bluuebunny/crossref_metadata_2025_split huggingface dataset:
Governance Framework and Public Private Partnership for Universal Health Coverage: Findings from India’s Federal Health Structure
Authors: Raman A. Venkat , Lahariya Chandrakant 
Published: July 2022

AbstractBackgroundThe role of private health sector in advancing universal health coverage is being recognized globally. A number of public private partnership (PPP) strategies have been implemented across the states in India. States (provinces) are primarily responsible for health service delivery in India.ObjectivesTo document various PPPs models in health sector across Indian states and to map the policy, legal and institutional eco-system governing such partnerships.MethodsDesk review followed up with field visits and in-depth interviews. A total of 52 in-depth interviews were conducted from various levels of stakeholders.ResultsNearly 250 PPP initiatives in health sector across all Indian states were identified and studied. Partnership with the private sector was predominantly in the areas of emergency transport, laboratory diagnosis, and in the delivery of selected primary care services. PPPs in health infrastructure (hospitals and medical colleges) and purchasing arrangements are rapidly emerging across most states. However, only few Indian states have health sector specific PPP policy or legal and/ or institutional framework governing PPPs and organizational units implementing partnership schemes. The capacity to conceive, design, implement, and manage PPPs in health sector was found either absent or insufficient in most states.ConclusionEffective partnerships with the private health sector for achieving country’s health goals requires a well enunciated policy and governance framework; detailed assessment of the private health sector market behavior; legal, regulatory, and oversight mechanisms; building organizational structures with capacities, and developing platforms for stakeholder dialogue. Findings from the Indian context could offer useful insights for other low- and middle-income countries aiming to advance towards achieving UHC.
The Lifestyle Factors of Physical Activity and Diet Balance associated with HPV Infection
Authors: Li Yantao , Liu Mengping , Huang Peng , Yang Zhongzhou , Wang Anli 
Published: July 2022

AbstractBackgroundHuman wellbeing has been linked with lifestyle factors such as physical activity, diet balance, sleep quality, depression, and anxiety. However, few studies illustrate the relationship between such lifestyle factors and HPV infection. In this study, we demonstrate that lifestyle factors might be crucial for reducing the burden of cervical cancer or HPV-related cancer.Participants and MethodsParticipants were recruited through a digital eHealth platform without vaccination from May 2020 to August 2021. Both lifestyle factors and cervicovaginal mucus (CVM) samples to test for HPV outcomes were collected from each participant. In addition, the eHealth platform recorded age and gynecological diseases, which were adjusted to apply for both univariable and multivariable logistic regression. Furthermore, lifestyle factors and HPV serotype were categorized as low, intermediate, and high risk in order to conduct stratification analysis. Finally, lifestyle factors were studied in connection with sole and multiple HPV serotypes.ResultsWe recruited 149 HPV positive and 346 HPV negative through HPV detection. Physical activity and diet balance were significantly associated with HPV infection in lifestyle factors (P-values < 0.001) after adjusting for age and gynecological diseases. However, stratified analysis showed three factors were insignificant for HPV infection – namely, sleep quality, depression, and anxiety. Most HPV infections involved a sole HPV serotype (83%), and diet balance was the most significant difference between sole and multiple HPV infections.ConclusionsAmong lifestyle factors, low physical activity or low diet balance can significantly increase HPV infection. In particular, diet balance might be related to the number of HPV serotypes. Our results suggest that exercising and regulating one’s diet may reduce the burden of HPV-related cancer.
Ethnic homophily affects vaccine prioritization strategies
Authors: Kadelka Claus , Islam Md Rafiul , McCombs Audrey , Alston Jake , Morton Noah 
Published: July 2022

AbstractPeople are more likely to interact with other people of their ethnicity—a phenomenon known as ethnic homophily. In the United States, people of color are known to hold proportionately more high-contact jobs and are thus more at risk of virus infection. At the same time, these ethnic groups are on average younger than the rest of the population. This gives rise to interesting disease dynamics and non-trivial trade-offs that should be taken into consideration when developing prioritization strategies for future mass vaccine roll-outs.Here, we study the spread of COVID-19 through the U.S. population, stratified by age, ethnicity, and occupation, using a detailed, previously-developed compartmental disease model. Based on historic data from the U.S. mass COVID-19 vaccine roll-out that began in December 2020, we show, (i) how ethnic homophily affects the choice of optimal vaccine allocation strategy, (ii) that, notwithstanding potential ethical concerns, differentiating by ethnicity in these strategies can improve outcomes (e.g., fewer deaths), and (iii) that the most likely social context in the United States is very different from the standard assumptions made by models which do not account for ethnicity and this difference affects which allocation strategy is optimal.HighlightsA social mixing model accounting for ethnic homophily and variable job-related risk level is developed.A scenario that differs strongly from standard homogeneous mixing assumptions best matches U.S. ethnicity-specific death and case counts.Two trade-offs are explored: Should (i) old or young, and (ii) people of color or White and Asian people first receive COVID-19 vaccines?Exhaustive simulation of a compartmental disease model identifies the optimal allocation strategy for different demographic groups.Optimal strategies depend on the underlying mixing pattern and strategies that differentiate vaccine access by ethnicity outperform others.
Integrative analysis of neuroblastoma by single-cell RNA sequencing identifies the NECTIN2-TIGIT axis as a target for immunotherapy
Authors: Wienke Judith , Visser Lindy L. , Kholosy Waleed M. , Keller Kaylee M. , Barisa Marta , Munnings-Tomes Sophie , Carlton Elizabeth , Poon Evon , Rodriguez Ana , Bernardi Ronald , van den Ham Femke , van Hooff Sander R. , Matser Yvette A.H. , Tas Michelle L. , Langenberg Karin P.S. , Lijnzaad Philip , Strijker Josephine G.M. , Sanchez-Bernabeu Alvaro , Cornel Annelisa M. , Holstege Frank C.P. , Gray Juliet , Tytgat Lieve A.M. , de Krijger Ronald R. , Scheijde-Vermeulen Marijn A. , Wijnen Marc H.W.A. , Dierselhuis Miranda , Straathof Karin , Behjati Sam , Wu Wei , Heck Albert J.R. , Koster Jan , Nierkens Stefan , Chesler Louis , Anderson John , Caron Hubert N. , Margaritis Thanasis , van Noesel Max M. , Molenaar Jan J. 
Published: July 2022

ABSTRACTPediatric patients with high-risk neuroblastoma have poor survival rates and urgently need more effective treatment options with less side effects. As novel and improved immunotherapies may fill this need, we dissected the immunoregulatory interactions in neuroblastoma by single-cell RNA-sequencing of 25 tumors (10 pre- and 15 post-chemotherapy, including 5 pairs) to identify strategies for optimizing immunotherapy efficacy. Neuroblastomas were infiltrated by NK, T and B cells, and immunosuppressive myeloid populations. NK cells showed reduced cytotoxicity and T cells had a dysfunctional profile. Interaction analysis revealed a vast immunoregulatory network and identified NECTIN2-TIGIT as a crucial immune checkpoint. Combined blockade of TIGIT and PD-L1 significantly reduced neuroblastoma growth, with complete responsesin vivo. Moreover, addition of TIGIT blockade to standard relapse treatment in a chemotherapy-resistantTh-ALKF1174L/MYCN129/SvJ syngeneic model significantly improved survival. Concluding, our integrative analysis of neuroblastoma’s vast immunoregulatory network provides novel targets and a rationale for immunotherapeutic combination strategies.
Plasticity of the proteasome-targeting signal Fat10 enhances substrate degradation
Authors: Negi Hitendra , Ravichandran Aravind , Dasgupta Pritha , Reddy Shridivya , Das Ranabir 
Published: July 2022

ABSTRACTThe proteasome controls levels of most cellular proteins, and its activity is regulated under stress, quiescence, and inflammation. However, factors determining the proteasomal degradation activity remain poorly understood. Proteasome substrates are conjugated with small proteins (tags) like ubiquitin and Fat10 to target them to the proteasome. It is unclear if the structural plasticity of proteasome-targeting tags influences substrate degradation. The tag Fat10 is activated during inflammation, and ambiguously, Fat10 and its substrates undergo rapid proteasomal degradation. We report that the rapid degradation of Fat10 substrates depends on its structural plasticity. While the ubiquitin tag is recycled at the proteasome, Fat10 is degraded with the substrate, and the mechanical unfolding kinetics of Fat10 regulates substrate degradation. Our studies reveal that long-range salt bridges are absent in the Fat10 structure, creating a plastic protein with partially unstructured regions suitable for proteasome engagement. Such a malleable structure also provides low resistance to mechanical unfolding and expedites proteasomal degradation. We also uncovered that the Fat10 plasticity destabilizes substrates significantly and creates partially unstructured regions in the substrate to enhance degradation. NMR-relaxation-derived order parameters and temperature dependence of chemical shifts identify the Fat10-induced partially unstructured regions in the substrate. They correlated excellently to the regions where Fat10 contacts the substrate, suggesting that the tag-substrate collision destabilizes the substrate. These results highlight a strong dependence of proteasomal degradation on the structural plasticity and thermodynamic properties of the proteasome-targeting tag.
Differential disruptions in population coding along the dorsal-ventral axis of CA1 in the APP/PS1 mouse model of Aβ pathology
Authors: Chockanthan Udaysankar , Padmanabhan Krishnan 
Published: July 2022

AbstractAlzheimer’s Disease (AD) is a progressive neurodegenerative disorder characterized by a range of behavioral alterations including memory loss as well as cognitive and psychiatric symptoms. While there is growing evidence that cellular and molecular pathologies, such as the accumulation of amyloid beta (Aβ) plaques may contribute to AD, it remains unclear how this histopathology can give rise to such disparate behavioral deficits. One hypothesis for these diverse behavioral presentations is that Aβ accumulation has differential effects on neuronal circuits across brain regions, depending on the diverse neurophysiological properties and connections within and between the neurons in these different areas. To test this, we recorded from large neuronal populations in the dorsal and ventral CA1 regions of the hippocampus, areas that are known to be structurally and functionally diverse, in both APP/PS1 animals, a mouse model of Aβ pathology, and age-matched C57BL/6 controls. Although we found similar levels of Aβ pathology in the two subregions, populations of neurons in dorsal and ventral CA1 in APP/PS1 mice showed distinct signatures of disrupted neuronal activity as animals navigated a virtual reality environment. In dorsal CA1, pairwise correlations and entropy, a measure of the diversity of activity patterns, were decreased in the APP/PS1 mice. However, in ventral CA1, the opposite findings were observed; pair-wise correlations and entropy was increased in APP/PS1 mice relative to C57BL/6 controls. When we attempted to connect the microscopic features of population activity (the correlations) with the macroscopic features of the population code (the entropy) using a pairwise Ising model, we found that the models’ performance decreased in predicting dorsal CA1 activity but increased in predicting vCA1 activity in APP/PS1 mice, as compared to the C57BL/6 animals. Taken together, these findings suggest that Aβ pathology exerts distinct effects across different hippocampal regions. Our results suggest that the diverse behavioral deficits associated with AD and the cellular pathology that arises from Aβ accumulation may be mechanistically linked by studying the dynamics of neural activity within these diverse hippocampal circuits.
Hippocampal blood flow rapidly and preferentially increases after a bout of moderate-intensity exercise in older adults with poor cerebrovascular health
Authors: Palmer Jacqueline A. , Morris Jill K , Billinger Sandra A. , Lepping Rebecca J , Martin Laura , Green Zachary , Vidoni Eric D. 
Published: July 2022

AbstractOver the course of aging, there is an early degradation of cerebrovascular health that may be attenuated with aerobic exercise training. Yet, the acute cerebrovascular response to a single bout of exercise remains elusive, particularly within key brain regions most affected by age-related disease processes. We investigated the acute global and region-specific cerebral blood flow (CBF) response to 15 minutes of moderate-intensity aerobic exercise in older adults (≥65years) (n=60) using arterial spin labeling magnetic resonance imaging. Within 0-6 minutes post-exercise, CBF decreased across all regions, an effect that was attenuated in the hippocampus. The exercise-induced CBF drop was followed by a rebound effect over the 24-minute post-exercise assessment period, an effect that was most robust in the hippocampus. Individuals with low baseline perfusion demonstrated the greatest hippocampal-specific CBF effect post-exercise, showing no immediate drop and a rapid increase in CBF that exceeded baseline levels within 6-12 minutes post-exercise. Gains in domain-specific cognitive performance post-exercise were not associated with changes in regional CBF, suggesting dissociable effects of exercise on acute neural and vascular plasticity. Together, the present findings support a precision-medicine framework for the use of exercise to target brain health that carefully considers age-related changes in the cerebrovascular system.
Synthetic yeast chromosome XI design enables extrachromosomal circular DNA formation on demand
Authors: Blount Benjamin A , Lu Xinyu , Driessen Maureen R M , Jovicevic Dejana , Sanchez Mateo I , Ciurkot Klaudia , Zhao Yu , Lauer Stephanie , McKiernan Robert M , Gowers Glen-Oliver F , Sweeney Fiachra , Fanfani Viola , Lobzaev Evgenii , Palacios-Flores Kim , Walker Roy , Hesketh Andy , Oliver Stephen G , Cai Yizhi , Stracquadanio Giovanni , Mitchell Leslie A , Bader Joel S , Boeke Jef D , Ellis Tom 
Published: July 2022

SummaryWe describe construction of the 660 kilobase synthetic yeast chromosome XI (synXI) and reveal how synthetic redesign of non-coding DNA elements impact the cell. To aid construction from synthesized 5 to 10 kilobase DNA fragments, we implemented CRISPR-based methods for synthetic crossovers in vivo and used these methods in an extensive process of bug discovery, redesign and chromosome repair, including for the precise removal of 200 kilobases of unexpected repeated sequence. In synXI, the underlying causes of several fitness defects were identified as modifications to non-coding DNA, including defects related to centromere function and mitochondrial activity that were subsequently corrected. As part of synthetic yeast chromosome design, loxPsym sequences for Cre-mediated recombination are inserted between most genes. Using the GAP1 locus from chromosome XI, we show here that targeted insertion of these sites can be used to create extrachromosomal circular DNA on demand, allowing direct study of the effects and propagation of these important molecules. Construction and characterization of synXI has uncovered effects of non-coding and extrachromosomal circular DNA, contributing to better understanding of these elements and informing future synthetic genome design.
A broad, exposome-type evaluation of xenobiotic phase II biotransformation in human biofluids by LC-MS/MS
Authors: Fareed Yasmin , Braun Dominik , Flasch Mira , Globisch Daniel , Warth Benedikt 
Published: July 2022

AbstractXenobiotics are chemicals foreign to a specific organism that humans are exposed to on a daily basis through their food, drugs and the environment. These molecules are frequently metabolized to increase polarity and subsequent excretion. During sample preparation, deconjugation of phase II metabolites is a critical step to capture the total exposure to chemicals in liquid chromatography mass spectrometry assays (LC-MS). Knowledge on deconjugation efficiencies of different enzymes and the extend of conjugation in human biofluids has primarily been investigated for single compounds or individual chemical classes. In this study, the performance of three β-glucuronidase and arylsulfatase mixtures from H. pomatia, from recombinant sources (BGS™), and from Escherichia coli combined with recombinant arylsulfatase (ASPC™) was compared and the efficiency of phase II deconjugation was monitored in breast milk, urine and plasma. An innovative LC-MS/MS biomonitoring method encompassing more than 80 highly diverse xenobiotics (e.g., plasticizers, industrial chemicals, mycotoxins, phytoestrogens, pesticides) was utilized for the comprehensive investigation of phase II conjugation in experiments investigating levels in breast milk and urine obtained from breastfeeding women. Overall, it was confirmed that H. pomatia is the most efficient enzyme in hydrolyzing different classes of xenobiotics for future exposome-scale biomonitoring studies. The recombinant BGS™ formulation, however, provided better results for breast milk samples, primarily due to lower background contamination, a major issue when employing the typically applied crude H. pomatia extracts. A deeper understanding of the global xenobiotic conjugation patterns will be essential for capturing environmental and food-related exposures within the exposome framework more comprehensively.Graphical abstract
Gibberellins promote polar auxin transport to regulate stem cell fate decisions in cambium
Authors: Mäkilä Riikka , Wybouw Brecht , Smetana Ondrej , Vainio Leo , Solé-Gil Anna , Lyu Munan , Ye Lingling , Wang Xin , Siligato Riccardo , Jenness Mark Kubo , Murphy Angus S. , Mähönen Ari Pekka 
Published: July 2022

AbstractVascular cambium contains bifacial stem cells, which produce secondary xylem to one side and secondary phloem to the other. However, how these fate decisions are regulated is unknown. Here, we show that the positioning of an auxin signalling maximum within the cambium determines the fate of stem cell daughters. The position is modulated by gibberellin-regulated, PIN1-dependent polar auxin transport. Gibberellin treatment broadens auxin maximum from the xylem side of the cambium towards the phloem. As a result, xylem-side stem cell daughter preferentially differentiates into xylem, while phloem-side daughter retains stem cell identity. Occasionally, this broadening leads to direct specification of both daughters as xylem, and consequently, adjacent phloem-identity cell reverts to being stem cell. Conversely, reduced gibberellin levels favour specification of phloem-side stem cell daughter as phloem. Together, our data provide a mechanism by which gibberellin regulates the ratio of xylem and phloem production.
Urban birds’ tolerance towards humans was largely unaffected by increased variation in human levels due to COVID-19 shutdowns
Authors: Mikula Peter , Bulla Martin , Blumstein Daniel T. , Benedetti Yanina , Floigl Kristina , Jokimäki Jukka , Kaisanlahti-Jokimäki Marja-Liisa , Markó Gábor , Morelli Federico , Møller Anders Pape , Siretckaia Anastasiia , Szakony Sára , Weston Michael A. , Zeid Farah Abou , Tryjanowski Piotr , Albrecht Tomáš 
Published: July 2022

AbstractThe coronavirus disease 2019 (COVID-19) pandemic dramatically altered human activities, and, during shutdowns. Here, we evaluated whether urban birds from five countries changed their tolerance towards humans during the COVID-19 shutdowns. We collected 6369 flight initiation distance estimates for 147 bird species and found that human numbers in parks (at a given hour, day, week or year - before and during the COVID-19 shutdowns) had a little effect on birds’ tolerance of approaching humans. Apart from the actual human numbers in the area (hourly scale), the effect of human activity at other temporal scales centered around zero. The results were similar across countries, for most species or when we restricted our analyses only to species sampled both before and during the COVID-19 shutdowns. As expected, the level of daily human presence in parks (measured by Google Mobility Reports) correlated negatively with the stringency of governmental restrictions (a weekly proxy for human presence) and was overall lower during COVID-19 shutdowns than during the post-shutdown year (2022). Our results highlight the resilience of birds to changes in human numbers on multiple temporal scales, the complexities of linking animal fear responses to human behavior, and the challenge of quantifying both simultaneouslyin situ.