bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical benefit of systolic blood pressure within the target range among patients with or without diabetes mellitus: a propensity score-matched analysis of two randomized clinical trials
Authors: Li Chao , Chen Kangyu , Shi Guoshuai , Shi Rui , Wu Zhenqiang , Yuan Xiaodan , Watson Vicky , Jiang Zhixin , Mai Hui , Yang Tian , Wang Duolao , Chen Tao 
Published: June 2022

Abstract
Background
Recent guidelines recommended a systolic blood pressure (SBP) target of < 130 mmHg for patients with or without diabetes but without providing a lower bound. Our study aimed to explore whether additional clinical benefits remain at achieved blood pressure (BP) levels below the recommended target.

Methods
We performed a secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) among the non-diabetic population and the Action to Control Cardiovascular Risk in Diabetes BP (ACCORD-BP) trial among diabetic subjects. We used the propensity score method to match patients from the intensive BP group to those from the standard group in each trial. Individuals with different achieved BP levels from the intensive BP group were used as “reference.” For each stratum, the trial-specific primary outcome (i.e., composite outcome of myocardial infarction (MI), acute coronary syndrome not resulting in MI, stroke, acute decompensated heart failure (HF), or cardiovascular death for SPRINT; non-fatal MI, non-fatal stroke, or cardiovascular death for ACCORD-BP) was compared by Cox regression.

Results
A non-linear association was observed between the mean achieved BP and incidence of composite cardiovascular events, regardless of treatment allocation. The significant treatment benefit for primary outcome remained at SBP 110–120 mmHg (hazard ratio, 0.59 [95% CI, 0.46, 0.76] for SPRINT; 0.67 [0.52, 0.88] for ACCORD-BP) and SBP 120–130 mmHg for SPRINT (0.47 [0.34, 0.63]) but not for ACCORD-BP (0.93 [0.70, 1.23]). The results were similar for the secondary outcomes including all-cause mortality, cardiovascular mortality, MI, stroke, and HF. Intensive BP treatment benefits existed among patients maintaining a diastolic BP of 60–70 mmHg but were less distinct.

Conclusions
The treatment benefit persists at as low as SBP 110–120 mmHg irrespective of diabetes status. Achieved very low BP levels appeared to increase cardiovascular events and all-cause mortality.
Optimizing the downstream MVA pathway using a combination optimization strategy to increase lycopene yield in Escherichia coli
Authors: Cheng Tao , Wang Lili , Sun Chao , Xie Congxia 
Published: June 2022

Abstract
Background
Lycopene is increasing in demand due to its widespread use in the pharmaceutical and food industries. Metabolic engineering and synthetic biology technologies have been widely used to overexpress the heterologous mevalonate pathway and lycopene pathway in Escherichia coli to produce lycopene. However, due to the tedious metabolic pathways and complicated metabolic background, optimizing the lycopene synthetic pathway using reasonable design approaches becomes difficult.

Results
In this study, the heterologous lycopene metabolic pathway was introduced into E. coli and divided into three modules, with mevalonate and DMAPP serving as connecting nodes. The module containing the genes (MVK, PMK, MVD, IDI) of downstream MVA pathway was adjusted by altering the expression strength of the four genes using the ribosome binding sites (RBSs) library with specified strength to improve the inter-module balance. Three RBS libraries containing variably regulated MVK, PMK, MVD, and IDI were constructed based on different plasmid backbones with the variable promoter and replication origin. The RBS library was then transformed into engineered E. coli BL21(DE3) containing pCLES and pTrc-lyc to obtain a lycopene producer library and employed high-throughput screening based on lycopene color to obtain the required metabolic pathway. The shake flask culture of the selected high-yield strain resulted in a lycopene yield of 219.7 mg/g DCW, which was 4.6 times that of the reference strain.

Conclusion
A strain capable of producing 219.7 mg/g DCW with high lycopene metabolic flux was obtained by fine-tuning the expression of the four MVA pathway enzymes and visual selection. These results show that the strategy of optimizing the downstream MVA pathway through RBS library design can be effective, which can improve the metabolic flux and provide a reference for the synthesis of other terpenoids.
Malaria-associated risk factors among adolescents living in areas with persistent transmission in Senegal: a case–control study
Authors: Tairou Fassiatou , Diallo Abdoulaye , Sy Ousmane , Kone Aminatou , Manga Isaac Akhenaton , Sylla Khadim , Lelo Souleye , Fall Cheikh Binetou , Sow Doudou , Ndiaye Magatte , Faye Babacar , Tine Roger C. K. 
Published: June 2022

Abstract
Background
In Senegal, malaria morbidity has sharply decreased over these past years. However, malaria epidemiology remains heterogeneous with persistent transmission in the southeastern part of the country and many cases among older children and adolescents. Little is known about factors associated with clinical malaria among this group. A better understanding of malaria transmission among this newly emerging vulnerable group will guide future interventions targeting this population group. This study aimed to identify factors associated with clinical malaria among adolescents in Senegal.

Methods
A case–control study was conducted from November to December 2020 in four health posts located in the Saraya district. Cases were defined as adolescents (10–19 years) with an uncomplicated malaria episode with fever (temperature > 37.5°) or a history of fever and positive malaria rapid diagnostic test (RDT). Controls were from the same age group, living in the neighbourhood of the case, presenting a negative RDT. A standardized, pre-tested questionnaire was administered to each study participant followed by a home visit to assess the participant's living conditions. Factors associated with clinical malaria were assessed using stepwise logistic regression analysis.

Results
In total, 492 individuals were recruited (246 cases and 246 controls). In a multivariate analysis, factors associated with clinical malaria included non-use of long-lasting insecticidal net (LLIN) (aOR = 2.65; 95% CI 1.58–4.45), non-use of other preventive measures (aOR = 2.51; 95% CI 1.53–4.11) and indoor sleeping (aOR = 3.22; 95% CI 1.66–6.23). Protective factors included 15–19 years of age (aOR = 0.38; 95% CI 0.23–0.62), absence of stagnant water around the house (aOR = 0.27; 95% CI 0.16–0.44), having a female as head of household (aOR = 0.47; 95% CI 0.25–0.90), occupation such as apprentice (OR = 0.24; 95% CI 0.11–0.52).

Conclusions
The study revealed that environmental factors and non-use of malaria preventive measures are the main determinants of malaria transmission among adolescents living in areas with persistent malaria transmission in Senegal. Strategies aimed at improving disease awareness and access to healthcare interventions, such as LLINs, are needed to improve malaria control and prevention among these vulnerable groups.
Open science at the science–policy interface: bringing in the evidence?
Authors: Reichmann Stefan , Wieser Bernhard 
Published: June 2022

AbstractPart of the current enthusiasm about open science stems from its promises to reform scientific practice in service of the common good, to ensure that scientific outputs will be found and reused more easily, and to enhance scientific impact on policy and society. With this article, we question this optimism by analysing the potential for open science practices to enhance research uptake at the science–policy interface. Science advice is critical to help policy-makers make informed decisions. Likewise, some interpretations of open science hold that making research processes and outputs more transparent and accessible will also enhance the uptake of results by policy and society at large. However, we argue that this hope is based on an unjustifiably simplistic understanding of the science–policy interface that leaves key terms (“impact”, “uptake”) undefined. We show that this understanding—based upon linear models of research uptake—likewise grounds the influential “evidence–policy gap” diagnosis which holds that to improve research uptake, communication and interaction between researchers and policy-makers need to be improved. The overall normative stance of both discussions has sidelined empirical description of the science–policy interface, ignoring questions about the underlying differences between the policy domain and academia. Importantly, both open science and literature on closing the evidence–policy gap recommend improving communication (in terms of either the content or the means) as a viable strategy. To correct some of these views, we combine insights from policy theory with a narrative review of the literature on the evidence–policy gap in the health domain and find that removing barriers to access by itself will not be enough to foster research uptake.
Neuroinflammation in the anterior cingulate cortex: the potential supraspinal mechanism underlying the mirror-image pain following motor fiber injury
Authors: Li Qiao-Yun , Chen Shao-Xia , Liu Jin-Yu , Yao Pei-Wen , Duan Yi-Wen , Li Yong-Yong , Zang Ying 
Published: June 2022

AbstractBackgroundPeripheral nerve inflammation or lesion can affect contralateral healthy structures, and thus result in mirror-image pain. Supraspinal structures play important roles in the occurrence of mirror pain. The anterior cingulate cortex (ACC) is a first-order cortical region that responds to painful stimuli. In the present study, we systematically investigate and compare the neuroimmune changes in the bilateral ACC region using unilateral- (spared nerve injury, SNI) and mirror-(L5 ventral root transection, L5-VRT) pain models, aiming to explore the potential supraspinal neuroimmune mechanism underlying the mirror-image pain.MethodsThe up-and-down method with von Frey hairs was used to measure the mechanical allodynia. Viral injections for the designer receptors exclusively activated by designer drugs (DREADD) were used to modulate ACC glutamatergic neurons. Immunohistochemistry, immunofluorescence, western blotting, protein microarray were used to detect the regulation of inflammatory signaling.ResultsIncreased expressions of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and chemokine CX3CL1 in ACC induced by unilateral nerve injury were observed on the contralateral side in the SNI group but on the bilateral side in the L5-VRT group, representing a stronger immune response to L5-VRT surgery. In remote ACC, both SNI and L5-VRT induced robust bilateral increase in the protein level of Nav1.6 (SCN8A), a major voltage-gated sodium channel (VGSC) that regulates neuronal activity in the mammalian nervous system. However, the L5-VRT-induced Nav1.6 response occurred at PO 3d, earlier than the SNI-induced one, 7 days after surgery. Modulating ACC glutamatergic neurons via DREADD-Gq or DREADD-Gi greatly changed the ACC CX3CL1 levels and the mechanical paw withdrawal threshold. Neutralization of endogenous ACC CX3CL1 by contralateral anti-CX3CL1 antibody attenuated the induction and the maintenance of mechanical allodynia and eliminated the upregulation of CX3CL1, TNF-α and Nav1.6 protein levels in ACC induced by SNI. Furthermore, contralateral ACC anti-CX3CL1 also inhibited the expression of ipsilateral spinal c-Fos, Iba1, CD11b, TNF-α and IL-6.ConclusionsThe descending facilitation function mediated by CX3CL1 and its downstream cascade may play a pivotal role, leading to enhanced pain sensitization and even mirror-image pain. Strategies that target chemokine-mediated ACC hyperexcitability may lead to novel therapies for the treatment of neuropathic pain.
Promoting respectful maternity care using a behavioral design approach in Zambia: results from a mixed-methods evaluation
Authors: Smith Jana , Schachter Allison , Banay Rachel , Zimmerman Emily , Vargas Ariadna , Sellman Abigail , Kamanga Ameck 
Published: June 2022

Abstract
Background
Respectful maternity care (RMC) has been elevated in the global discourse, however, instances of disrespect and abuse remain prevalent. While several studies have highlighted promising approaches to promote RMC, this body of literature is still limited and few approaches have been scaled outside the initial study sites. Building on formative research conducted through a behavioral science lens, we sought to develop and test evidence-based, low-cost solutions to promote RMC which would be well-positioned for scale-up. Our study highlights the effectiveness of the solution package on provider provision of respectful care and client satisfaction, as well as intermediary outcomes and behavioral mechanisms.

Methods
A quasi-experimental evaluation, informed by the behavioral design approach, was completed to test the effectiveness of a 5-component solution package in Chipata, Zambia. Quantitative surveys were collected from health facility providers and postpartum clients at baseline and endline in intervention and comparison facilities. Additional qualitative interviews were conducted with health facility providers and postpartum clients at endline. We also conducted interviews with health facility in-charges and observed labor and delivery practices at intervention facilities over the course of implementation.

Results
Evidence suggested that at endline, clients at implementation facilities were less likely to experience disrespect and abuse compared to clients at comparison facilities (ß = − 0.15 p = 0.01). Clients at intervention facilities were more likely to request pain management compared to clients at comparison facilities (ß = 0.33, p = 0.003). The solutions were simple for providers to implement and were easily integrated into existing services by providers during labor and delivery. Providers at intervention facilities also described the pain management toolkit as helpful in expanding the types of pain management techniques used during labor.

Conclusions
The results of this small-scale study act as a proof of concept, demonstrating that the behavioral design approach can lead to solutions that show potential for impact. In other settings where providers face similar barriers to providing RMC, an adaptation of this solution package might lead to similarly positive results. Given the global scale of disrespectful care, these low-cost solutions hold promise for improving the quality of care women receive during labor and delivery.
The impact of training on self-reported performance in reproductive, maternal, and newborn health service delivery among healthcare workers in Tanzania: a baseline- and endline-survey
Authors: Mwansisya Tumbwene , Mbekenga Columba , Isangula Kahabi , Mwasha Loveluck , Mbelwa Stewart , Lyimo Mary , Kisaka Lucy , Mathias Victor , Pallangyo Eunice , Edwards Grace , Mantel Michaela , Konteh Sisawo , Rutachunzibwa Thomas , Mrema Secilia , Kidanto Hussein , Temmerman Marleen 
Published: June 2022

Abstract
Background
Delivery of quality reproductive health services has been documented to depend on the availability of healthcare workers who are adequately supported with appropriate training. However, unmet training needs among healthcare workers in reproductive, maternal, and newborn health (RMNH) in low-income countries remain disproportionately high. This study investigated the effectiveness of training with onsite clinical mentorship towards self-reported performance in RMNH among healthcare workers in Mwanza Region, Tanzania.

Methods
The study used a quasi-experimental design with pre-and post-intervention evaluation strategy. The baseline was compared with two endline groups: those with intervention (training and onsite mentorship) and those without. The differences among the three groups in the sociodemographic characteristics were analyzed by using chi-square test for categorical variables, independent-sample t-test for continuous variables and Mann–Whitney U test for ordinal or skewed continuous data. The independent sample t-test was used to determine the effect of the intervention by comparing the computed self-reported performance on RMNH services between the intervention and control groups. The paired-samples t-test was used to measure the differences between before and after intervention groups. Significance was set at a 95% confidence interval with p ≤ 0.05.

Results
The study included a sample of 216 participants with before and after intervention groups comprising of 95 (44.0%) and 121 (56.0%) in the control group. The comparison between before and after intervention groups revealed a statistically significant difference (p ≤ 0.05) in all the dimensions of the self-reported performance scores. However, the comparison between intervention groups and controls indicated a statistical significant difference on intra-operative care (t = 3.10, df = 216, p = 0.002), leadership skills (t = 1.85, df = 216, p = 0.050),
Comprehensive emergency obstetric and newborn care (CEMONC) (t = 34.35, df = 216, p ≤ 0.001), and overall self-reported performance in RMNH (t = 3.15, df = 216, p = 0.002).

Conclusions
This study revealed that the training and onsite clinical mentorship to have significant positive changes in self-reported performance in a wide range of RMNH services especially on intra-operative care, leadership skills and CEMONC. However, further studies with rigorous designs are warranted to evaluate the long-term effect of such training programs on RMNH outcomes.
Rethinking the tools in the toolbox
Authors: George Hornby T. 
Published: June 2022

AbstractThe commentary by Dr. Labruyere on the article by Kuo et al. (J Neuroeng Rehabil. 2021; 18:174) posits that randomized trials evaluating the comparative efficacy of robotic devices for patients with neurological injury may not be needed. The primary argument is that researchers and clinicians do not know how to optimize training parameters to maximize the benefits of this therapy, and studies vary in how they deliver robotic-assisted training. While I concur with the suggestion that additional trials using robotic devices as therapeutic tools are not warranted, an alternative hypothesis is that future studies will yield similar equivocal results regardless of the training parameters used. Attempts are made to detail arguments supporting this premise, including the notion that the original rationale for providing robotic-assisted walking training, particularly with exoskeletal devices, was flawed and that the design of some of the more commonly used devices places inherent limitations on the ability to maximize neuromuscular demands during training. While these devices arrived nearly 20 years ago amid substantial enthusiasm, we have since learned valuable lessons from robotic-assisted and other rehabilitation studies on some of the critical parameters that influence neuromuscular and cardiovascular activity during locomotor training, and different strategies are now needed to optimize rehabilitation outcomes.
Leveraging WHO’s Global Benchmarking Tool to strengthen capacity in clinical trials oversight for public health emergencies: the GHPP VaccTrain model
Authors: Owusu Sekyere Solomon , Škrnjug-Yudov Ivana , Ateba Ngoa Ulysse , Juárez Hernández Marcela , Abiri Onome T. , Komeh James P. , Janneh Kaira Markieu , Marenah Essa , Kercula Juwe Darnuwele , Smith Keturah , Rassokhina Olga , Meyer Heidi , Conrad Christoph 
Published: June 2022

Abstract
Background
A stable, well-functioning and integrated national medicines regulatory system is a core component of health systems resilient against infectious disease outbreaks. In many low- and middle-income countries, however, sizable gaps exist in the emergency preparedness framework of national regulatory authorities (NRAs). RegTrain-VaccTrain is a project of Germany Ministry of Health’s Global Health Protection Programme that contributes to global efforts aimed at strengthening such regulatory systems by providing technical support and advice to partner NRAs. In this study, we probed the outputs of our capacity-strengthening activities for clinical trials oversight (CTO) to take stock of progress made and examine remaining priorities in order to provide specialized technical assistance in addressing them to improve operational readiness for emergencies.

Method
Data validated from NRA self-benchmarking results in 2017 and worksheet records of November 2021 were utilized to assess the emergency preparedness capacity for CTO in three VaccTrain partner NRAs (Liberia, Sierra Leone, The Gambia) before and after interventional capacity-strengthening partnership, using specific public health emergency-related (sub-)indicators of the WHO Global Benchmarking Tool.

Results
A generally weak and vulnerable structural framework for CTO characterized the emergency preparedness capacity in all three partner NRAs at baseline, thus putting their operational readiness for public health emergencies at risk. VaccTrain’s collaborative work was successful at supporting individual NRAs to develop the full spectrum of operational structures (including (draft) regulations, guidelines, and standard operating procedures) required to improve regulatory preparedness. A gap in the formal approval and implementation of developed legal documents in two of three NRAs still remains. Notwithstanding, a robust emergency framework now exists and the NRAs stand better prepared to respond to (future) locally-concerning health emergencies, during which time clinical trials activity was observed to heighten.

Conclusions
These results exemplify a north-south capacity-strengthening partnership model that effectively contributes in developing structures to enhance regulatory oversight and support expeditious product development in response to crises. They further underscore the equally critical role local/national processes play in facilitating the full implementation of developed structures.