal expression patterns. We also conducted a retrospective examination of weight and metabolic outcomes in patients who received risperidone (RIS) for the treatment of serious mental illness and observed a significant association between time of dosing and severity of RIS-induced metabolic side-effects. Time restricted feeding (TRF) has been shown in both mouse and some human studies to be an effective therapeutic intervention against obesity and metabolic disease. We demonstrate, for the first time, that TRF is an effective intervention to reduce AP-induced metabolic side effects in mice. These studies identify highly effective and translatable interventions with potential to mitigate AP-induced metabolic side effects.
Breast lesion detection using an anchor-free network from ultrasound images with segmentation-based enhancement
Authors: Wang Yu , Yao Yudong 
Published: August 2022

AbstractThe survival rate of breast cancer patients is closely related to the pathological stage of cancer. The earlier the pathological stage, the higher the survival rate. Breast ultrasound is a commonly used breast cancer screening or diagnosis method, with simple operation, no ionizing radiation, and real-time imaging. However, ultrasound also has the disadvantages of high noise, strong artifacts, low contrast between tissue structures, which affect the effective screening of breast cancer. Therefore, we propose a deep learning based breast ultrasound detection system to assist doctors in the diagnosis of breast cancer. The system implements the automatic localization of breast cancer lesions and the diagnosis of benign and malignant lesions. The method consists of two steps: 1. Contrast enhancement of breast ultrasound images using segmentation-based enhancement methods. 2. An anchor-free network was used to detect and classify breast lesions. Our proposed method achieves a mean average precision (mAP) of 0.902 on the datasets used in our experiment. In detecting benign and malignant tumors, precision is 0.917 and 0.888, and recall is 0.980 and 0.963, respectively. Our proposed method outperforms other image enhancement methods and an anchor-based detection method. We propose a breast ultrasound image detection system for breast cancer detection. The system can locate and diagnose benign and malignant breast lesions. The test results on single dataset and mixed dataset show that the proposed method has good performance.
Psychiatrically relevant signatures of domain-general decision-making and metacognition in the general population
Authors: Benwell Christopher S. Y. , Mohr Greta , Wallberg Jana , Kouadio Aya , Ince Robin A. A. 
Published: August 2022

AbstractHuman behaviours are guided by how confident we feel in our abilities. When confidence does not reflect objective performance, this can impact critical adaptive functions and impair life quality. Distorted decision-making and confidence have been associated with mental health problems. Here, utilising advances in computational and transdiagnostic psychiatry, we sought to map relationships between psychopathology and both decision-making and confidence in the general population across two online studies (N’s = 344 and 473, respectively). The results revealed dissociable decision-making and confidence signatures related to distinct symptom dimensions. A dimension characterised by compulsivity and intrusive thoughts was found to be associated with reduced objective accuracy but, paradoxically, increased absolute confidence, whereas a dimension characterized by anxiety and depression was associated with systematically low confidence in the absence of impairments in objective accuracy. These relationships replicated across both studies and distinct cognitive domains (perception and general knowledge), suggesting that they are reliable and domain general. Additionally, whereas Big-5 personality traits also predicted objective task performance, only symptom dimensions related to subjective confidence. Domain-general signatures of decision-making and metacognition characterise distinct psychological dispositions and psychopathology in the general population and implicate confidence as a central component of mental health.
Construction of a semi‐dense point cloud model for a tube‐to‐tubesheet welding robot
Authors: Wang Hui , Rong Youmin , Liu Chao , Huang Yu 
Published: August 2022

AbstractTube‐to‐tubesheet welding is widely applied in industrial fields. However, the current tubesheet welding robot still mainly relies on manual tubesheet models. Aiming to solve this problem, this paper proposed an improved direct method to automatically establish a tubesheet semi‐dense point cloud model based on a selected monocular camera and a one‐dimension (1D) laser rangefinder. Firstly, a laser filtering method was designed to acquire the distance between the camera and tubesheet through the 1D laser rangefinder. Then, from combing the 1D laser rangefinder data with keyframe data, the scale factor was obtained and proceeded to be processed by the Kalman filter to reduce the error. Then, the computed scale factor and all the keyframes were calculated to construct the tubesheet point cloud model through the graph optimisation algorithm. The experimental results showed that the semi‐dense point cloud model of the tubesheet could be efficiently established by the proposed algorithm with row error and column error both less than 1 mm, satisfying the welding requirements.
Modulated conductive bridge memory characteristics by radio frequency input and non‐volatile switching of frequency multiplication
Authors: Yin Yifei , Uchida Chihiro , Tsukamoto Keito , Hayashi Hitoshi , Nakaoka Toshihiro 
Published: August 2022

AbstractThe authors present an Ag‐GeTe‐based conductive bridge memory that allows radio frequency (RF) input and transmission. The RF input modifies the resistance switching characteristics and the memory device can switch the order of harmonics of the transmitted RF wave. The transmittance for the RF input above 500 MHz was higher than 0.5 for both the low‐resistance state (LRS) and the high‐resistance state (HRS). Below 500 MHz the transmittance decreased with decreasing frequency and depended on the resistance state (LRS or HRS). At 20 MHz, the transmission for the HRS was 0.02, while that for the LRS was 0.2. An RF input of 20 MHz at 10 dBm modified the SET voltage from 0.19 to 0.05 V, and the RESET voltage from −0.17 to −0.05 V. The RF wave transmitted through the LRS consisted almost entirely of fundamental waves, while that in the HRS provided harmonics or frequency multiplication up to the fifth order at 150 MHz at 10 dBm. Heat cycle measurements with RF input revealed the difference between the non‐linear resistance producing the frequency multiplication and the DC resistance.
Energy router interconnection system: A solution for new distribution network architecture toward future carbon neutrality
Authors: Liu Bin , Zhu Bingzhao , Guan Ziyou , Mao Chengxiong , Wang Dan 
Published: August 2022

AbstractUnder the background of carbon neutrality, distribution networks are facing many new challenges, including providing higher power supply reliability and power quality, additional power supply forms, and better information sharing. The traditional distribution network has difficulty coping with these challenges; thus, it is imperative to transform the traditional distribution network architecture. An energy router (ER) is a type of intelligent power electronic device, and has the potential to play a great role in the transformation of the distribution network. This paper proposes the basic architecture of an ER interconnection system (ERIS), where multiple ERs are gathered together to play a stronger role. Aiming for two different stages of the transformation process of the distribution network, two types of ERISs are employed for a single prosumer and multiple prosumers, respectively. The equivalent modelling, main control strategies, and energy management schemes of the two types of ERIS are respectively illustrated. Several ERIS simulation cases are investigated, and the results verify the advantages and satisfactory performance of the ERIS. The proposed ERIS provides an effective solution for building a new distribution network to adapt to the new challenges in a future carbon neutral era.
Second harmonic voltage injection‐based self impedance estimation for effective decoupled droop control in a microgrid
Authors: Malakondaiah Muli , Boddeti Kalyan Kumar , Naidu Bonu Ramesh , Bajpai Prabodh 
Published: August 2022

AbstractIn an islanded microgrid (IMG), droop control effectively shares real and reactive power demands among distributed generators (DGs), thereby regulating the frequency and voltage in high X/R ratio networks. However, there is a strong coupling between the real power voltage and reactive power frequency in medium‐ and low‐voltage microgrids due to the low X/R ratio. For effective droop control, the coupling between the real power voltage and reactive power frequency should be eliminated through decoupling factors. Existing methods in the literature on decoupled droop control do not consider the effect of changing network conditions. This study proposes a decoupling method for improved power sharing among parallel‐operated inverter‐based DGs. Each DG injects a second‐harmonic voltage, based on which a second‐harmonic self‐impedance is calculated at the DG terminal. With certain assumptions, the fundamental self‐impedance is computed and used to determine the decoupling factors. The proposed method was implemented on two test cases and compared with existing droop methods. In comparison, the power‐sharing ratio is close to the actual value of the proposed method. The simulation results clearly demonstrate that the proposed method improves power‐sharing accuracy despite varying the load and network topology.
Improvement of VSG Transient Performance Based on Power Feedforward Decoupling Control
Authors: Liu Andong , Liu Jun , Wu Qiong 
Published: August 2022

AbstractThe suppression of power grid frequency fluctuation, the inhibition of output active power oscillation, and the coupling of active and reactive power at the output of the virtual synchronous generator (VSG) are all investigated in this work. The connection between VSG output active power oscillation inhibition and grid frequency fluctuation suppression is explored, as well as the difficulties of achieving both power oscillation suppression and frequency fluctuation suppression for VSG at the same time. To overcome this problem, a control approach incorporating notch filter power feedforward decoupling and modifying virtual damping coefficient is presented, it is called power feedforward decoupling control (PFDC). The virtual resistance will worsen the P/Q coupling, whereas the virtual inductance will have no effect, according to the results of the P/Q coupling analysis. It can be demonstrated that the suggested solution does not jeopardize P/Q decoupling performance for VSG active power oscillation suppression and grid frequency fluctuation suppression. The understanding of VSG transient performance is deepened by the comprehensive investigation of the three issues. Finally, simulation is used to verify the soundness of the theoretical analysis and proposed strategy, while VSG's transient performance is increased even more.
Robust stability analysis of a novel droop‐based distributed control scheme for islanded operation of DC microgrids
Authors: Mirjafari Mohammadreza , Banejad Mahdi , Molla‐Ahmadian Hamed , Sedehi Ali , Blaabjerg Frede 
Published: August 2022

AbstractDC microgrid is a high‐efficiency plan for exploiting and controlling distributed generation (DG) resources that can supply local loads in grid‐connected or islanded mode. Conventionally, the droop control method is utilized to attain proper load sharing among the DGs as a decentralized approach in DC microgrids. However, accurate current sharing among DG units with different line resistances is not achievable by the conventional droop control, whereas this method also increases the DC bus voltage deviation. In this paper, a new droop‐based distributed control method is proposed in the secondary control level to overcome the limitations of droop control. To implement the proposed method, only the amount of precalculated virtual voltage drop of DG units is shared with adjacent DGs through a low‐bandwidth communication, and other calculations are local. So, there is no need to define and share new parameters, and get feedback from the DC bus voltage. By employing the proposed method, not only accurate current sharing among the DG units is guaranteed but also DC bus voltage is restored to the nominal value. To ensure the stability of the proposed method, the robust stability and performance of the closed‐loop system are analyzed by structured singular value (µ) under resistive load and communication delay changes. Finally, a DC microgrid is evaluated using MATLAB/Simulink as well as experimental tests to illustrate the validity and efficiency of the proposed method.
Prinzipien der Osteosynthese im Bereich des Gesichtsschädels
Authors: Wilde Frank , Schramm Alexander 
Published: August 2022

ZusammenfassungWährend sich die Grundprinzipien der Osteosyntheseverfahren bei der Gesichtsschädelrekonstruktion in den letzten Jahren wenig verändert haben, fand durch Weiterentwicklung der Osteosynthesesysteme und -instrumente sowie durch die Implementierung der computerassistierten Chirurgie einschließlich der Verwendung anatomisch präformierter oder patientenspezifischer Implantate eine entscheidende Weiterentwicklung statt.
Update nephrotisches Syndrom – neue pathophysiologische Konzepte 2022
Authors: Hoxha Elion 
Published: August 2022

Was ist neu?
Pathogenese der MGN Die Identifikation der für die Entstehung der MGN verantwortlichen Autoantikörper ermöglicht es, die Diagnose und Therapie an die molekulare Pathogenese der Erkrankung anzupassen. Die zugrunde liegenden Mechanismen der PLA2R1-Antikörper-Entstehung sind noch unklar. Umweltfaktoren wie Luftverschmutzung sowie genetische Faktoren spielen möglicherweise eine wichtige Rolle. Bei der THSD7A-assoziierten MGN können THSD7A-exprimierende Tumore zur Entstehung der THSD7A-Antikörper beitragen.
Klinische Anwendung Eine antigenspezifische Diagnose ist hilfreich, um die anschließende Differenzialdiagnostik der MGN, z. B. eine Tumorsuche, zu individualisieren. PLA2R1-Antikörper sind sehr spezifisch für die Diagnose einer MGN und ermöglichen eine personalisierte Entscheidung für oder gegen eine Nierenbiopsie zur Diagnosesicherung, abhängig von der klinischen und laborchemischen Präsentation der Patienten. Die PLA2R1-Antikörper ermöglichen eine stärkere Anpassung der Therapie an die Pathogenese und der immunologischen Aktivität der MGN. Der PLA2R1-Antikörperspiegel wird sowohl zur Risikoeinteilung als auch für Therapie-Entscheidungen genutzt.
PLA2R1-Antikörperbestimmung PLA2R1-Antikörper können gegen verschiede Bindungsstellen am PLA2R1 gerichtet sein. Aktuell ist im klinischen Alltag die Bestimmung der Gesamt-PLA2R1-Antikörperspiegel entscheidend für die Prognose und Therapieüberwachung.
Neue potenzielle Antigene der MGN In den letzten Jahren wurde eine Vielzahl weiterer potenzieller Antigene bei Patienten mit MGN beschrieben. Ihre pathophysiologische Rolle ist noch nicht geklärt. Je nach beschriebenem Antigen wurden Assoziationen der MGN mit verschiedenen Erkrankungen berichtet.
Pathogenese der MCD und FSGS bleibt ungeklärt. Eine T-Zell-Störung wurde seit Langem als mögliche Ursache angenommen, während in den letzten Jahren auch für B-Zellen und Autoantikörper zunehmend eine pathogenetische Rolle postuliert wird.
Diagnose und Therapie Für die Diagnose einer MCD und FSGS bei Erwachsenen ist die Nierenbiopsie obligat. In der Therapie der primären MCD und FSGS bleibt auch in den neuen KDIGO-Therapie-Empfehlungen die Steroidtherapie die 1. Wahl. In der Zweitlinientherapie werden vor allem Calcineurin-Inhibitoren eingesetzt. Als weitere Therapieoptionen gelten Cyclophosphamid, MMF und Rituximab.
Medikamentenbeschichtete Ballons bei PAVK
Authors: Böhme Tanja , Zeller Thomas 
Published: August 2022

Was ist neu?Paclitaxel-beschichtete Ballons bei femoropoplitealen Läsionen Für die Behandlung femoropoplitealer Gefäßläsionen, bei Verschlusslängen unter 25 cm sowie bei längeren Verschlüssen (wenn kein Venenmaterial vorliegt und/oder das Operationsrisiko hoch ist), wird die endovaskuläre Therapie empfohlen. Um Restenosierungen und Reinterventionen zu vermeiden, wird dabei die Verwendung von medikamentenbeschichteten Ballons empfohlen. Durch die Weiterentwicklung des Ballondesigns kann die Effektivität noch gesteigert werden.Paclitaxel-beschichtete Ballons bei infrapoplitealen Läsionen Im Stadium der kritischen Extremitäten-Ischämie wird bei infrapoplitealen Gefäßläsionen primär ebenfalls ein endovaskulärer Therapieansatz empfohlen. Aufgrund von inkonsistenten, teilweise widersprüchlichen Ergebnissen verschiedener klinischer Studien, kann der Vorteil medikamentenbeschichteter Ballons bei der Angioplastie infrapoplitealer Arterien bislang nicht ausreichend beurteilt werden.Sicherheitsaspekt Paclitaxel-beschichteter Ballons Zahlreiche Real-World-Studien und Nachauswertungen prospektiver Studien konnten den in einer früheren Metaanalyse postulierten Zusammenhang einer höheren Mortalität nach Anwendung Paclitaxel-beschichteter Devices weder bestätigen noch einen möglichen Pathomechanismus oder eine Dosis-Wirkungs-Beziehung aufzeigen. Dennoch wurden die Empfehlungen des Bundesinstituts für Arzneimittel und Medizinprodukte (BfArM) zur sorgfältigen Nutzen-Risiko-Abwägung und Aufklärungspflicht noch nicht angepasst.Sirolimus-beschichtete Ballons Mit dem Zytostatikum Sirolimus steht eine weitere antiproliferativ und zusätzlich antientzündlich wirkende Substanz zur Vermeidung von Restenosierungen bei femoropoplitealen und infrapoplitealen Läsionen zur Verfügung. Die therapeutische Breite von Sirolimus ist zwar größer als die von Paclitaxel, dennoch ist die Gewebeabsorption und -retention von Sirolimus deutlich schwieriger. Erste Ergebnisse aus kleineren Studien, die die Sicherheit und Effektivität Sirolimus-beschichteter Ballons untersuchten, sind vielversprechend, müssen allerdings noch in großen, prospektiven, randomisierten Studien bewiesen werden.
Mitral Annulus Disjunction and Arrhythmic Mitral Valve Prolapse: Emerging Role of Cardiac Magnetic Resonance Imaging in the Workup
Authors: Kulkarni Amol A. , Chudgar Priya D. , Burkule Nitin J. , Kamat Nikhil V. 
Published: August 2022

AbstractMitral valve prolapse is a commonly described entity with a highly variable and benign course. However, it is associated with ventricular arrhythmias and sudden cardiac death in a small subset of patients. Recent studies have yielded insight into myocardial mechanics and the causation of ventricular arrhythmias in these groups of patients.Mitral annular disjunction (MAD) characterized by detachment of mitral annulus from left ventricular myocardium is associated with morphological and functional remodeling of the left ventricular myocardium. Resultant fibrosis acts as a substrate of ventricular arrhythmia and sudden cardiac death.We present two such cases of arrhythmic mitral valve prolapse associated with MAD. Cardiac magnetic resonance imaging provides excellent morphological information and also helps in the assessment of fibrosis.