bluuebunny/crossref_metadata_2025_split huggingface dataset:
Balancing the safeguarding of privacy and data sharing: perceptions of genomic professionals on patient genomic data ownership in Australia
Authors: Malakar Yuwan , Lacey Justine , Twine Natalie A. , McCrea Rod , Bauer Denis C. 
Published: January 2023

AbstractThere are inherent complexities and tensions in achieving a responsible balance between safeguarding patients’ privacy and sharing genomic data for advancing health and medical science. A growing body of literature suggests establishing patient genomic data ownership, enabled by blockchain technology, as one approach for managing these priorities. We conducted an online survey, applying a mixed methods approach to collect quantitative (using scale questions) and qualitative data (using open-ended questions). We explored the views of 117 genomic professionals (clinical geneticists, genetic counsellors, bioinformaticians, and researchers) towards patient data ownership in Australia. Data analysis revealed most professionals agreed that patients have rights to data ownership. However, there is a need for a clearer understanding of the nature and implications of data ownership in this context as genomic data often is subject to collective ownership (e.g., with family members and laboratories). This research finds that while the majority of genomic professionals acknowledge the desire for patient data ownership, bioinformaticians and researchers expressed more favourable views than clinical geneticists and genetic counsellors, suggesting that their views on this issue may be shaped by how closely they interact with patients as part of their professional duties. This research also confirms that stronger health system infrastructure is a prerequisite for enabling patient data ownership, which needs to be underpinned by appropriate digital infrastructure (e.g., central vs. decentralised data storage), patient identity ownership (e.g., limited vs. self-sovereign identity), and policy at both federal and state levels.
Preclinical evaluation of FLT190, a liver-directed AAV gene therapy for Fabry disease
Authors: Jeyakumar Jey M. , Kia Azadeh , Tam Lawrence C. S. , McIntosh Jenny , Spiewak Justyna , Mills Kevin , Heywood Wendy , Chisari Elisa , Castaldo Noemi , Verhoef Daniël , Hosseini Paniz , Kalcheva Petya , Cocita Clement , Miranda Carlos J. , Canavese Miriam , Khinder Jaminder , Rosales Cecilia , Hughes Derralynn , Sheridan Rose , Corbau Romuald , Nathwani Amit 
Published: January 2023

AbstractFabry disease is an X-linked lysosomal storage disorder caused by loss of alpha-galactosidase A (α-Gal A) activity and is characterized by progressive accumulation of glycosphingolipids in multiple cells and tissues. FLT190, an investigational gene therapy, is currently being evaluated in a Phase 1/2 clinical trial in patients with Fabry disease (NCT04040049). FLT190 consists of a potent, synthetic capsid (AAVS3) containing an expression cassette with a codon-optimized human GLA cDNA under the control of a liver-specific promoter FRE1 (AAV2/S3-FRE1-GLAco). For mouse studies FLT190 genome was pseudotyped with AAV8 for efficient transduction. Preclinical studies in a murine model of Fabry disease (Gla-deficient mice), and non-human primates (NHPs) showed dose-dependent increases in plasma α-Gal A with steady-state observed 2 weeks following a single intravenous dose. In Fabry mice, AAV8-FLT190 treatment resulted in clearance of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) in plasma, urine, kidney, and heart; electron microscopy analyses confirmed reductions in storage inclusion bodies in kidney and heart. In NHPs, α-Gal A expression was consistent with the levels of hGLA mRNA in liver, and no FLT190-related toxicities or adverse events were observed. Taken together, these studies demonstrate preclinical proof-of-concept of liver-directed gene therapy with FLT190 for the treatment of Fabry disease.
Seasonal temperatures in West Antarctica during the Holocene
Authors: Jones Tyler R. , Cuffey Kurt M. , Roberts William H. G. , Markle Bradley R. , Steig Eric J. , Stevens C. Max , Valdes Paul J. , Fudge T. J. , Sigl Michael , Hughes Abigail G. , Morris Valerie , Vaughn Bruce H. , Garland Joshua , Vinther Bo M. , Rozmiarek Kevin S. , Brashear Chloe A. , White James W. C. 
Published: January 2023

AbstractThe recovery of long-term climate proxy records with seasonal resolution is rare because of natural smoothing processes, discontinuities and limitations in measurement resolution. Yet insolation forcing, a primary driver of multimillennial-scale climate change, acts through seasonal variations with direct impacts on seasonal climate1. Whether the sensitivity of seasonal climate to insolation matches theoretical predictions has not been assessed over long timescales. Here, we analyse a continuous record of water-isotope ratios from the West Antarctic Ice Sheet Divide ice core to reveal summer and winter temperature changes through the last 11,000 years. Summer temperatures in West Antarctica increased through the early-to-mid-Holocene, reached a peak 4,100 years ago and then decreased to the present. Climate model simulations show that these variations primarily reflect changes in maximum summer insolation, confirming the general connection between seasonal insolation and warming and demonstrating the importance of insolation intensity rather than seasonally integrated insolation or season duration2,3. Winter temperatures varied less overall, consistent with predictions from insolation forcing, but also fluctuated in the early Holocene, probably owing to changes in meridional heat transport. The magnitudes of summer and winter temperature changes constrain the lowering of the West Antarctic Ice Sheet surface since the early Holocene to less than 162 m and probably less than 58 m, consistent with geological constraints elsewhere in West Antarctica4–7.
An electric molecular motor
Authors: Zhang Long , Qiu Yunyan , Liu Wei-Guang , Chen Hongliang , Shen Dengke , Song Bo , Cai Kang , Wu Huang , Jiao Yang , Feng Yuanning , Seale James S. W. , Pezzato Cristian , Tian Jia , Tan Yu , Chen Xiao-Yang , Guo Qing-Hui , Stern Charlotte L. , Philp Douglas , Astumian R. Dean , Goddard William A. , Stoddart J. Fraser 
Published: January 2023

AbstractMacroscopic electric motors continue to have a large impact on almost every aspect of modern society. Consequently, the effort towards developing molecular motors1–3 that can be driven by electricity could not be more timely. Here we describe an electric molecular motor based on a [3]catenane4,5, in which two cyclobis(paraquat-p-phenylene)6 (CBPQT4+) rings are powered by electricity in solution to circumrotate unidirectionally around a 50-membered loop. The constitution of the loop ensures that both rings undergo highly (85%) unidirectional movement under the guidance of a flashing energy ratchet7,8, whereas the interactions between the two rings give rise to a two-dimensional potential energy surface (PES) similar to that shown by FOF1 ATP synthase9. The unidirectionality is powered by an oscillating10 voltage11,12 or external modulation of the redox potential13. Initially, we focused our attention on the homologous [2]catenane, only to find that the kinetic asymmetry was insufficient to support unidirectional movement of the sole ring. Accordingly, we incorporated a second CBPQT4+ ring to provide further symmetry breaking by interactions between the two mobile rings. This demonstration of electrically driven continual circumrotatory motion of two rings around a loop in a [3]catenane is free from the production of waste products and represents an important step towards surface-bound14 electric molecular motors.
Financial incentives for vaccination do not have negative unintended consequences
Authors: Schneider Florian H. , Campos-Mercade Pol , Meier Stephan , Pope Devin , Wengström Erik , Meier Armando N. 
Published: January 2023

AbstractFinancial incentives to encourage healthy and prosocial behaviours often trigger initial behavioural change1–11, but a large academic literature warns against using them12–16. Critics warn that financial incentives can crowd out prosocial motivations and reduce perceived safety and trust, thereby reducing healthy behaviours when no payments are offered and eroding morals more generally17–24. Here we report findings from a large-scale, pre-registered study in Sweden that causally measures the unintended consequences of offering financial incentives for taking the first dose of a COVID-19 vaccine. We use a unique combination of random exposure to financial incentives, population-wide administrative vaccination records and rich survey data. We find no negative consequences of financial incentives; we can reject even small negative impacts of offering financial incentives on future vaccination uptake, morals, trust and perceived safety. In a complementary study, we find that informing US residents about the existence of state incentive programmes also has no negative consequences. Our findings inform not only the academic debate on financial incentives for behaviour change but also policy-makers who consider using financial incentives to change behaviour.
γδ T cells are effectors of immunotherapy in cancers with HLA class I defects
Authors: de Vries Natasja L. , van de Haar Joris , Veninga Vivien , Chalabi Myriam , Ijsselsteijn Marieke E. , van der Ploeg Manon , van den Bulk Jitske , Ruano Dina , van den Berg Jose G. , Haanen John B. , Zeverijn Laurien J. , Geurts Birgit S. , de Wit Gijs F. , Battaglia Thomas W. , Gelderblom Hans , Verheul Henk M. W. , Schumacher Ton N. , Wessels Lodewyk F. A. , Koning Frits , de Miranda Noel F. C. C. , Voest Emile E. 
Published: January 2023

AbstractDNA mismatch repair-deficient (MMR-d) cancers present an abundance of neoantigens that is thought to explain their exceptional responsiveness to immune checkpoint blockade (ICB)1,2. Here, in contrast to other cancer types3–5, we observed that 20 out of 21 (95%) MMR-d cancers with genomic inactivation of β2-microglobulin (encoded by B2M) retained responsiveness to ICB, suggesting the involvement of immune effector cells other than CD8+ T cells in this context. We next identified a strong association between B2M inactivation and increased infiltration by γδ T cells in MMR-d cancers. These γδ T cells mainly comprised the Vδ1 and Vδ3 subsets, and expressed high levels of PD-1, other activation markers, including cytotoxic molecules, and a broad repertoire of killer-cell immunoglobulin-like receptors. In vitro, PD-1+ γδ T cells that were isolated from MMR-d colon cancers exhibited enhanced reactivity to human leukocyte antigen (HLA)-class-I-negative MMR-d colon cancer cell lines and B2M-knockout patient-derived tumour organoids compared with antigen-presentation-proficient cells. By comparing paired tumour samples from patients with MMR-d colon cancer that were obtained before and after dual PD-1 and CTLA-4 blockade, we found that immune checkpoint blockade substantially increased the frequency of γδ T cells in B2M-deficient cancers. Taken together, these data indicate that γδ T cells contribute to the response to immune checkpoint blockade in patients with HLA-class-I-negative MMR-d colon cancers, and underline the potential of γδ T cells in cancer immunotherapy.
Fully automated closed-loop insulin delivery in adults with type 2 diabetes: an open-label, single-center, randomized crossover trial
Authors: Daly Aideen B. , Boughton Charlotte K. , Nwokolo Munachiso , Hartnell Sara , Wilinska Malgorzata E. , Cezar Alina , Evans Mark L. , Hovorka Roman 
Published: January 2023

AbstractIn adults with type 2 diabetes, the benefits of fully closed-loop insulin delivery, which does not require meal bolusing, are unclear. In an open-label, single-center, randomized crossover study, 26 adults with type 2 diabetes (7 women and 19 men; (mean ± s.d.) age, 59 ± 11 years; baseline glycated hemoglobin (HbA1c), 75 ± 15 mmol mol−1 (9.0% ± 1.4%)) underwent two 8-week periods to compare the CamAPS HX fully closed-loop app with standard insulin therapy and a masked glucose sensor (control) in random order, with a 2-week to 4-week washout between periods. The primary endpoint was proportion of time in target glucose range (3.9–10.0 mmol l−1). Analysis was by intention to treat. Thirty participants were recruited between 16 December 2020 and 24 November 2021, of whom 28 were randomized to two groups (14 to closed-loop therapy first and 14 to control therapy first). Proportion of time in target glucose range (mean ± s.d.) was 66.3% ± 14.9% with closed-loop therapy versus 32.3% ± 24.7% with control therapy (mean difference, 35.3 percentage points; 95% confidence interval (CI), 28.0–42.6 percentage points; P < 0.001). Time > 10.0 mmol l−1 was 33.2% ± 14.8% with closed-loop therapy versus 67.0% ± 25.2% with control therapy (mean difference, −35.2 percentage points; 95% CI, −42.8 to −27.5 percentage points; P < 0.001). Mean glucose was lower during the closed-loop therapy period than during the control therapy period (9.2 ± 1.2 mmol l−1 versus 12.6 ± 3.0 mmol l−1, respectively; mean difference, −3.6 mmol l−1; 95% CI, −4.6 to −2.5 mmol l−1; P < 0.001). HbA1c was lower following closed-loop therapy (57 ± 9 mmol mol−1 (7.3% ± 0.8%)) than following control therapy (72 ± 13 mmol mol−1 (8.7% ± 1.2%); mean difference, −15 mmol mol−1; 95% CI, −11 to −20 mmol l−1 (mean difference, −1.4%; 95% CI, −1.0 to −1.8%); P < 0.001). Time < 3.9 mmol l−1 was similar between treatments (a median of 0.44% (interquartile range, 0.19–0.81%) during the closed-loop therapy period versus a median of 0.08% (interquartile range, 0.00–1.05%) during the control therapy period; P = 0.43). No severe hypoglycemia events occurred in either period. One treatment-related serious adverse event occurred during the closed-loop therapy period. Fully closed-loop insulin delivery improved glucose control without increasing hypoglycemia compared with standard insulin therapy and may represent a safe and efficacious method to improve outcomes in adults with type 2 diabetes. This study is registered with ClinicalTrials.gov (NCT04701424).
Outdoor artificial light at night, air pollution, and risk of childhood acute lymphoblastic leukemia in the California Linkage Study of Early-Onset Cancers
Authors: Zhong Charlie , Wang Rong , Morimoto Libby M. , Longcore Travis , Franklin Meredith , Rogne Tormod , Metayer Catherine , Wiemels Joseph L. , Ma Xiaomei 
Published: January 2023

AbstractAcute lymphoblastic leukemia (ALL) is the most common type of cancer in children (age 0–14 years); however, the etiology remains incompletely understood. Several environmental exposures have been linked to risk of childhood ALL, including air pollution. Closely related to air pollution and human development is artificial light at night (ALAN), which is believed to disrupt circadian rhythm and impact health. We sought to evaluate outdoor ALAN and air pollution on risk of childhood ALL. The California Linkage Study of Early-Onset Cancers is a large population-based case–control in California that identifies and links cancer diagnoses from the California Cancer Registry to birth records. For each case, 50 controls with the same year of birth were obtained from birth records. A total of 2,782 ALL cases and 139,100 controls were identified during 2000–2015. ALAN was assessed with the New World Atlas of Artificial Night Sky Brightness and air pollution with an ensemble-based air pollution model of particulate matter smaller than 2.5 microns (PM2.5). After adjusting for known and suspected risk factors, the highest tertile of ALAN was associated with an increased risk of ALL in Hispanic children (odds ratio [OR] = 1.15, 95% confidence interval [CI] 1.01–1.32). There also appeared to be a borderline association between PM2.5 level and risk of ALL among non-Hispanic White children (OR per 10 µg/m3 = 1.24, 95% CI 0.98–1.56). We observed elevated risk of ALL in Hispanic children residing in areas of greater ALAN. Further work is needed to understand the role of ALAN and air pollution in the etiology of childhood ALL in different racial/ethnic groups.
Lifespan changes in postural control
Authors: Van Humbeeck Nathan , Kliegl Reinhold , Krampe Ralf T. 
Published: January 2023

AbstractLifespan development of postural control shows as an inverted U-shaped function with optimal performance in young adults and similar levels of underperformance in children and older adults. However, similarities in children and older adults might conceal differences in underlying control processes. We mapped out age-related differences in postural control using center-of-pressure trajectories of 299 participants ranging from 7 to 81 years old in three tasks: stable stance, compromised vision, and narrowed base of support. Summary statistics (path length, ellipse area) replicated the well-known U-shape function also showing that compromising vision and narrowing the base of support affected older adults more than children. Stabilogram diffusion analysis (SDA) allows to assess postural control performance in terms of diffusion at short (< 1 s) and longer timescales. SDA parameters showed the strongest short-term drift in older adults, especially under compromised vision or narrowed base of support conditions. However, older adults accommodated their poor short-term control by corrective adjustments as reflected in long-term diffusion under eyes closed conditions and initiating anti-persistent behavior earlier compared with children and young adults in tandem stance. We argue that these results highlight the adaptability of the postural control system and warrant a reinterpretation of previous postural control frameworks.
Oxidative stress-induced MMP- and γ-secretase-dependent VE-cadherin processing is modulated by the proteasome and BMP9/10
Authors: Ivaldo Caterina , Passalacqua Mario , Furfaro Anna Lisa , d’Abramo Cristina , Ruiz Santiago , Chatterjee Prodyot K. , Metz Christine N. , Nitti Mariapaola , Marambaud Philippe 
Published: January 2023

AbstractClassical cadherins, including vascular endothelial (VE)-cadherin, are targeted by matrix metalloproteinases (MMPs) and γ-secretase during adherens junction (AJ) disassembly, a mechanism that might have relevance for endothelial cell (EC) integrity and vascular homeostasis. Here, we show that oxidative stress triggered by H2O2exposure induced efficient VE-cadherin proteolysis by MMPs and γ-secretase in human umbilical endothelial cells (HUVECs). The cytoplasmic domain of VE-cadherin produced by γ-secretase, VE-Cad/CTF2—a fragment that has eluded identification so far—could readily be detected after H2O2treatment. VE-Cad/CTF2, released into the cytosol, was tightly regulated by proteasomal degradation and was sequentially produced from an ADAM10/17-generated C-terminal fragment, VE-Cad/CTF1. Interestingly, BMP9 and BMP10, two circulating ligands critically involved in vascular maintenance, significantly reduced VE-Cad/CTF2 levels during H2O2challenge, as well as mitigated H2O2-mediated actin cytoskeleton disassembly during VE-cadherin processing. Notably, BMP9/10 pretreatments efficiently reduced apoptosis induced by H2O2, favoring endothelial cell recovery. Thus, oxidative stress is a trigger of MMP- and γ-secretase-mediated endoproteolysis of VE-cadherin and AJ disassembly from the cytoskeleton in ECs, a mechanism that is negatively controlled by the EC quiescence factors, BMP9 and BMP10.
Awareness and use of HIV pre-exposure prophylaxis and factors associated with awareness among MSM in Beijing, China
Authors: Sun Yanming , Lu Hongyan , Ye Jingrong , Li Dongmin , Li Guiying 
Published: January 2023

AbstractHuman immunodeficiency virus (HIV) sexual transmission among men who have sex with men (MSM) has increased markedly in Beijing, China in the past decade. Pre-exposure prophylaxis (PrEP) is a highly efficacious biomedical prevention strategy that remarkably reduces HIV-transmission risk. This study examined PrEP awareness among MSM and the factors influencing it. From April to July 2021, respondent-driven sampling was used to conduct a cross-sectional survey among MSM in Beijing, China. Demographic, behavior, and awareness data regarding PrEP were collected. The factors influencing PrEP awareness were assessed using univariate and multivariable logistic regression. In total, 608 eligible responders were included in the study. Among the respondents, 27.9% had PrEP awareness, 3.3% had taken PrEP, and 57.9% expressed interest in receiving PrEP, if required. Greater odds of PrEP awareness were associated with higher education level (adjusted odds ratio [aOR] 3.525, 95% confidence interval [CI] 2.013–6.173, P < 0.0001), greater HIV-related knowledge (aOR 3.605, 95% CI 2.229–5.829, P < 0.0001), HIV testing (aOR 2.647, 95% CI 1.463–4.788, P = 0.0013), and sexually transmitted infections (aOR 2.064, 95% CI 1.189–3.584, P = 0.0101). Lower odds of PrEP awareness were associated with higher stigma score (aOR 0.729, 95% CI 0.591–0.897, P = 0.0029). The findings indicate sub-optimal awareness and low utilization of PrEP in Beijing and highlight PrEP inequities among MSM with stigma. Strengthening the training of peer educators in disseminating PrEP knowledge and reducing stigma are critical for improving PrEP awareness.
Space-resolved chemical information from infrared extinction spectra
Authors: Thuiya Hennadige Yushmantha Ishan Kalpa de Silva , Akbar Proity Nayeeb , Blümel Reinhold 
Published: January 2023

AbstractA new method is presented for the extraction of the complex index of refraction from the extinction efficiency, $$Q_{ext} {({\tilde{\nu }})}$$

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, of homogeneous and layered dielectric spheres that simultaneously removes scattering effects and corrects measured extinction spectra for systematic experimental errors such as baseline shifts, tilts, curvature, and scaling. No reference spectrum is required and fit functions may be used that automatically satisfy the Kramers–Kronig relations. Thus, the method yields the complex refractive index of a sample for unambiguous interpretation of the chemical information of the sample. In the case of homogeneous spheres, the method also determines the radius of the sphere. In the case of layered spheres, the method determines the substances within each layer. Only a single-element detector is required. Using numerically computed $$Q_{ext}({\tilde{\nu }})$$

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data of polymethyl-methacrylate and polystyrene homogeneous and layered spheres, we show that the new reconstruction algorithm is accurate and reliable. Reconstructing the complex refractive index from a published, experimentally measured raw absorbance spectrum shows that the new method simultaneously corrects spectra for scattering effects and, given shape information, corrects raw spectra for systematic errors that result in spectral distortions such as baseline shifts, tilts, curvature, and scaling.