bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic alterations of Keap1 confers chemotherapeutic resistance through functional activation of Nrf2 and Notch pathway in head and neck squamous cell carcinoma
Authors: Islam Syed S. , Qassem Khawlah , Islam Shafiqul , Parag Rashed R. , Rahman Mohammed Z. , Farhat Walid A. , Yeger Herman , Aboussekhra Abdelilah , Karakas Bedri , Noman Abu Shadat M. 
Published: August 2022

AbstractKeap1 mutations regulate Nrf2 activity and lead to chemoresistance in cancers. Yet the underlying molecular mechanisms of chemoresistance are poorly explored. By focusing and genotyping head and neck squamous cell carcinoma (HNSCC) that had available pathologic and clinical data, we provide evidence that Keap1 displays frequent alterations (17%) in HNSCC. Functional loss of Keap1 results in significant activation of Nrf2 and promotes cancer cell growth, proliferation, and elevated cancer stem cell (CSCs) self-renewal efficiency and resistance to oxidative stress. Furthermore, decreased Keap1 activity in these cells increased nuclear accumulation of Nrf2 and activation of the Notch pathway, causing enhanced transcriptional alterations of antioxidants, xenobiotic metabolism enzymes, and resistance to chemotherapeutic treatment. Limiting the Nrf2 activity by either Keap1 complementation or by Nrf2 silencing increased the sensitivity to chemotherapy in Keap1-mutated cells and repressed the CSC self-renewal activity. Our findings suggest that Keap1 mutations define a distinct disease phenotype and the Keap1-Nrf2 pathway is one of the leading molecular mechanisms for clinical chemotherapeutic resistance. Targeting this pathway may provide a potential and attractive personalized treatment strategy for overcoming chemotherapeutic resistance conferred by Keap1 mutations.
Transferability of genetic loci and polygenic scores for cardiometabolic traits in British Pakistani and Bangladeshi individuals
Authors: Huang Qin Qin , Sallah Neneh , Dunca Diana , Trivedi Bhavi , Hunt Karen A. , Hodgson Sam , Lambert Samuel A. , Arciero Elena , Wright John , Griffiths Chris , Trembath Richard C. , Hemingway Harry , Inouye Michael , Finer Sarah , van Heel David A. , Lumbers R. Thomas , Martin Hilary C. , Kuchenbaecker Karoline 
Published: August 2022

AbstractIndividuals with South Asian ancestry have a higher risk of heart disease than other groups but have been largely excluded from genetic research. Using data from 22,000 British Pakistani and Bangladeshi individuals with linked electronic health records from the Genes & Health cohort, we conducted genome-wide association studies of coronary artery disease and its key risk factors. Using power-adjusted transferability ratios, we found evidence for transferability for the majority of cardiometabolic loci powered to replicate. The performance of polygenic scores was high for lipids and blood pressure, but lower for BMI and coronary artery disease. Adding a polygenic score for coronary artery disease to clinical risk factors showed significant improvement in reclassification. In Mendelian randomisation using transferable loci as instruments, our findings were consistent with results in European-ancestry individuals. Taken together, trait-specific transferability of trait loci between populations is an important consideration with implications for risk prediction and causal inference.
Ultrafast small-scale soft electromagnetic robots
Authors: Mao Guoyong , Schiller David , Danninger Doris , Hailegnaw Bekele , Hartmann Florian , Stockinger Thomas , Drack Michael , Arnold Nikita , Kaltenbrunner Martin 
Published: August 2022

AbstractHigh-speed locomotion is an essential survival strategy for animals, allowing populating harsh and unpredictable environments. Bio-inspired soft robots equally benefit from versatile and ultrafast motion but require appropriate driving mechanisms and device designs. Here, we present a class of small-scale soft electromagnetic robots made of curved elastomeric bilayers, driven by Lorentz forces acting on embedded printed liquid metal channels carrying alternating currents with driving voltages of several volts in a static magnetic field. Their dynamic resonant performance is investigated experimentally and theoretically. These robust and versatile robots can walk, run, swim, jump, steer and transport cargo. Their tethered versions reach ultra-high running speeds of 70 BL/s (body lengths per second) on 3D-corrugated substrates and 35 BL/s on arbitrary planar substrates while their maximum swimming speed is 4.8 BL/s in water. Moreover, prototype untethered versions run and swim at a maximum speed of 2.1 BL/s and 1.8 BL/s, respectively.
Connecting omics signatures and revealing biological mechanisms with iLINCS
Authors: Pilarczyk Marcin , Fazel-Najafabadi Mehdi , Kouril Michal , Shamsaei Behrouz , Vasiliauskas Juozas , Niu Wen , Mahi Naim , Zhang Lixia , Clark Nicholas A. , Ren Yan , White Shana , Karim Rashid , Xu Huan , Biesiada Jacek , Bennett Mark F. , Davidson Sarah E. , Reichard John F. , Roberts Kurt , Stathias Vasileios , Koleti Amar , Vidovic Dusica , Clarke Daniel J. B. , Schürer Stephan C. , Ma’ayan Avi , Meller Jarek , Medvedovic Mario 
Published: August 2022

AbstractThere are only a few platforms that integrate multiple omics data types, bioinformatics tools, and interfaces for integrative analyses and visualization that do not require programming skills. Here we present iLINCS (http://ilincs.org), an integrative web-based platform for analysis of omics data and signatures of cellular perturbations. The platform facilitates mining and re-analysis of the large collection of omics datasets (>34,000), pre-computed signatures (>200,000), and their connections, as well as the analysis of user-submitted omics signatures of diseases and cellular perturbations. iLINCS analysis workflows integrate vast omics data resources and a range of analytics and interactive visualization tools into a comprehensive platform for analysis of omics signatures. iLINCS user-friendly interfaces enable execution of sophisticated analyses of omics signatures, mechanism of action analysis, and signature-driven drug repositioning. We illustrate the utility of iLINCS with three use cases involving analysis of cancer proteogenomic signatures, COVID 19 transcriptomic signatures and mTOR signaling.
Structural and biochemical basis for DNA and RNA catalysis by human Topoisomerase 3β
Authors: Yang Xi , Saha Sourav , Yang Wei , Neuman Keir C. , Pommier Yves 
Published: August 2022

AbstractIn metazoans, topoisomerase 3β (TOP3B) regulates R-loop dynamics and mRNA translation, which are critical for genome stability, neurodevelopment and normal aging. As a Type IA topoisomerase, TOP3B acts by general acid-base catalysis to break and rejoin single-stranded DNA. Passage of a second DNA strand through the transient break permits dissipation of hypernegative DNA supercoiling and catenation/knotting. Additionally, hsTOP3B was recently demonstrated as the human RNA topoisomerase, required for normal neurodevelopment and proposed to be a potential anti-viral target upon RNA virus infection. Here we elucidate the biochemical mechanisms of human TOP3B. We delineate the roles of divalent metal ions, and of a conserved Lysine residue (K10) in the differential catalysis of DNA and RNA. We also demonstrate that three regulatory factors fine-tune the catalytic performance of TOP3B: the TOP3B C-terminal tail, its protein partner TDRD3, and the sequence of its DNA/RNA substrates.
Crustal melting in orogenic belts revealed by eclogite thermal properties
Authors: Zhang Baohua , Fei Hongzhan , Ge Jianhua , Zeng Lingsen , Xia Qunke 
Published: August 2022

AbstractPartial melting in the continental crust may play a critical role on the behavior of continents during collision. However, the occurrence of partial melt in orogenic continental crust is not well understood. Since the temperature of the orogen is controlled by the thermal properties of constituent rocks, we measured the thermal conductivity and diffusivity of eclogite, the most important ultrahigh pressure metamorphic rocks, as a function of pressure, temperature, composition, and water content, and simulated the thermal structure of the Sulu and Himalaya-Tibet orogens in eastern and southwestern China, respectively. Our results show that the temperature at ~30-km depth beneath the orogens reaches the solidus of wet granite and phengite (~940 K), therefore, the partial melting in the orogenic continental crust is well explained. The melt may facilitate the exhumation of subducted crust, produce the low seismic-velocity zone, and cause the high-conductivity anomaly in the shallow depth of orogenic belts.
A lightweight magnetically shielded room with active shielding
Authors: Holmes Niall , Rea Molly , Chalmers James , Leggett James , Edwards Lucy J. , Nell Paul , Pink Stephen , Patel Prashant , Wood Jack , Murby Nick , Woolger David , Dawson Eliot , Mariani Christopher , Tierney Tim M. , Mellor Stephanie , O’Neill George C. , Boto Elena , Hill Ryan M. , Shah Vishal , Osborne James , Pardington Rosemarie , Fierlinger Peter , Barnes Gareth R. , Glover Paul , Brookes Matthew J. , Bowtell Richard 
Published: August 2022

AbstractMagnetically shielded rooms (MSRs) use multiple layers of materials such as MuMetal to screen external magnetic fields that would otherwise interfere with high precision magnetic field measurements such as magnetoencephalography (MEG). Optically pumped magnetometers (OPMs) have enabled the development of wearable MEG systems which have the potential to provide a motion tolerant functional brain imaging system with high spatiotemporal resolution. Despite significant promise, OPMs impose stringent magnetic shielding requirements, operating around a zero magnetic field resonance within a dynamic range of ± 5 nT. MSRs developed for OPM-MEG must therefore effectively shield external sources and provide a low remnant magnetic field inside the enclosure. Existing MSRs optimised for OPM-MEG are expensive, heavy, and difficult to site. Electromagnetic coils are used to further cancel the remnant field inside the MSR enabling participant movements during OPM-MEG, but present coil systems are challenging to engineer and occupy space in the MSR limiting participant movements and negatively impacting patient experience. Here we present a lightweight MSR design (30% reduction in weight and 40–60% reduction in external dimensions compared to a standard OPM-optimised MSR) which takes significant steps towards addressing these barriers. We also designed a ‘window coil’ active shielding system, featuring a series of simple rectangular coils placed directly onto the walls of the MSR. By mapping the remnant magnetic field inside the MSR, and the magnetic field produced by the coils, we can identify optimal coil currents and cancel the remnant magnetic field over the central cubic metre to just |B|= 670 ± 160 pT. These advances reduce the cost, installation time and siting restrictions of MSRs which will be essential for the widespread deployment of OPM-MEG.
Play ontogeny in young chickens is affected by domestication and early stress
Authors: Gabrielle Lundén , Rebecca Oscarsson , Louise Hedlund , Johanna Gjøen , Per Jensen 
Published: August 2022

AbstractPlay is common in young homeotherm animals and has an important role as a tentative indicator of positive states of welfare. Furthermore, during domestication play is believed to have increased in frequency in several species as part of the domestication syndrome. Here, we studied the ontogeny of play in chickens in two experiments. The first compared the behavioural development between domesticated White Leghorn (WL) laying hen chicks and ancestral Red Junglefowl (RJF) and the second compared the same between WL chicks that had experienced the stress of commercial hatchery routines and a control group, hatched under calm conditions. In both experiments, 10 groups of four chicks each from each of the groups were moved twice per week to an enriched and fully enclosed play arena, starting at day 8 and finishing day 39 or 53 after hatch. In the arena, the frequency of play behaviours was recorded during 30 min and divided into object, locomotory and social play. In experiment one, total play as well as object play was significantly more common in WL whereas locomotor and social play was more common in RJF. In experiment two, total play was significantly more frequent in commercially hatched chicks, despite that none of the sub-categories differed significantly between the groups. In conclusion, domestication as well as early stress does affect the occurrence of play in chickens, but the effects are complex and require further research.
Detection of maternal carriers of common α-thalassemia deletions from cell-free DNA
Authors: Doan Phuoc-Loc , Nguyen Duy-Anh , Le Quang Thanh , Hoang Diem-Tuyet Thi , Nguyen Huu Du , Nguyen Canh Chuong , Doan Kim Phuong Thi , Tran Nhat Thang , Ha Thi Minh Thi , Trinh Thu Huong Nhat , Nguyen Van Thong , Bui Chi Thuong , Lai Ngoc-Diep Thi , Duong Thanh Hien , Mai Hai-Ly , Huynh Pham-Uyen Vinh , Huynh Thu Thanh Thi , Le Quang Vinh , Vo Thanh Binh , Dao Thi Hong-Thuy , Vo Phuong Anh , Le Duy-Khang Nguyen , Tran Ngoc Nhu Thi , Tran Quynh Nhu Thi , Van Yen-Linh Thi , Tran Huyen-Trang Thi , Nguyen Hoai Thi , Nguyen Phuong-Uyen , Do Thanh-Thuy Thi , Truong Dinh-Kiet , Tang Hung Sang , Cao Ngoc-Phuong Thi , Lam Tuan-Thanh , Tran Le Son , Nguyen Hoai-Nghia , Giang Hoa , Phan Minh-Duy 
Published: August 2022

Abstractα-Thalassemia is a common inherited blood disorder manifested mainly by the deletions of α-globin genes. In geographical areas with high carrier frequencies, screening of α-thalassemia carrier state is therefore of vital importance. This study presents a novel method for identifying female carriers of common α-thalassemia deletions using samples routinely taken for non-invasive prenatal tests for screening of fetal chromosomal aneuploidies. A total of 68,885 Vietnamese pregnant women were recruited and α-thalassemia statuses were determined by gap-PCR, revealing 5344 women (7.76%) carried deletions including αα/−−SEA (4.066%), αα/−α3.7 (2.934%), αα/−α4.2 (0.656%), and rare genotypes (0.102%). A two-stage model was built to predict these α-thalassemia deletions from targeted sequencing of the HBA gene cluster on maternal cfDNA. Our method achieved F1-scores of 97.14–99.55% for detecting the three common genotypes and 94.74% for detecting rare genotypes (−α3.7/−α4.2, αα/−−THAI, −α3.7/−−SEA, −α4.2/−−SEA). Additionally, the positive predictive values were 100.00% for αα/αα, 99.29% for αα/−−SEA, 94.87% for αα/−α3.7, and 96.51% for αα/−α4.2; and the negative predictive values were 97.63%, 99.99%, 99.99%, and 100.00%, respectively. As NIPT is increasingly adopted for pregnant women, utilizing cfDNA from NIPT to detect maternal carriers of common α-thalassemia deletions will be cost-effective and expand the benefits of NIPT.
A state‐dependent switching controller design approach for linear systems under control constraints
Authors: Chen Danhong , Peng Yunfei 
Published: August 2022

AbstractIn the present work, a state‐dependent switching controller design approach for controlled systems under control constraints is proposed. First, the controlled system with control gain parameters is converted into a single‐degree‐of‐freedom vibration system by using an invertible transform. Second, based on the physical significance of the single‐degree‐of‐freedom linear vibration systems, two pairs of gain parameters are properly chosen to obtain two subsystems with sufficiently small equivalent negative‐damping coefficients and sufficiently large equivalent stiffness coefficient difference. Third, by introducing an identical invertible transform, two subsystems are converted into the form of vibration systems simultaneously. As such, it is reasonable to compare the two corresponding energy functions directly. Fourth, two switching lines with maximum and minimum energy ratio between two subsystems are derived to construct a state‐dependent switching law. Combining the selected control gain parameters, a state‐dependent switching controller is then designed for stabilizing the original controlled system with control constraints. In the end, the effectiveness and robustness of the developed control approach are illustrated by three numerical examples.
Mobile application tool for remote rehabilitation after discharge from coronavirus disease‐19 rehabilitation unit
Authors: Emedoli Daniele , Alemanno Federica , Houdayer Elise , Brugliera Luigia , Iannaccone Sandro , Tettamanti Andrea 
Published: August 2022

AbstractA smartphone application (Medico‐Amico) has been developed by the collaboration of San Raffaele Scientific Institute and Khymeia Group S.R.L. with the aim of providing physical exercises and communicating with patients after their hospitalization in a coronavirus disease (COVID)‐rehabilitation unit. Thirty patients used the application for remote rehabilitation for 4 weeks. They were prescribed personalized motor exercises to perform three times a week. Clinicians could interact with each patient by an encrypted video call in order to give encouragement, mental support, modify intensity during training sessions, or to prescribe new exercises. Patients were asked to perform motor exercises and also to monitor their vital signs, such as temperature, blood pressure, and oxygen saturation, inserting scores in a specific section of the application. After 4 weeks of remote rehabilitation patients showed improvements in independence during activity of daily living and strength. Also, satisfaction and mobile application usability scores reached patients’ appreciation and enjoyment.
Der Stellenwert der onkoplastischen Brustrekonstruktion nach
Tumorektomie in der chirurgischen Brustkrebs-Behandlung
Authors: Weinzierl Andrea , Schmauss Daniel , Harder Yves 
Published: August 2022

ZusammenfassungBrusterhaltende Therapie (BET), also Tumorektomie in Kom- bination mit
systemischer Therapie und lokoregionärer Be- strahlung hat sich als
bevorzugte Behandlungsmethode bei Brustkrebs im Frühstadium etabliert.
Insgesamt exzellente Raten für Rezidiv-freies Überleben und
Langzeitüberleben haben dazu geführt, dass Brustchirurgen heute
dauerhafte und ästhetisch ansprechende Ergebnisse liefern
müssen, um den hohen Patientenansprüchen gerecht zu werden. Die
onkoplastische Brustchirurgie (OPBC) ist hierbei ein innovativer Ansatz, um das
Indikationenspektrum der BET zu erweitern, beziehungsweise deren
Gesamtergebnisse zu verbessern. Meist von einem Team aus einem plastischen
Chirurgen und einem Gynäkologen oder onkologischen Brustchirurgen
durchgeführt, kann OPBC Brustdeformitäten aktiv vorbeugen, ohne
dabei die onkologische Sicherheit zu gefährden. Aufgrund der stetig
wachsenden Bedeutsamkeit der OPBC soll die vorliegende Übersichtsarbeit
einen Einblick in ihre Grundprinzipien geben, sowie deren Vor- und Nachteile
diskutieren, um diese in den Kontext der rekonstruktiven Brustchirurgie
einzuordnen.
Hochintensives Intervalltraining im Schulsetting – effektiv
zur Verbesserung der kardiovaskulären
Leistungsfähigkeit?
Authors: Engel Florian A. , Bauer Nikolai 
Published: August 2022

ZusammenfassungDas hochintensive Intervalltraining (HIIT) hat das Potenzial, bei Kindern und
Jugendlichen die gesundheitsrelevante Fitness zu verbessern. Aus diesem Grund
haben Studien HIIT im Sportunterricht oder in anderen Bereichen des
Schulsettings, wie zum Beispiel im Klassenzimmer, eingesetzt.Das Ziel dieses Artikels ist, die Effektivität von
HIIT-Interventionsstudien im Sportunterricht sowie im Schulkontext
außerhalb des Sportunterrichts, bezogen auf die kardiovaskuläre
Fitness von Kindern und Jugendlichen, mittels narrativer
Überblicksarbeit darzustellen.Die Mehrzahl der Studien zeigen deutliche Verbesserungen der
kardiovaskulären Fitness von Kindern und Jugendlichen nach den HIIT
Interventionen im Sportunterricht sowie im Schulkontext außerhalb des
Sportunterrichts.Das gute Verhältnis von Aufwand und Nutzen hinsichtlich
gesundheitsrelevanter Fitness macht das hochintensive Intervalltraining zu einer
geeigneten Trainingsform für die Verbesserung der gesundheitsrelevanten
Fitness von Kindern und Jugendlichen im Schulsetting.
HIT im Alterungsprozess
Authors: Gießing Jürgen 
Published: August 2022

ZusammenfassungDas Hochintensitätstraining (HIT) ist eine methodische Alternative zum
klassischen Krafttraining und ist gekennzeichnet durch hohe
Anstrengungsintensität bei geringem Trainingsvolumen und Betonung
technisch korrekter Übungsausführungen. Das HIT eignet sich
für alle post-pubertären Altersstufen und ist kürzlich
verstärkt in den Fokus geraten als geeignete Maßnahme zur
Prävention und Therapie von Sarkopenie bei Älteren.
Praxisbeispiel HIIT in der Onkologie
Authors: Bauer Nikolai , Wiskemann Joachim , Rosenberger Friederike 
Published: August 2022

ZusammenfassungOnkologischen PatientInnen wird ein regelmäßiges
körperliches Training explizit empfohlen. Das Hochintensive
Intervalltraining (HIIT) rückt dank steigender Evidenzlage in
unterschiedlichen Diagnosegruppen vermehrt in den Fokus der onkologischen Sport-
und Bewegungstherapie. Die Betrachtung der aktuellen Literatur zeigt, dass das
HIIT für Krebspatienten nach Abschluss der Therapie eine potenziell
sichere sowie durchführbare Trainingsmethode ist. Darüber hinaus
kann das HIIT positive Effekte auf die verringerte körperliche
Leistungsfähigkeit von Krebspatienten haben. In diesem Zusammenhang ist
sowohl das „4×4“- als auch das
„10×1“-Protokoll mit onkologischen PatientInnen nach
Abschluss der Therapie auf dem Fahrradergometer durchführbar, wobei
insbesondere das „4×4“-Schema zur Realisierung von
intensiven Trainingsreizen geeignet ist. Trotz zunehmender Untersuchungen
bezüglich der Effekte von HIIT auf onkologische PatientInnen werden in
diesem Forschungsbereich weitere qualitativ hochwertige Studien mit
großer Teilnehmendenzahl benötigt.
Continuing Education in Plastic, Reconstructive and Aesthetic Surgery
in Europe and its Relevance for Patient Safety
Authors: Giunta Riccardo E. 
Published: August 2022

Dear Readers,In this issue, the European Society of Plastic, Reconstructive and Aesthetic Surgery
(ESPRAS) has dealt with the quality of continuing education in plastic surgery in
Europe in the form of an “ESPRAS Survey”. An overview of the high
quality criteria that are necessary in all countries in order to successfully
complete specialist training in plastic and aesthetic surgery is summarised clearly
and in detail. In Europe, as in Germany, specialist training generally includes
training in all body regions, a training period of about 6 years, a rotation in
intensive care units for the care of critically ill patients as well as surgical
catalogues and specialist examinations.