bluuebunny/crossref_metadata_2025_split huggingface dataset:
Asymmetrical Bi-antennary Glycans Prepared by a Stop-and-Go Strategy Reveal Receptor Binding Evolution of Human Influenza A Viruses
Authors: Ma Shengzhou , Liu Lin , Eggink Dirk , Herfst Sander , Fouchier Ron A.M. , de Vries Robert P. , Boons Geert-Jan 
Published: November 2023

ABSTRACTGlycan binding properties of respiratory viruses have been difficult to probe due to a lack of biological relevant glycans for binding studies. Here, a stop-and-go chemoenzymatic methodology is presented that gave access to a panel of 32 asymmetrical bi-antennaryN-glycans having various numbers ofN-acetyl lactosamine (LacNAc) repeating units capped by α2,3- or α2,6-sialosides resembling structures found in airway tissues. It exploits that the branching enzymes MGAT1 and MGAT2 can utilize unnatural UDP-2-deoxy-2-trifluoro-N-acetamido-glucose (UDP-GlcNTFA) as donor. The TFA moiety of the resulting glycans can be hydrolyzed to give GlcNH2at one of the antennae that temporarily blocks extension by glycosyl transferases. TheN-glycans were printed as a microarray that was probed for receptor binding specificities of evolutionary distinct human A(H3N2) and A(H1N1)pdm09 viruses. It was found that not only the sialoside type but also the length of the LacNAc chain and presentation at the α1,3-antenna ofN-glycans is critical for binding. Early A(H3N2) viruses bound to 2,6-sialosides at a single LacNAc moiety at the α1,3-antenna whereas later viruses required the sialoside to be presented at a tri-LacNAc moiety. Surprisingly, most of the A(H3N2) viruses that appeared after 2021 regained binding capacity to sialosides presented at a di-LacNAc moiety. As a result, these viruses agglutinate erythrocytes again, commonly employed for antigenic characterization of influenza viruses. Human A(H1N1)pdm09 viruses have similar receptor binding properties as recent A(H3N2) viruses. The data indicates that an asymmetricN-glycan having 2,6-sialoside at a di-LacNAc moiety is a commonly employed receptor by human influenza A viruses.
Disease-specific variant interpretation highlighted the genetic findings in 2325 Japanese patients with retinitis pigmentosa and allied diseases
Authors: Goto Kensuke , Koyanagi Yoshito , Akiyama Masato , Murakami Yusuke , Fukushima Masatoshi , Fujiwara Kohta , Iijima Hanae , Yamaguchi Mitsuyo , Endo Mikiko , Hashimoto Kazuki , Ishizu Masataka , Hirakata Toshiaki , Mizobuchi Kei , Takayama Masakazu , Ota Junya , Sajiki Ai Fujita , Kominami Taro , Ushida Hiroaki , Fujita Kosuke , Kaneko Hiroki , Ueno Shinji , Hayashi Takaaki , Terao Chikashi , Hotta Yoshihiro , Murakami Akira , Kuniyoshi Kazuki , Kusaka Shunji , Wada Yuko , Abe Toshiaki , Nakazawa Toru , Ikeda Yasuhiro , Momozawa Yukihide , Sonoda Koh-Hei , Nishiguchi Koji M. 
Published: November 2023

AbstractBackgroundAs gene-specific therapy for inherited retinal dystrophy (IRD) advances, unified variant interpretation across institutes is becoming increasingly important. This study aims to update the genetic findings of 86 retinitis pigmentosa (RP)–related genes in a large number of Japanese RP patients by applying the standardized variant interpretation guidelines for Japanese IRD patients (J-IRD-VI guidelines) built upon ACMG/AMP rules and assess the contribution of these genes in RP-allied diseases.MethodsWe assessed 2325 probands with RP (n=2155, including n=1204 sequenced previously with the same sequencing panel) and allied diseases (n=170, all newly analyzed), including Usher syndrome, Leber congenital amaurosis, and cone-rod dystrophy (CRD). Target sequencing using a panel of 86 genes was performed. The variants were interpreted according to the J-IRD-VI guidelines.ResultsA total of 3564 variants were detected, of which 524 variants were interpreted as pathogenic or likely pathogenic. Among these 524 variants, 280 (53.4%) had been either undetected or interpreted as variants of unknown significance or benign variants in our earlier study of 1204 RP patients. This led to a genetic diagnostic rate in 38.6% of RP patients, withEYSaccounting for 46.7% of the genetically solved patients, showing a 9% increase in diagnostic rate from our earlier study. The genetic diagnostic rate for CRD patients was 28.2%, with RP-related genes significantly contributing over other allied diseases.ConclusionA large-scale genetic analysis using the J-IRD-VI guidelines highlighted the unique genetic findings for Japanese IRD patients; these findings serve as a foundation for the clinical application of gene-specific therapies.
Clinical Effectiveness of cardiac rehabilitation utilisation and the barriers to its completion among patients of low socioeconomic status living in rural areas: a mixed methods study
Authors: Beleigoli Alline , Dafny Hila Ariela , de Plaza Maria Alejandra Pinero , Hutchinson Claire , Marin Tania , Ramos Joyce S , Suebkinorn Orathai , Gebremichael Lemlem G. , Bulamu Norma B. , Keech Wendy , Ludlow Marie , Hendriks Jeroen , Versace Vincent , Clark Robyn A. 
Published: November 2023

AbstractBackgroundLow socioeconomic status (LSES) and rurality are associated with poor cardiovascular outcomes and reduced cardiac rehabilitation (CR) participation.AimTo investigate CR utilization and effectiveness, factors, needs and barriers associated with non-completion among patients of LSES in rural Australia.MethodsThrough a concurrent triangulation mixed methods design we converged the results of a retrospective cohort and a qualitative study. A Cox survival model applied to a population balanced by inverse probability weighting assessed the association between CR utilization and 12-month mortality/cardiovascular readmissions. Associations with non-completion were tested by logistic regression. Barriers and needs to CR completion were evaluated by thematic analysis of semi-structured interviews and focus groups with 28 participants.ResultsAmong 16,159 eligible separations, 44.3% were referred and 11.2% completed CR. Completing CR (HR 0.65; 95%CI 0.57-0.74; p<0.001) led to a lower risk of cardiovascular readmission/death. Living alone (OR 1.38; 95%CI 1.00-1.89; p=0.048), having diabetes (OR 1.48; 95%CI 1.02-2.13; p=0.037), or having depression (OR 1.54; 95%CI 1.14-2.08; p=0.005), were associated with a higher risk of non-completion whereas enrolment in a telehealth program was associated with a lower risk of non-completion (OR 0.26; 95%CI 0.18-0.38; p<0.001). Themes related to logistic issues, social support, transition of care challenges, lack of care integration, and of person-centeredness emerged as barriers to CR completion.ConclusionsCR completion was low but effective in reducing mortality/cardiovascular readmissions. Understanding and addressing barriers and needs through mixed methods can help tailor CR programs to vulnerable populations and improve completion and outcomes.
Deuteration provides a general strategy to enhance azobenzene-based photopharmacology
Authors: Roßmann Kilian , Gonzalez-Hernandez Alberto J. , Bhuyan Rahul , Börjesson Karl , Levitz Joshua , Broichhagen Johannes 
Published: November 2023

ABSTRACTHerein, we present deuterated azobenzene photoswitches as a general means of enhancing photopharmacological molecules. Deuteration can improve azobenzene performance in terms of light sensitivity, photoswitch efficiency, and photoswitch kinetics with minimal alteration to the underlying structure of the photopharmacological ligand. We report synthesized deuterated azobenzene-based ligands for the optimized optical control of ion channel and G protein-coupled receptor function in live cells, setting the stage for the straightforward, widespread adoption of this approach.
Social isolation recruits amygdala-cortical circuitry to escalate alcohol drinking
Authors: Patel Reesha R. , Patarino Makenzie , Kim Kelly , Pamintuan Rachelle , Taschbach Felix H. , Li Hao , Lee Christopher R. , van Hoek Aniek , Castro Rogelio , Cazares Christian , Miranda Raymundo L. , Jia Caroline , Delahanty Jeremy , Batra Kanha , Keyes Laurel R. , Libster Avraham , Wichmann Romy , Pereira Talmo D. , Benna Marcus K. , Tye Kay M. 
Published: November 2023

AbstractHow do social factors impact the brain and contribute to increased alcohol drinking? We found that social rank predicts alcohol drinking, where subordinates drink more than dominants. Furthermore, social isolation escalates alcohol drinking, particularly impacting subordinates who display a greater increase in alcohol drinking compared to dominants. Using cellular resolution calcium imaging, we show that the basolateral amygdala-medial prefrontal cortex (BLA-mPFC) circuit predicts alcohol drinking in a rank-dependent manner, unlike non-specific BLA activity. The BLA-mPFC circuit becomes hyperexcitable during social isolation, detecting social isolation states. Mimicking the observed increases in BLA-mPFC activity using optogenetics was sufficient to increase alcohol drinking, suggesting the BLA-mPFC circuit may be a neural substrate for the negative impact of social isolation. To test the hypothesis that the BLA-mPFC circuit conveys a signal induced by social isolation to motivate alcohol consumption, we first determined if this circuit detects social information. Leveraging optogenetics in combination with calcium imaging and SLEAP automated pose tracking, we found that BLA-mPFC circuitry governs social behavior and neural representation of social contact. We further show that BLA-mPFC stimulation mimics social isolation-induced mPFC encoding of sucrose and alcohol, and inhibition of the BLA-mPFC circuit decreases alcohol drinking following social isolation. Collectively, these data suggest the amygdala-cortical circuit mirrors a neural encoding state similar to social isolation and underlies social isolation-associated alcohol drinking.
Energetics and Clinical Factors for the Time Required to Walk 400 Meters The Study of Muscle, Mobility and Aging (SOMMA)
Authors: Cummings Steven R. , Lui Li-Yung , Glynn Nancy W. , Mau Theresa , Cawthon Peggy M. , Kritchevsky Stephen B. , Coen Paul M. , Goodpaster Bret , Marcinek David J. , Hepple Russell T. , Patel Sheena , Newman Anne B. 
Published: November 2023

AbstractBackgroundWalking slows with aging often leading to mobility disability. Mitochondrial energetics has been found to influence gait speed over short distances. Additionally, walking is a complex activity but few clinical factors that may influence walk time have been studied.MethodsWe examined 879 participants ≥70 years and measured the time to walk 400m. We tested the hypothesis that decreased mitochondrial energetics by respirometry in muscle biopsies and magnetic resonance spectroscopy in the thigh, is associated with longer time to walk 400m. We also used cardiopulmonary exercise testing to assess the energetic costs of walking: maximum oxygen consumption (VO2peak) and energy cost-capacity (the ratio of VO2, at a slow speed to VO2peak). In addition, we tested the hypothesis that selected clinical factors would also be associated with 400m walk time.ResultsLower Max OXPHOS was associated with longer walk time and the association was explained by the energetics costs of walking, leg power and weight. Additionally, a multivariate model revealed that longer walk time was also significantly associated with lower VO2peak, greater cost-capacity ratio, weaker leg power, heavier weight, hip and knee stiffness, peripheral neuropathy, greater perceived exertion while walking slowly, greater physical fatigability, less moderate-to-vigorous exercise, less sedentary time and anemia. Significant associations between age, sex, muscle mass, and peripheral artery disease with 400m walk time were explained by other clinical and physiologic factors.ConclusionsLower mitochondrial energetics is associated with needing more time to walk 400m. This supports the value of developing interventions to improve mitochondrial energetics. Additionally, doing more moderate-to-vigorous exercise, increasing leg power, reducing weight, treating hip and knee stiffness, and screening for and treating anemia may reduce the time required to walk 400m and reduce the risk of mobility disability.
Evolutionary dynamics of 1,976 lymphoid malignancies predict clinical outcome
Authors: Gabbutt Calum , Duran-Ferrer Martí , Grant Heather , Mallo Diego , Nadeu Ferran , Househam Jacob , Villamor Neus , Krali Olga , Nordlund Jessica , Zenz Thorsten , Campo Elias , Lopez-Guillermo Armando , Fitzgibbon Jude , Barnes Chris P , Shibata Darryl , Martin-Subero José I , Graham Trevor A 
Published: November 2023

AbstractCancer development, progression, and response to treatment are evolutionary processes, but characterising the evolutionary dynamics at sufficient scale to be clinically-meaningful has remained challenging. Here, we develop a new methodology called EVOFLUx, based upon natural DNA methylation barcodes fluctuating over time, that quantitatively infers evolutionary dynamics using only a bulk tumour methylation profile as input. We apply EVOFLUx to 1,976 well-characterised lymphoid cancer samples spanning a broad spectrum of diseases and show that tumour growth rates, malignancy age and epimutation rates vary by orders of magnitude across disease types. We measure that subclonal selection occurs only infrequently within bulk samples and detect occasional examples of multiple independent primary tumours. Clinically, we observe that tumour growth rates are higher in more aggressive disease subtypes, and in two series of chronic lymphocytic leukaemia patients, evolutionary histories are independent prognostic factors. Phylogenetic analyses of longitudinal CLL samples using EVOFLUx detect the seeds of future Richter transformation many decades prior to presentation. We provide orthogonal verification of EVOFLUx inferences using additional genetic and clinical data. Collectively, we show how widely- available, low-cost bulk DNA methylation data precisely measures cancer evolutionary dynamics, and provides new insights into cancer biology and clinical behaviour.
Immortalised murine R349P desmin knock-in myotubes exhibit a reduced proton leak and decreased ADP/ATP translocase levels in purified mitochondria
Authors: Berwanger Carolin , Terres Dominic , Pesta Dominik , Eggers Britta , Marcus Katrin , Wittig Ilka , Wiesner Rudolf J. , Schröder Rolf , Clemen Christoph S. 
Published: November 2023

AbstractDesmin gene mutations cause myopathies and cardiomyopathies. Our previously characterised R349P desminopathy mice, which carry the ortholog of the common human desmin mutation R350P, showed marked alterations in mitochondrial morphology and function in muscle tissue. By isolating skeletal muscle myoblasts from offspring of R349P desminopathy and p53 knock-out mice, we established an immortalised cellular disease model. Heterozygous and homozygous R349P desmin knock-in and wild-type myoblasts could be well differentiated into multinucleated spontaneously contracting myotubes. The desminopathy myoblasts showed the characteristic disruption of the desmin cytoskeleton and desmin protein aggregation, and the desminopathy myotubes showed the characteristic myofibrillar irregularities. Long-term electrical pulse stimulation promoted myotube differentiation and markedly increased their spontaneous contraction rate. In both heterozygous and homozygous R349P desminopathy myotubes, this treatment restored a regular myofibrillar cross-striation pattern as seen in wild-type myotubes. High-resolution respirometry of mitochondria purified from myotubes by density gradient ultracentrifugation revealed normal oxidative phosphorylation capacity, but a significantly reduced proton leak in mitochondria from the homozygous R349P desmin knock-in cells. Consistent with a reduced proton flux across the inner mitochondrial membrane, our quantitative proteomic analysis of the purified mitochondria revealed significantly reduced levels of ADP/ATP translocases in the homozygous R349P desmin knock-in genotype. As this alteration was also detected in the soleus muscle of R349P desminopathy mice, which, in contrast to the mitochondria purified from cultured cells, showed a variety of other dysregulated mitochondrial proteins, we consider this finding to be an early step in the pathogenesis of secondary mitochondriopathy in desminopathy.HighlightsR349P desminopathy immortalised murine myoblasts as a cellular disease modelElectrical stimulation improves myofibrillar maturation in desminopathy myotubesReduced proton leak in mitochondria of homozygous R349P desmin knock-in myotubesReduced ADP/ATP translocase levels in mitochondria of desminopathy myotubesEarly signs of secondary mitochondriopathy in desminopathy in cultured myotubes
The specific factors of heterogeneity characterizing investors' beliefs
Authors: Chenini Hajer , Jarboui Anis 
Published: November 2023

PurposeA separate study of the different behavioral biases does not allow for a full understanding of the complexity and stability of the heterogeneity of beliefs. Therefore, through a more global view of these anomalies, the authors wish to show that they can converge on a single concept, which is the heterogeneity of beliefs.Design/methodology/approachIt is therefore essential to stress that the importance of this study is mainly reflected in the methodological approach used in the construction and analysis of the map and not only in the results achieved. This contribution states that structural analysis, as a means of building the cognitive map, can facilitate the task of investors and other decision-makers, in the identification and analysis of the heterogeneity of beliefs that can therefore guide investors' strategy in decision-making.FindingsThe authors have studied the behavior of the investor and its way of interpreting the information and the authors have emphasized the value of studying the concept of heterogeneity of beliefs in its complexity. So that part of the work seems to be relevant and crucial to filling, if you will, that void. In this sense, the authors have shown that behavioral abnormalities are multidimensional concepts: “self-deception”, “cognitive bias”, “emotional bias” and “social bias”.Originality/valueIn particular, this article will aim to achieve the objective of proposing a model for measuring the heterogeneity of beliefs. Thus, the authors want to show that the heterogeneity of beliefs can be measured directly through the different behavioral anomalies.
Spatial accessibility dynamics of urban parks in Nanjing, China: implications for spatial equity
Authors: Liu Zhe , Liu Weibo , Zhao Bin 
Published: November 2023

PurposeThis study aimed to explore the spatial accessibility dynamics of urban parks and their driving forces from 1901 to 2010 in terms of the dynamic relationships between spatial morphology and road networks, taking Nanjing City as an example.Design/methodology/approachThis study mapped and examined the spatiotemporal distribution of urban parks and road networks in four time points at Nanjing: the 1910s, 1930s, 1960s and 2010s, using the analysis methodology of spatial design network analysis, kernel density estimation and buffer analysis. Two approaches of spatial overlaying and data analysis were adopted to investigate the accessibility dynamics. The spatial overlaying compared the parks' layout and the road networks' core, subcore and noncore accessible areas; the data analysis clarified the average data on the city-wide and local scales of the road networks within the park buffer zone.FindingsThe analysis of the changing relationships between urban parks and the spatial morphology of road networks showed that the accessibility of urban parks has generally improved. This was influenced by six main factors: planning implementation, political policies, natural resources, historical heritage and cultural and economic levels.Social implicationsThe results provide a reference for achieving spatial equity, improving urban park accessibility and supporting sustainable urban park planning.Originality/valueAn increasing number of studies have explored the spatial accessibility of urban parks through the relationships between their spatial distribution and road networks. However, few studies have investigated the dynamic changes in accessibility over time. Discussing parks' accessibility over relatively long-time scales has practical, innovative and theoretical values; because it can reveal correlational laws and internal influences not apparent in short term and provide reference and implications for parks' spatial equity.
The nexus of research and development investment, financial development, energy use, and environmental degradation in Asian economies
Authors: Azam Khan Muhammad , Sarwar Ghulam , Hafeez Muhammad Haroon , Khan Himayatullah , Ur Rahman Haseeb 
Published: November 2023

AbstractThis study explores the impact of research and development () investment and financial development on environmental degradation measured by carbon emissions (CO2), and energy use along with some other variables in a panel of 12 Asian economies using balanced panel data from 1997 to 2020. The empirical estimates of and dynamic ordinary least squares reveal that spending, financial development, and globalization lower environmental degradation by reducing emissions. In contrast, economic growth, energy use, population, and industrialization increase environmental degradation (Model 1). Moreover, economic growth, R&D spending, financial development, environmental degradation, and industrialization have a positive direct effect on energy use, whereas population and globalization have an inverse relationship with energy use (Model 2). These empirical findings recommend that the management authorities of Asian economies need to develop thoughtful action plans to achieve a balance between economic growth, financial and industrial development, and the accomplishment of sustainable development goals by reducing carbon emissions and sustaining energy consumption.
Clinical manifestations and outcomes associated with PICU admission in children with multisystem inflammatory syndrome in Taiwan: A retrospective cohort study
Authors: Tseng Chi‐Teng , Lin Jainn‐Jim , Huang Jing‐Long , Chiu Cheng‐Hsun , Wu Chao‐Yi 
Published: November 2023

AbstractBackgroundMultisystem inflammatory syndrome in children (MIS‐C) is a rare and serious systemic inflammatory disorder that occurs following a severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. This study aims to investigate the clinical manifestations, risk factors associated with pediatric intensive care unit (PICU) admission, and outcome among children with MIS‐C in Taiwan.MethodsA retrospective analysis was conducted among pediatric patients diagnosed with MIS‐C between June 2022 and February 2023 at Chang Gung Memorial Hospital, Linkou, Taiwan. Data on demographics, clinical features, laboratory findings, treatment modalities, and outcomes were collected and analyzed.ResultsTwenty‐eight MIS‐C patients, including 9 boys and 19 girls, with an average age of 5.3 ± 3.8 years old, were enrolled. Most of the cases (78.6%) were diagnosed following the first pandemic wave of COVID‐19 in Taiwan. The leading clinical manifestations observed were fever (100%), skin rash (64.3%), tachycardia (46.4%), and vomiting (46.4%). Nine patients (32.1%) were admitted to the PICU due to hypotension or neurological manifestations. Higher levels of band‐form white blood cells, procalcitonin, ferritin, d‐dimer, prothrombin time, NT‐proBNP, and lower platelet levels on arrival were associated with PICU admission (p = 3.9 × 10−2,9 × 10−3, 4 × 10−3,1 × 10−3, 5 × 10−3, 4.1 × 10−2, and 3.4 × 10−2, respectively). Arrhythmia in one case (3.5%) and coronary artery abnormalities, including dilatation in two cases (7.1%) and small aneurysms in one case (3.5%) were identified. Regardless of ICU admission, no patients experienced systolic dysfunction or mortality following treatment.ConclusionMIS‐C cases in Taiwan have a favorable outcome. Although one‐third of the patients required PICU admission, none of the MIS‐C cases resulted in severe cardiovascular morbidity or mortality. This study provides valuable insights into the clinical manifestations and outcomes associated with PICU admission in children with MIS‐C in Taiwan.