bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiparametric and accurate functional analysis of genetic sequence variants using CRISPR-Select
Authors: Niu Yiyuan , Ferreira Azevedo Catarina A. , Li Xin , Kamali Elahe , Haagen Nielsen Ole , Storgaard Sørensen Claus , Frödin Morten 
Published: December 2022

AbstractDetermining the functional role of thousands of genetic sequence variants (mutations) associated with genetic diseases is a major challenge. Here we present clustered regularly interspaced short palindromic repeat (CRISPR)-SelectTIME, CRISPR-SelectSPACE and CRISPR-SelectSTATE, a set of flexible knock-in assays that introduce a genetic variant in a cell population and track its absolute frequencies relative to an internal, neutral control mutation as a function of time, space or a cell state measurable by flow cytometry. Phenotypically, CRISPR-Select can thereby determine, for example, pathogenicity, drug responsiveness/resistance or in vivo tumor promotion by a specific variant. Mechanistically, CRISPR-Select can dissect how the variant elicits the phenotype by causally linking the variant to motility/invasiveness or any cell state or biochemical process with a flow cytometry marker. The method is applicable to organoids, nontransformed or cancer cell lines. It is accurate, quantitative, fast and simple and works in single-well or 96-well higher throughput format. CRISPR-Select provides a versatile functional variant assay for research, diagnostics and drug development for genetic disorders.
The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location
Authors: Liu Ilon , Jiang Li , Samuelsson Erik R. , Marco Salas Sergio , Beck Alexander , Hack Olivia A. , Jeong Daeun , Shaw McKenzie L. , Englinger Bernhard , LaBelle Jenna , Mire Hafsa M. , Madlener Sibylle , Mayr Lisa , Quezada Michael A. , Trissal Maria , Panditharatna Eshini , Ernst Kati J. , Vogelzang Jayne , Gatesman Taylor A. , Halbert Matthew E. , Palova Hana , Pokorna Petra , Sterba Jaroslav , Slaby Ondrej , Geyeregger Rene , Diaz Aaron , Findlay Izac J. , Dun Matthew D. , Resnick Adam , Suvà Mario L. , Jones David T. W. , Agnihotri Sameer , Svedlund Jessica , Koschmann Carl , Haberler Christine , Czech Thomas , Slavc Irene , Cotter Jennifer A. , Ligon Keith L. , Alexandrescu Sanda , Yung W. K. Alfred , Arrillaga-Romany Isabel , Gojo Johannes , Monje Michelle , Nilsson Mats , Filbin Mariella G. 
Published: December 2022

AbstractHistone 3 lysine27-to-methionine (H3-K27M) mutations most frequently occur in diffuse midline gliomas (DMGs) of the childhood pons but are also increasingly recognized in adults. Their potential heterogeneity at different ages and midline locations is vastly understudied. Here, through dissecting the single-cell transcriptomic, epigenomic and spatial architectures of a comprehensive cohort of patient H3-K27M DMGs, we delineate how age and anatomical location shape glioma cell-intrinsic and -extrinsic features in light of the shared driver mutation. We show that stem-like oligodendroglial precursor-like cells, present across all clinico-anatomical groups, display varying levels of maturation dependent on location. We reveal a previously underappreciated relationship between mesenchymal cancer cell states and age, linked to age-dependent differences in the immune microenvironment. Further, we resolve the spatial organization of H3-K27M DMG cell populations and identify a mitotic oligodendroglial-lineage niche. Collectively, our study provides a powerful framework for rational modeling and therapeutic interventions.
Efficacy of empagliflozin in heart failure with preserved versus mid-range ejection fraction: a pre-specified analysis of EMPEROR-Preserved
Authors: Anker Stefan D. , Butler Javed , Usman Muhammad Shariq , Filippatos Gerasimos , Ferreira João Pedro , Bocchi Edimar , Böhm Michael , Rocca Hans Pieter Brunner-La , Choi Dong-Ju , Chopra Vijay , Chuquiure Eduardo , Giannetti Nadia , Gomez-Mesa Juan Esteban , Janssens Stefan , Januzzi James L. , González-Juanatey José R. , Merkely Bela , Nicholls Stephen J. , Perrone Sergio V. , Piña Ileana L. , Ponikowski Piotr , Senni Michele , Sim David , Spinar Jindrich , Squire Iain , Taddei Stefano , Tsutsui Hiroyuki , Verma Subodh , Vinereanu Dragos , Zhang Jian , Iwata Tomoko , Schnee Janet M. , Brueckmann Martina , Pocock Stuart J. , Zannad Faiez 
Published: December 2022

AbstractThe EMPEROR-Preserved trial showed that the sodium–glucose co-transporter 2 inhibitor empagliflozin significantly reduces the risk of cardiovascular death or hospitalization for heart failure (HHF) in heart failure patients with left ventricular ejection fraction (LVEF)  > 40%. Here, we report the results of a pre-specified analysis that separately evaluates these patients stratified by LVEF: preserved (≥ 50%) (n = 4,005; 66.9%) or mid-range (41–49%). In patients with LVEF  ≥ 50%, empagliflozin reduced the risk of cardiovascular death or HHF (the primary endpoint) by 17% versus placebo (hazard ratio (HR) 0.83; 95% confidence interval (CI): 0.71–0.98, P = 0.024). For the key secondary endpoint, the HR for total HHF was 0.83 (95%CI: 0.66–1.04, P = 0.11). For patients with an LVEF of 41–49%, the HR for empagliflozin versus placebo was 0.71 (95%CI: 0.57–0.88, P = 0.002) for the primary outcome (Pinteraction = 0.27), and 0.57 (95%CI: 0.42–0.79, P < 0.001) for total HHF (Pinteraction = 0.06). These results, together with those from the EMPEROR-Reduced trial in patients with LVEF < 40%, support the use of empagliflozin across the full spectrum of LVEF in heart failure.
Wave-driven electron inward transport in a magnetic nozzle
Authors: Takahashi Kazunori , Charles Christine , Boswell Rod W. 
Published: December 2022

AbstractPlasma flows in divergent magnetic fields resembling a magnetic nozzle can be found over wide scales ranging from astrophysical objects to terrestrial plasma devices. Plasma detachment from a magnetic nozzle is a frequent occurrence in natural plasmas, e.g., plasma ejection from the Sun and release from the Sun’s magnetic field, forming the solar wind. Plasma detachment has also been a challenging problem relating to space propulsion devices utilizing a magnetic nozzle, especially the detachment of the magnetized electrons having a gyro-radius smaller than the system’s scale is required to maintain zero net current exhausted from the system. Here we experimentally demonstrate that a cross-field transport of the electrons toward the main nozzle axis, which contributes to neutralizing the ions detached from the nozzle, is induced by the spontaneously excited magnetosonic wave having the frequency considerably higher than the ion cyclotron frequency and close to the lower hybrid frequency, driving an E × B drift that only effects the electrons. Wave-induced transport and loss have been one of many important issues in plasma physics over the past several decades. Conversely, the presently observed electron inward transport has a beneficial effect on the detachment by reducing the divergence of the expanding plasma beam; this finding will open a new perspective for the role of waves and instabilities in plasmas.
A survey of vocal mimicry in companion parrots
Authors: Benedict Lauryn , Charles Alexandra , Brockington Amirah , Dahlin Christine R 
Published: December 2022

AbstractParrots are one of the rare animal taxa with life-long vocal learning. Parrot vocal repertoires are difficult to study in the wild, but companion parrots offer a valuable data source. We surveyed the public about mimicry repertoires in companion parrots to determine whether vocal learning varied by (1) species, (2) sex, (3) age, and (4) social interaction with other parrots. Species differed significantly in mimicry ability, with grey parrots (Psittacus erithacus) having the largest mimicry repertoires. Analyses of all birds (n = 877) found no overarching effects of sex, age, or parrot-parrot social interactions on mimicry repertoires. Follow up analyses (n = 671), however, revealed a human bias to assume that talking parrots are male, and indicated that five of the 19 best-sampled species exhibited sex differences. Age-specific analyses of grey parrots (n = 187) indicated that repertoire size did not increase during adulthood. Most parrots were capable of improvisation (e.g. rearranging words) and used mimicry in appropriate human contexts. Results indicate that parrot vocal production learning varies among and within species, suggesting that the mechanisms and functions of learning also vary. Our data provide a rich foundation for future comparative research on avian vocalizations, and broaden our understanding of the underpinnings of communicative behavior and learning across all animals.
Morphometric study of percutaneous A1 pulley of thumb release
Authors: Zhong Wei-xing , Chen Zu-jiang , Peng Wei-jie , Gu Rui-bin , Li Jun-hua , Li Yi-kai 
Published: December 2022

AbstractThrough anatomy, microscope, histopathology, and simulating needle knife operation on specimens, to accumulate the relevant parameters of the A1 pulley of thumb, and to provide an anatomical evidence for the needle knife therapy of stenosing flexor tenosynovitis. A total of 20 fingers were selected from 20 intact adult upper limb specimens, a small amount of emerald green waterproof dye was injected from the needle insertion point, dissected layer by layer, and the A1 pulley and neurovascular bundle were observed. Observe the loosening of the thumb A1 pulley after 5 and 10 times of simulated needle knife cutting on the specimen; observe the relationship between the needle knife entry point and the A1 pulley under the thumb extension and abduction, and the thumb extension neutral position respectively; further observe the histological characteristics, and the relationship between needle entry point and A1 pulley by microscope. ① In general observation, the A1 pulleys of each finger were transverse fibers perpendicular to the flexor tendon, tough in texture, connected with synovial fibers at the proximal end. It is difficult to distinguish, and connected with oblique fibers at the distal end. ② The release rate of the thumb A1 pulley after 5 and 10 times of simulated needle knife cutting on the specimen were (40.46 ± 2.22)% and (63.52 ± 4.49)%, respectively. ③ In the neutral position of the thumb straightening, the needle entry point is 3.06 ± 0.14 mm from the proximal side of the proximal edge of the A1 pulley, which overlaps with the needle entry point where the thumb is straight and abducted. ④ Observed under a microscope, the A1 pulley is a dense transverse fiber with a pale yellow dense connective tissue, both ends are continuous with the synovial fibers. It is thin and translucent, and loose connective tissue. The A1 pulley is a dense transverse fiber with a pale yellow dense connective tissue. The anatomical key points of the needle knife therapy lie in the extended and abducted position of the thumb. Currently, it is believed that cutting the proximal edge of the A1 pulley is sufficient, and there is no need to cut the entire A1 pulley.
Access to basic drinking water services, safe water storage, and household water treatment practice in rural communities of northwest Ethiopia
Authors: Gizaw Zemichael , Gebrehiwot Mulat , Destaw Bikes , Nigusie Adane 
Published: December 2022

AbstractProtecting water from cross contamination at source and point of use is an important strategy to improve water quality. However, water safety measures at the source and point of use may not be implemented in the rural communities. This community-based cross-sectional study was, therefore, conducted among 1190 randomly selected households in a rural setting of northwest Ethiopia to assess access to basic drinking water services, safe water storage, and household water treatment practices. Water service level was determined using JMP criteria and practices that prevent cross contamination of water at point of use were used to determine safe water storage. Results showed that 23.0% of the households had access to basic water services; 37.0% practiced safe water storage; and 15.4% practiced one or more household water treatment methods. Public taps (54.5%) and protected spring (25.1%) were the common water sources to rural communities in northwest Ethiopia. Boiling (43.2%), chlorination or water guard (26.8%), and plain sedimentation (23.0%) were among the household water treatment methods commonly practiced in the area. In conclusion, rural households in the studied region has low access to basic water services. Safe water storage practice was also low in the area and household water treatment is not commonly practiced.
All-atmospheric fabrication of Ag–Cu core–shell nanowire transparent electrodes with Haacke figure of merit >600 × 10–3 Ω−1
Authors: DiGregorio Steven J. , Miller Collin E. , Prince Kevin J. , Hildreth Owen J. , Wheeler Lance M. 
Published: December 2022

AbstractTransparent conducting electrodes (TCEs) are essential components in devices such as touch screens, smart windows, and photovoltaics. Metal nanowire networks are promising next-generation TCEs, but best-performing examples rely on expensive metal catalysts (palladium or platinum), vacuum processing, or transfer processes that cannot be scaled. This work demonstrates a metal nanowire TCE fabrication process that focuses on high performance and simple fabrication. Here we combined direct and plating metallization processes on electrospun nanowires. We first directly metallize silver nanowires using reactive silver ink. The silver catalyzes subsequent copper plating to produce Ag–Cu core–shell nanowires and eliminates nanowire junction resistances. The process allows for tunable transmission and sheet resistance properties by adjusting electrospinning and plating time. We demonstrate state-of-the-art, low-haze TCEs using an all-atmospheric process with sheet resistances of 0.33 Ω sq−1 and visible light transmittances of 86% (including the substrate), leading to a Haacke figure of merit of 652 × 10–3 Ω−1. The core–shell nanowire electrode also demonstrates high chemical and bending durability.
Sap flow of sweet cherry reveals distinct effects of humidity and wind under rain covered and netted protected cropping systems
Authors: Stone C. H. , Close D. C. , Corkrey R. , Goodwin I. 
Published: December 2022

AbstractProtected cropping systems (PCS) alter the plant growing environment, though understanding of this in ventilated systems and how the new climate affects tree water uptake is limited. Sap flow sensors and weather stations were deployed in 16-year-old ‘Lapins’ on ‘Colt’ rootstock cherry trees under a ventilated Voen PCS and in an adjacent bird netted PCS. Average and maximum temperatures were consistently higher (14.7 °C and 22.9 °C) while total daily solar radiation and average wind were consistently lower (12.9 MJ/m2 and 0.2 m/s) in rain covered, in contrast to netted, PCS (13.9 °C, 21.3 °C, 13.7 MJ/m2 and 0.9 m/s). Over the season, a threefold lower daily sap flow rate was observed under rain covered PCS. Using generalised additive modelling (GAM), the influence of individual climate parameters on sap flow were predicted. Whilst sap flow was only slightly affected by relative humidity (RH) less than 60%, above this threshold sap flow rapidly declined under rain covered PCS whereas sap flow more gradually declined above 20% RH under netted PCS. Overall, our novel modelling approach led to the discovery of the 60% RH critical threshold on predicted sap flow and the indirect effect that wind speeds have on sap flow under PCS.
A fully-automated paper ECG digitisation algorithm using deep learning
Authors: Wu Huiyi , Patel Kiran Haresh Kumar , Li Xinyang , Zhang Bowen , Galazis Christoforos , Bajaj Nikesh , Sau Arunashis , Shi Xili , Sun Lin , Tao Yanda , Al-Qaysi Harith , Tarusan Lawrence , Yasmin Najira , Grewal Natasha , Kapoor Gaurika , Waks Jonathan W. , Kramer Daniel B. , Peters Nicholas S. , Ng Fu Siong 
Published: December 2022

AbstractThere is increasing focus on applying deep learning methods to electrocardiograms (ECGs), with recent studies showing that neural networks (NNs) can predict future heart failure or atrial fibrillation from the ECG alone. However, large numbers of ECGs are needed to train NNs, and many ECGs are currently only in paper format, which are not suitable for NN training. We developed a fully-automated online ECG digitisation tool to convert scanned paper ECGs into digital signals. Using automated horizontal and vertical anchor point detection, the algorithm automatically segments the ECG image into separate images for the 12 leads and a dynamical morphological algorithm is then applied to extract the signal of interest. We then validated the performance of the algorithm on 515 digital ECGs, of which 45 were printed, scanned and redigitised. The automated digitisation tool achieved 99.0% correlation between the digitised signals and the ground truth ECG (n = 515 standard 3-by-4 ECGs) after excluding ECGs with overlap of lead signals. Without exclusion, the performance of average correlation was from 90 to 97% across the leads on all 3-by-4 ECGs. There was a 97% correlation for 12-by-1 and 3-by-1 ECG formats after excluding ECGs with overlap of lead signals. Without exclusion, the average correlation of some leads in 12-by-1 ECGs was 60–70% and the average correlation of 3-by-1 ECGs achieved 80–90%. ECGs that were printed, scanned, and redigitised, our tool achieved 96% correlation with the original signals. We have developed and validated a fully-automated, user-friendly, online ECG digitisation tool. Unlike other available tools, this does not require any manual segmentation of ECG signals. Our tool can facilitate the rapid and automated digitisation of large repositories of paper ECGs to allow them to be used for deep learning projects.
Impact of partial bile duct ligation with or without repeated magnetic resonance imaging examinations in mice
Authors: Chen Taili , Zhou Zi-Yi , Liu Jia-Yi , Zheng Li-Yun , Wang Zi-Wei , Zhang Xiao-Jie , Zeng Shan 
Published: December 2022

AbstractPartial bile duct ligation (pBDL) is considered a well-tolerated cholestatic model. Magnetic resonance imaging (MRI) is one of the most widely used tools in noninvasive imaging. However, no systematic studies have reported the possible effects of repeated MRI assessments in the pBDL model. Sixty BALB/C mice were investigated. MRI images of each mouse were recorded once every 2 weeks for 6 weeks after pBDL or sham surgery. The reproducibility of the pBDL model and the reliability of MRI were examined by behavioral, physiological, biochemical, and pathological parameters. The mice showed no alterations on behavioral and physiological tests (P > 0.05) at 2, 4, and 6 weeks after pBDL. Repeated general anesthesia did not result in any impairment after pBDL (P > 0.05). The behavioral and biochemical parameters were not affected by repeated MRIs or repeated contrast-enhanced MRIs (P > 0.05). Pathological staining showed the homogeneous formation of collagenous fiber in the pBDL mice and did not indicate any influence of repeated contrast-enhanced MRI on the number of inflammatory cells or fibrotic formation (P > 0.05). Thus, pBDL is a reproducible model with many advantages for animal welfare and scientific research. Additionally, MRI, as a safe tool for longitudinal evaluation and is well tolerated in mice with cholestasis.
Chest x-ray imaging score is associated with severity of COVID-19 pneumonia: the MBrixia score
Authors: Jensen Christian M. , Costa Junia C. , Nørgaard Jens C. , Zucco Adrian G. , Neesgaard Bastian , Niemann Carsten U. , Ostrowski Sisse R. , Reekie Joanne , Holten Birgit , Kalhauge Anna , Matthay Michael A. , Lundgren Jens D. , Helleberg Marie , Moestrup Kasper S. 
Published: December 2022

AbstractSpatial resolution in existing chest x-ray (CXR)-based scoring systems for coronavirus disease 2019 (COVID-19) pneumonia is low, and should be increased for better representation of anatomy, and severity of lung involvement. An existing CXR-based system, the Brixia score, was modified to increase the spatial resolution, creating the MBrixia score. The MBrixia score is the sum, of a rule-based quantification of CXR severity on a scale of 0 to 3 in 12 anatomical zones in the lungs. The MBrixia score was applied to CXR images from COVID-19 patients at a single tertiary hospital in the period May 4th–June 5th, 2020. The relationship between MBrixia score, and level of respiratory support at the time of performed CXR imaging was investigated. 37 hospitalized COVID-19 patients with 290 CXRs were identified, 22 (59.5%) were admitted to the intensive care unit and 10 (27%) died during follow-up. In a Poisson regression using all 290 MBrixia scored CXRs, a higher MBrixia score was associated with a higher level of respiratory support at the time of performed CXR. The MBrixia score could potentially be valuable as a quantitative surrogate measurement of COVID-19 pneumonia severity, and future studies should investigate the score’s validity and capabilities of predicting clinical outcomes.
Short course palliative radiotherapy in advanced solid tumors: a pooled analysis (the SHARON project)
Authors: Donati Costanza Maria , Macchia Gabriella , Siepe Giambattista , Zamagni Alice , Benini Anna , Cellini Francesco , Buwenge Milly , Cilla Savino , Cammelli Silvia , Rizzo Stefania , Caravatta Luciana , Wondemagegnhu Tigeneh , Uddin A. F. M. Kamal , Deressa Biniyam Tefera , Sumon Mostafa A. , Lodi Rizzini Elisa , Bazzocchi Alberto , Morganti Alessio G. , Deodato Francesco , Farina Eleonora 
Published: December 2022

AbstractPrevious trials showed the tolerability and efficacy of a palliative radiotherapy (RT) regimen (SHARON) based on the 4 fractions delivered in 2 days in different oncological settings. In order to identify possible predictors of symptomatic response, the purpose of this study is to perform a pooled analysis of previous trials. We analyzed the impact on symptomatic response of the following parameters: tumor site, histological type, performance status (ECOG), dominant symptom, and RT dose using the Chi-square test and Fisher’s exact test. One-hundred-eighty patients were analyzed. Median RT dose was 20 Gy (range: 14–20 Gy). The overall response rate was 88.8% (95% CI 83.3–92.7%) while pre- and post-treatment mean VAS was 5.3 (± 7.7) and 2.2 (± 2.2), respectively (p < 0.001). The overall response rate of pain, dyspnea, bleeding, dysphagia, and other symptoms was 86.2%, 90.9%, 100%, 87.5%, and 100%, respectively. Comparing the symptomatic effect based on the analyzed parameters no significant differences were recorded. However, patients with locally advanced disease showed a higher rate of symptomatic responses than metastatic ones (97.3% vs 83.0%; p = 0.021). Finally, the complete pain response rate was more than double in patients with mild to moderate (VAS: 4–7) compared to those with severe (VAS > 7) pain (36.0% vs 14.3%; p = 0.028). This pooled analysis showed high efficacy of the SHARON regimen in the relief of several cancer-related symptoms. The markedly and significantly higher complete pain response rate, in patients with mild-moderate pain, suggests early referral to palliative RT for patients with cancer-related pain.