bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential of Photon-Counting Detector CT for Radiation Dose Reduction for the Assessment of Interstitial Lung Disease in Patients With Systemic Sclerosis
Authors: Jungblut Lisa , Euler André , von Spiczak Jochen , Sartoretti Thomas , Mergen Victor , Englmaier Vanessa , Landsmann Anna , Mihai Carmen-Marina , Distler Oliver , Alkadhi Hatem , Frauenfelder Thomas , Martini Katharina 
Published: May 2022

Objective
The aim of this study was to determine the potential of photon-counting detector computed tomography (PCD-CT) for radiation dose reduction compared with conventional energy-integrated detector CT (EID-CT) in the assessment of interstitial lung disease (ILD) in systemic sclerosis (SSc) patients.

Methods
In this retrospective study, SSc patients receiving a follow-up noncontrast chest examination on a PCD-CT were included between May 2021 and December 2021. Baseline scans were generated on a dual-source EID-CT by selecting the tube current-time product for each of the 2 x-ray tubes to obtain a 100% (D100), a 66% (D66), and a 33% dose image (D33) from the same data set. Slice thickness and kernel were adjusted between the 2 scans. Image noise was assessed by placing a fixed region of interest in the subcutaneous fat. Two independent readers rated subjective image quality (5-point Likert scale), presence, extent, diagnostic confidence, and accuracy of SSc-ILD. D100 interpreted by a radiologist with 22 years of experience served as reference standard. Interobserver agreement was calculated with Cohen κ, and mean variables were compared by a paired t test.

Results
Eighty patients (mean 56 ± 14; 64 women) were included. Although CTDIvol of PCD-CT was comparable to D33 (0.72 vs 0.76 mGy, P = 0.091), mean image noise of PCD-CT was comparable to D100 (131 ± 15 vs 113 ± 12, P > 0.05). Overall subjective image quality of PCD-CT was comparable to D100 (4.72 vs 4.71; P = 0.874). Diagnostic accuracy was higher in PCD-CT compared with D33/D66 (97.6% and 92.5%/96.3%, respectively) and comparable to D100 (98.1%).

Conclusions
With PCD-CT, a radiation dose reduction of 66% compared with EID-CT is feasible, without penalty in image quality and diagnostic performance for the evaluation of ILD.
Integrative molecular profiling identifies two molecularly and clinically distinct subtypes of blastic plasmacytoid dendritic cell neoplasm
Authors: Künstner Axel , Schwarting Julian , Witte Hanno M. , Bernard Veronica , Stölting Stephanie , Kusch Kathrin , Nagarathinam Kumar , von Bubnoff Nikolas , Murga Penas Eva M. , Merz Hartmut , Busch Hauke , Feller Alfred C. , Gebauer Niklas 
Published: May 2022

AbstractBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive malignancy assumed to originate from plasmacytoid dendritic cells (pDCs), which mostly affects the skin, bone marrow, lymph nodes and sequentially other organ systems. RNA-, targeted- and exome sequencing studies have identified molecular characteristics, associated with BPDCN-pathogenesis, yet an integrative molecular assessment of BPDCN remains pending. Here, we combined paired WES/RNA-Seq with genome-wide copy-number analysis to characterize 47 BPDCN patients for mutational drivers, cytogenetic aberrations and gene-expression profiles. We identified alterations in epigenetic regulators (TET2, EP300, DNMT3A, SF3B1, EZH2) and a mutational disruption of RTK-RAS signaling (NF1, NRAS, EGFR) as drivers of BPDCN alongside deletions of tumor suppressors (CDKN2A, RB1, TP53), amplifications of oncogenes (IDH2, MET, EZH2) and recurrent fusions (MYB, ALK). The mutational landscape further provides evidence for frequent induction of PDGF signaling and extracellular matrix interactions as well as a gender specificity and a subset of MSIhigh patients. Many genes affected in BPDCN are shared with chronic myelomonocytic leukemia (CMML), emphasizing a close relationship between these entities and to a lesser extent with acute myeloid leukemia (AML). Ontological assessment of RNA-Seq data revealed two BPDCN subtypes, a typical pDC-derived subtype (C1) and a (common) cDC-enriched subtype (C2), which were then shown to exhibit distinct mutational (EP300, ARID2, NF1 mutations in typical pDC vs. DNMT3A, SRSF2 mutations in the cDC-enriched subtype) and clinical features.In summary, our hitherto most comprehensive characterization of BPDCN reveals molecular hallmarks alongside actionable vulnerabilities and highlights two novel subtypes that are molecularly and clinically distinct.Key Points-Paired WES/RNA-Seq and copy number analysis of a large BPDCN cohort reveals two molecularly and clinically distinct subtypes.-Multi-omics identify recurrent therapeutic targets and vulnerabilities including MSIhigh and mutations within epigenetic regulation of gene expression and RTK-RAS signaling.
Governance is key to controlling SARS-CoV-2’s vaccine resistance
Authors: Okamoto Kenichi W. , Chaves Luis F. , Wallace Rodrick , Wallace Robert G. 
Published: May 2022

AbstractLittle attention has been paid to governance’s impacts on the evolution of SARS-CoV-2, the virus that causes COVID-19. To evaluate such impacts on the evolution of vaccine resistance, we analyzed a stochastic compartmental model to quantify the risk a mutant strain capable of evading immunity emerges post-vaccine rollout. We calibrated the model with publicly available data for four territories in the Western Hemisphere qualitatively differing in pandemic interventions. The model shows an immune-evading strain to be readily selected over all infectivities in Texas. In Panama, only a high level of transmission permits immune evasion to evolve. No invasion appears likely in Costa Rica and Uruguay. Programs combining pharmaceutical and nonpharmaceutical interventions are best positioned to remove the epidemiological space SARS-CoV-2 needs to evolve vaccine resistance.One Sentence SummaryModes of governance and production help set the evolutionary trajectories of vaccine resistance in SARS-CoV-2 before vaccine campaigns begin.
FPocketWeb: Protein pocket hunting in a web browser
Authors: Kochnev Yuri , Durrant Jacob D. 
Published: May 2022

ABSTRACTMotivationDetecting macromolecular (e.g., protein) cavities where small molecules bind is an early step in computer-aided drug discovery. Multiple pocket-detection algorithms have been developed over the past several decades. Among them, fpocket, created by Schmidtke and Le Guilloux, is particularly popular. Like many programs used in computational-biology research, fpocket requires users to download and install an executable file. That file must also be run via a command-line interface, further complicating use. An existing fpocket server application effectively addresses these challenges, but it requires users to upload their possibly proprietary structures to a third-party server.ResultsThe FPocketWeb web app builds on this prior work. It runs the fpocket3 executable entirely in a web browser without requiring installation. The pocket-finding calculations occur on the user’s computer rather than on a remote server.AvailabilityA working version of the open-source FPocketWeb app can be accessed free of charge from http://durrantlab.com/fpocketweb.
Incidence of Post-Covid Syndrome and Associated Symptoms in Outpatient Care in Bavaria, Germany
Authors: Donnachie Ewan , Hapfelmeier Alexander , Linde Klaus , Tauscher Martin , Gerlach Roman , Greißel Anna , Schneider Antonius 
Published: May 2022

AbstractObjectivesTo estimate the treatment incidence of Post-Covid Syndrome in the context of office-based care in Bavaria, Germany, and to establish whether related diagnoses occur more frequently than in patients with no known history of COVID-19.DesignRetrospective analysis of routinely collected claims data.SettingOffice-based care in Bavaria, Germany.Participants391,990 patients with confirmed COVID-19 diagnosis, 62,659 patients with other respiratory infection, and a control group of 659,579 patients with no confirmed or suspected diagnosis COVID-19.Primary and Secondary Outcome MeasuresPrimary outcome is diagnosis of a Post-COVID Syndrome by an office-based physician. Secondary outcomes are: Chronic Fatigue Syndrome (CFS), psychological disorder, fatigue, mild cognitive impairment, disturbances of taste and smell, dyspnea, pulmonary embolism and myalgia.ResultsAmong all patients with confirmed COVID-19 infection, 14.2% (95% CI: 14.0-14.5) received a diagnosis of a Post-COVID Syndrome, and 6.7% (6.5-6.9) received the diagnosis in at least two quarterly periods during a two-year follow-up. Compared with patients with other respiratory infections and with controls, patients with COVID-19 more frequently received a variety of diagnoses including CFS (1.6% vs. 0.6% and 0.3%, respectively), fatigue (13.3% vs. 9.2% and 6.0%), dyspnea (9.9% vs. 5.1% and 3.2%) and disturbances of taste and smell (3.2% vs. 1.2% and 0.5%). The treatment incidence of Post-COVID Syndrome was highest among adults aged 40-59 (19.0%) and lowest among children aged below 12 years (2.6%).ConclusionsOur results demonstrate a moderately high incidence of Post-COVID Syndrome two years after infection with COVID-19. There is an urgent need to find efficient and effective solutions to help patients with mental disorders, dyspnea, fatigue and loss of smell. Guidelines and treatment algorithms, including referral criteria, occupational and physical therapy, require promptly and coherent implementation. Further research is required both to find new therapeutic options and to assess the implications of Post-COVID Syndrome for health services.Strengths and Limitations of the StudyThe data cover all statutory health insurance companies in Bavaria and have high generalisability to the general population.By considering the proportion of COVID-19 patients consulting a physician, our results are better able to differentiate between everyday complaints and medically significant illness than data from a self-reported questionnaire.Follow-up of up to two years enables first assessment of the proportion requiring continuous care for a Post-COVID Syndrome.The routinely collected data are not audited and contain little information regarding the severity of the symptoms.
The SARS-CoV-2 accessory factor ORF7a downregulates MHC class I surface expression
Authors: Zheng Shuxuan , de Buhr Hendrik , Praest Patrique , Evers Anouk , Brak-Boer Ingrid , van Grinsven Mariëlle , Longo Ylenia , de Vries Liset , Nijenhuis Wilco , Kapitein Lukas C. , Beekman Jeffrey M. , Nijhuis Monique , Drexler Ingo , Wiertz Emmanuel J. H. J. , Lebbink Robert Jan 
Published: May 2022

AbstractThe pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in over 500 million infections and more than six million deaths worldwide. Although the viral genomes of SARS-CoV-1 and SARS-CoV-2 share high sequence homology, the clinical and pathological features of COVID-19 differ profoundly from those of SARS. It is apparent that changes in viral genes contribute to the increased transmissibility of SARS-CoV-2 and pathology of COVID-19.Cytotoxic T lymphocytes play a key role in the elimination of virus-infected cells, mediated by recognition of virus-derived peptides that are presented on MHC class I molecules. Here, we show that SARS-CoV-2 can interfere with antigen presentation thereby evading immune surveillance. SARS-CoV-2 infection of monkey and human cell lines resulted in reduced cell-surface expression of MHC class I molecules. We identified a single viral gene product, the accessory factor open reading frame 7a (ORF7a), that mediates this effect. ORF7a interacts with HLA class I molecules in the ER, resulting in ER retention or impaired HLA heavy chain (HC) trafficking to the Golgi. Ultimately, these actions result in reduced HLA class I surface expression on infected cells. Whereas ORF7a from SARS-CoV-2 reduces surface HLA class I levels, the homologous ORF7a from the 2002 pandemic SARS-CoV-1 did not, suggesting that SARS-CoV-2 ORF7a acquired the ability to downregulate HLA-I during evolution of the virus. We identified a single amino acid in the SARS-CoV-1 ORF7a luminal domain that, upon mutating to the corresponding SARS-CoV-2 ORF7a sequence, induced a gain-of-function in HLA surface downregulation. By abrogating HLA class I antigen presentation via ORF7a, SARS-CoV-2 may evade host immune responses by inhibiting anti-viral cytotoxic T cell activity, thereby contributing to the pathology of COVID-19.
Genome similarities between human-derived and mink-derived SARS-CoV-2 make mink a potential reservoir of the virus
Authors: Khalid Mohammad , Al-ebini Yousef 
Published: May 2022

AbstractThe SARS-CoV-2 has RNA as the genome, which makes the virus more prone to mutations. Occasionally, mutations help a virus to cross the species barrier. The SARS-CoV-2 infection to humans and minks (Neovison vison) are examples of zoonotic spillover. Many studies have been published on the analysis of human-derived SARS-CoV-2, here we performed mutation analysis on the minks-derived SARS-CoV-2 genome sequences. We analyzed all available full-length mink derived SARS-CoV-2 genome sequences on GISAID (214 from Netherlands and 133 from Denmark). We found that the mutation pattern in the Netherlands and Denmark derived samples were different. Out of a total of 201 mutations, we found in this study, only 13 mutations were common in the Netherlands and Denmark derived samples. We found 4 mutations prevailed in the Netherlands and Denmark mink derived samples and these 4 mutations are also reported to prevail in human-derived SARS-CoV-2.
The generic status ofAnacolosa(Olacaceae) in Africa withA. deniseaea new species to science of Endangered submontane forest liana from Simandou, Republic of Guinea
Authors: Cheek Martin , Molmou Denise , Gosline George , Magassouba Sekou 
Published: May 2022

SummaryAnacolosa deniseaeCheek (Olacaceae) a submontane gallery forest canopy liana is described as a new species to science and assessed as Endangered using the IUCN 2012 standard due to threats of habitat destruction connected with mining. The roots smell of benzaldehyde when scraped, and the plant reproduces from root suckers. The species is restricted globally to two locations in the Loma-Man Highlands of the Republic of Guinea, all records but one being in the Pic de Fon Fôret Classé of the Simandou Range.We show that this and the only other continental African species ascribed to the genusAnacolosa, A. unciferaof DRC, Gabon & C.A.R., differ in so many architectural, floral and vegetative characters from the remaining species of the genus, which occur from Madagascar to the Western Pacific, including the typeA. frutescens(S.E. Asia and Indo-China), that they clearly represent a separate genus. The African genus represented by these two species is unique within the Olacaceae (excluding Erythropalaceae) in being a climber (vs. shrubs or trees inAnacolosa sensu stricto). Climbing in the two African species is achieved by perennial hook-like structures formed by a combination of five separate traits each of which is unknown elsewhere in the Olacaceae. We formally delimit and describe this new genus, discussing its characteristics, but in the absence of molecular phylogenetic data, refrain from naming it.
A VPSl5-like kinase regulates apicoplast biogenesis and autophagy by promoting PI3P generation in Toxoplasma gondii
Authors: Rawat Rahul Singh , Bansal Priyanka , Sharma Pushkar 
Published: May 2022

AbstractPhosphoinositides are important second messengers that regulate key cellular processes in eukaryotes. While it is know that a single phosphoinositol-3 kinase (PI3K) catalyses the formation of 3’-phosphorylated phosphoinositides (PIPs) in apicomplexan parasites Plasmodium and Toxoplasma, how its activity and PI3P formation is regulated has remained unknown. Present studies involving a unique Vps15 like protein (TgVPS15) in Toxoplasma gondii provide insights into the regulation of phosphatidyl-3-phosphate (PI3P) generation and unravel a novel pathway that regulates parasite development. Detailed investigations suggested that TgVPS15 regulates PI3P formation in Toxoplasma gondii, which is important for the inheritance of the apicoplast-a plastid like organelle present in most apicomplexans and parasite replication. Interestingly, TgVPS15 also regulates autophagy in T. gondii under nutrient-limiting conditions as it promotes autophagosome formation. For both these processes, TgVPS15 uses PI3P-binding protein TgATG18 and regulates trafficking and conjugation of TgATG8 to the apicoplast and autophagosomes, which is important for biogenesis of these organelles. TgVPS15 has a protein kinase domain but lacks several key residues conserved in conventional protein kinases. Interestingly, two critical residues in its active site are important for PI3P formation and parasitic functions of this kinase. Collectively, these studies unravel a signalling cascade involving TgVPS15, a novel effector of PI3-kinase in T. gondii and possibly other Apicomplexa, that regulate critical processes like apicoplast biogenesis and autophagy.
Genetic diversity assessment of Pacific oyster Magallana gigas (Crassostrea gigas) populations from the two southern coastal farms in South Korea
Authors: Tran Biet Thanh , Park Su-Jin , Park Hong Keun , Park Dongjin , Choi Youn Hee 
Published: May 2022

AbstractSouth Korea is among the major producers of the Pacific oyster, Magallana gigas (Crassostrea gigas), which is one of the most valued aquaculture species. Since the early 1990s, climatic and anthropogenic factors have incurred the reduction of their wild seeds, whereby the dependence on hatchery-produced seeds has constantly increased in South Korea, thus raising concerns about losing genetic diversity and accelerating genetic deterioration. To better understand their genetic make-up, we assessed the genetic diversity of M. gigas populations from two farms (Tongyeong and Gadeokdo) in the southern coast, where about 80% of the cultivated oysters in Korea are produced. Tongyeong showed slightly higher diversity than Gadeokdo, but both populations had a similar genetic structure characterized by low nucleotide diversity. Comparative haplotype analyses provided data supporting unique genetic features of the populations that include (1) weak genotype-locality relationship, (2) low levels of gene flow between populations, and (3) seasonal fluctuation of genetic variation within a population. Furthermore, the highly alike haplotype network patterns were observed between the wild and farm populations as well as among the populations in neighboring countries, which suggests that the genetic structure is conserved between wild and hatchery populations, and geographic proximity has minimal influence on the genetic composition. These results warrant further study in biological and ecological contexts and will be invaluable in formulating genetic monitoring and sustainable long-term management of M. gigas.
The termination of UHRF1-dependent PAF15 ubiquitin signaling is regulated by USP7 and ATAD5
Authors: Miyashita Ryota , Nishiyama Atsuya , Chiba Yoshie , Kori Satomi , Kato Norie , Konishi Chieko , Kumamoto Soichiro , Kozuka-Hata Hiroko , Oyama Masaaki , Kawasoe Yoshitaka , Tsurimoto Toshiki , Takahashi Tatsuro S , Arita Kyohei , Nakanishi Makoto 
Published: May 2022

AbstractUHRF1-dependent ubiquitin signaling plays an integral role in the regulation of maintenance DNA methylation. UHRF1 catalyzes transient dual mono-ubiquitylation of PAF15 (PAF15Ub2), which regulates the localization and activation of DNMT1 at DNA methylation sites during DNA replication. Although the initiation of UHRF1-mediated PAF15 ubiquitin signaling has been relatively well characterized, mechanisms underlying its termination and how they are coordinated with the completion of maintenance DNA methylation have not yet been clarified. This study shows that deubiquitylation by USP7 and unloading by ATAD5 (ELG1 in yeast) are pivotal processes for the removal of PAF15 from chromatin. On replicating chromatin, USP7 specifically interacts with PAF15Ub2 in a complex with DNMT1. USP7 depletion or inhibition of the interaction between USP7 and PAF15 results in abnormal accumulation of PAF15Ub2 on chromatin. Furthermore, we also find that the non-ubiquitylated form of PAF15 (PAF15Ub0) is removed from chromatin in an ATAD5-dependent manner. PAF15Ub2 was retained at high levels on chromatin when the catalytic activity of DNMT1 was inhibited, suggesting that the completion of maintenance DNA methylation is essential for termination of UHRF1-mediated ubiquitin signaling. This finding provides a molecular understanding of how the maintenance DNA methylation machinery is disassembled at the end of the S phase.
Retinoic acid signaling modulation guides in vitro specification of human heart field-specific progenitor pools
Authors: Zawada Dorota , Kornherr Jessica , Meier Anna B. , Santamaria Gianluca , Dorn Tatjana , Ortmann Daniel , Lachmann Mark , Ortiz Mariaestela , Harmer Stephen C. , Nobles Muriel , Tinker Andrew , Pedersen Roger A. , Grote Phillip , Laugwitz Karl-Ludwig , Moretti Alessandra , Goedel Alexander 
Published: May 2022

AbstractCardiogenesis relies on the precise spatiotemporal coordination of multiple progenitor populations. Understanding the specification and differentiation of these distinct progenitor pools during human embryonic development is crucial for advancing our knowledge of congenital cardiac malformations and designing new regenerative therapies. By combining genetic labelling, single-cell transcriptomics, and ex vivo human-mouse embryonic chimeras we uncovered that modulation of retinoic acid signaling instructs human pluripotent stem cells to form heart field-specific progenitors with distinct fate potentials. In addition to the classical first and second heart fields, we observed the appearance of juxta-cardiac field progenitors giving rise to both myocardial and epicardial cells. Applying these findings to stem-cell based disease modelling we identified specific transcriptional dysregulation in first and second heart field progenitors derived from stem cells of a patient with hypoplastic left heart syndrome. This highlights the suitability of our in vitro differentiation platform for studying human cardiac development and disease.
Lipid-mediated organization of prestin in the outer hair cell membrane and its implications in sound amplification
Authors: Dehghani-Ghahnaviyeh Sepehr , Zhao Zhiyu , Tajkhorshid Emad 
Published: May 2022

AbstractPrestin is a high-density motor protein in the outer hair cells (OHCs), whose conformational response to acoustic signals alters the shape of the cell, thereby playing a major role in sound amplification by the cochlea. Despite recent structural determination in active and inhibited states, the details of prestin’s intimate interactions with the membrane, which are central to its function remained unresolved. Here, employing a large set (collectively, more than 0.5 ms) of coarse-grained molecule dynamics simulations, we characterize the nature of prestin’s lipid-protein interactions, demonstrating their impact on the organization of prestin at densities relevant to the OHCs and its effectiveness in reshaping OHCs. Beyond local enrichment/depletion of various lipid types, prestin causes drastic anisotropic membrane deformation, which in turn mediates a preferential membrane organization of prestin in which deformation patterns by neighboring prestin copies are aligned constructively. The reduced membrane rigidity accompanying this arrangement is hypothesized to maximize the mechanical impact of prestin on OHC reshaping during cochlear sound amplification. Prestin’s preferential arrangement is further verified by extended simulations demonstrating strong correlation between prestin neighbors in their orientations. These results demonstrate a strong case of protein-protein cooperative communication in membrane, purely mediated by their interactions with lipids.