bluuebunny/crossref_metadata_2025 huggingface dataset:
Moving Beyond the Characterization of Activity Intensity Bouts as Square Waves Signals
Authors: O’Brien Myles W. , Petterson Jennifer L. , Pellerine Liam P. , Shivgulam Madeline E. , Kimmerly Derek S. , Frayne Ryan J. , Hettiarachchi Pasan , Johansson Peter J.
Published: April 2023

Wearable activity monitors provide objective estimates of time in different physical activity intensities. Each continuous stepping period is described by its length and a corresponding single intensity (in metabolic equivalents of task [METs]), creating square wave–shaped signals. We argue that physiological responses do not resemble square waves, with the purpose of this technical report to challenge this idea and use experimental data as a proof of concept and direct potential solutions to better characterize activity intensity. Healthy adults (n = 43, 19♀; 23 ± 5 years) completed 6-min treadmill stages (five walking and five jogging/running) where oxygen consumption (3.5 ml O2·kg−1·min−1 = 1 MET) was recorded throughout and following the cessation of stepping. The time to steady state was ∼1–1.5 min, and time back to baseline following exercise was ∼1–2 min, with faster stepping stages generally exhibiting longer durations. Instead of square waves, the duration intensity signal reflected a trapezoid shape for each stage. The METs per minute during the rise to steady state (upstroke slopes; average: 1.7–6.3 METs/min for slow walking to running) may be used to better characterize activity intensity for shorter activity bouts where steady state is not achieved (within ∼90 s). While treating each activity bout as a single intensity is a much simpler analytical procedure, characterizing each bout in a continuous manner may better reflect the true physiological responses to movement. The information provided herein may be used to improve the characterization of activity intensity, definition of bout breaks, and act as a starting point for researchers and software developers interested in using wearables to measure activity intensity.
Overcoming the limitations of Kolbe coupling with waveform-controlled electrosynthesis
Authors: Hioki Yuta , Costantini Matteo , Griffin Jeremy , Harper Kaid C. , Merini Melania Prado , Nissl Benedikt , Kawamata Yu , Baran Phil S.
Published: April 2023

The Kolbe reaction forms carbon-carbon bonds through electrochemical decarboxylative coupling. Despite more than a century of study, the reaction has seen limited applications owing to extremely poor chemoselectivity and reliance on precious metal electrodes. In this work, we present a simple solution to this long-standing challenge: Switching the potential waveform from classical direct current to rapid alternating polarity renders various functional groups compatible and enables the reaction on sustainable carbon-based electrodes (amorphous carbon). This breakthrough enabled access to valuable molecules that range from useful unnatural amino acids to promising polymer building blocks from readily available carboxylic acids, including biomass-derived acids. Preliminary mechanistic studies implicate the role of waveform in modulating the local pH around the electrodes and the crucial role of acetone as an unconventional reaction solvent for Kolbe reaction.
Bird shots
Authors: Cohen Jon
Published: April 2023

As an avian influenza virus devastates the poultry industry, the United States considers an unprecedented step: vaccinating its flocks
Rational design of a highly immunogenic prefusion-stabilized F glycoprotein antigen for a respiratory syncytial virus vaccine
Authors: Che Ye , Gribenko Alexey V. , Song Xi , Handke Luke D. , Efferen Kari S. , Tompkins Kristin , Kodali Srinivas , Nunez Lorna , Prasad A. Krishna , Phelan Lynn M. , Ammirati Mark , Yu Xiaodi , Lees Joshua A. , Chen Wei , Martinez Lyndsey , Roopchand Vidia , Han Seungil , Qiu Xiayang , DeVincenzo John P. , Jansen Kathrin U. , Dormitzer Philip R. , Swanson Kena A.
Published: April 2023

Respiratory syncytial virus (RSV) is the leading, global cause of serious respiratory disease in infants and is an important cause of respiratory illness in older adults. No RSV vaccine is currently available. The RSV fusion (F) glycoprotein is a key antigen for vaccine development, and its prefusion conformation is the target of the most potent neutralizing antibodies. Here, we describe a computational and experimental strategy for designing immunogens that enhance the conformational stability and immunogenicity of RSV prefusion F. We obtained an optimized vaccine antigen after screening nearly 400 engineered F constructs. Through in vitro and in vivo characterization studies, we identified F constructs that are more stable in the prefusion conformation and elicit ~10-fold higher serum-neutralizing titers in cotton rats than DS-Cav1. The stabilizing mutations of the lead construct (847) were introduced onto F glycoprotein backbones of strains representing the dominant circulating genotypes of the two major RSV subgroups, A and B. Immunization of cotton rats with a bivalent vaccine formulation of these antigens conferred complete protection against RSV challenge, with no evidence of disease enhancement. The resulting bivalent RSV prefusion F investigational vaccine has recently been shown to be efficacious against RSV disease in two pivotal phase 3 efficacy trials, one for passive protection of infants by immunization of pregnant women and the second for active protection of older adults by direct immunization.
Mutant Prevention Concentration, Frequency of Spontaneous Mutant Selection, and Mutant Selection Window—a New Approach to the
In Vitro
Determination of the Antimicrobial Potency of Compounds
Authors: Krajewska Joanna , Tyski Stefan , Laudy Agnieszka E.
Published: April 2023

The analysis of antimicrobial activity is usually MIC- and minimal bactericidal concentration (MBC)-focused, though also crucial are resistance-related parameters, e.g., the frequency of spontaneous mutant selection (FSMS), the mutant prevention concentration (MPC), and the mutant selection window (MSW).
In vitro
-determined MPCs, however, are sometimes variable, poorly repeatable, and not always reproducible
in vivo
. We propose a new approach to the
in vitro
determination of MSWs, along with novel parameters: MPC-D, MSW-D (for dominant mutants, i.e., selected with a high frequency, without a fitness loss), and MPC-F, MSW-F (for inferior mutants, i.e., with an impaired fitness).
Clinical Efficacy and Safety of a Novel Antifungal, Fosmanogepix, in Patients with Candidemia Caused by Candida auris
:
Results from a Phase 2 Trial
Authors: Vazquez Jose A. , Pappas Peter G. , Boffard Kenneth , Paruk Fathima , Bien Paul A. , Tawadrous Margaret , Ople Eric , Wedel Pamela , Oborska Iwona , Hodges Michael R.
Published: April 2023

Fosmanogepix (FMGX), a novel antifungal available in intravenous (IV) and oral formulations, has broad-spectrum activity against pathogenic yeasts and molds, including fungi resistant to standard of care antifungals. This multicenter, open-label, single-arm study evaluated FMGX safety and efficacy for treatment of candidemia and/or invasive candidiasis caused by
Candida auris
.
NlpE Is an OmpA-Associated Outer Membrane Sensor of the Cpx Envelope Stress Response
Authors: Cho Timothy H. S. , Wang Junshu , Raivio Tracy L.
Published: April 2023

The envelope is not only a barrier that protects bacteria from the environment but also a crucial site for the transduction of signals critical for colonization and pathogenesis. The discovery of novel complexes between NlpE and OmpA contributes to an emerging understanding of the key contribution of OM β-barrel protein and lipoprotein complexes to envelope stress signaling.
Novel Clinical mNGS-Based Machine Learning Model for Rapid Antimicrobial Susceptibility Testing of Acinetobacter baumannii
Authors: Hu Xuejiao , Zhao Yunhu , Han Peng , Liu Suling , Liu Weijiang , Mai Cong , Deng Qianyun , Ren Jing , Luo Jiajie , Chen Fangyuan , Jia Xuefeng , Zhang Jing , Rao Guanhua , Gu Bing
Published: April 2023

Multidrug-resistant (MDR) bacteria are important public health problems. Antibiotic susceptibility testing (AST) currently uses time-consuming culture-based procedures, which cause treatment delays and increased mortality. We developed a machine learning model using
Acinetobacter baumannii
as an example to explore a fast AST approach using metagenomic next-generation sequencing (mNGS) data.
Interspecies/Intergroup Complementation of Orthotospovirus Replication and Movement through Reverse Genetics Systems
Authors: Feng Mingfeng , Chen Minglong , Yuan Yulong , Liu Qinhai , Cheng Ruixiang , Yang Tongqing , Li Luyao , Guo Rong , Dong Yongxin , Chen Jing , Yang Yawen , Yan Yuling , Cui Hongmin , Jing Dong , Kang Jinrui , Chen Shuxian , Li Jia , Zhu Min , Huang Changjun , Zhang Zhongkai , Kormelink Richard , Tao Xiaorong
Published: April 2023

Orthotospoviruses are agriculturally important negative-strand RNA viruses and cause severe yield-losses on many crops worldwide. Whereas the emergence of new animal-infecting bunyaviruses is frequently associated with genetic reassortants, this issue remains underexposed with the plant-infecting orthotospovirus.
Quantifying Shared and Unique Gene Content across 17 Microbial Ecosystems
Authors: Zimmerman Samuel , Tierney Braden T. , Patel Chirag J. , Kostic Aleksandar D.
Published: April 2023

The amount of shared genetic elements has not been quantified between the human microbiome and other host- and non-host-associated microbiomes. Here, we made a gene catalog of 17 different microbial ecosystems and compared them.
Shiga Toxin (Stx) Phage-Encoded Lytic Genes Are Not Required for the Mouse Virulence of O157:H7 Escherichia coli Stx2-Producing Clinical Isolates
Authors: Atitkar R. R. , Hauser J. R. , Melton-Celsa A. R.
Published: April 2023

The release of Stx from STEC has been thought to be tied to phage-mediated lysis of the host bacterial cell. In this study, we found that the
stx
2a
phage lytic genes are not required for the virulence of pathogenic O157:H7 clinical isolates in a murine model of STEC infection or for release of Stx2a into the supernatant of bacterial cultures. These results point to an alternate mechanism for Stx2a release from STEC strains.
Comparison of Treatment Outcomes of Cavitary Mycobacterium avium Complex Pulmonary Disease with Streptomycin or Amikacin Use
Authors: Kim Seong Min , Chong Yong Pil , Lee Hyun Joo , Shim Tae Sun , Jo Kyung-Wook
Published: April 2023

We found that among the participants with cavitary MAC-PD who received guideline-based treatment for ≥1 year, the selection of either streptomycin or amikacin in the treatment regimen led to similar rates of culture conversion at treatment completion. In addition, the adverse reaction development rate did not differ significantly for streptomycin and amikacin.
Gut Microbiota Contribution to Weight-Independent Glycemic Improvements after Gastric Bypass Surgery
Authors: Hankir Mohammed K. , Kovatcheva-Datchary Petia , Springer Rebecca , Hoffmann Annett , Vogel Jörg , Seyfried Florian , Arora Tulika
Published: April 2023

Metabolic surgery remains the most effective treatment modality for severe obesity and its comorbidities, including type 2 diabetes. Roux-en-Y gastric bypass (RYGB) is a commonly performed type of metabolic surgery that reconfigures gastrointestinal anatomy and profoundly remodels the gut microbiota.
Mineralization and genesis of the orogenic gold system in the Kalamaili area, East Junggar, Xinjiang, northwestern China
Authors: Gu Xuexiang , Zhang Yongmei , Ge Zhanlin , Chen Weizhi
Published: April 2023

There are many lode gold deposits and occurrences in the Kalamaili area of the East Junggar, northwestern China. However, little is known about the specifics of ore geology and geochemistry of these gold deposits because of very limited exploration and research work in this region. Field geology, fluid inclusions, stable isotopes, trace elements in quartz, and hydrothermal zircon U-Pb dating are combined in this study to constrain the nature and source of ore fluids, the timing of mineralization, and the mechanism of gold precipitation in Kalamaili. The gold deposits are confined to a narrow zone between two regional NW- to NWW-trending shear zones and are structurally controlled by secondary, high-angle faults of the shears. The orebodies occur in the Middle Devonian and Lower Carboniferous, zeolite to lower greenschist facies clastic sedimentary and pyroclastic rocks. Gold mineralization occurs as auriferous quartz-sulfide ± tourmaline veins/veinlets and disseminated ores in the immediate altered wall rocks. The ore mineralogy is relatively simple and dominated by quartz with minor to trace amounts of sulfides (pyrite and arsenopyrite), sericite, calcite, and native gold. Quartz of various generations contains three types of fluid inclusions, including predominant H2O-CO2-NaCl inclusions and subordinate H2O-NaCl inclusions and CO2 ± CH4 ± N2 inclusions. The mineralizing fluid is uniformly characterized by a medium to high homogenization temperature (mostly 240−330 °C), low salinity (typically <6 wt% NaCl equivalent), reduced, and CO2-rich-H2O-NaCl ± CH4 fluid. The hydrogen and oxygen isotope data (δ18OH2O = +5.6‰ to +14.3‰, δDH2O = −99‰ to −62‰) indicate a metamorphic origin for the mineralizing fluid. The majority of sulfide δ34S values range between 0‰ and +10‰, indicative of a largely sedimentary rock reservoir of sulfur in the ore-forming fluids. Geochemically, the auriferous quartz is characterized by low concentrations of most trace elements including Ti, Al, Li, Ge, and Sb. Laser ablation−inductively coupled plasma−mass spectrometry U-Pb isotope dating of hydrothermal zircons from the auriferous quartz vein yielded a weighted mean 206Pb/238U age of ca. 313 Ma. Phase separation of ore fluids and fluid-rock interaction are suggested as key mechanisms for the gold precipitation. Integrated geological and geochemical evidence indicates that formation of the orogenic gold system in Kalamaili is related to the transition from compressional to transcurrent deformation during the Late Carboniferous. Target gold exploration in this region should focus on the northeast side of the Kalamaili fault zone, where there exist suitable structural and stratigraphic trap sites with high fluid flux and potential gold mineralization.
Dietary sugar consumption and health: umbrella review
Authors: Huang Yin , Chen Zeyu , Chen Bo , Li Jinze , Yuan Xiang , Li Jin , Wang Wen , Dai Tingting , Chen Hongying , Wang Yan , Wang Ruyi , Wang Puze , Guo Jianbing , Dong Qiang , Liu Chengfei , Wei Qiang , Cao Dehong , Liu Liangren
Published: April 2023

Objective

To evaluate the quality of evidence, potential biases, and validity of all available studies on dietary sugar consumption and health outcomes.

Design

Umbrella review of existing meta-analyses.

Data sources

PubMed, Embase, Web of Science, Cochrane Database of Systematic Reviews, and hand searching of reference lists.

Inclusion criteria

Systematic reviews and meta-analyses of randomised controlled trials, cohort studies, case-control studies, or cross sectional studies that evaluated the effect of dietary sugar consumption on any health outcomes in humans free from acute or chronic diseases.

Results

The search identified 73 meta-analyses and 83 health outcomes from 8601 unique articles, including 74 unique outcomes in meta-analyses of observational studies and nine unique outcomes in meta-analyses of randomised controlled trials. Significant harmful associations between dietary sugar consumption and 18 endocrine/metabolic outcomes, 10 cardiovascular outcomes, seven cancer outcomes, and 10 other outcomes (neuropsychiatric, dental, hepatic, osteal, and allergic) were detected. Moderate quality evidence suggested that the highest versus lowest dietary sugar consumption was associated with increased body weight (sugar sweetened beverages) (class IV evidence) and ectopic fatty accumulation (added sugars) (class IV evidence). Low quality evidence indicated that each serving/week increment of sugar sweetened beverage consumption was associated with a 4% higher risk of gout (class III evidence) and each 250 mL/day increment of sugar sweetened beverage consumption was associated with a 17% and 4% higher risk of coronary heart disease (class II evidence) and all cause mortality (class III evidence), respectively. In addition, low quality evidence suggested that every 25 g/day increment of fructose consumption was associated with a 22% higher risk of pancreatic cancer (class III evidence).

Conclusions

High dietary sugar consumption is generally more harmful than beneficial for health, especially in cardiometabolic disease. Reducing the consumption of free sugars or added sugars to below 25 g/day (approximately 6 teaspoons/day) and limiting the consumption of sugar sweetened beverages to less than one serving/week (approximately 200-355 mL/week) are recommended to reduce the adverse effect of sugars on health.

Systematic review registration

PROSPERO CRD42022300982.
Association of hemoglobin A1c stability with mortality and diabetes complications in older adults with diabetes
Authors: Conlin Paul R , Zhang Libin , Li Donglin , Nelson Richard E , Prentice Julia C , Mohr David C
Published: April 2023

Introduction

Hemoglobin A1c (A1c) treatment goals in older adults should be individualized to balance risks and benefits. It is unclear if A1c stability over time within unique target ranges also affects adverse outcomes.

Research design and methods

We conducted a retrospective observational cohort study from 2004 to 2016 of veterans with diabetes and at least four A1c tests during a 3-year baseline. We generated four distinct categories based on the percentage of time that baseline A1c levels were within patient-specific target ranges: ≥60% time in range (TIR), ≥60% time below range (TBR), ≥60% time above range (TAR), and a mixed group with all times <60%. We assessed associations of these categories with mortality, macrovascular, and microvascular complications.

Results

We studied 397 634 patients (mean age 76.9 years, SD 5.7) with an average of 5.5 years of follow-up. In comparison to ≥60% A1c TIR, mortality was increased with ≥60% TBR, ≥60% TAR, and the mixed group, with HRs of 1.12 (95% CI 1.11 to 1.14), 1.10 (95% CI 1.08 to 1.12), and 1.06 (95% CI 1.04 to 1.07), respectively. Macrovascular complications were increased with ≥60% TBR and ≥60% TAR, with estimates of 1.04 (95% CI 1.01 to 1.06) and 1.06 (95% CI 1.03 to 1.09). Microvascular complications were lower with ≥60% TBR (HR 0.97, 95% CI 0.95 to 1.00) and higher with ≥60% TAR (HR 1.11, 95% CI 1.08 to 1.14). Results were similar with higher TIR thresholds, shorter follow-up, and competing risk of mortality.

Conclusions

In older adults with diabetes, mortality and macrovascular complications are associated with increased time above and below individualized A1c target ranges. Higher A1c TIR may identify patients with lower risk of adverse outcomes.
Prevalence estimates of major depressive disorder in 27 European countries from the European Health Interview Survey: accounting for imperfect diagnostic accuracy of the PHQ-8
Authors: Fischer Felix , Zocholl Dario , Rauch Geraldine , Levis Brooke , Benedetti Andrea , Thombs Brett , Rose Matthias , Kostoulas Polychronis
Published: April 2023

Background

Cut-offs on self-report depression screening tools are designed to identify many more people than those who meet criteria for major depressive disorder. In a recent analysis of the European Health Interview Survey (EHIS), the percentage of participants with Patient Health Questionnaire-8 (PHQ-8) scores ≥10 was reported as major depression prevalence.

Objective

We used a Bayesian framework to re-analyse EHIS PHQ-8 data, accounting for the imperfect diagnostic accuracy of the PHQ-8.

Methods

The EHIS is a cross-sectional, population-based survey in 27 countries across Europe with 258 888 participants from the general population. We incorporated evidence from a comprehensive individual participant data meta-analysis on the accuracy of the PHQ-8 cut-off of ≥10. We evaluated the joint posterior distribution to estimate the major depression prevalence, prevalence differences between countries and compared with previous EHIS results.

Findings

Overall, major depression prevalence was 2.1% (95% credible interval (CrI) 1.0% to 3.8%). Mean posterior prevalence estimates ranged from 0.6% (0.0% to 1.9%) in the Czech Republic to 4.2% (0.2% to 11.3%) in Iceland. Accounting for the imperfect diagnostic accuracy resulted in insufficient power to establish prevalence differences. 76.4% (38.0% to 96.0%) of observed positive tests were estimated to be false positives. Prevalence was lower than the 6.4% (95% CI 6.2% to 6.5%) estimated previously.

Conclusions

Prevalence estimation needs to account for imperfect diagnostic accuracy.

Clinical implications

Major depression prevalence in European countries is likely lower than previously reported on the basis of the EHIS survey.
Burden experienced by informal caregivers of children with sickle cell disease (SCD): a qualitative exploratory study at Tamale Teaching Hospital, Ghana
Authors: Mumuni Najart Deborah , Osman Wahab , Alhassan Basour Adam , Alhassan Afizu
Published: April 2023

Objective

This study sought to explore the burden experienced by informal caregivers in caring for their children with sickle cell disease (SCD).

Design

A qualitative exploratory design was employed in the study using in-depth interviews.

Setting

The study was conducted at the sickle cell clinic of the Tamale Teaching Hospital, Ghana.

Participants

Data were gathered from 15 purposively selected informal caregivers, whose children with SCD received care at the sickle cell clinic of the Tamale Teaching Hospital, using a semistructured in-depth interview guide in May–June 2021. Their responses were audio-taped, transcribed and analysed using the reflexive thematic analysis approach.

Results

Five major themes emerged from data analysis. These were: the burden of children’s ill-health; financial burden; employment challenges; psychosocial burden and determinants of caregivers’ burden. These burdens destabilised the personal lives, financial standing, social relationships, and employment of caregivers in general and that of other immediate family members, thus, impacting family processes and health.

Conclusions

Health professionals must devise strategies for counselling, early diagnosis and effective management of children with SCD across Ghana. The Ministry of Health must subsidise medications and laboratory services for children with SCD to help minimise the financial burden on caregivers. Further, counselling and psychological support services must be established in hospitals to assist caregivers to cope effectively.
Codesigning a social prescribing pathway to address the social determinant of health concerns of children with cerebral palsy and their families in Australia: a protocol for a mixed-methods formative research study
Authors: Ostojic Katarina , Paget Simon , Martin Tanya , Dee-Price Betty-Jean , McIntyre Sarah , Smithers Sheedy Hayley , Mimmo Laurel , Burnett Heather , Scott Timothy , Berg Alison , Masi Anne , Scarcella Michele , Calderan Jack , Azmatullah Sheikh , Mohamed Masyitah , Woodbury Mackenzie , Wilkinson Alunya , Zwi Karen , Dale Russell , Eapen Valsamma , Lingam Raghu , Strnadová Iva , Woolfenden Susan
Published: April 2023

Introduction

Social determinants of health (SDH) are contributors to health inequities experienced by some children with cerebral palsy and pose barriers to families engaging with complex and fragmented healthcare systems. There is emerging evidence to support ‘social prescribing’ interventions that systematically identify SDH concerns and refer patients to non-medical social care support and services to address their needs. To date, social prescribing has not been trialled specifically for children with neurodevelopmental disabilities, including cerebral palsy, in Australia. This study aims to codesign a social prescribing programme to address SDH concerns of children with cerebral palsy and their families who attend one of the three tertiary paediatric rehabilitation services in New South Wales, Australia.

Methods and analysis

This is a qualitative multi-site study conducted at the three NSW paediatric hospitals’ rehabilitation departments using a codesign approach. Children aged 12–18 years with cerebral palsy, parents/caregivers of children (aged 0–18 years) with cerebral palsy, and clinicians will be involved in all stages to codesign the social prescribing programme. The study will consist of three components: (1) ‘what we need’, (2) ‘creating the pathways’ and (3) ‘finalising and sign off’. This project is overseen by two advisory groups: one group of young adults with cerebral palsy and one group of parents of young people with cerebral palsy. The study will be guided by the biopsychosocial ecological framework, and analysis will follow Braun and Clark’s thematic approach.

Ethics and dissemination

The study protocol was approved by the human research ethics committee of the Sydney Children’s Hospitals Network. This codesign study will inform a future pilot study of feasibility and acceptability, then if indicated, a pilot clinical trial of efficacy. We will collaborate with all project stakeholders to disseminate findings and undertake further research to build sustainable and scalable models of care.

Trial registration number

ACTRN12622001459718.
Study protocol of a phase 2, randomised, placebo-controlled, double-blind, adaptive, parallel group clinical study to evaluate the efficacy and safety of recombinant alpha-1-microglobulin in subjects at high risk for acute kidney injury following open-chest cardiac surgery (AKITA trial)
Authors: Mazer C David , Siadati-Fini Niloufar , Boehm Johannes , Wirth Felix , Myjavec Andrej , Brown Craig D , Koyner Jay L , Boening Andreas , Engelman Daniel T , Larsson Tobias E , Renfurm Ronny , de Varennes Benoit , Noiseux Nicolas , Thielmann Matthias , Lamy Andre , Laflamme Maxime , von Groote Thilo , Ronco Claudio , Zarbock Alexander
Published: April 2023

Introduction

Acute kidney injury (AKI) is a common complication after cardiac surgery (CS) and is associated with adverse short-term and long-term outcomes. Alpha-1-microglobulin (A1M) is a circulating glycoprotein with antioxidant, heme binding and mitochondrial-protective mechanisms. RMC-035 is a modified, more soluble, variant of A1M and has been proposed as a novel targeted therapeutic protein to prevent CS-associated AKI (CS-AKI). RMC-035 was considered safe and generally well tolerated when evaluated in four clinical phase 1 studies.

Methods and analysis

This is a phase 2, randomised, double-blind, adaptive design, parallel group clinical study that evaluates RMC-035 compared with placebo in approximately 268 cardiac surgical patients at high risk for CS-AKI. RMC-035 is administered as an intravenous infusion. In total, five doses will be given. Dosing is based on presurgery estimated glomerular filtration rate (eGFR), and will be either 1.3 or 0.65 mg/kg.

The primary study objective is to evaluate whether RMC-035 reduces the incidence of postoperative AKI, and key secondary objectives are to evaluate whether RMC-035 improves postoperative renal function compared with placebo. A blinded interim analysis with potential sample size reassessment is planned once 134 randomised subjects have completed dosing. An independent data monitoring committee will evaluate safety and efficacy data at prespecified intervals throughout the trial. The study is a global multicentre study at approximately 30 sites.

Ethics and dissemination

The trial was approved by the joint ethics committee of the physician chamber Westfalen-Lippe and the University of Münster (code ‘2021-778 f-A’) and subsequently approved by the responsible ethics committees/relevant institutional review boards for the participating sites. The study is conducted in accordance with Good Clinical Practice, the Declaration of Helsinki and other applicable regulations. Results of this study will be published in a peer-reviewed scientific journal.

Trial registration number

NCT05126303.
Hospitalisation profile in England and Wales, 1999 to 2019: an ecological study
Authors: Naser Abdallah Y
Published: April 2023

Objective

Hospital-related indicators are used to prioritise, benchmark and monitor certain healthcare components to improve quality. This study aimed to determine the hospital admissions profile in England and Wales between 1999 and 2019.

Design

Ecological study.

Setting

A population-based study of hospitalised patients in England and Wales.

Participants

All patients of all ages and genders who were hospitalised in National Health Service (NHS) hospitals and NHS-funded independent sector hospitals.

Outcome measure

Hospital admission rates in England and Wales related to various diseases/causes, which were identified using the diagnostic codes (A00-Z99).

Results

There was a 48.5% rise in hospital admission rates from 246 366.7 (95% CI 246 249.8 to 246 483.7) in 1999 to 365 858.7 (95% CI 365 736.3 to 365 981.2) in 2019 per million persons (p<0.05). The most common causes of hospital admissions were diseases of the digestive system; symptoms, signs, and abnormal clinical and laboratory findings; and neoplasms, which accounted for 11.5%, 11.4% and 10.5%, respectively. The age range of 15–59 years accounted for 43.4% of all hospital admissions. Around 56.0% of all hospital admissions were by female patients. In comparison to 1999, the hospital admission rate for males grew by 53.7%, from 218 363.7 (95% CI 218 203.2 to 218 524.3) to 335 618.9 (95% CI 335 448.1 to 335 789.6) per million persons in 2019. When compared with 1999, the hospital admission rate for females increased by 44.7%, rising from 273 032.5 (95% CI 272 863.5 to 273 201.5) to 395 154.6 (95% CI 394 979.9 to 395 329.4) per million persons.

Conclusion

A notable increase was observed in the rate of hospital admissions for all causes in England and Wales. Elderly age and female gender were significant factors that influenced the rate of hospital admissions. Future research is required to identify preventable risk factors for hospital admission.
Addressing food insecurity and chronic conditions in community health centres: protocol of a quasi-experimental evaluation of Recipe4Health
Authors: Rosas Lisa G , Chen Steven , Xiao Lan , Emmert-Aronson Benjamin O , Chen Wei-ting , Ng Elliot , Martinez Erica , Baiocchi Mike , Thompson-Lastad Ariana , Markle Elizabeth A , Tester June
Published: April 2023

Introduction

Chronic conditions, such as diabetes, obesity, heart disease and depression, are highly prevalent and frequently co-occur with food insecurity in communities served by community health centres in the USA. Community health centres are increasingly implementing ‘Food as Medicine’ programmes to address the dual challenge of chronic conditions and food insecurity, yet they have been infrequently evaluated.

Methods and analysis

The goal of this quasi-experimental study was to evaluate the effectiveness of Recipe4Health, a ‘Food as Medicine’ programme. Recipe4Health includes two components: (1) a ‘Food Farmacy’ that includes 16 weekly deliveries of produce and (2) a ‘Behavioural Pharmacy’ which is a group medical visit. We will use mixed models to compare pre/post changes among participants who receive the Food Farmacy alone (n=250) and those who receive the Food Farmacy and Behavioural Pharmacy (n=140). The primary outcome, fruit and vegetable consumption, and secondary outcomes (eg, food security status, physical activity, depressive symptoms) will be collected via survey. We will also use electronic health record (EHR) data on laboratory values, prescriptions and healthcare usage. Propensity score matching will be used to compare Recipe4Health participants to a control group of patients in clinics where Recipe4Health has not been implemented for EHR-derived outcomes. Data from surveys, EHR, group visit attendance and produce delivery is linked with a common identifier (medical record number) and then deidentified for analysis with use of an assigned unique study ID. This study will provide important preliminary evidence on the effectiveness of primary care-based strategies to address food insecurity and chronic conditions.

Ethics and dissemination

This study was approved by the Stanford University Institutional Review Board (reference protocol ID 57239). Appropriate study result dissemination will be determined in partnership with the Community Advisory Board.
Use of YouTube by academic medical centres during the COVID-19 pandemic: an observational study in Taiwan
Authors: Kuo Yen-Ling , Lin Ching-Heng , Wang Ya-Yu , Shieh Gow-Jen , Chu Wei-Min
Published: April 2023

Objectives

YouTube has been of immense importance in conveying essential information on COVID-19 and promoting the latest healthcare policies during the outbreak. However, there have been few studies that have focused on how healthcare organisations have used YouTube to communicate with the public and increase their awareness during the pandemic, as well as its effectiveness.

Design

A nationwide observational study.

Settings

We analysed all YouTube video posts culled from the official accounts of all medical centres in Taiwan from December 2019 to August 2021.

Participants

All YouTube videos were categorised as either COVID-19 or non-COVID-19 related. The COVID-19-related videos were divided into five categories, and detailed metrics for each video were recorded. For comparison, we also surveyed all YouTube video posts placed by the Ministry of Health and Welfare and the Taiwan Centers for Disease Control (TCDC).

Results

We analysed official YouTube channels from 17 academic medical centres, involving a total of 943 videos. We found a relationship between the quantity of YouTube videos uploaded by the TCDC and the trend of confirmed cases (Pearson’s correlation coefficient was 0.25, p=0.02). Data from private hospitals revealed that they posted more COVID-19 videos (103 vs 56) when compared with public hospitals. In addition, multivariate linear regression showed that more ‘likes’ (estimate 41.1, 95% CI 38.8 to 43.5) and longer lengths (estimate 10 800, 95% CI 6968.0 to 14 632.0) of COVID-19-related videos correlated significantly with an increased number of ‘views’.

Conclusions

This nationwide observational study, performed in Taiwan, demonstrates well the trend and effectiveness of academic medical centres in promoting sound healthcare advice regarding COVID-19 through YouTube due to the channel’s easy accessibility and usability.
Improving sleep and learning in rehabilitation after stroke, part 2 (INSPIRES2): study protocol for a home-based randomised control trial of digital cognitive behavioural therapy (dCBT) for insomnia
Authors: Weightman Matthew , Robinson Barbara , Fallows Ricky , Henry Alasdair L , Kyle Simon D , Garratt Emma , Pick Anton , Teal Rachel , Ajina Sara , Demeyere Nele , Espie Colin A , Seymour Ben , Johansen-Berg Heidi , Fleming Melanie K
Published: April 2023

Introduction

Consolidation of motor skill learning, a key component of rehabilitation post-stroke, is known to be sleep dependent. However, disrupted sleep is highly prevalent after stroke and is often associated with poor motor recovery and quality of life. Previous research has shown that digital cognitive behavioural therapy (dCBT) for insomnia can be effective at improving sleep quality after stroke. Therefore, the aim of this trial is to evaluate the potential for sleep improvement using a dCBT programme, to improve rehabilitation outcomes after stroke.

Methods and analysis

We will conduct a parallel-arm randomised controlled trial of dCBT (Sleepio) versus treatment as usual among individuals following stroke affecting the upper limb. Up to 100 participants will be randomly allocated (2:1) into either the intervention (6–8 week dCBT) or control (continued treatment as usual) group. The primary outcome of the study will be change in insomnia symptoms pre to post intervention compared with treatment as usual. Secondary outcomes include improvement in overnight motor memory consolidation and sleep measures between intervention groups, correlations between changes in sleep behaviour and overnight motor memory consolidation in the dCBT group and changes in symptoms of depression and fatigue between the dCBT and control groups. Analysis of covariance models and correlations will be used to analyse data from the primary and secondary outcomes.

Ethics and dissemination

The study has received approval from the National Research Ethics Service (22/EM/0080), Health Research Authority (HRA) and Health and Care Research Wales (HCRW), IRAS ID: 306 291. The results of this trial will be disseminated via presentations at scientific conferences, peer-reviewed publication, public engagement events, stakeholder organisations and other forms of media where appropriate.

Trial registration number

NCT05511285.
Association between the number of prehospital defibrillation attempts and a sustained return of spontaneous circulation: a retrospective, multicentre, registry-based study
Authors: Ko Byuk Sung , Kim Youn-Jung , Han Kap Su , Jo You Hwan , Shin JongHwan , Park Incheol , Kang Hyunggoo , Lim Tae Ho , Hwang SO , Kim Won Young
Published: April 2023

Background

Currently, there is no consensus on the number of defibrillation attempts that should be made before transfer to a hospital in patients with out-of-hospital cardiac arrest (OHCA). This study aimed to evaluate the association between the number of defibrillations and a sustained prehospital return of spontaneous circulation (ROSC).

Methods

A retrospective analysis of a multicentre, prospectively collected, registry-based study in Republic of Korea was conducted for OHCA patients with prehospital defibrillation. The primary outcome was sustained prehospital ROSC, and the secondary outcome was a good neurological outcome at hospital discharge, defined as Cerebral Performance Category score 1 or 2. Cumulative incidence of sustained prehospital ROSC and good neurological outcome according to number of defibrillations were examined. Multivariable logistic regression analysis was used to examine whether the number of defibrillations was independently associated with the outcomes.

Results

Excluding 172 patients with missing data, a total of 1983 OHCA patients who received prehospital defibrillation were included. The median time from arrest to first defibrillation was 10 (IQR 7–15) min. The numbers of patients with sustained prehospital ROSC and good neurological outcome were 738 (37%) and 549 (28%), respectively. Sustained ROSC rates decreased as the number of defibrillation attempts increased from the first to the sixth (16%, 9%, 5%, 3%, 2% and 1%, respectively). The cumulative sustained ROSC rate, and good neurological outcome rate from initial defibrillation to sixth defibrillation were 16%, 25%, 30%, 34%, 36%, 36% and 11%, 18%, 22%, 25%, 26%, 27%, respectively. With adjustment for clinical characteristics and time to defibrillation, a higher number of defibrillations was independently associated with a lower chance of a sustained ROSC (OR 0.81, 95% CI 0.76 to 0.86) and a lower chance of good neurological outcome (OR 0.86, 95% CI 0.80 to 0.92).

Conclusions

We observed no significant increase in ROSC after five defibrillations, and no absolute increase in ROSC after seven defibrillations. These data provide a starting point for determination of the optimal defibrillation strategy prior to consideration for prehospital extracorporeal cardiopulmonary resuscitation (ECPR) or conveyance to a hospital with an ECPR capability.

Trial registration number

NCT03222999
Association of Life’s Simple 7 and ideal cardiovascular health in American Indians/Alaska Natives
Authors: Rawal Smita , Johnson Blake Ryan , Young Henry Nolan , Gaye Bamba , Sattler Elisabeth Lilian Pia
Published: April 2023

Objective

American Indians and Alaska Natives (AI/ANs) are an understudied population at high risk for cardiovascular diseases (CVDs); little is known about contextual factors contributing to CVDs in AI/ANs. This study examined the association of Life’s Simple 7 (LS7) factors and social determinants of health (SDH) with CVD outcomes in a nationally representative sample of AI/ANs.

Methods

We conducted a cross-sectional study of 8497 AI/ANs using 2017 Behavioural Risk Factor Surveillance Survey data. Individual LS7 factors were summarised as ideal and poor levels. Coronary heart disease, myocardial infarction and stroke were defined as CVD outcomes. Healthcare access measures represented SDH. Logistic regression analyses examined associations of LS7 factors and SDH with CVD outcomes. Population attributable fractions (PAFs) quantified individual contributions of LS7 factors to CVD outcomes.

Results

N=1,297 (15%) participants with CVD outcomes were identified. Smoking, physical inactivity, diabetes, hypertension and hyperlipidaemia were LS7 factors associated with CVD outcomes. Hypertension was the largest contributor to CVD (aPAF 42%; 95% CI 37% to 51%), followed by hyperlipidaemia (aPAF 27%; 95% CI 17% to 36%) and diabetes (aPAF 18%; 95% CI 7% to 23%). Compared with individuals with poor LS7 levels, participants with ideal levels showed 80% lower odds of CVD outcomes (aOR 0.20; 95% CI 0.16 to 0.25). Access to health insurance (aOR 1.43, 95% CI 1.08 to 1.89) and a regular care provider (aOR 1.47, 95% CI 1.24 to 1.76) were associated with CVD outcomes.

Conclusions

Effective interventions are needed to address SDH and attain ideal LS7 factors to improve cardiovascular health among AI/ANs.
Contralateral oblique view can prevent dural puncture in fluoroscopy-guided cervical epidural access: a prospective observational study
Authors: Kwon Hyun-Jung , Kim Chan-Sik , Kim Jinsun , Kim Sungwon , Shin Jae Young , Choi Seong-Soo , Shin Jin-Woo , Kim Doo-Hwan
Published: April 2023

Introduction

Although the contralateral oblique (CLO) view at 50°±5° is clinically useful for cervical epidural access, no previous studies have confirmed its safety. This prospective observational study was conducted to assess the safety profile, including the risk of dural puncture, in fluoroscopically guided cervical epidural access using the CLO view.

Methods

In cervical epidural access using the CLO view, the incidence of dural puncture was investigated as the primary outcome. Other intraprocedural complications, including intravascular entry, subdural entry, spinal cord injury and vasovagal injury, and postprocedural complications were investigated as secondary outcomes. Procedural variables including first-pass success, final success, needling time, total number of needle passes and false loss of resistance (LOR) were evaluated.

Results

Of the 393 patients who underwent cervical interlaminar epidural access were included for analysis, no instances of dural puncture or spinal cord injury were observed. The incidence of intravascular entry, vasovagal reaction and subdural entry were 3.1%, 0.5% and 0.3%, respectively. All procedures were successfully performed, with 85.0% of first-pass success rate. The mean needling time was 133.8 (74.9) s. The false-positive and false-negative LOR rates were 8.2% and 2.0%, respectively. All needle tips were visualized clearly during the procedure.

Conclusions

The fluoroscopy-guided CLO view at 50°±5° avoided dural puncture or spinal cord injury and decreased the incidence of false LOR during cervical epidural access with a paramedian approach.

Trial registration number

NCT04774458.
Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy postoperative symptomatology: palliative care impact
Authors: Sneider Abigail P , Dhiman Ankit , Morgan Ryan , Tun Sandy , Turaga Kiran K , Eng Oliver S
Published: April 2023

Objectives

Palliative care (PC) for patients with advanced cancer has been associated with improved symptom burden and quality of life (QoL). This study aimed to characterise postoperative symptoms of cytoreductive surgery (CRS)/hyperthermic intraperitoneal chemotherapy (HIPEC) patients and to assess PC impact by analysing symptom burden before and after PC interventions.

Methods

CRS/HIPEC patients with two PC visits within 5 months postoperatively (2016–2021) at a tertiary care centre were identified from a retrospective database. For each patient, documentation of QoL-associated symptoms at the initial PC visit and changes in symptomatology at the second PC visit were recorded. Descriptive statistics were performed.

Results

46 patients were included in this study. Median age was 62.2 (range 31.9–84.6) years. Median peritoneal cancer index was 23.5 (range 0–39). The most common histologies were colorectal (32.6%) and appendiceal (30.4%). Symptoms most frequently reported were pain (84.8%), fatigue (54.3%) and appetite loss/change (52.2%). Following PC interventions, most symptoms were stable or improved. The mean number of symptoms per patient was 3.7, with an average of 3.5 improved/stable and 0.5 worse/new onset at follow-up (p<0.001).

Conclusion

CRS/HIPEC patients experienced a high QoL-associated symptom burden. Following postoperative PC interventions, significantly more symptoms were reported as improved/stable, compared with worse/new onset.
Evidence of $$A_{CP}(D^0\rightarrow \pi ^+\pi ^-)$$ implies observable CP asymmetry in the $$D^0\rightarrow \pi ^0\pi ^0$$ decay
Authors: Wang Di
Published: April 2023

Inspired by the recent measurement of CP asymmetry in the individual mode on LHCb, we study CP asymmetry of the $$D\rightarrow \pi \pi $$

D
→
π
π

system in the isospin and topological analysis. The ratio between penguin and tree amplitudes $$P/(T+C)$$

P
/
(
T
+
C
)

in the $$D\rightarrow \pi \pi $$

D
→
π
π

system is found to be greater than two in most values of the relative strong phase. And $$D^0\rightarrow \pi ^0\pi ^0$$

D
0

→

π
0

π
0

is a potential mode to reveal the CP asymmetry of the order of $$10^{-3}$$

10

-
3

, which would be observed by Belle II in the future. The large CP asymmetry in the $$D\rightarrow \pi \pi $$

D
→
π
π

system might be understood in the t-channel final-state interaction.
Dusty plasma in active galactic nuclei
Authors: Czerny Bożena , Zajaček Michal , Naddaf Mohammad-Hassan , Sniegowska Marzena , Panda Swayamtrupta , Różanska Agata , Adhikari Tek P. , Pandey Ashwani , Jaiswal Vikram Kumar , Karas Vladimír , Borkar Abhijeet , Martínez-Aldama Mary Loli , Prince Raj
Published: April 2023

For many years we have known that dust in the form of a dusty-molecular torus is responsible for the obscuration in active galactic nuclei (AGN) at large viewing angles and, thus, for the widely used phenomenological classification of AGN. Recently, we gained new observational and theoretical insights into the geometry of the torus region and the role of dust in the dynamics of emerging outflows and failed winds. We will briefly touch on all these aspects and provide a more detailed update of our dust-based model (FRADO—Failed Radiatively Accelerated Dusty Outflow) capable of explaining the processes of formation of Balmer lines in AGN.

Graphic abstract