bluuebunny/crossref_metadata_2025_split huggingface dataset:
The causes and consequences of Alzheimer’s disease: phenome-wide evidence from Mendelian randomization
Authors: Korologou-Linden Roxanna , Bhatta Laxmi , Brumpton Ben M. , Howe Laura D. , Millard Louise A. C. , Kolaric Katarina , Ben-Shlomo Yoav , Williams Dylan M. , Smith George Davey , Anderson Emma L. , Stergiakouli Evie , Davies Neil M. 
Published: August 2022

AbstractAlzheimer’s disease (AD) has no proven causal and modifiable risk factors, or effective interventions. We report a phenome-wide association study (PheWAS) of genetic liability for AD in 334,968 participants of the UK Biobank study, stratified by age. We also examined the effects of AD genetic liability on previously implicated risk factors. We replicated these analyses in the HUNT study. PheWAS hits and previously implicated risk factors were followed up in a Mendelian randomization (MR) framework to identify the causal effect of each risk factor on AD risk. A higher genetic liability for AD was associated with medical history and cognitive, lifestyle, physical and blood-based measures as early as 39 years of age. These effects were largely driven by the APOE gene. The follow-up MR analyses were primarily null, implying that most of these associations are likely to be a consequence of prodromal disease or selection bias, rather than the risk factor causing the disease.
Bioengineered corneal tissue for minimally invasive vision restoration in advanced keratoconus in two clinical cohorts
Authors: Rafat Mehrdad , Jabbarvand Mahmoud , Sharma Namrata , Xeroudaki Maria , Tabe Shideh , Omrani Raha , Thangavelu Muthukumar , Mukwaya Anthony , Fagerholm Per , Lennikov Anton , Askarizadeh Farshad , Lagali Neil 
Published: August 2022

AbstractVisual impairment from corneal stromal disease affects millions worldwide. We describe a cell-free engineered corneal tissue, bioengineered porcine construct, double crosslinked (BPCDX) and a minimally invasive surgical method for its implantation. In a pilot feasibility study in India and Iran (clinicaltrials.gov no.NCT04653922), we implanted BPCDX in 20 advanced keratoconus subjects to reshape the native corneal stroma without removing existing tissue or using sutures. During 24 months of follow-up, no adverse event was observed. We document improvements in corneal thickness (mean increase of 209 ± 18 µm in India, 285 ± 99 µm in Iran), maximum keratometry (mean decrease of 13.9 ± 7.9 D in India and 11.2 ± 8.9 D in Iran) and visual acuity (to a mean contact-lens-corrected acuity of 20/26 in India and spectacle-corrected acuity of 20/58 in Iran). Fourteen of 14 initially blind subjects had a final mean best-corrected vision (spectacle or contact lens) of 20/36 and restored tolerance to contact lens wear. This work demonstrates restoration of vision using an approach that is potentially equally effective, safer, simpler and more broadly available than donor cornea transplantation.
Detection of early seeding of Richter transformation in chronic lymphocytic leukemia
Authors: Nadeu Ferran , Royo Romina , Massoni-Badosa Ramon , Playa-Albinyana Heribert , Garcia-Torre Beatriz , Duran-Ferrer Martí , Dawson Kevin J. , Kulis Marta , Diaz-Navarro Ander , Villamor Neus , Melero Juan L. , Chapaprieta Vicente , Dueso-Barroso Ana , Delgado Julio , Moia Riccardo , Ruiz-Gil Sara , Marchese Domenica , Giró Ariadna , Verdaguer-Dot Núria , Romo Mónica , Clot Guillem , Rozman Maria , Frigola Gerard , Rivas-Delgado Alfredo , Baumann Tycho , Alcoceba Miguel , González Marcos , Climent Fina , Abrisqueta Pau , Castellví Josep , Bosch Francesc , Aymerich Marta , Enjuanes Anna , Ruiz-Gaspà Sílvia , López-Guillermo Armando , Jares Pedro , Beà Sílvia , Capella-Gutierrez Salvador , Gelpí Josep Ll. , López-Bigas Núria , Torrents David , Campbell Peter J. , Gut Ivo , Rossi Davide , Gaidano Gianluca , Puente Xose S. , Garcia-Roves Pablo M. , Colomer Dolors , Heyn Holger , Maura Francesco , Martín-Subero José I. , Campo Elías 
Published: August 2022

AbstractRichter transformation (RT) is a paradigmatic evolution of chronic lymphocytic leukemia (CLL) into a very aggressive large B cell lymphoma conferring a dismal prognosis. The mechanisms driving RT remain largely unknown. We characterized the whole genome, epigenome and transcriptome, combined with single-cell DNA/RNA-sequencing analyses and functional experiments, of 19 cases of CLL developing RT. Studying 54 longitudinal samples covering up to 19 years of disease course, we uncovered minute subclones carrying genomic, immunogenetic and transcriptomic features of RT cells already at CLL diagnosis, which were dormant for up to 19 years before transformation. We also identified new driver alterations, discovered a new mutational signature (SBS-RT), recognized an oxidative phosphorylation (OXPHOS)high–B cell receptor (BCR)low-signaling transcriptional axis in RT and showed that OXPHOS inhibition reduces the proliferation of RT cells. These findings demonstrate the early seeding of subclones driving advanced stages of cancer evolution and uncover potential therapeutic targets for RT.
The association between comorbidities and stigma among breast cancer survivors
Authors: Zhang Yuxin , Zhao Jie , Jiang Nan , Liu Yongyi , Wang Ting , Yu Xi , Wang Jiwei , Yu Jinming 
Published: August 2022

AbstractThis study aimed to explore the association between types and numbers of comorbidities and stigma among breast cancer survivors (BCSs). A cross-sectional study was conducted among 937 BCSs in Shanghai Cancer Rehabilitation Club. All participants were asked to fill in an online questionnaire including Stigma Scale for Chronic Illnesses 8-item version (SSCI-8) and questions on sociodemographic characteristics and health status. Multivariate linear regression was used to analyze the association between comorbidities and stigma, adjusting for confounding factors. Results showed that nearly 70% of the participants had one or more comorbidities. The participants with stroke, digestive diseases or musculoskeletal diseases had significantly higher stigma than those without the above comorbidities. In addition, stigma was higher among survivors in the group with a greater number of comorbidities. Thus, it is important to strengthen the management of stigma in BCSs, especially for those with comorbidities.
Drivers of avian habitat use and detection of backyard birds in the Pacific Northwest during COVID-19 pandemic lockdowns
Authors: Sanderfoot O. V. , Kaufman J. D. , Gardner B. 
Published: August 2022

AbstractBirds living in developed areas contend with numerous stressors, including human disturbance and light, noise, and air pollution. COVID-19 pandemic lockdowns presented a unique opportunity to disentangle these effects during a period of reduced human activity. We launched a community science project in spring 2020 to explore drivers of site use by and detection of common birds in cities under lockdown in the U.S. Pacific Northwest. Our goals were twofold: (1) consider how intensity of urbanization, canopy cover, and availability of bird feeders and bird baths influenced avian habitat use; and (2) quantify how daily changes in weather, air pollution, and human mobility influenced detection of birds. We analyzed 6,640 surveys from 367 volunteers at 429 monitoring sites using occupancy models for 46 study species. Neither land cover nor canopy cover influenced site use by 50% of study species, suggesting that backyard birds may have used a wider range of habitats during lockdowns. Human mobility affected detection of 76% of study species, suggesting that birds exhibited species-specific behavioral responses to day-to-day changes in human activity beginning shortly after initial lockdown restrictions were implemented. Our study also showcases how existing community science platforms can be leveraged to support local monitoring efforts.
Protocol and reference values for minimal detectable change of MyotonPRO and ultrasound imaging measurements of muscle and subcutaneous tissue
Authors: Muckelt Paul E. , Warner Martin B. , Cheliotis-James Tom , Muckelt Rachel , Hastermann Maria , Schoenrock Britt , Martin David , MacGregor Robert , Blottner Dieter , Stokes Maria 
Published: August 2022

AbstractThe assessment of muscle health is of paramount importance, as the loss of muscle mass and strength can affect performance. Two non-invasive tools that have been found to be useful in this are the MyotonPRO and rehabilitative ultrasound imaging, both have shown to be reliable in previous studies many of which conducted by the research team. This study aims to determine the reliability of previously unassessed local body structures and to determine their minimal detectable changes (MDC) to support both researchers and clinicians. Twenty healthy participants were recruited to determine the reliability of seven skin positions out of a previously established protocol. Reliability was determined between three independent raters, and day to day reliability was assessed with one rater a week apart. Intraclass Correlation Coefficients (ICC) between raters and between days for tissue stiffness, tone and elasticity range from moderate to excellent (ICC 0.52–0.97), with most good or excellent. ICCs for subcutaneous thickness between days was good or excellent (ICC 0.86–0.91) and moderate to excellent between raters (ICC 0.72–0.96), in muscles it was moderate to excellent between raters and days (ICC 0.71–0.95). The protocol in this study is repeatable with overall good reliability, it also provides established MDC values for several measurement points.
Vitamin D status and associations with substance use patterns among people with severe substance use disorders in Western Norway
Authors: Bemanian Mitra , Chowdhury Ranadip , Stokke Krister , Aas Christer Frode , Johansson Kjell Arne , Vold Jørn Henrik , Fadnes Lars Thore 
Published: August 2022

AbstractChronic and harmful substance use is associated with a cluster of harms to health, including micronutrient deficiencies. Maintaining adequate levels of vitamin D is important for musculoskeletal and other aspects of health. In this prospective longitudinal cohort study, 666 participants drawn from outpatient opioid agonist therapy (OAT) clinics and community care clinics for substance use disorder in Western Norway were assessed annually for determination of serum 25-hydroxyvitamin D [s-25(OH)D] levels. Fifty-seven percent were deficient at baseline (s-25(OH)D < 50 nmol/l), and 19% were severely deficient (s-25(OH)D < 25 nmol/l). Among those deficient/severely deficient at baseline, 70% remained deficient/severely deficient at the last measurement (mean duration 714 days). Substance use patterns and dosage of opioids for OAT were not associated with vitamin D levels. One exception was found for cannabis, where consumption on a minimum weekly basis was associated with lower levels at baseline (mean difference: −5.2 nmol/l, 95% confidence interval [CI]: −9.1, − 1.3), but without clear time trends (mean change per year: 1.4 nmol/l, CI: − 0.86, 3.7). The high prevalence of sustained vitamin D deficiency in this cohort highlights the need for targeted monitoring and supplementation for this and similar at-risk populations.
[S-methyl-11C]-L-methionine positron emission tomography/computed tomography imaging parameters to evaluate early response for esophageal cancer with neoadjuvant carbon ion radiotherapy
Authors: Narushima Kazuo , Nishii Ryuichi , Okazumi Shinichi , Shimada Hideaki , Akutsu Yasunori , Maeda Takamasa , Yasuda Shigeo , Yamada Shigeru , Shuto Kiyohiko , Tamura Kentaro , Yamazaki Kana , Shinoto Makoto , Ishikawa Hitoshi , Mori Mikito , Matsubara Hisahiro 
Published: August 2022

AbstractThis study aimed to evaluate the uptake of the clinical effectiveness of [S-methyl-11C]-L-methionine positron emission tomography/computed tomography (MET PET/CT) in patients with esophageal cancer and to investigate MET PET/CT imaging parameters to assess early response for esophageal cancer with neoadjuvant carbon ion radiotherapy (CIRT). MET PET/CT scans were performed in nineteen patients before and 3 weeks after completion of CIRT. After Surgery, the effect of neoadjuvant CIRT was investigated by examining the relationship between each parameter of MET uptake and the histological assessment (grade and tumor residual ratio). Four parameters of MET uptake were the maximum and minimum standardized uptake values of pre and post CIRT (pre-SUVmax, pre-SUVmean, post-SUVmax, and post-SUVmean). MET PET/CT imaging of esophageal cancer was clearly demonstrated. The post-SUVmax was the most suitable parameter. When the cutoff value was set as post-SUVmax = 6.21, the sensitivity, the specificity, and the accuracy of Grades 3 were 100.0%, 63.6%, and 78.9%, respectively. And there was a positive relationship between the tumor residual ratio and post-SUVmax (R2 = 0.38, p < 0.005). MET PET/CT is clinically useful for the assessment of early response to neoadjuvant CIRT in esophageal cancer. Particularly, post-SUVmax is considered a promising PET imaging parameter.
Endophytic bacteria from in vitro culture of Leucojum aestivum L. a new source of galanthamine and elicitor of alkaloid biosynthesis
Authors: Ptak Agata , Morańska Emilia , Warchoł Marzena , Gurgul Artur , Skrzypek Edyta , Dziurka Michał , Laurain-Mattar Dominique , Spina Rosella , Jaglarz Anita , Simlat Magdalena 
Published: August 2022

AbstractLeucojum aestivum is known for its ability to biosynthesize alkaloids with therapeutic properties, among which galanthamine used for the treatment of Alzheimer's disease. New sources of this alkaloid are still being explored. In this study, a novel strain PLV of endophytic bacterium Paenibacillus lautus was isolated from in vitro L. aestivum plants. We report the whole genome sequence of that strain and its capacity to produce alkaloids and growth regulators. The effect of elicitation with autoclaved bacteria on the production of alkaloids was examined. Ten alkaloids were identified in bacteria extracts: galanthamine, lycorine, ismine, lycoramine, haemanthamine, tazettine, galanthine, homolycorine, 1,2-dihydrochlidanthine, and hippeastrine. The mean contents of galanthamine and lycorine were 37.51 µg/g of dry weight (DW) and 129.93 µg/g of DW, respectively. Moreover, isolated P. lautus strain synthesized: indole-3-acetic acid, t-zeatin, c-zeatin, kinetin, gibberellin A1, abscisic acid, salicylic acid, benzoic acid. In vitro elicitation of cultures with P. lautus increased dry biomass, stimulated galanthamine and lycorine production, contributed to 8,9-desmethylenebis (oxy)-7,9 dimethoxy-crinan biosynthesis, change pigments content, and antioxidant enzymes activities. Our findings for the first time point out that galanthamine can be synthesized by an microorganism. Moreover isolated strain can be used as a new elictor of Amaryllidaceae alkaloids biosynthesis.
Enhancing secrecy performance of energy harvesting NOMA systems using IoT user scheduling under untrusted users
Authors: Largani Noushin Khosravi , Akhbari Bahareh 
Published: August 2022

AbstractIn this work, multiple energy‐limited Internet of Things (IoT) users are intended to communicate with their destination (). The scheduled IoT user harvests the energy from a source signal and uses this energy to forward a mixture of its message and the source message to the and the source destination based on non‐orthogonal multiple access (NOMA). Since the messages are transmitted at the same resource block, the far untrusted user (source destination) has the opportunity to access the message destined for the near user () by successive interference cancellation. Therefore, an IoT user scheduling strategy is proposed to achieve the reliability and security of transmission in the network. To indicate the superiority of the proposed scheduling scheme and the impact of different parameters on the network performance under untrusted users, the secrecy outage probability of the system is derived by tracking exact and asymptotic analyses and then it is compared with that of benchmarks through simulations. The results reveal the crucial role of the near user threshold secrecy rate as the system's bottleneck and the negligible impact of the power allocation coefficients and the untrusted far user threshold rate on the secrecy performance with increasing the signal‐to‐noise‐ratio.
Optimal design of high frequency high efficiency and high‐power density DC–DC power module based on GaN
Authors: Liu Guowang , Ouyang Honglin , Xiao Muxuan 
Published: August 2022

AbstractThis paper develops a railway power module with wide range voltage (dc 60—dc 160 V) input and constant voltage output (24 V/10 A) . The power module adopts a two‐stage topology structure to realize voltage conversion. Use the most advanced GaN (gallium nitride) as the main power switching devices. The first stage circuit architecture uses a two‐phase interleaved buck converter convert the wide range input voltage into a constant intermediate bus voltage (48 V) through closed‐loop control, and then the LLC resonant converter converts the intermediate bus voltage (dc 48 V) into a constant output voltage (dc 24 V) through open‐loop control, and realize the primary side and secondary side dc 3000 V electrical isolation. This article from the circuit topology, the power devices selection, buck converter magnetic integrated coupling inductance design, planar magnetic integration LLC resonant transformer optimization design has carried on the detailed discuss and analysis. All circuits are integrated in a standard quarter power brick module, the final prototype can reach 96.1% peak efficiency, the power density can reach 185 W/in.3.
Betreuung von Menschen mit Diabetes in Deutschland – was läuft schief?
Authors: Ziegelasch Hans-Jürgen , Schiel Ralf , Ebert Thomas , Ziegelasch Michael 
Published: August 2022

ZusammenfassungDeutschland hat ein insgesamt gutes Gesundheitssystem. Für Menschen mit Diabetes gibt es neben der hausärztlichen Versorgung, Diabetes-Schwerpunktpraxen (DSP) und Reha-Kliniken. Jedoch ist die Betreuung von Personen mit Diabetes in unserem Land nicht optimal. Was sind die Ursachen dessen und was können wir tun?Regionale Unterschiede in der Definition und Abgrenzung einer DSP zu anderen Diagnosen, Mangel an Diabetologen und DSP, Werbung für ungesunde Lebensmittel und ungenügende Selbstkontrollen sind nur einige der Ursachen.Eine Erfassung der betroffenen Personen mit Diabetes in einem nationalen Register ähnlich dem Schwedens, eine deutliche Verbesserung prophylaktischer Maßnahmen sowie Ausbildung der diabetologischen Fachkräfte sind mögliche Ansatzpunkte für eine Änderung zum Positiven.
Differentialdiagnose Vaskulitis und Vaskulopathie aus dermatologischer Sicht
Authors: Mitschang Carolin , Ehrchen Jan , Görge Tobias 
Published: August 2022

ZusammenfassungVaskulopathien und Vaskulitiden stellen diagnostisch und therapeutisch eine interdisziplinäre Herausforderung dar. Zugrunde liegen unterschiedliche pathophysiologische Mechanismen, die zu vielfältigen klinischen Krankheitsbildern führen können und therapeutisch unterschiedliche Ansätze erlauben. Sowohl Vaskulitiden als auch Vaskulopathien müssen nicht zwangsläufig mit einer Systembeteiligung einhergehen, sondern können auch als rein kutane Varianten auftreten. Aufgrund mangelnder pathognomonischer Laborparameter ist die Diagnose häufig klinisch zu stellen. Dieser Artikel soll den differentialdiagnostischen Blick, insbesondere auf die kutanen Manifestationsformen bei Vaskulopathien und Vaskulitiden, schärfen.
Dihydroartemesinin and Curcumin Based Self-Microemulsifying Drug
Delivery System for Antimalarial Activity
Authors: Srivastava Richa , Fatima Zeeshan , Sahoo Jagannath , Joshi Prince , Tripathi Renu 
Published: August 2022

AbstractMalaria is a significant global problem which still persists despite the
development of various effective antimalarial drugs. It is challenging to treat
this disease due to the parasite’s complex life cycle and high
recrudensce of antimalarial drugs. A new self-micro emulsifying drug delivery
system has been developed to improve the solubility of dihydroartemisinin and
curcumin. The prepared formulation contained Dihydroartemesinin, curcumin,
Groundnut Oil, Cremephor RH, and Tween 80. Self-micro emulsification time, zeta
potential, droplet size, polydispersity index, transmission electron microscopy,
drug release, and in-vivo studies were performed for characterization. The
globule size was found to be 25.59±0.40 nm and the zeta
potential was-5.75±0.18 mV. The globules prepared were spherical
in shape. The in-vitro dissolution performance of formulation of
dihydroartemisinin and curcumin self emulsifying drug delivery system showed
significantly (p<0.05, Origin Pro 8.5) higher release as compared to the
pure drugs. The results of the study suggested that the prepared self
emulsifying drug delivery system combination of Dihydroartemesinin and curcumin
has a better potential to cure parasitemia as compared to the individual
drug.
Sklerodermie – „die harte Haut“
Authors: Speidel Jil , Hunzelmann Nicolas , Moinzadeh Pia 
Published: August 2022

ZusammenfassungUnter dem Begriff Sklerodermie ist eine heterogene Gruppe von Erkrankungen zusammengefasst, die eine kutane Sklerose gemeinsam haben. Die einzelnen Erkrankungen variieren in der Beteiligung betroffener Strukturen wie Haut, Fettgewebe, Muskulatur, Gelenkstrukturen, Knochen, innerer Organe und der damit einhergehenden Krankheitsausprägung. Es lassen sich grundsätzlich zwei verschiedene Subtypen unterscheiden: die lokalisierte Sklerodermie (LoS) und die systemische Sklerose (SSc), die sich jeweils in weitere Subgruppen unterteilen lassen. Es handelt sich um zwei verschiedene Erkrankungen, die sich in der Ausprägung der Hautsklerosierung, der Beteiligung innerer Organe, im Antikörper-Profil, im Krankheitsmanagement sowie der Prognose unterscheiden. Darüber hinaus gibt es Krankheitsbilder, die eine Sklerodermie imitieren und daher als sklerodermie-artige Erkrankungen oder auch als Pseudosklerodermien bezeichnet werden. Um die richtige Diagnose stellen zu können, ist ein standardisiertes diagnostisches Vorgehen bedeutsam. Die frühe Diagnosestellung ist wichtig, um frühzeitige eine Therapie einleiten zu können, und so funktionelle kutane und extrakutane Einschränkungen und auch kosmetische Schäden gering halten zu können.
Transition-Metal-Free N-Arylation of N-Methoxysulfonamides and N,O-Protected Hydroxylamines with Trimethoxyphenyliodonium (III) Acetates
Authors: Kikushima Kotaro , Kita Yasuyuki , Dohi Toshifumi , Morita Aki , Elboray Elghareeb E. , Bae Taeho , Miyamoto Naoki 
Published: August 2022

AbstractTrimethoxyphenyliodonium(III) acetate [TMP-iodonium(III) acetate] functions as an efficient arylation reagent for N,O-protected hydroxylamines, generating aniline derivatives in the absence of transition metal catalysts. Various N-methoxysulfonamides participated in the amination reaction to produce the corresponding N-methoxysulfonylanilines. This amination reaction was compatible with several protecting groups, including Troc (2,2,2-trichloroethoxycarbonyl), Cbz (benzyloxycarbonyl), Boc (tert-butoxycarbonyl), benzyl, acetyl, and silyl groups. This method uses TMP-iodonium(III) acetate and efficiently synthesizes various aniline derivatives that are versatile synthetic intermediates for functional organic molecules.