bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multicentre, prospective, non-interventional study evaluating the safety of dapagliflozin in patients with type 2 diabetes in routine clinical practice in China (DONATE)
Authors: Guo Lixin , Wang Jing , Li Li , Yuan Lin , Chen Sheng , Wang Hui , Li Tonghuan , Qi Lin , Yang Hong 
Published: June 2023

AbstractBackgroundThere are few large-scale studies evaluating the safety of the sodium-glucose cotransporter-2 inhibitor, dapagliflozin, in Chinese patients with type 2 diabetes. DONATE, a multicentre, single-arm, prospective, non-interventional study, is the first real-world study evaluating the safety of dapagliflozin in Chinese patients with type 2 diabetes in routine clinical practice.MethodsBetween August 2017 and July 2020, patients with type 2 diabetes who had initiated dapagliflozin therapy and received ≥1 dose were prospectively recruited from 88 hospitals in China. Patients were subsequently followed up for 24 weeks; if patients discontinued dapagliflozin they were followed up for an additional 7 days after treatment discontinuation. The primary outcome was the proportion of patients with adverse events and serious adverse events, particularly key adverse events of special interest (AESI) including urinary tract infection, genital tract infection (typical symptoms with or without microbiological diagnosis) and hypoglycaemia (typical symptoms with or without blood glucose ≤3.9 mmol/L, or blood glucose ≤3.9 mmol/L without symptoms). Exploratory outcomes included the absolute change in metabolic parameters and the proportion of patients with other AESI including volume depletion, abnormal blood electrolytes, polyuria, renal impairment, diabetic ketoacidosis, hepatic impairment and haematuria.ResultsA total of 3000 patients were enrolled, of whom 2990 (99.7%) were included in the safety analysis set. Mean (SD) age was 52.6 (12.0) years, and 65.8% of patients were male. Mean (SD) duration of type 2 diabetes at enrolment was 8.4 (7.1) years. Mean (SD) treatment duration of dapagliflozin was 209.1 (157.6) days. Adverse events were reported in 35.4% (n = 1059) of patients during the 24-week follow-up period. Overall, 9.0% (n = 268) were related to treatment and 6.2% (n = 186) were serious. Urinary tract infection, genital tract infection and hypoglycaemia were reported in 2.3% (n = 70), 1.3% (n = 39) and 1.1% (n = 32) of patients, respectively. The proportion of patients with other AESI was also low: polyuria (0.7%;n = 21), volume depletion (0.3%;n = 9), renal impairment (0.3%;n = 8), hepatic impairment (0.2%;n = 7), haematuria (0.2%;n = 6) and diabetic ketoacidosis (0.1%;n = 2).ConclusionsThis study demonstrated that once-daily dapagliflozin was well tolerated in Chinese patients with type 2 diabetes and the overall safety profile of dapagliflozin in clinical practice in China was consistent with that reported in clinical trials.Trial registrationClinicalTrials.gov, NCT03156985. Registered on 16 May, 2017.
The intermediate filament protein nestin serves as a molecular hub for smooth muscle cytoskeletal signaling
Authors: Wang Yinna , Liao Guoning , Wu Yidi , Wang Ruping , Tang Dale D. 
Published: June 2023

Abstract
Background
The recruitment of the actin-regulatory proteins cortactin and profilin-1 (Pfn-1) to the membrane is important for the regulation of actin cytoskeletal reorganization and smooth muscle contraction. Polo-like kinase 1 (Plk1) and the type III intermediate filament protein vimentin are involved in smooth muscle contraction. Regulation of complex cytoskeletal signaling is not entirely elucidated. The aim of this study was to evaluate the role of nestin (a type VI intermediate filament protein) in cytoskeletal signaling in airway smooth muscle.

Methods
Nestin expression in human airway smooth muscle (HASM) was knocked down by specific shRNA or siRNA. The effects of nestin knockdown (KD) on the recruitment of cortactin and Pfn-1, actin polymerization, myosin light chain (MLC) phosphorylation, and contraction were evaluated by cellular and physiological approaches. Moreover, we assessed the effects of non-phosphorylatable nestin mutant on these biological processes.

Results
Nestin KD reduced the recruitment of cortactin and Pfn-1, actin polymerization, and HASM contraction without affecting MLC phosphorylation. Moreover, contractile stimulation enhanced nestin phosphorylation at Thr-315 and the interaction of nestin with Plk1. Nestin KD also diminished phosphorylation of Plk1 and vimentin. The expression of T315A nestin mutant (alanine substitution at Thr-315) reduced the recruitment of cortactin and Pfn-1, actin polymerization, and HASM contraction without affecting MLC phosphorylation. Furthermore, Plk1 KD diminished nestin phosphorylation at this residue.

Conclusions
Nestin is an essential macromolecule that regulates actin cytoskeletal signaling via Plk1 in smooth muscle. Plk1 and nestin form an activation loop during contractile stimulation.
Policymaker perspectives on self-management of disease and disabilities using information and communication technologies
Authors: Gauthier-Beaupré Amélie , Battistini Bruno J. , Kuziemsky Craig , Jutai Jeffrey W. 
Published: June 2023

Abstract
Background
Policies that support health self-management are malleable and highly dependent on various factors that influence governments. Within a world that is shifting toward digitalization due to pressures such as the COVID-19 pandemic and labor shortages, policymaking on older adults’ self-management of chronic diseases and disability using information and communication technologies (ICTs) needs to be better understood. Using the province of Ontario, in Canada, as a case study, the research question was What is the environment that policymakers must navigate through in development and implementation of policies related to older adults’ self-management of disease and disability using information and communication technologies (ICTs)?

Methods
This study used a qualitative approach where public servants from 4 ministries within the government of Ontario were invited to participate in a 1-h, one-on-one, semi-structured interview. The audio-recorded interviews were based on an adapted model of the policy triangle, where the researcher asked questions about the influences from the different sources identified in the model. The interviews were later transcribed and analyzed using a deductive-inductive coding approach.

Results
Ten participants across 4 different Ministries participated in the interviews. Participants shared insights on various aspects of context, process and actors that help shape the current content of policies. The analysis revealed that policies, in the form of programs, services, legislation and regulations, are the result of collaborations and dialogue between different actors and get developed and implemented via a set of complex government processes. In addition, policy actions come from a plethora of sectors which all get influenced by several predictable and unpredictable external pressures.

Conclusions
The environment for policymaking in the government of Ontario regarding older adults’ self-management of disease and disability using ICTs is one that is mostly reactive to external pressures, while organized within a set of complex processes and multi-sectoral collaborations. The present research helped us to understand the complexity of policymaking on the topic and highlights the need for increased foresight and proactive policymaking, regardless of which governments are in-place.
A qualitative analysis of factors influencing the implementation of antiretroviral treatment adherence policy in Ghana: stakeholders perspective
Authors: Abdulai Martha Ali , Mevissen Fraukje E. F. , Marien Veerle , Ruiter Robert A. C. , Owusu-Agyei Seth , Asante Kwaku Poku , Bos Arjan E. R. 
Published: June 2023

Abstract
Background
The Joint United Nations Programme on HIV/AIDS launched the 90-90-90 initiative. Failure to meet the target reflects the difficulties in successfully implementing HIV treatment policy. There are research gaps in exploring personal and external factors influencing HIV treatment in Ghana. To fill this gap, we explored individual and environmental (interpersonal, community and structural) factors influencing stakeholders' HIV treatment policy implementation in Ghana.

Methods
Fifteen qualitative semi-structured in-depth interviews were conducted among representatives in different management positions at hospitals, health directorates, the Ghana AIDS Commission, the National AIDS and STI control program, and the National Association of People Living with HIV.

Results
Using thematic analysis, the findings suggest that individual and environmental factors such as attitude towards policy, awareness of HIV treatment policy, training received on policy implementation, difficulties related to patient factors, alternate sources of HIV care, inefficient policy decision-making, monitoring and evaluation of HIV treatment policy, lack of HIV treatment policy implementation training, poor availability of logistics, policy and guidelines, infrastructure, organization of training, and staff availability may hinder successful HIV treatment policy implementation.

Conclusion
Several individual and environmental (interpersonal, community and structural) factors seem to influence HIV treatment policy implementation. To ensure successful policy implementation stakeholders need to receive training on new policies, availability of sufficient supplies of material resources, inclusive decision-making, receive supportive monitoring of policy implementation, and oversight.
Changes in sodium levels in Australian packaged foods between 2014 and 2019: an interrupted time series analysis of the impact of the Victorian Salt Reduction Partnership’s media advocacy strategy
Authors: Rosewarne Emalie , Santos Joseph Alvin , Di Tanna Gian Luca , Shahid Maria , Grimes Carley , Bolton Kristy A. , Webster Jacqui , Neal Bruce , Woodward Mark , Coyle Daisy , Trieu Kathy 
Published: June 2023

Abstract
Background
The Victorian Salt Reduction Partnership (VSRP) implemented a media advocacy strategy (intervention) to stimulate food manufacturers to reduce sodium levels across targeted Australian packaged foods between 2017 and 2019. This study assessed changes in sodium levels of targeted and non-targeted packaged foods during the intervention (2017 to 2019) compared to before the intervention (2014 to 2016) in Australia.

Methods
Annually collected branded-food composition data from 2014 to 2019 were used. Interrupted time series analyses was conducted to compare the trend in sodium levels in packaged foods during the intervention (2017–2019) to the trend in the pre-intervention period (2014–2016). The difference between these trends was derived to estimate the effect of the intervention.

Results
A total of 90,807 products were included in the analysis, of which 14,743 were targeted by the intervention. The difference in before and during intervention trends between targeted and non-targeted food categories was 2.59 mg/100 g (95% CI: -13.88 to 19.06). There was a difference in the pre-intervention slope (2014, 2015, 2016) and intervention slope (2017, 2018, 2019) for four of 17 targeted food categories. There was a decrease in sodium levels (mg/100 g) in one food category: frozen ready meals (-13.47; 95% CI: -25.40 to -1.53), and an increase in three categories: flat bread (20.46; 95% CI: 9.11 to 31.81), plain dry biscuits (24.53; 95% CI: 5.87 to 43.19), and bacon (44.54; 95% CI: 6.36 to 82.72). For the other 13 targeted categories, the difference in slopes crossed the line of null effect.

Conclusions
The VSRP’s media advocacy strategy did not result in a meaningful reduction in sodium levels of targeted packaged food products during the intervention years compared to trends in sodium levels before the intervention. Our study suggests media advocacy activities highlighting the differences in sodium levels in packaged food products and industry meetings alone are not sufficient to lower average sodium levels in packaged foods in the absence of government leadership and measurable sodium targets.
Comparison of Epstein–Barr virus and Kaposi’s sarcoma-associated herpesvirus viral load in peripheral blood mononuclear cells and oral fluids of HIV-negative individuals aged 3–89 years from Uganda
Authors: Nalwoga Angela , Marshall Vickie , Miley Wendell , Labo Nazzarena , Whitby Denise , Newton Robert , Rochford Rosemary 
Published: June 2023

AbstractWe previously found that age, sex and malaria were associated with KSHV in individuals from Uganda. In this study, we have evaluated these same factors in relation to EBV in the same specimens. Overall, 74% (oral fluids) and 46% (PBMCs) had detectable EBV. This was significantly higher than observed for KSHV (24% oral fluids and 11% PBMCs). Individuals with EBV in PBMCs were more likely to have KSHV in PBMCs (P = 0.011). The peak age for detection of EBV in oral fluids was 3–5 years while that of KSHV was 6–12 years. In PBMCs, there was a bimodal peak age for detection of EBV (at 3–5 years and 66 + years) while for KSHV there was a single peak at 3–5 years. Individuals with malaria had higher levels of EBV in PBMCs compared to malaria-negative individuals (P = 0.002). In summary, our results show that younger age and malaria are associated with higher levels of EBV and KSHV in PBMCs suggesting malaria impacts immunity to both gamma-herpesviruses.
Does closed-loop automated oxygen control reduce the duration of supplementary oxygen treatment and the amount of time spent in hyperoxia? A randomised controlled trial in ventilated infants born at or near term
Authors: Kaltsogianni Ourania , Dassios Theodore , Jenkinson Allan , Greenough Anne 
Published: June 2023

AbstractBackgroundVentilated infants frequently require supplemental oxygen, but its use should be monitored carefully due to associated complications. The achievement of oxygen saturation (SpO2) targets can be challenging as neonates experience frequent fluctuations of their oxygen levels that further increase the risk of complications.Closed-loop automated oxygen control systems (CLAC) improve achievement of oxygen saturation targets, reduce hyperoxaemic episodes and facilitate weaning of the inspired oxygen concentration in ventilated infants born at or near term. This study investigates whether CLAC compared with manual oxygen control reduces the time spent in hyperoxia and the overall duration of supplemental oxygen treatment in ventilated infants born at or above 34 weeks gestation.MethodsThis randomised controlled trial performed at a single tertiary neonatal unit is recruiting 40 infants born at or above 34 weeks of gestation and within 24 h of initiation of mechanical ventilation. Infants are randomised to CLAC or manual oxygen control from recruitment till successful extubation. The primary outcome is the percentage of time spent in hyperoxia (SpO2 > 96%). The secondary outcomes are the overall duration of supplementary oxygen treatment, the percentage of time spent with an oxygen requirement above thirty per cent, the number of days on mechanical ventilation and the length of neonatal unit stay. The study is performed following informed parental consent and was approved by the West Midlands-Edgbaston Research Ethics Committee (Protocol version 1.2, 10/11/2022).DiscussionThis trial will investigate the effect of CLAC on the overall duration of oxygen therapy and the time spent in hyperoxia. These are important clinical outcomes as hyperoxic injury is related to oxidative stress that can adversely affect multiple organ systems.Trial registrationClinicalTrials.Gov NCT05657795. Registered on 12/12/2022.
A perception into binary and ternary copper (II) complexes: synthesis, characterization, DFT modeling, antimicrobial activity, protein binding screen, and amino acid interaction
Authors: El-Sayed Doaa S. , Tawfik Eman M. , Elhusseiny Amel F. , El-Dissouky Ali 
Published: June 2023

AbstractEnsuring healthy lives and promoting well-being for all at all ages is the third goal of the sustainable development plan, so it was necessary to identify the most important problems that threaten health in our world. The World Health Organization declared that antibiotic resistance is one of the uppermost global public health threats facing humanity and searching for new antibiotics is slow. This problem can be approached by improving available drugs to combat various bacterial threats. To circumvent bacterial resistance, three copper(II) complexes based on the pefloxacin drug were prepared and characterized using analytical, spectroscopic, and thermal techniques. The resulting data suggested the formation of one octahedral binary and two distorted square pyramidal ternary complexes. Fluorescence spectra results revealed the formation of a turn-on fluorophore for amino acid detection. Computational calculations investigated quantum and reactivity parameters. Molecular electrostatic potential profiles and noncovalent bond interaction-reduced density gradient analysis indicated the active sites on the complex surface. The complexes were subjected to six microbial species, where the octahedral binary complex provoked its antimicrobial potency in comparison with ternary complexes. The enhanced antimicrobial activity against gram-negative bacterium E-coli compared to gentamicin was exhibited by the three complexes. Docking simulation was performed based on the crystal structure of E. coli and S. pneumoniae receptors using 5I2D and 6O15 codes. The binary complex exhibited a potent fitness score with 5I2D (TBE = − 107 kcal/mol) while ternary complexes displayed the highest docked score of fitness with 6O15.
Scoping review of Culex mosquito life history trait heterogeneity in response to temperature
Authors: Moser S. Kane , Barnard Martha , Frantz Rachel M. , Spencer Julie A. , Rodarte Katie A. , Crooker Isabel K. , Bartlow Andrew W. , Romero-Severson Ethan , Manore Carrie A. 
Published: June 2023

Abstract
Background
Mosquitoes in the genus Culex are primary vectors in the US for West Nile virus (WNV) and other arboviruses. Climatic drivers such as temperature have differential effects on species-specific changes in mosquito range, distribution, and abundance, posing challenges for population modeling, disease forecasting, and subsequent public health decisions. Understanding these differences in underlying biological dynamics is crucial in the face of climate change.

Methods
We collected empirical data on thermal response for immature development rate, egg viability, oviposition, survival to adulthood, and adult lifespan for Culex pipiens, Cx. quinquefasciatus, Cx. tarsalis, and Cx. restuans from existing literature according to the PRISMA scoping review guidelines.

Results
We observed linear relationships with temperature for development rate and lifespan, and nonlinear relationships for survival and egg viability, with underlying variation between species. Optimal ranges and critical minima and maxima also appeared varied. To illustrate how model output can change with experimental input data from individual Culex species, we applied a modified equation for temperature-dependent mosquito type reproduction number for endemic spread of WNV among mosquitoes and observed different effects.

Conclusions
Current models often input theoretical parameters estimated from a single vector species; we show the need to implement the real-world heterogeneity in thermal response between species and present a useful data resource for researchers working toward that goal.

Graphical Abstract
Shank2 identifies a subset of glycinergic neurons involved in altered nociception in an autism model
Authors: Olde Heuvel Florian , Ouali Alami Najwa , Aousji Oumayma , Pogatzki-Zahn Esther , Zahn Peter K. , Wilhelm Hanna , Deshpande Dhruva , Khatamsaz Elmira , Catanese Alberto , Woelfle Sarah , Schön Michael , Jain Sanjay , Grabrucker Stefanie , Ludolph Albert C. , Verpelli Chiara , Michaelis Jens , Boeckers Tobias M. , Roselli Francesco 
Published: June 2023

AbstractBackgroundAutism Spectrum Disorders (ASD) patients experience disturbed nociception in the form of either hyposensitivity to pain or allodynia. A substantial amount of processing of somatosensory and nociceptive stimulus takes place in the dorsal spinal cord. However, many of these circuits are not very well understood in the context of nociceptive processing in ASD.MethodsWe have used a Shank2−/−mouse model, which displays a set of phenotypes reminiscent of ASD, and performed behavioural and microscopic analysis to investigate the role of dorsal horn circuitry in nociceptive processing of ASD.ResultsWe determined that Shank2−/−mice display increased sensitivity to formalin pain and thermal preference, but a sensory specific mechanical allodynia. We demonstrate that high levels of Shank2 expression identifies a subpopulation of neurons in murine and human dorsal spinal cord, composed mainly by glycinergic interneurons and that loss of Shank2 causes the decrease in NMDAR in excitatory synapses on these inhibitory interneurons. In fact, in the subacute phase of the formalin test, glycinergic interneurons are strongly activated in wild type (WT) mice but not in Shank2−/−mice. Consequently, nociception projection neurons in laminae I are activated in larger numbers in Shank2−/−mice.LimitationsOur investigation is limited to male mice, in agreement with the higher representation of ASD in males; therefore, caution should be applied to extrapolate the findings to females. Furthermore, ASD is characterized by extensive genetic diversity and therefore the findings related to Shank2 mutant mice may not necessarily apply to patients with different gene mutations. Since nociceptive phenotypes in ASD range between hyper- and hypo-sensitivity, diverse mutations may affect the circuit in opposite ways.ConclusionOur findings prove that Shank2 expression identifies a new subset of inhibitory interneurons involved in reducing the transmission of nociceptive stimuli and whose unchecked activation is associated with pain hypersensitivity. We provide evidence that dysfunction in spinal cord pain processing may contribute to the nociceptive phenotypes in ASD.