bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health Related Quality of Life and Hospitalizations In Chronic Thromboembolic Pulmonary Hypertension Versus Idiopathic Pulmonary Arterial Hypertension: An Analysis from the Pulmonary Hypertension Association (PHAR)
Authors: Minhas Jasleen , Narasimmal Sai Prasanna , Bull Todd , De Marco Teresa , McConnell John Wesley , Lammi Matthew R. , Thenappan Thenappan , Feldman Jeremy , Sager Jeffrey , Badesch David , Ryan John J. , Grinnan Daniel , Zwicke Dianne , Horn Evelyn , Elwing Jean M. , Moss John E. , Eggert Michael , Shlobin Oksana A. , Frantz Robert , Bartolome Sonja , Mathai Stephen C. , Mazimba Sula , Pugliese Steven , Al-Naamani Nadine 
Published: July 2021

AbstractChronic thromboembolic pulmonary hypertension (CTEPH) is a rare, morbid, potentially curable subtype of pulmonary hypertension that negatively impacts health-related quality of life (HRQoL). Little is known about differences in HRQoL and hospitalization between CTEPH patients and idiopathic pulmonary arterial hypertension (IPAH) patients. Using multivariable linear regression and mixed effects models, we examined differences in HRQoL assessed by emPHasis-10 (E10) and SF-12 between CTEPH and IPAH patients in the Pulmonary Hypertension Association Registry, a prospective multicenter cohort of patients newly evaluated at a Pulmonary Hypertension Care Center. Multivariable negative binomial regression models were used to estimate incidence rate ratios (IRR) for hospitalization amongst the two groups. We included 461 IPAH and 169 CTEPH patients. 21% of CTEPH patients underwent pulmonary thrombendarterectomy (PTE) before the end of follow-up. At baseline, patients with CTEPH had significantly worse HRQoL (higher E10 scores) (ß 2.83, SE 1.11, p=0.01); however, differences did not persist over time. CTEPH patients had higher rates of hospitalization (excluding the hospitalization for PTE) compared to IPAH after adjusting for age, sex, body mass index, WHO functional class and six-minute walk distance (IRR 1.66, 95%CI 1.04 – 2.65, p=0.03). CTEPH patients who underwent PTE had improved HRQoL as compared to those that were medically managed, but patients who underwent PTE were younger, had higher cardiac outputs and greater six-minute walk distances. In this large, prospective, multicenter cohort, CTEPH patients had significantly worse baseline HRQoL and higher rates of hospitalizations than those with IPAH. CTEPH patients who underwent PTE had significant improvements in HRQoL.
Regulation of DNA damage response by trimeric G-protein Signaling
Authors: Abd El-Hafeez Amer Ali , Sun Nina , Chakraborty Anirban , Ear Jason , Roy Suchismita , Chamarthi Pranavi , Rajapakse Navin , Das Soumita , Luker Kathryn E. , Hazra Tapas K. , Luker Gary D. , Ghosh Pradipta 
Published: July 2021

AbstractUpon sensing DNA double-strand breaks (DSBs), eukaryotic cells either die or repair DSBs via one of two competing pathways, i.e., non-homologous end-joining (NHEJ) or homologous recombination (HR). We show that cell fate after DNA damage hinges on the guanine nucleotide-exchange modulator of heterotrimeric G-protein, Giα•βγ, GIV/Girdin. GIV suppresses HR by binding and sequestering BRCA1, a key coordinator of multiple steps within the HR pathway, away from DSBs; it does so using a C-terminal motif that binds BRCA1’s BRCT-modules via both phospho-dependent and -independent mechanisms. GIV promotes NHEJ, and binds and activates Gi and enhances the ‘free’ Gβγ→PI-3-kinase→Akt pathway, thus revealing the enigmatic origin of prosurvival Akt signals during dsDNA repair. Absence of GIV, or the loss of either of its two functions impaired DNA repair, and induced cell death when challenged with numerous cytotoxic agents. That GIV selectively binds few other BRCT-containing proteins suggests convergent signaling such that heterotrimeric G-proteins may finetune sensing, repair, and outcome after DNA damage.GRAPHIC ABSTRACTHIGHLIGHTSNon-receptor G protein modulator, GIV/Girdin binds BRCA1Binding occurs in both canonical and non-canonical modesGIV sequesters BRCA1 away from dsDNA breaks, suppresses HRActivation of Gi by GIV enhances Akt signals, favors NHEJIN BRIEFIn this work, the authors show that heterotrimeric G protein signaling that is triggered by non-receptor GEF, GIV/Girdin, in response to double-stranded DNA breaks is critical for decisive signaling events which favor non-homologous end-joining (NHEJ) and inhibit homologous recombination (HR).
NetSolP: predicting protein solubility in E. coli using language models
Authors: Thumuluri Vineet , Martiny Hannah-Marie , Armenteros Jose J. Almagro , Salomon Jesper , Nielsen Henrik , Johansen Alexander R. 
Published: July 2021

AbstractSolubility and expression levels of proteins can be a limiting factor for large-scale studies and industrial production. By determining the solubility and expression directly from the protein sequence, the success rate of wet-lab experiments can be increased.In this study, we focus on predicting the solubility and usability for purification of proteins expressed in Escherichia coli directly from the sequence. Our model NetSolP is based on deep learning protein language models called transformers and we show that it achieves state-of-the-art performance and improves extrapolation across datasets. As we find current methods are built on biased datasets, we curate existing datasets by using strict sequence-identity partitioning and ensure that there is minimal bias in the sequences.The predictor is available at https://services.healthtech.dtu.dk/service.php?NetSolP-1.0
Intra-Articular Delivery of an Indoleamine 2,3-Dioxygenase Galectin-3 Fusion Protein for Osteoarthritis Treatment in Male Lewis Rats
Authors: Partain Brittany D. , Bracho-Sanchez Evelyn , Farhadi Shaheen A. , Yarmola Elena G. , Keselowsky Benjamin G. , Hudalla Gregory A. , Allen Kyle D. 
Published: July 2021

AbstractObjectiveControlling joint inflammation can improve osteoarthritis (OA) symptoms; however, current treatments often fail to provide long-term effects. We have developed an indoleamine 2,3-dioxygenase and galectin-3 fusion protein (IDO-Gal3). IDO converts tryptophan to kynurenines, directing the local environment toward an anti-inflammatory state; Gal3 binds carbohydrates and extends IDO’s joint residence time. In this study, we evaluated IDO-Gal3’s ability to alter OA-associated inflammation and pain-related behaviors in a rat model of established knee OA.MethodsJoint residence was first evaluated with an analog Gal3 fusion protein (NanoLuc™ and Gal3, NL-Gal3) that produces luminescence from furimazine. OA was induced in male Lewis rats via a medial collateral ligament and medial meniscus transection (MCLT+MMT). At 8 weeks, NL or NL-Gal3 were injected intra-articularly (n=8 per group), and bioluminescence was tracked for 4 weeks. Next, IDO-Gal3’s ability to modulate OA pain and inflammation was assessed. Again, OA was induced via MCLT+MMT in male Lewis rats, with IDO-Gal3 or saline injected into OA-affected knees at 8 weeks post-surgery (n=7 per group). Gait and tactile sensitivity were then assessed weekly. At 12 weeks, intra-articular levels of IL6, CCL2, and CTXII were assessed.ResultsThe Gal3 fusion increased joint residence in OA and contralateral knees (p<0.0001). In OA-affected animals, IDO-Gal3 improved tactile sensitivity (p=0.002), increased walking velocities (p≤0.033), and improved vertical ground reaction forces (p≤0.04). Finally, IDO-Gal3 decreased intra-articular IL6 levels within the OA-affected joint (p=0.0025).ConclusionIntra-articular IDO-Gal3 delivery provided long-term modulation of joint inflammation and pain-related behaviors in rats with established OA.
Genome-wide association study identifies susceptibility loci for acute myeloid leukemia
Authors: Lin Wei-Yu , Fordham Sarah E , Hungate Eric , Sunter Nicola J , Elstob Claire , Xu Yaobo , Park Catherine , Quante Anne , Strauch Konstantin , Gieger Christian , Skol Andrew , Rahman Thahira , Sucheston-Campbell Lara , Wang Junke , Hahn Theresa , Clay-Gilmour Alyssa I , Jones Gail L , Marr Helen J , Jackson Graham H , Menne Tobias , Collin Mathew , Ivey Adam , Hills Robert K , Burnett Alan K , Russell Nigel H , Fitzgibbon Jude , Larson Richard A , Le Beau Michelle M , Stock Wendy , Heidenreich Olaf , Alharbi Abrar , Allsup David J , Houlston Richard S , Norden Jean , Dickinson Anne M , Douglas Elisabeth , Lendrem Clare , Daly Ann K , Palm Louise , Piechocki Kim , Jeffries Sally , Bornhäuser Martin , Röllig Christoph , Altmann Heidi , Ruhnke Leo , Kunadt Desiree , Wagenführ Lisa , Cordell Heather J , Darlay Rebecca , Andersen Mette K , Fontana Maria C , Martinelli Giovanni , Marconi Giovani , Sanz Miguel A , Cervera José , Gómez-Seguí Inés , Cluzeau Thomas , Moreilhon Chimène , Raynaud Sophie , Sill Heinz , Voso Maria Teresa , Lo-Coco Francesco , Dombret Hervé , Cheok Meyling , Preudhomme Claude , Gale Rosemary E , Linch David , Gaal-Wesinger Julia , Masszi Andras , Nowak Daniel , Hofmann Wolf-Karsten , Gilkes Amanda , Porkka Kimmo , Milosevic Feenstra Jelena D , Kralovics Robert , Grimwade David , Meggendorfer Manja , Haferlach Torsten , Krizsán Szilvia , Bödör Csaba , Stölzel Friedrich , Onel Kenan , Allan James M 
Published: July 2021

AbstractAcute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we performed a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identified a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 × 10-8; KMT5B). We also identified a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N=1287) at 6p21.32 (rs3916765; P = 1.51 × 10-10; HLA). Our results inform on AML etiology by identifying putative functional genes operating in histone methylation (KMT5B) and immune function (HLA).
The role of mouthwash sampling in SARS-CoV-2 diagnosis
Authors: Biber Asaf , Lev Dana , Mandelboim Michal , Lustig Yaniv , Harmelin Geva , Shaham Amit , Erster Oran , Schwartz Eli 
Published: July 2021

AbstractBackgroundThe current practice of COVID-19 diagnosis worldwide is the use of oro-nasopharyngeal (ONP) swabs. Our study aim was to explore mouthwash (MW) as an alternative diagnostic method, in light of the disadvantages of ONP swabs.MethodsCovid-19 outpatients molecular-confirmed by ONP-swab were repeatedly examined with ONP-swab and MW with normal-saline (0.9%). Other types of fluids were compared to normal-saline. The Cq values obtained with each method were compared.ResultsAmong 137 pairs of ONP-swabs and MW samples, 84.6% (116/137) of ONP-swabs were positive by at least one of the genes (N, E, R). However MW detected 70.8% (97/137) of samples as positive, which means 83.6% (97/116) out of positive ONP-swabs, missing mainly Cq value>30. In both methods, the N gene was the most sensitive one. Therefore MW samples targeting N-gene, which was positive in 95/137 (69.3%), is comparable to ONP-swabs targeting E and R genes which gave equal results – 95/137 (69.3%) and 90/137 (65.7%) respectively.Comparing saline MW to distilled-water gave equal results, while commercial mouth-rinsing solutions were less sensitive.ConclusionsMW with normal-saline, especially when tested by N gene, can effectively detect COVID-19 patients. Furthermore, this method was not inferior when compared to R and E genes of ONP-swabs, which are common targets in many laboratories around the world.
A collaborative maternity and newborn dashboard (CoMaND) for the COVID-19 pandemic: a protocol for timely, adaptive monitoring of perinatal outcomes in Melbourne, Australia
Authors: Hui Lisa , Marzan Melvin Barrientos , Potenza Stephanie , Rolnik Daniel L. , Said Joanne M. , Palmer Kirsten R , Whitehead Clare L. , Sheehan Penelope M. , Ford Jolyon , Pritchard Natasha , Mol Ben W. , Walker Susan P. 
Published: July 2021

ABSTRACTBackgroundThe COVID-19 pandemic has resulted in a range of unprecedented disruptions to the delivery of maternity care globally and has been associated with regional changes in perinatal outcomes such as stillbirth and preterm birth. Metropolitan Melbourne endured one of the longest and most stringent lockdowns in 2020. This paper presents the protocol for a collaborative maternity dashboard project to monitor perinatal outcomes in Melbourne, Australia, during the COVID-19 pandemic.MethodsDe-identified maternal and newborn outcomes will be collected monthly from all public maternity services in Melbourne, allowing rapid analysis of a multitude of perinatal indicators. Weekly outcomes will be displayed as run charts according to established methods for detecting non-random ‘signals’ in health care. A pre-pandemic median for all indicators will be calculated for the period of January 2018 to March 2020. A significant shift is defined as ≤ six consecutive weeks, all above or below the pre-pandemic median. Additional statistical analyses such as regression, time-series, and survival analyses will be performed for an in-depth examination of maternal and perinatal outcomes of interests.Ethics and DisseminationThis study has been registered as an observational study with the Australian and New Zealand Clinical Trials Registry (ACTRN12620000878976).Strengths and weaknesses of this study⍰ This project is the first clinician-led, multi-centre perinatal data collection system for metropolitan Melbourne.⍰ It complements the state government data collection, with the significant benefits of more timely and flexible reporting of outcomes, and granular detail on emerging areas of concern.⍰ The study relies on primary source coding of exposure and outcomes from each hospital that have not been internally validated during the study period.⍰ Data from private maternity hospitals, containing 25% of Melbourne births, are not available.⍰ This resource will support data-informed hospital pandemic responses through to the end of 2022.
Matrix elasticity gradients guide neuronal polarity by controlling microtubule network mobility
Authors: Burute Mithila , Jansen Klara I. , Mihajlovic Marko , Vermonden Tina , Kapitein Lukas C. 
Published: July 2021

ABSTRACTNeuronal polarization and axon specification depend on extracellular cues, intracellular signaling, cytoskeletal rearrangements and polarized transport, but the interplay between these processes has remained unresolved. The polarized transport of kinesin-1 into a specific neurite is an early marker for axon identity, but the mechanisms that govern neurite selection and polarized transport are unknown. We show that extracellular elasticity gradients control polarized transport and axon specification, mediated by Rho-GTPases whose local activation is necessary and sufficient for polarized transport. Selective Kinesin-1 accumulation furthermore depends on differences in microtubule network mobility between neurites and local control over this mobility is necessary and sufficient for proper polarization, as shown using optogenetic anchoring of microtubules. Together, these results explain how mechanical cues can instruct polarized transport and axon specification.
ADAR mediated A-to-I RNA editing affects SARS-CoV-2 characteristics and fuels its evolution
Authors: Song Yulong , He Xiuju , Yang Wenbing , Tang Tian , Zhang Rui 
Published: July 2021

AbstractUpon SARS-CoV-2 infection, viral intermediates activate the Type I interferon (IFN) response through MDA5-mediated sensing and accordingly induce ADAR1 p150 expression, which might lead to A-to-I RNA editing of SARS-CoV-2. Here, we developed an RNA virus-specific editing identification pipeline, surveyed 7622 RNA-seq data from diverse types of samples infected with SARS-CoV-2, and constructed an atlas of A-to-I RNA editing sites in SARS-CoV-2. We found that A-to-I editing was dynamically regulated, and on average, approximately 91 editing events were deposited at viral dsRNA intermediates per sample. Moreover, editing hotspots were observed, including recoding sites in the spike gene that affect viral infectivity and antigenicity. Finally, we provided evidence that RNA editing accelerated SARS-CoV-2 evolution in humans. Collectively, our data suggest that SARS-CoV-2 hijacks components of the host antiviral machinery to edit its genome and fuel its evolution.
Origin and evolutionary landscape of Nr2f transcription factors across Metazoa
Authors: Coppola Ugo , Waxman Joshua S. 
Published: July 2021

AbstractBackgroundNuclear Receptor Subfamily 2 Group F (Nr2f) orphan nuclear hormone transcription factors (TFs) are fundamental regulators of many developmental processes in invertebrates and vertebrates. Despite the importance of these TFs throughout metazoan development, previous work has not clearly outlined their evolutionary history.ResultsWe integrated molecular phylogeny with comparisons of intron/exon structure, domain architecture, and syntenic conservation to define critical evolutionary events that distinguish the Nr2f gene family in Metazoa. Our data indicate that a single ancestral pre-metazoan Nr2f gene, we have termed Nr2f1/2/5/6, predated six main Bilateria subfamilies, which include a single Nr2f1/2/5 homolog that is present throughout protostomes and invertebrate deuterostomes, Nr2f1/2 homologs in agnathans, and Nr2f1, Nr2f2, Nr2f5, Nr2f6 orthologs that are found in gnathostomes. The three Nr2f1/2 members in agnathans are due to independent expansions not found in gnathostomes, while the vertebrate Nr2f1, Nr2f2, Nr2f5 members arose from whole-genome duplications (WGDs). However, Nr2f6 members are the most divergent subfamily, likely originating from an ancient duplication, and are only retained by gnathostomes. Interestingly, Nr2f5 TFs have been independently lost in both cartilaginous fish and amniotes, such as humans. Furthermore, our analysis shows there are differential expansions and losses of Nr2f genes in teleosts following their additional rounds of WGDs.ConclusionOverall, our evolutionary genomic analysis of Nr2f proteins helps to reveal the origins and previously unrecognized relationships of this ancient transcription factor family, which may allow for greater insights into the conservation of Nr2f functions that shape Metazoan body plans.
Review and selection of commercially available IMU for a short time inertial navigation
Authors: Borodacz Krystian , Szczepański Cezary , Popowski Stanisław 
Published: July 2021

Purpose
The selection of a suitable inertial measurement unit (IMU) is a critical step in an inertial navigation system (INS) design. Nevertheless, inertial sensors manufacturers are unwilling to publish their products’ accurate performance parameters along with a price. This paper aims to summarise the current IMU market review and point out parameters important for short-term inertial navigation.

Design/methodology/approach
The market review is based on the information published by manufacturers in brochures, datasheets and websites. Some information, including price, was also collected from sensors distributors. The entire collection of data includes data of over 150 sensors from 32 manufacturers and is valid for the first half of the year 2020.

Findings
This paper answers the following questions: •Why and where use inertial navigation? •Which parameters should one emphasise during IMU selection?•What is currently available on the IMU market? •Which parameters have a significant influence on price? •What are the advantages of specific sensor technology?

Originality/value
This paper gathers data published by IMU manufacturers, allowing for a quick overview of the current market. Based on real data, different sensor technologies are compared. The performed analysis presents the statistical basis for the IMU selection. By theoretical considerations a significance of sensor parameters is drawn and an approach to an IMU selection based on limited number of parameters is proposed. Although the considerations have been carried out regarding inertial navigation, the results from an extensive analysis of commercially available sensors may also be useful for other applications.
Identification of potential biomechanical risk factors for low back disorders during repetitive rebar lifting
Authors: Antwi-Afari Maxwell Fordjour , Li Heng , Edwards David John , Pärn Erika Anneli , Owusu-Manu De-Graft , Seo Joonoh , Wong Arnold Yu Lok 
Published: July 2021

Purpose
Work-related low back disorders (LBDs) are prevalent among rebar workers although their causes remain uncertain. The purpose of this study is to examine the self-reported discomfort and spinal biomechanics (muscle activity and spinal kinematics) experienced by rebar workers.

Design/methodology/approach
In all, 20 healthy male participants performed simulated repetitive rebar lifting tasks with three different lifting weights, using either a stoop (n = 10) or a squat (n = 10) lifting posture, until subjective fatigue was reached. During these tasks, trunk muscle activity and spinal kinematics were recorded using surface electromyography and motion sensors, respectively.

Findings
A mixed-model, repeated measures analysis of variance revealed that an increase in lifting weight significantly increased lower back muscle activity at L3 level but decreased fatigue and time to fatigue (endurance time) (p < 0.05). Lifting postures had no significant effect on spinal biomechanics (p < 0.05). Test results revealed that lifting different weights causes disproportional loading upon muscles, which shortens the time to reach working endurance and increases the risk of developing LBDs among rebar workers.

Research limitations/implications
Future research is required to: broaden the research scope to include other trades; investigate the effects of using assistive lifting devices to reduce manual handling risks posed; and develop automated human condition-based solutions to monitor trunk muscle activity and spinal kinematics.

Originality/value
This study fulfils an identified need to study laboratory-based simulated task conducted to investigate the risk of developing LBDs among rebar workers primarily caused by repetitive rebar lifting.