bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rice small secreted peptide, OsRALF26, recognized by FERONIA‐like receptor 1 induces immunity in rice and Arabidopsis
Authors: Kwon Oh‐Kyu , Moon Hyeran , Jeong A‐Ram , Yeom Gunn , Park Chang‐Jin 
Published: March 2024

SUMMARYRapid alkalinization factors (RALFs), belonging to a family of small secreted peptides, have been considered as important signaling molecules in diverse biological processes, including immunity. Current studies on RALF‐modulated immunity mainly focus on Arabidopsis, but little is reported in crop plants. The rice immune receptor XA21 confers immunity to the bacterial blight pathogen, Xanthomonas oryzae pv. oryzae (Xoo). Here, we pursued functional characterization of rice RALF26 (OsRALF26) up‐regulated by Xoo during XA21‐mediated immune response. When applied exogenously as a recombinant peptide, OsRALF26 induced a series of immune responses, including pathogenesis‐related genes (PRs) induction, reactive oxygen species (ROS) production, and callose deposition in rice and/or Arabidopsis. Transgenic rice and Arabidopsis overexpressing OsRALF26 exhibited significantly enhanced resistance to Xoo and Pseudomonas syringae pv. tomato DC3000 (Pst DC3000), respectively. In yeast two‐hybrid, pull‐down assays, and co‐immunoprecipitation analyses, rice FER‐like receptor 1 (OsFLR1) was identified as a receptor of OsRALF26. Transient expression of OsFLR1 in Nicotiana benthamiana leaves displayed significantly increased ROS production and callose deposition after OsRALF26 treatment. Together, we propose that OsRALF26 induced by Xoo in an XA21‐dependent manner is perceived by OsFLR1 and may play a novel role in the enforcement of XA21‐mediated immunity.
Evaluation of economic inequality in ‘the Belt and Road’ region – The application of night‐time satellite imagery
Authors: Yang Zhen , Zhang Lu , Liu Chengkun , Chen Yu , Wu Rongwei , Zheng Yaomin 
Published: March 2024

AbstractThe main aim of this paper is to explore economic inequality in ‘the Belt and Road’ region where the investigation of the economic status is important but remains underdeveloped. The application of night‐time satellite imagery in 2015 can effectively make up for the shortcomings of insufficient data at various scales, especially for developing countries. We explored inequality at a multi‐scale level using the Theil decomposition method. As a result, (1) night‐time light data can present economic development and assess inequality in ‘the Belt and Road’ region. (2) The between‐sub‐region inequality contributed most to disparity, while the between‐country inequality was the least. Night‐time light data in West Asia and Central and Eastern Europe was higher than that in other sub‐regions. Countries within Central, Southeast and West Asia exhibited high inequalities, indicating an obvious sub‐regional pattern. (3) Both positive and negative impacts of economic growth on inequality are observed, indicating that ‘the Belt and Road’ countries are in different stages of economic development. Nightlight satellite imagery can effectively monitor social‐economic development and will play an important role in the implementation of ‘the Belt and Road’ initiative and achieving the sustainable development goals.
Influence of Amputation on Kinetic Chain Musculature Activity During Basic and Modified Core Exercises
Authors: Liu Kaiqi , Ji Linhong , Lu Yijia 
Published: March 2024

Purpose: Core strength is vital for athletic performance, and many more exercises that involve the kinetic chain have been designed for able-bodied athletes. Disabilities that impair the kinetic chain can reduce the effectiveness of strength training. However, the impact of amputation on core strength training of people with disabilities and its underlying mechanism remains unclear. This study aimed to evaluate the muscle activation patterns and levels in athletes with amputation during 4 basic and modified weight-bearing core strength-training exercises. Methods: Fifteen elite athletes with unilateral amputation (170.6 [7.3] cm; 63.9 [11.9] kg; 25.9 [5.3] y) volunteered for this study. Surface electromyography was used to measure the muscle activity mainly in the lumbopelvic–hip complex-stabilizing muscles during 4 kinetic chain trunk exercises with and without modifications. Results: The significance level was set at α = .05. The results showed a significant difference in muscle activation between different body sides (P < .05). Specifically, amputation on the support position resulted in a diagonal pattern of muscle activation, and amputation on the free distal segments resulted in a unilateral dominant pattern with higher activation in muscles on the nonamputated side (P < .05). Modifications led to significant decreases in muscle activation asymmetry index (P < .05). Conclusions: Amputation caused muscle activation asymmetry and 2 activation patterns. Modifications by enhancing proximal stability and adjusting distal loading effectively reduced the asymmetry of muscle activation. Coaches and clinicians can use these results to tailor exercises for athletes with disabilities in training and rehabilitation.
Restoration of virulence in the attenuated Candid#1 vaccine virus requires reversion at both positions 168 and 427 in the envelope glycoprotein GPC
Authors: Nunberg Jack H. , Westover Jonna B. , York Joanne , Jung Kie Hoon , Bailey Kevin W. , Boardman Kirsten M. , Li Minghao , Furnell Rachel S. , Wasson Samantha R. , Murray Justin S. , Kaundal Rakesh , Thomas Aaron J. , Gowen Brian B. 
Published: March 2024

ABSTRACT

Live-attenuated virus vaccines provide long-lived protection against viral disease but carry inherent risks of residual pathogenicity and genetic reversion. The live-attenuated Candid#1 vaccine was developed to protect Argentines against lethal infection by the Argentine hemorrhagic fever arenavirus, Junín virus. Despite its safety and efficacy in Phase III clinical study, the vaccine is not licensed in the US, in part due to concerns regarding the genetic stability of attenuation. Previous studies had identified a single F427I mutation in the transmembrane domain of the Candid#1 envelope glycoprotein GPC as the key determinant of attenuation, as well as the propensity of this mutation to revert upon passage in cell culture and neonatal mice. To ascertain the consequences of this reversion event, we introduced the I427F mutation into recombinant Candid#1 (I427F rCan) and investigated the effects in two validated small-animal models: in mice expressing the essential virus receptor (human transferrin receptor 1; huTfR1) and in the conventional guinea pig model. We report that I427F rCan displays only modest virulence in huTfR1 mice and appears attenuated in guinea pigs. Reversion at another attenuating locus in Candid#1 GPC (T168A) was also examined, and a similar pattern was observed. By contrast, virus bearing both revertant mutations (A168T+I427F rCan) approached the lethal virulence of the pathogenic Romero strain in huTfR1 mice. Virulence was less extreme in guinea pigs. Our findings suggest that genetic stabilization at both positions is required to minimize the likelihood of reversion to virulence in a second-generation Candid#1 vaccine.

IMPORTANCE
Live-attenuated virus vaccines, such as measles/mumps/rubella and oral poliovirus, provide robust protection against disease but carry with them the risk of genetic reversion to the virulent form. Here, we analyze the genetics of reversion in the live-attenuated Candid#1 vaccine that is used to protect against Argentine hemorrhagic fever, an often-lethal disease caused by the Junín arenavirus. In two validated small-animal models, we find that restoration of virulence in recombinant Candid#1 viruses requires back-mutation at two positions specific to the Candid#1 envelope glycoprotein GPC, at positions 168 and 427. Viruses bearing only a single change showed only modest virulence. We discuss strategies to genetically harden Candid#1 GPC against these two reversion events in order to develop a safer second-generation Candid#1 vaccine virus.
Temporal trends of ambulance time intervals for suspected stroke/transient ischaemic attack (TIA) before and during the COVID-19 pandemic in Ireland: a quasi-experimental study
Authors: Burton Edel , Quinn Rory , Crosbie-Staunton Kieran , Deasy Conor , Masterson Siobhan , O'Donnell Cathal , Merwick Áine , Willis David , Kearney Patricia M. , Mc Carthy Vera J.C. , Buckley Claire M. 
Published: March 2024

ObjectivesTime is a fundamental component of acute stroke and transient ischaemic attack (TIA) care, thus minimising prehospital delays is a crucial part of the stroke chain of survival. COVID-19 restrictions were introduced in Ireland in response to the pandemic, which resulted in major societal changes. However, current research on the effects of the COVID-19 pandemic on prehospital care for stroke/TIA is limited to early COVID-19 waves. Thus, we aimed to investigate the effect of the COVID-19 pandemic on ambulance time intervals and suspected stroke/TIA call volume for adults with suspected stroke and TIA in Ireland, from 2018 to 2021.DesignWe conducted a secondary data analysis with a quasi-experimental design.SettingWe used data from the National Ambulance Service in Ireland. We defined the COVID-19 period as ‘1 March 2020–31 December 2021’ and the pre-COVID-19 period ‘1 January 2018–29 February 2020’.Primary and secondary outcome measuresWe compared five ambulance time intervals: ‘allocation performance’, ‘mobilisation performance’, ‘response time’, ‘on scene time’ and ‘conveyance time’ between the two periods using descriptive and regression analyses. We also compared call volume for suspected stroke/TIA between the pre-COVID-19 and COVID-19 periods using interrupted time series analysis.ParticipantsWe included all suspected stroke/TIA cases ≥18 years who called the National Ambulance Service from 2018 to 2021.Results40 004 cases were included: 19 826 in the pre-COVID-19 period and 20 178 in the COVID-19 period. All ambulance time intervals increased during the pandemic period compared with pre-COVID-19 (p<0.001). Call volume increased during the COVID-19-period compared with the pre-COVID-19 period (p<0.001).ConclusionsA ’shock' like a pandemic has a negative impact on the prehospital phase of care for time-sensitive conditions like stroke/TIA. System evaluation and public awareness campaigns are required to ensure maintenance of prehospital stroke pathways amidst future healthcare crises. Thus, this research is relevant to routine and extraordinary prehospital service planning.
Self-help friendliness and cooperation with self-help groups among rehabilitation clinics in Germany (KoReS): a mixed-methods study protocol
Authors: Ziegler Elâ , Bartzsch Thea , Trojan Alf , Usko Nicole , Krahn Ines , Bütow Sabine , Kofahl Christopher 
Published: March 2024

IntroductionSelf-help is an important complement to medical rehabilitation for people with chronic diseases and disabilities. It contributes to stabilising rehabilitation success and further coping with disease and disability. Rehabilitation facilities are central in informing and referring patients to self-help groups. However, sustainable cooperation between rehabilitation and self-help, as can be achieved using the concept of self-help friendliness in healthcare, is rare, as is data on the cooperation situation.Methods and analysisThe KoReS study will examine self-help friendliness and cooperation between rehabilitation clinics and self-help associations in Germany, applying a sequential exploratory mixed-methods design. In the first qualitative phase, problem-centred interviews and focus groups are conducted with representatives of self-help-friendly rehabilitation clinics, members of their cooperating self-help groups and staff of self-help clearinghouses involved based on a purposeful sampling. Qualitative data collected will be analysed through content analysis using MAXQDA. The findings will serve to develop a questionnaire for a quantitative second phase. Cross-sectional online studies will survey staff responsible for self-help in rehabilitation clinics nationwide, representatives of self-help groups and staff of self-help clearinghouses. Quantitative data analysis with SPSS will include descriptive statistics, correlation, subgroup and multiple regression analyses. Additionally, a content analysis of rehabilitation clinics’ websites will evaluate the visibility of self-help in their public relations.Ethics and disseminationThe University Medical Center Hamburg-Eppendorf Local Psychological Ethics Committee at the Center for Psychosocial Medicine granted ethical approval (reference number LPEK-0648; 10.07.2023). Informed consent will be obtained from all participants. Results dissemination will comprise various formats such as workshops, presentations, homepages and publications for the international scientific community, rehabilitation centres, self-help organisations and the general public in Germany. For relevant stakeholders, practical guides and recommendations to implement self-help friendliness will derive from the results to strengthen patient orientation and cooperation between rehabilitation and self-help to promote the sustainability of rehabilitation processes.
Call for sustainable food systems including (medical) nutrition for hospitalised children and their families
Authors: Verbruggen Sascha C A T , Cochius den Otter Suzan , Bakker Johanna , Briassoulis George , Ilia Stavroula , Latten Lynne , Joosten Koen , Rooze Shancy , van Zanten Eva , Beattie R Mark , Marino Luise V 
Published: March 2024

The climate emergency presents a profound threat to global health, adversely affecting the health and well-being of children who are projected to bear a substantial disease burden, as well as impacting children’s right to food, water, healthcare and education. The healthcare sector strives to prioritise preventative healthcare policies improving the health of individuals across the life course. However, current healthcare practices significantly contribute to greenhouse gas (GHG) emissions and waste generation, in which (medical) nutrition plays an important role.Plant-based proteins offer sustainability benefits, and potential health advantages, and have a lower climate footprint, although there may also be unintended consequences of land-use change and deforestation for certain crops. However, to develop suitable plant-based alternatives to medical nutrition, it will be necessary to address regulatory obstacles as well as ensure nutritional profiles are suitable, particularly protein (amino acid) and micronutrient composition. Additionally, the development of heat-tolerant and water-efficient plant genotypes could bolster adaptation to changing climatic conditions.Effective waste management, including wasted food and medical nutrition, emerges as a key strategy in mitigating the climate impact of medical nutrition. While research on food waste in healthcare settings is limited, minimising waste spillage in medical nutrition is a crucial area to explore. Healthcare professionals must acknowledge their roles in curbing the climate footprint of medical nutrition as well as recommendations for food-based approaches. This review aims to investigate the sustainability of medical nutrition for paediatric care, focusing on factors contributing to GHG emissions, plant-based alternatives, waste management and plastic packaging. Such an exploration is vital for healthcare professionals to fulfil their responsibilities in addressing the climate crisis while advocating for change.
First evidence of a biomarker-based dose-response relationship in chronic pain using physiological closed-loop spinal cord stimulation
Authors: Muller Leah , Pope Jason , Verrills Paul , Petersen Erika , Kallewaard Jan Willem , Gould Ian , Karantonis Dean M 
Published: March 2024

Background and objectivesIn spinal cord stimulation (SCS) therapy, electricity is the medication delivered to the spinal cord for pain relief. In contrast to conventional medication where dose is determined by desired therapeutic plasma concentration, there is lack of equivalent means of determining dose delivery in SCS. In open-loop (OL) SCS, due to the dynamic nature of the epidural space, the activating electric field delivered is inconsistent at the level of the dorsal columns. Recent Food and Drug Administration guidance suggests accurate and consistent therapy delivered using physiologic closed-loop control (PCLC) devices can minimize underdosage or overdosage and enhance medical care. PCLC-based evoked compound action potential (ECAP)-controlled technology provides the ability to prescribe a precise stimulation dose unique to each patient, continuously measure neural activation, and objectively inform SCS therapy optimization.MethodsNeurophysiological indicator metrics of therapy dose, usage above neural activation threshold, and accuracy of SCS therapy were assessed for relationship with pain reduction in over 600 SCS patients.ResultsSignificant relationships between objective metrics and pain relief across the patient population are shown, including first evidence for a dose-response relationship in SCS.ConclusionsHigher dose, more time over ECAP threshold, and higher accuracy are associated with better outcomes across patients. There is potential to optimize individual patient outcomes based on unique objective measurable electrophysiological inputs.
A Compound That Inhibits Glycolysis in Prostate Cancer Controls Growth of Advanced Prostate Cancer
Authors: Uo Takuma , Ojo Kayode K. , Sprenger Cynthia C.T. , Epilepsia Kathryn S. , Perera B. Gayani K. , Damodarasamy Mamatha , Sun Shihua , Kim Soojin , Hogan Hannah H. , Hulverson Matthew A. , Choi Ryan , Whitman Grant R. , Barrett Lynn K. , Michaels Samantha A. , Xu Linda H. , Sun Vicky L. , Arnold Samuel L.M. , Pang Haley J. , Nguyen Matthew M. , Vigil Anna-Lena B.G. , Kamat Varun , Sullivan Lucas B. , Sweet Ian R. , Vidadala Ram , Maly Dustin J. , Van Voorhis Wesley C. , Plymate Stephen R. 
Published: March 2024

Abstract
Metastatic castration-resistant prostate cancer remains incurable regardless of recent therapeutic advances. Prostate cancer tumors display highly glycolytic phenotypes as the cancer progresses. Nonspecific inhibitors of glycolysis have not been utilized successfully for chemotherapy, because of their penchant to cause systemic toxicity. This study reports the preclinical activity, safety, and pharmacokinetics of a novel small-molecule preclinical candidate, BKIDC-1553, with antiglycolytic activity. We tested a large battery of prostate cancer cell lines for inhibition of cell proliferation, in vitro. Cell-cycle, metabolic, and enzymatic assays were used to demonstrate their mechanism of action. A human patient-derived xenograft model implanted in mice and a human organoid were studied for sensitivity to our BKIDC preclinical candidate. A battery of pharmacokinetic experiments, absorption, distribution, metabolism, and excretion experiments, and in vitro and in vivo toxicology experiments were carried out to assess readiness for clinical trials. We demonstrate a new class of small-molecule inhibitors where antiglycolytic activity in prostate cancer cell lines is mediated through inhibition of hexokinase 2. These compounds display selective growth inhibition across multiple prostate cancer models. We describe a lead BKIDC-1553 that demonstrates promising activity in a preclinical xenograft model of advanced prostate cancer, equivalent to that of enzalutamide. BKIDC-1553 demonstrates safety and pharmacologic properties consistent with a compound that can be taken into human studies with expectations of a good safety margin and predicted dosing for efficacy. This work supports testing BKIDC-1553 and its derivatives in clinical trials for patients with advanced prostate cancer.
AKAP12 Upregulation Associates With PDE8A to Accelerate Cardiac Dysfunction
Authors: Qasim Hanan , Rajaei Mehrdad , Xu Ying , Reyes-Alcaraz Arfaxad , Abdelnasser Hala Y. , Stewart M. David , Lahiri Satadru K. , Wehrens Xander H.T. , McConnell Bradley K. 
Published: March 2024

BACKGROUND:
In heart failure, signaling downstream the β2-adrenergic receptor is critical. Sympathetic stimulation of β2-adrenergic receptor alters cAMP (cyclic adenosine 3′,5′-monophosphate) and triggers PKA (protein kinase A)-dependent phosphorylation of proteins that regulate cardiac function. cAMP levels are regulated in part by PDEs (phosphodiesterases). Several AKAPs (A kinase anchoring proteins) regulate cardiac function and are proposed as targets for precise pharmacology. AKAP12 is expressed in the heart and has been reported to directly bind β2-adrenergic receptor, PKA, and PDE4D. However, its roles in cardiac function are unclear.

METHODS:

cAMP accumulation in real time downstream of the β2-adrenergic receptor was detected for 60 minutes in live cells using the luciferase-based biosensor (GloSensor) in AC16 human-derived cardiomyocyte cell lines overexpressing AKAP12 versus controls. Cardiomyocyte intracellular calcium and contractility were studied in adult primary cardiomyocytes from male and female mice overexpressing cardiac AKAP12 (AKAP12
OX
) and wild-type littermates post acute treatment with 100-nM isoproterenol (ISO). Systolic cardiac function was assessed in mice after 14 days of subcutaneous ISO administration (60 mg/kg per day). AKAP12 gene and protein expression levels were evaluated in left ventricular samples from patients with end-stage heart failure.

RESULTS:

AKAP12 upregulation significantly reduced total intracellular cAMP levels in AC16 cells through PDE8. Adult primary cardiomyocytes from AKAP12
OX
mice had significantly reduced contractility and impaired calcium handling in response to ISO, which was reversed in the presence of the selective PDE8 inhibitor (PF-04957325). AKAP12
OX
mice had deteriorated systolic cardiac function and enlarged left ventricles. Patients with end-stage heart failure had upregulated gene and protein levels of AKAP12.

CONCLUSIONS:
AKAP12 upregulation in cardiac tissue is associated with accelerated cardiac dysfunction through the AKAP12-PDE8 axis.
Long-Term Blood Pressure Reductions Following Catheter-Based Renal Denervation: A Systematic Review and Meta-Analysis
Authors: Sesa-Ashton Gianni , Nolde Janis M. , Muente Ida , Carnagarin Revathy , Macefield Vaughan G. , Dawood Tye , Lambert Elisabeth A. , Lambert Gavin W. , Walton Antony , Esler Murray D. , Schlaich Markus P. 
Published: March 2024

BACKGROUND:
Renal denervation is a recognized adjunct therapy for hypertension with clinically significant blood pressure (BP)-lowering effects. Long-term follow-up data are critical to ascertain durability of the effect and safety. Aside from the 36-month follow-up data available from randomized control trials, recent cohort analyses extended follow-up out to 10 years. We sought to analyze study-level data and quantify the ambulatory BP reduction of renal denervation across contemporary randomized sham-controlled trials and available long-term follow-up data up to 10 years from observational studies.

METHODS:
A systematic review was performed with data from 4 observational studies with follow-up out to 10 years and 2 randomized controlled trials meeting search and inclusion criteria with follow-up data out to 36 months. Study-level data were extracted and compared statistically.

RESULTS:

In 2 contemporary randomized controlled trials with 36-month follow-up, an average sham-adjusted ambulatory systolic BP reduction of −12.7±4.5 mm Hg from baseline was observed (
P
=0.05). Likewise, a −14.8±3.4 mm Hg ambulatory systolic BP reduction was found across observational studies with a mean long-term follow-up of 7.7±2.8 years (range, 3.5–9.4 years;
P
=0.0051). The observed reduction in estimated glomerular filtration rate across the long-term follow-up was in line with the predicted age-related decline. Antihypertensive drug burden was similar at baseline and follow-up.

CONCLUSIONS:
Renal denervation is associated with a significant and clinically meaningful reduction in ambulatory systolic BP in both contemporary randomized sham-controlled trials up to 36 months and observational cohort studies up to 10 years without adverse consequences on renal function.