bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical study of six patients with pure dysarthria and dysarthria—(Central) facial nerve palsy/isolated central facial nerve palsy caused by extracerebellar infarction
Authors: Ogawa Katsuhiko , Akimoto Takayoshi , Hara Makoto , Fujishiro Midori , Nakajima Hideto
Published: October 2023

Background

The corticobulbar tract (CBT) exerts bilateral supply to the cerebral nuclei. The cerebellar motor circuit controls the coordination and regulation of voluntary movements including speech function, and consists of input and feedback pathways including the parietopontine fibers (PPFs) which descend along with the CBT.

Aim

The pathogenesis of dysarthria caused by ischemic extracerebellar lesions was studied.

Methods

Six patients with extracerebellar lesions comprising two patients with pure dysarthria, three patients with dysarthria—(central) facial nerve palsy, and one patient with isolated central facial paresis were enrolled.

Results

Lesions were located in the corona radiata in four patients and the posterior limb of the internal capsule (PLIC) in two patients. Lesions were lateralized on the right side in three patients and the left side in three patients. Lesions in the corona radiata and the PLIC included the middle parts where the CBT exists.

Conclusions

Based on the hypothesis of bilateral supply to the cerebral nuclei for speech function through the cerebellar motor circuit, it was explicable that unilateral involvement of the PPFs caused dysfunction of the bilateral CBT, which led to the incidence of dysarthria in our case series. Involvement of the PPFs might play a crucial role in the incidence of dysarthria caused by ischemic extracerebellar lesions.
Extreme drought can deactivate ABA biosynthesis in embolism‐resistant species
Authors: Mercado‐Reyes Joel A. , Pereira Talitha Soares , Manandhar Anju , Rimer Ian M. , McAdam Scott A. M.
Published: October 2023

The phytohormone abscisic acid (ABA) is synthesised by plants during drought to close stomata and regulate desiccation tolerance pathways. Conifers and some angiosperms with embolism‐resistant xylem show a peaking‐type (p‐type) response in ABA levels, in which ABA levels increase early in drought then decrease as drought progresses, declining to pre‐stressed levels. The mechanism behind this dynamic remains unknown. Here, we sought to characterise the mechanism driving p‐type ABA dynamics in the conifer Callitris rhomboidea and the highly drought‐resistant angiosperm Umbellularia californica. We measured leaf water potentials (Ψl), stomatal conductance, ABA, conjugates and phaseic acid (PA) levels in potted plants during a prolonged but non‐fatal drought. Both species displayed a p‐type ABA dynamic during prolonged drought. In branches collected before and after the peak in endogenous ABA levels in planta, that were rehydrated overnight and then bench dried, ABA biosynthesis was deactivated beyond leaf turgor loss point. Considerable conversion of ABA to conjugates was found to occur during drought, but not catabolism to PA. The mechanism driving the decline in ABA levels in p‐type species may be conserved across embolism‐resistant seed plants and is mediated by sustained conjugation of ABA and the deactivation of ABA accumulation as Ψl becomes more negative than turgor loss.
Multicenter Canadian case series of pediatric patients less than 12 years of age with moderate‐to‐severe atopic dermatitis treated with dupilumab
Authors: Martinez‐Cabriales Sylvia , Marcoux Danielle , Liy‐Wong Carmen , Prajapati Vimal H. , Sibbald Cathryn , Cunningham Natalie , Lansang Perla , Tonkin Rochelle , Joseph Marissa , Wong Lauren , Spring Shanna , Gavigan Genevieve , Ramien Michele
Published: October 2023

Background

Dupilumab is approved for moderate‐severe atopic dermatitis (AD) in patients aged ≥6 months by the US Food and Drug Administration and Health Canada; however, there are little real‐world data because providers have limited practical experience with this recently approved therapy.

Objectives

To describe the real‐world effectiveness and safety in patients aged <12 years with moderate‐severe AD currently receiving or previously having received dupilumab.

Methods

A multicenter retrospective study was conducted at six Canadian sites. Cases were divided into Group 1 ≤2 years old, Group 2 >2 to <6 years old, and Group 3 ≥6 to <12 years old. Medical history and details of dupilumab treatment were collected. The primary outcome was to measure the improvement in eczema area and severity index. Secondary outcomes examined included the children's dermatology life quality index/infant's dermatitis quality of life, peak pruritus numerical rating scale, and delay to dupilumab access for patients who were considered off‐label for dupilumab due to their age.

Results

Sixty three pediatric patients (37 males) with moderate‐to‐severe AD were included; the mean age was 6.4 years old (range: 2–11) when dupilumab treatment was started. Overall, 75% (36/48) achieved EASI‐75% and 71% (34/48) achieved EASI‐90. EASI‐75 and EASI‐90 were achieved in 90% (17/19) and 73% (12/19) in patients <6 years old, and 76% (22/29) and 59% (17/29) in patients >6 years old, respectively. No serious adverse events were reported.

Conclusions

Dupilumab is safe and effective for patients under the age of 12. However, even for experienced providers, access to the medication was challenging.
PcENO3 interacts with patchoulol synthase to positively affect the enzymatic activity and patchoulol biosynthesis in Pogostemon cablin
Authors: Wu Daidi , Chen Lang , Zhong Baiyang , Zhang Zhongsheng , Huang Huiling , Gong Lizhen , Zou Xuan , Zhan Ruoting , Chen Likai
Published: October 2023

Patchouli alcohol, a significant bioactive component of the herbal plant Pogostemon cablin, has considerable medicinal and commercial potential. Several genes and transcription factors involved in the biosynthesis pathway of patchouli alcohol have been identified. However, so far, regulatory factors directly interacting with patchouli synthase (PTS) have not been reported. This study was conducted to analyze the interaction between PcENO3 and PcPTS to explore the molecular regulation effect of PcENO3 on patchouli alcohol biosynthesis. PcENO3, a homologous protein of Arabidopsis ENO3 belonging to the enolase family, was identified and characterized. Subcellular localization experiments in Arabidopsis protoplast cells indicated that the PcENO3 protein was localized in both the cytoplasm and nucleus. The physical interaction between PcENO3 and PcPTS was confirmed through yeast two‐hybrid (Y2H), GST pull‐down, and bimolecular fluorescence complementation assays. Furthermore, the Y2H assay demonstrated that PcENO3 could also interact with JAZ proteins in the JA pathway. Enzymatic assays showed that the interaction with PcENO3 increased the catalytic activity of patchoulol synthase. Additionally, suppression of PcENO3 expression with VIGS (virus‐induced gene silencing) decreased patchouli alcohol content compared to the control. These findings suggest that PcENO3 interacts with patchoulol synthase and modulates patchoulol biosynthesis by enhancing the enzymatic activity of PcPTS.
Genetic improvement of oysters: Current status, challenges, and prospects
Authors: Jiang Kunyin , Chen Chen , Jiang Gaowei , Chi Yong , Xu Chengxun , Kong Lingfeng , Yu Hong , Liu Shikai , Li Qi
Published: October 2023

Oysters are one of the most commercially important shellfish species and have been cultured for thousands of years. Oyster aquaculture supports the major aquaculture industries in many countries. Over the last few decades, the oyster breeding and aquaculture industries have developed rapidly to meet the continually growing demand. Many researchers have made significant efforts toward the genetic improvement of commercially important traits in oysters. Some strains with fast‐growing, disease‐resistant, and stable shell‐colours have been developed through selective breeding. Some hybrid varieties have been developed by crossing different geographical populations or cultivated strains. Several hybrids exhibit considerable genetic variation and improved productive performance. Additionally, polyploid induction technologies have been applied in the oyster aquaculture industry, which provides a useful tool for performance improvement and genetic containment of cultured stocks. At present, the development of molecular breeding also provides a great opportunity for oyster genetic improvement. These advances in oyster breeding have improved the quality of oysters, brought great economic benefits, and been conducive to the sustainability of oyster production. Nonetheless, there are still some limitations and obstacles in oyster breeding, such as infectious diseases, summer mortality, conservation of germplasm resources, environmental contamination, and climate change. The present review provides an overview of the current status, challenges, and prospects in oyster breeding.
Plane–strain condition in plane–strain grooved tensile (PSGT) specimens during traction and creep loading at room and high temperature
Authors: Ovalle C. , Broudin M. , Laiarinandrasana L.
Published: October 2023

ISO 23228:2011 proposed a testing method in which the plastic material, experimental resins or compounds for pipes and fittings, can be exposed to stress conditions that mimic internally pressurised end‐capped pipes. The stress conditions are mimicked by the use of a plaque specimen having a grooved reduced section called plane–strain grooved tensile (PSGT) specimens producing a biaxial state of stress under uniaxial loading. In this study, PSGT specimens were cut out from high‐density polyethylene (HDPE) pipes. Two shape ratios, ratio between the width and the groove thickness, were used. Both the axial and transverse displacements and strain fields were followed by a digital image correlation (DIC) camera during tensile and creep loading, both at room and high temperature; furthermore, DIC images were used to estimate the notch opening displacement. The increasing effect of the temperature in both the axial and transverse displacement and strain was highlighted. No significant effect of the width was noticed. The results have evidenced that, as the plane–strain condition in the width is assured during the tests, PSGT specimens can be used to mimic internally pressurised pipes under monotonic increasing or constant‐in‐time loading at both room and high temperature, but it must be better to use specimens with a higher shape ratio, that is, higher width. The results contribute to the 9th Sustainable Development Goal: Industry, Innovation and Infrastructure by promoting a sustainable industrialisation and fostering innovation.
Lessons learned: Development of an organ transplant caregiver educational resource
Authors: Bruschwein Heather , Chen Gloria , Balliet Wendy , Hart Jan , Canavan Kelley , Jesse Michelle
Published: October 2023

Background

Organ transplant lay caregivers perform an essential and complex role, but there is a paucity of comprehensive, accessible education regarding transplant caregiving. We sought to create a broad, multifaceted educational toolkit for transplant caregivers. Given the complexities of this population, we report on lessons learned by organising diverse stakeholder engagement to develop an educational resource covering the breadth and depth of organ transplantation.

Approach

Following a call from organ transplant patients and caregivers, the American Society of Transplantation (AST) formed an Organ Transplant Caregiver Initiative with the aim to develop a comprehensive educational toolkit for transplant caregivers. The AST Organ Transplant Caregiver Toolkit was created through a shared, multi‐step process involving transplant professionals and caregivers, who formed an education subcommittee to develop and refine content domains. The caregiver toolkit was reviewed with relevant external stakeholders and through an internal organisational review process.

Evaluation

Lessons learned included seeking guidance from others with experience creating similar resources, flexibility in project development, creativity in engaging stakeholders and routine communication between all entities involved. Insights gained contributed to the caregiver toolkit completion despite project challenges.

Implications

The AST Organ Transplant Caregiver Toolkit can be utilised by health care professionals to educate and counsel transplant patients and caregivers. Lessons learned from the development of the caregiver toolkit can provide guidance to health care professionals and clinical teachers for the development of future education resources.
III–V semiconductor devices grown by metalorganic chemical vapor deposition—The development of the Swiss Army Knife for semiconductor epitaxial growth
Authors: Dupuis Russell D.
Published: October 2023

Metalorganic chemical vapor deposition (MOCVD) epitaxial materials technology for the growth of compound semiconductors has been developed over the past 60-plus years to become the dominant process for both research and production of light-emitting devices as well as many other electronic and optoelectronic devices. Today, MOCVD has become the “Swiss Army Knife” of semiconductor epitaxial growth, covering a wide variety of compound semiconductors and device applications. Because of the flexibility and control offered by this process and the material quality produced by MOCVD, many important III–V semiconductor devices have become commercially viable. This paper attempts to provide a personal view of the early development of MOCVD and some brief historical discussion of this important and highly versatile materials technology for the growth of high-quality devices employing ultrathin layers and heterojunctions of III–V compound semiconductors, e.g., quantum-well lasers, light-emitting diodes, heterojunction solar cells, transistors, and photonic integrated circuits.
Altering under-represented DNA sequences elevates bacterial transformation efficiency
Authors: Hu Shuai , Giacopazzi Stefani , Modlin Ryan , Karplus Kevin , Bernick David L. , Ottemann Karen M.
Published: October 2023

A cornerstone of bacterial molecular biology is the ability to genetically manipulate the microbe under study. Many bacteria are difficult to manipulate genetically, a phenotype due in part to robust removal of newly acquired DNA, for example, by restriction-modification (R-M) systems. Here, we report approaches that dramatically improve bacterial transformation efficiency, piloted using a microbe that is challenging to transform due to expression of many R-M systems,
Helicobacter pylori
. Initially, we identified conditions that dampened expression of several R-M systems and concomitantly enhanced transformation efficiency. We then identified an approach that would broadly protect newly acquired DNA. We computationally predicted under-represented short DNA sequences in the
H. pylori
genome, with the idea that these sequences reflect targets of sequence-based surveillance such as R-M systems. We then used this information to modify and eliminate such sites in antibiotic resistance cassettes, creating a “stealth” version. Modifying antibiotic resistance cassettes in this way resulted in significantly higher transformation efficiency compared to non-modified cassettes, a response that was genomic loci independent. Our results suggest that avoiding R-M systems, via modification of under-represented DNA sequences or transformation conditions, is a powerful method to enhance DNA transformation. Our approach to identify under-represented sequences is applicable to any microbe with a sequenced genome.

IMPORTANCE

Manipulating the genomes of bacteria is critical to many fields. Such manipulations are made by genetic engineering, which often requires new pieces of DNA to be added to the genome. Bacteria have robust systems for identifying and degrading new DNA, some of which rely on restriction enzymes. These enzymes cut DNA at specific sequences. We identified a set of DNA sequences that are missing normally from a bacterium’s genome, more than would be expected by chance. Eliminating these sequences from a new piece of DNA allowed it to be incorporated into the bacterial genome at a higher frequency than new DNA containing the sequences. Removing such sequences appears to allow the new DNA to fly under the bacterial radar in “stealth” mode. This transformation improvement approach is straightforward to apply and likely broadly applicable.
Rotavirus capping enzyme VP3 inhibits interferon expression by inducing MAVS degradation during viral replication
Authors: Dai Jin , Agbemabiese Chantal A. , Griffin Ashley N. , Patton John T.
Published: October 2023

The binding of viral RNA to RIG-I-like receptors triggers the formation of mitochondrial antiviral signaling (MAVS) protein aggregates critical for interferon (IFN) expression. Several rotavirus strains have been shown to suppress IFN expression by inducing MAVS degradation. Relying on transient expression assays, previous studies reached different conclusions regarding the identity of the rotavirus protein responsible for MAVS degradation, suggesting it was an activity of the rotavirus capping enzyme VP3 or the interferon antagonist NSP1. Here, we have used recombinant SA11 rotaviruses to identify the endogenous viral protein responsible for MAVS degradation and to analyze how the attack on MAVS impacts IFN expression. The recombinant viruses included those expressing modified VP3 or NSP1 proteins deficient in the ability to induce the degradation of MAVS or interferon regulatory factor-3 (IRF3), or both. With these viruses, we determined that VP3 directs the proteasomal degradation of MAVS but plays no role in IRF3 degradation. Moreover, NSP1 was determined to induce IRF3 degradation but to have no impact on MAVS degradation. Analysis of rotavirus-infected cells indicated that IRF3 degradation was more efficient than MAVS degradation and that NSP1 was primarily responsible for suppressing IFN expression in infected cells. However, VP3-mediated MAVS degradation contributed to IFN suppression in cells that failed to produce functional NSP1, pointing to a subsidiary role for VP3 in the IFN antagonist activity of NSP1. Thus, VP3 is a multifunctional protein with several activities that counter anti-rotavirus innate immune responses, including capping of viral (+)RNAs, hydrolysis of the RNase L 2–5A (2′−5′ oligoadenylate) signaling molecule, and proteasomal degradation of MAVS.

IMPORTANCE

Rotavirus is an enteric RNA virus that causes severe dehydrating gastroenteritis in infants and young children through infection of enterocytes in the small intestine. Timely clearance of the virus demands a robust innate immune response by cells associated with the small intestine, including the expression of interferon (IFN). Previous studies have shown that some rotavirus strains suppress the production of interferon, by inducing the degradation of mitochondrial antiviral signaling (MAVS) protein and interferon regulatory factor-3 (IRF3). In this study, we have used reverse genetics to generate recombinant rotaviruses expressing compromised forms of VP3 or NSP1, or both, to explore the function of these viral proteins in the degradation of MAVS and IRF3. Our results demonstrate that VP3 is responsible for MAVS depletion in rotavirus-infected cells, and through this activity, helps to suppress IFN production. Thus, VP3 functions to support the activity of rotavirus NSP1, the major interferon antagonist of the virus.
Complete genome sequence of
Bacillus thuringiensis
strain RC340, isolated from a temperate forest soil sample in New England
Authors: Sullivan Brendan , Kitzmiller Claire E. , Tran Wyatt C. , Choudoir Mallory , Simoes Rachel , Dayarathne Nipuni , DeAngelis Kristen M.
Published: October 2023

The complete genome sequence of
Bacillus thuringiensis
strain RC340, isolated from an environmental microbiology experiment soil sample is presented here.
B. thuringiensis
strain RC340 sequenced by GridION consists of a single genome consisting of 5.86 million bases, 8,152 predicted genes, and 0.23% contamination.
Complete genome sequences of microbacterium phages Tedro and BAjuniper
Authors: Anderson Grace M. , Anderson Olivia E. , Bosma Clayton A. , Brouwer Erin E. , DeGroot Kleyton M. , Hede Owen C. , Jonouchi Daiki , Kirkeby Dylan J. , Klinghagen Jayron T. , Kralik Kate J. , Kutz Julia S. , Lott Olivia F. , McKenney Erika J. , Pavik Victoria L. , Penner Cayli H. , Raymon Garrett , Rozeboom Leah B. , Skrien Jett L. , Slight Jessica K. , Stokes Maegan J. , Tiensvold Jonas D. , Wajer Kyra J. , Trevino Alaena L. , Noordewier Byron , Tolsma Sara S.
Published: October 2023

We purified two novel bacteriophages from soil collected in Sioux County, Iowa: BAjuniper and Tedro. These bacteriophages were isolated from the host,
Microbacterium foliorum
. BAjuniper was assigned to cluster EB, and Tedro was assigned to cluster EF. Both phages display genomes typical of other phages in their clusters.
The novel bacteriocin romsacin from
Staphylococcus haemolyticus
inhibits Gram-positive WHO priority pathogens
Authors: Wolden Runa , Ovchinnikov Kirill V. , Venter Hermoine J. , Oftedal Thomas F. , Diep Dzung B. , Cavanagh Jorunn Pauline
Published: October 2023

Staphylococcus haemolyticus
is an increasingly relevant nosocomial pathogen. The combination of multi-drug resistance and ability to form biofilms makes
S. haemolyticus
infections difficult to treat. Bacteriocins are ribosomally synthesized antimicrobial peptides produced by bacteria to inhibit growth of often closely related bacteria. Due to differences in the modes of action between bacteriocins and antibiotics, bacteriocins are normally equally potent against antibiotic-resistant and antibiotic-sensitive strains. To find bacteriocins able to inhibit
S. haemolyticus
and related species, clinical and commensal
S. haemolyticus
isolates (
n
= 174) were assayed for bacteriocin production. One commensal isolate produced an antimicrobial substance inhibiting
S. haemolyticus
and
Staphylococcus aureus
. The substance had physicochemical properties that are characteristic of bacteriocins. Purification, whole-genome sequencing, and mass spectrometry identified the antimicrobial as a novel two-peptide lantibiotic, hereafter named romsacin. The bacteriocin was active against a broad range of Gram-positive bacteria, such as the World Health Organization priority pathogens
S. aureus
[methicillin-resistant
S. aureus
(MRSA)] and
Enterococcus faecium
[vancomycin-resistant
E. faecium
(VRE)]. Importantly, the bacteriocin also eradicated
S. haemolyticus
,
Staphylococcus epidermidis
, MRSA, and VRE biofilms.

IMPORTANCE

Bacteria produce bacteriocins to inhibit growth of other bacterial species. We have studied the antimicrobial activity of a new bacteriocin produced by the skin bacterium
S. haemolyticus
. The bacteriocin is effective against several types of Gram-positive bacteria, including highly virulent and antibiotic-resistant strains such as
Staphylococcus aureus
and
Enterococcus faecium
. Effective antimicrobials are important for the treatment of infections and the success of major surgery and chemotherapy. Bacteriocins can be part of the solution to the global concern of antimicrobial resistance.
Machine learning to predict ceftriaxone resistance using single nucleotide polymorphisms within a global database of
Neisseria gonorrhoeae
genomes
Authors: Ha Sung Min , Lin Eric Y. , Klausner Jeffrey D. , Adamson Paul C.
Published: October 2023

Antimicrobial resistance (AMR) in
Neisseria gonorrhoeae
is an urgent global health issue. Machine learning (ML) is a powerful tool that can aid in identifying mutations and predicting their impact on AMR. The study aimed to use ML models to predict ceftriaxone susceptibility and decreased susceptibility (S/DS). A public database of
N. gonorrhoeae
genomes with minimum inhibitory concentration (MIC) data was used to evaluate seven ML models using 97 single nucleotide polymorphisms (SNPs) known to be associated with ceftriaxone resistance. Ceftriaxone MICs ≤ 0.064 mg/L were classified as susceptible, and ceftriaxoneMICs > 0.064 mg/L were classified as DS. The contributions of individual SNPs to predict S/DS were calculated using SHapley Additive exPlanation (SHAP) values. An ML model was retrained using different combinations of SNPs with the highest SHAP values. The performance of ML models was assessed using different metrics including area under the curve (AUC) and balanced accuracy (bAcc). The ML analyses included 9,540
N
.
gonorrhoeae
genomes; 368 (0.04%) were classified as DS. Of the models evaluated, the model trained with a random forest classifier had the highest performance (AUC 0.965; bAcc 0.926). A model retrained the top five SNPs, according to SHAP values, demonstrated a similar performance (AUC 0.916; bAcc 0.879) as the model with 97 SNPs. An ML approach using mutations in
N. gonorrhoeae
can be used to predict S/DS to ceftriaxone. The results highlight a practical application of ML to identify mutations most associated with S/DS to ceftriaxone, which can aid in the development of assays to predict AMR.

IMPORTANCE

Antimicrobial resistance in
Neisseria gonorrhoeae
is an urgent global health issue. The objectives of the study were to use a global collection of 12,936
N
.
gonorrhoeae
genomes from the PathogenWatch database to evaluate different machine learning models to predict ceftriaxone susceptibility/decreased susceptibility using 97 mutations known to be associated with ceftriaxone resistance. We found the random forest classifier model had the highest performance. The analysis also reported the relative contributions of different mutations within the ML model predictions, allowing for the identification of the mutations with the highest importance for ceftriaxone resistance. A machine learning model retrained with the top five mutations performed similarly to the model using all 97 mutations. These results could aid in the development of molecular tests to detect resistance to ceftriaxone in
N. gonorrhoeae
. Moreover, this approach could be applied to building and evaluating machine learning models for predicting antimicrobial resistance in other pathogens.
Can earlier biomarker measurements explain a treatment effect on diabetes incidence? A robust comparison of five surrogate markers
Authors: Parast Layla , Tian Lu , Cai Tianxi , Palaniappan Latha P
Published: October 2023

Introduction

We measured and compared five individual surrogate markers—change from baseline to 1 year after randomization in hemoglobin A1c (HbA1c), fasting glucose, 2-hour postchallenge glucose, triglyceride–glucose index (TyG) index, and homeostatic model assessment of insulin resistance (HOMA-IR)—in terms of their ability to explain a treatment effect on reducing the risk of type 2 diabetes mellitus at 2, 3, and 4 years after treatment initiation.

Research design and methods

Study participants were from the Diabetes Prevention Program study, randomly assigned to either a lifestyle intervention (n=1023) or placebo (n=1030). The surrogate markers were measured at baseline and 1 year, and diabetes incidence was examined at 2, 3, and 4 years postrandomization. Surrogacy was evaluated using a robust model-free estimate of the proportion of treatment effect explained (PTE) by the surrogate marker.

Results

Across all time points, change in fasting glucose and HOMA-IR explained higher proportions of the treatment effect than 2-hour glucose, TyG index, or HbA1c. For example, at 2 years, glucose explained the highest (80.1%) proportion of the treatment effect, followed by HOMA-IR (77.7%), 2-hour glucose (76.2%), and HbA1c (74.6%); the TyG index explained the smallest (70.3%) proportion.

Conclusions

These data suggest that, of the five examined surrogate markers, glucose and HOMA-IR were the superior surrogate markers in terms of PTE, compared with 2-hour glucose, HbA1c, and TyG index.
Exercise testing to guide safe discharge from hospital in COVID-19: a scoping review to identify candidate tests
Authors: Rhys Gwenllian Haf , Wakeling Tara , Moore Jonathan P , Subbe Christian Peter
Published: October 2023

Objectives

We aimed to identify exercise tests that have been validated to support a safe discharge to home in patients with or without COVID-19.

Study design

Scoping review, using PRISMA-ScR reporting standards. Medline, PubMed, AMED, Embase, CINAHL and LitCovid databases were searched between 16 and 22 February 2021, with studies included from any publication date up to and including the search date.

Intervention

Short exercise tests.

Primary outcome measures

Safe discharge from hospital, readmission rate, length of hospital stay, mortality. Secondary outcomes measures: safety, feasibility and reliability.

Results

Of 1612 original records screened, 19 studies were included in the analysis. These used a variety of exercise tests in patients with chronic obstructive pulmonary disease, suspected pulmonary embolism and pneumocystis carinii pneumonia, heart failure or critical illness. Only six studies had examined patients with COVID-19, of these two were still recruiting to evaluate the 1 min sit-to-stand test and the 40-steps test. There was heterogeneity in patient populations, tests used and outcome measures. Few exercise tests have been validated to support discharge decisions. There is currently no support for short exercise tests for triage of care in patients with COVID-19.

Conclusions

Further research is needed to aid clinical decision-making at discharge from hospital.
What happens when pharmacist independent prescribers lead on medicine management in older people’s care homes: a qualitative study
Authors: Birt Linda , Dalgarno Lindsay , Poland Fiona , Wright David , Bond Christine
Published: October 2023

Objective

Older people in care homes frequently experience polypharmacy, increasing the likelihood of medicine-related burden. Pharmacists working within multidisciplinary primary care teams are ideally placed to lead on medication reviews. A randomised controlled trial placed pharmacists, with independent prescribing rights (PIPs), into older people care homes. In the intervention service, PIPs worked with general practitioners (GPs) and care home staff for 6 months, to optimise medicine management at individual resident and care home level. PIP activity included stopping medicines that were no longer needed or where potential harms outweighed benefits. This analysis of qualitative data examines health and social care stakeholders’ perceptions of how the service impacted on care home medicine procedures and resident well-being.

Design

Pragmatic research design with secondary analysis of interviews.

Setting

Primary care pharmacist intervention in older people care homes in England, Scotland and Northern Ireland.

Participants

Recruited from intervention arm of the trial: PIPs (n=14), GPs (n=8), care home managers (n=9) and care home staff (n=6).

Results

There were resonances between different participant groups about potential benefits to care home residents of a medicine service provided by PIPs. There were small differences in perceptions about changes related to communication between professionals. Results are reported through three themes (1) ‘It’s a natural fit’—pharmacists undertaking medication review in care homes fitted within multidisciplinary care; (2) ‘The resident is cared for’—there were subjective improvements in residents’ well-being; (3) ‘Moving from “firefighting” to effective systems’—there was evidence of changes to care home medicine procedures.

Conclusion

This study suggests that pharmacist independent prescribers in primary care working within the multidisciplinary team can manage care home residents’ medicines leading to subjective improvements in residents’ well-being and medicine management procedures. Care home staff appreciated contact with a dedicated person in the GP practice.

Trial registration

ISRCTN 17847169
Adolescent’s anhedonia and association with childhood trauma among Chinese adolescents: a cross-sectional study
Authors: Han Jing , Zhang Liu-hong , Zhang Cai-yi , Bi Liuna , Wang Lin-lin , Cai Yan-xiu
Published: October 2023

Objectives

To estimate the level of anhedonia among adolescents and explore the association between anhedonia and childhood trauma (CT).

Design

A stratified random cluster sample of adolescents participated in a survey, which included three questionnaires: Snaith-Pamilton Pleasure Scale, Childhood Trauma Questionnaire and Patient Health Questionnaire-9.

Setting

The study was conducted in 60 classes in 10 primary, middle and high schools in five economically developed cities along the Southeast Coast of China from April to October 2022.

Participants

One thousand seven hundred and forty-five adolescents with ages ranging from 9 to 18 years participated in the study.

Primary and secondary outcomes

The primary outcome was the level of anhedonia, CT and depression among adolescents. The association between anhedonia and CT was determined.

Results

The mean scores of anhedonia, CT and depression were 24.88 (6.18), 36.75 (8.87) and 4.46 (5.36), respectively. Anhedonia scores of boys (24.24±6.12) and girls (25.62±6.16) were different (t=−4.69, p<0.01). After controlling for sex, age, the presence of siblings and depression, CT was associated with adolescent anhedonia. Emotional abuse (β=0.14), emotional neglect (β=0.15) and physical neglect (β=0.10) positively predicted adolescent anhedonia (p<0.01), whereas physical abuse negatively predicted adolescent anhedonia (β=−0.07, p<0.01). Sex had a moderating effect on the relationship between adolescent anhedonia and emotional neglect during childhood, and the negative effect of emotional neglect on adolescent anhedonia in girls was greater than in boys.

Conclusions

CT, including emotional abuse, physical abuse, emotional neglect, and physical neglect, was an independent predictor of adolescents’ ability to experience pleasure in daily life. Therefore, awareness of CT should be promoted. Emotional neglect had a more severe effect on anhedonia among girls than among boys, suggesting that emotional neglect should be paid much attention among girls
Estimation of non-health gross domestic product (NHGDP) loss due to COVID-19 deaths in West Bengal, India
Authors: Bhattacharya Paramita , John Denny , Mukherjee Nirmalaya , MS Narassima , Menon Jaideep , Banerjee Amitava
Published: October 2023

Objectives

The state of West Bengal witnessed a significant surge of COVID-19 in all three waves. However, there is a gap in understanding the economic loss associated with COVID-19. This study estimates future non-health gross domestic product (NHGDP) losses associated with COVID-19 deaths in West Bengal, India.

Setting

Various open domains were used to gather data on COVID-19 deaths in West Bengal and the aforementioned estimates.

Primary and secondary outcome measures

The NHGDP losses were evaluated using the cost-of-illness approach. Future NHGDP losses were discounted at 3%. Excess death estimates by the WHO and Global Burden of Disease (GBD) were used. Sensitivity analysis was carried out by varying discount rates and average age of death (AAD).

Results

21 532 deaths in West Bengal from 17 March 2020 to 31 December 2022 decreased the future NHGDP by $0.92 billion. Nearly 90% of loss was due to deaths occurring in the age group of 30 years and above. Majority of the NHGDP loss was borne by the 46–60 years age group. NHGDP loss/death was $55,171; however, the average loss/death declined with rise in age. Based on the GBD and WHO excess death estimates, the NHGDP loss increased to $9.38 billion and $9.42 billion, respectively. When the lower age interval is considered as AAD, the NHGDP loss increased to $1.3 billion. At 5% and 10% discount rates, the losses reduced to $0.767 billion and $0.549 billion, respectively.

Conclusions

Results from the study suggest that COVID-19 contributed to a major economic loss in West Bengal. The mortality and morbidity caused by COVID-19, the substantial economic costs at individual and population levels in West Bengal, and probably across India and other countries, is another economic argument for better infection control strategies across the globe to minimise the impact of COVID-19.
Implementation model for a national learning health system (IMPLEMENT-National LHS): a concept analysis and systematic review protocol
Authors: Gartner Jean-Baptiste , Benharbit Boutheina , Layani Géraldine , Sasseville Maxime , Lemaire Célia , Bergeron Frédéric , Wilhelmy Catherine , Menear Matthew , Côté André
Published: October 2023

Introduction

Despite efforts and repeated calls to improve the organisation and quality of healthcare and services, and in view of the many challenges facing health systems, the results and capacity to adapt and integrate innovations and new knowledge remain suboptimal. Learning health systems (LHS) may be an effective model to accelerate the application of research for real quality improvement in healthcare. However, while recognising the enormous potential of LHS, the literature suggests the model remains more of an aspiration than a reality.

Methods and analysis

To reach a fine understanding of the implementation of the concepts involved in LHS, we will use a hybrid method which combines concept analyses with systematic review methodology. We will use a two-step analysis, a content analysis to analyse the definitions, uses and attributes of the concept and a systematic review to analyse the concept’s implementation mechanisms. We will search eight databases and grey literature and present a broad synthesis of the available evidence regarding design, implementation and evaluation of LHS in a multilevel perspective. We will follow the latest Preferred Reporting Items for Systematic Review and Meta-Analysis statement for conducting and reporting a systematic review. Two reviewers will independently screen the titles and abstracts against the eligibility criteria followed by full-text screening of potentially relevant articles for final inclusion decision. Conflicts will be resolved with a senior author. We will include published primary studies that use qualitative, quantitative or mixed methods. The assessment of risk of bias will be made using the Mixed-Methods Appraisal Tool.

Ethics and dissemination

This systematic review is exempt from ethics approval. The results formulated will highlight evidence-based interventions that support the implementation of a national LHS. They will be of particular interest to decision makers, researchers, managers, clinicians and patients allowing finally to implement the promising proposal of LHSs at national scale.

PROSPERO registration number

CRD42023393565.
Recruitment strategies and interventions to increase participation in lung cancer screening programmes: a systematic review protocol
Authors: Djuric Olivera , Venturelli Francesco , Bassi Maria Chiara , Gorini Giuseppe , Paci Eugenio , Mantellini Paola , Giorgi Rossi Paolo
Published: October 2023

Introduction

Despite strong evidence for the efficacy of low-radiation dose CT (LDCT) in reducing lung cancer (LC) mortality, implementing LC screening (LCS) programmes remains a challenge. We aim to systematically review the evidence on the strategies used to recruit the adult population at risk of LC to LDCT within LCS programmes and to estimate the effectiveness of interventions identified, used to reach the potentially eligible population, increase participation and informed choice, and ensure equitable access.

Methods and analysis

This sequential systematic literature review will consist of three steps: (1) a scoping review of existing strategies and organisational models for LCS; (2) selecting papers reporting relevant outcomes (test coverage, screening participation and informed choice) and comparing results among different models; (3) a systematic review of interventions implemented to increase participation in LCS programmes. Each step will follow the methodological guidelines provided by the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Data sources include electronic databases such as Medline (PubMed version), Embase, CINAHL (Ebsco version), Scopus and Cochrane CENTRAL. The search will be limited to studies published from January 2000 to March 2023 in English, Italian, French, Spanish, Serbian and Croatian language. Findings will be synthesised quantitatively and qualitatively as appropriate. Risk of bias assessment will be only applied to studies selected in the second and third steps. The quality of evidence will be summarised for each outcome using the Grading Recommendation Assessment, Development and Evaluation methodology.

Ethics and dissemination

Given that this is a review of existing literature, ethics approval is not required. The results will be published in peer-reviewed scientific journals and presented at relevant conferences. The findings of this review will help guide health authorities in organising LCS programmes and developing recommendations, policies, and actions at national and regional levels.

PROSPERO registration number

CRD42023408357.
Protocol of the Berlin Long-term Observation of Vascular Events (BeLOVE): a prospective cohort study with deep phenotyping and long-term follow up of cardiovascular high-risk patients
Authors: Weber Joachim E , Ahmadi Michael , Boldt Leif-Hendrik , Eckardt Kai-Uwe , Edelmann Frank , Gerhardt Holger , Grittner Ulrike , Haubold Kathrin , Hübner Norbert , Kollmus-Heege Jil , Landmesser Ulf , Leistner David M , Mai Knut , Müller Dominik N , Nolte Christian H , Pieske Burkert , Piper Sophie K , Rattan Simrit , Rauch Geraldine , Schmidt Sein , Schmidt-Ott Kai M , Schönrath Katharina , Schulz-Menger Jeanette , Schweizerhof Oliver , Siegerink Bob , Spranger Joachim , Ramachandran Vasan S , Witzenrath Martin , Endres Matthias , Pischon Tobias
Published: October 2023

Introduction

The Berlin Long-term Observation of Vascular Events is a prospective cohort study that aims to improve prediction and disease-overarching mechanistic understanding of cardiovascular (CV) disease progression by comprehensively investigating a high-risk patient population with different organ manifestations.

Methods and analysis

A total of 8000 adult patients will be recruited who have either suffered an acute CV event (CVE) requiring hospitalisation or who have not experienced a recent acute CVE but are at high CV risk. An initial study examination is performed during the acute treatment phase of the index CVE or after inclusion into the chronic high risk arm. Deep phenotyping is then performed after ~90 days and includes assessments of the patient’s medical history, health status and behaviour, cardiovascular, nutritional, metabolic, and anthropometric parameters, and patient-related outcome measures. Biospecimens are collected for analyses including ‘OMICs’ technologies (e.g., genomics, metabolomics, proteomics). Subcohorts undergo MRI of the brain, heart, lung and kidney, as well as more comprehensive metabolic, neurological and CV examinations. All participants are followed up for up to 10 years to assess clinical outcomes, primarily major adverse CVEs and patient-reported (value-based) outcomes. State-of-the-art clinical research methods, as well as emerging techniques from systems medicine and artificial intelligence, will be used to identify associations between patient characteristics, longitudinal changes and outcomes.

Ethics and dissemination

The study was approved by the Charité—Universitätsmedizin Berlin ethics committee (EA1/066/17). The results of the study will be disseminated through international peer-reviewed publications and congress presentations.

Study registration

First study phase: Approved WHO primary register: German Clinical Trials Register:https://drks.de/search/de/trial/DRKS00016852; WHO International Clinical Registry Platform:http://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00016852. Recruitment started on July 18, 2017.

Second study phase: Approved WHO primary register: German Clinical Trials Register DRKS00023323, date of registration: November 4, 2020, URL:http://www.drks.de/DRKS00023323. Recruitment started on January 1, 2021.
Infection with SARS-CoV-2 during pregnancy and risk of stillbirth: a Scandinavian registry study
Authors: Magnus Maria Christine , Örtqvist Anne Kristina , Urhoj Stine Kjaer , Aabakke Anna , Mortensen Laust Hvas , Gjessing Håkon , Nybo Andersen Anne-Marie , Stephansson Olof , Håberg Siri Eldevik
Published: October 2023

Background

A few studies indicate that women infected with SARS-CoV-2 during pregnancy might have an increased risk of stillbirth. Our aim was to investigate the risk of stillbirth according to infection with SARS-CoV-2 during pregnancy also taking the variant into account.

Methods

We conducted a register-based study using the Swedish, Danish and Norwegian birth registries. A total of 389 949 births (1013 stillbirths) after 22 completed gestational weeks between 1 May 2020 and end of follow-up (27 January 2022 for Sweden and Norway; 31 December 2021 for Denmark). We estimated the risk of stillbirth following SARS-CoV-2 infection after 22 completed gestational weeks using Cox regression for each country, and combined the results using a random-effects meta-analysis.

Results

SARS-CoV-2 infection after 22 completed gestational weeks was associated with an increased risk of stillbirth (adjusted HR 2.40; 95% CI 1.22 to 4.71). The risk was highest during the first weeks following infection, with an adjusted HR of 5.48 (95% CI 3.11 to 9.63) during the first 2 weeks, 4.38 (95% CI 2.41 to 7.98) during the first 4 weeks, and 3.71 (95% CI 1.81 to 7.59) during the first 6 weeks. Furthermore, the risk was greatest among women infected during the Delta-dominated period (adjusted HR 8.23; 95% CI 3.65 to 18.59), and more modest among women infected during the Index (adjusted HR 3.66; 95% CI 1.89 to 7.06) and Alpha (adjusted HR 2.73; 95% CI 1.13 to 6.59) dominated periods.

Conclusions

We found an increased risk of stillbirth among women who were infected with SARS-CoV-2 after 22 gestational weeks, with the greatest risk during the Delta-dominated period.
Self-managed medication abortion trajectories: results from a prospective observational study in Argentina, Nigeria and Southeast Asia
Authors: Pleasants Elizabeth A , Jayaweera Ruvani T , Egwuatu Ijeoma , Nmezi Sybil , Kristianingrum Ika Ayu , Zurbriggen Ruth , Grosso Belén , Bercu Chiara , Motana Relebohile , Gerdts Caitlin , Moseson Heidi
Published: October 2023

Objectives

Time is a crucial factor in abortion-seeking because options for care change with pregnancy duration, and most people prefer to access abortion care early in pregnancy. We aimed to collect data on the timing of steps in accompanied self-managed abortion-seeking experiences in legally restrictive settings.

Methods

In this prospective, observational, cohort study we recruited callers from three abortion accompaniment groups in Argentina, Nigeria and a country in Southeast Asia. Participants completed a baseline survey before starting a self-managed medication abortion (SMA) and two follow-up surveys (approximately 1 and 3 weeks after taking medication). Primary outcomes of interest included: (1) time from abortion decision to contacting the hotline, (2) time from contacting the hotline to obtaining pills and (3) time from obtaining pills to taking the first dose. We explored relationships between participant characteristics and each of these outcomes and evaluated differences in overall abortion time using survival analyses.

Results

Between July 31, 2019 and October 01, 2020 we enrolled 1352 eligible callers; 1148 provided data for this analysis. After deciding to have an abortion, participants took 12.2 days on average (95% CI: 11.6, 12.9) to start medications for abortion. On average, participants at later pregnancy durations progressed through the SMA process more quickly (<4 weeks: 20.9 days, 4 weeks: 11 days, 5–6 weeks: 10.1 days, 7–9 weeks, 10.4 days, 10+ weeks: 9.1 days; p<0.001).

Conclusions

Overall, participants accessed accompaniment group support and started abortion regimens quickly and at relatively early pregnancy durations. SMA with accompaniment provided a time-efficient route for obtaining abortions.