bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome‐wide association study of multiyear dynamic growth traits in hybrid Liriodendron identifies robust genetic loci associated with growth trajectories
Authors: Xia Hui , Hao Ziyuan , Shen Yufang , Tu Zhonghua , Yang Lichun , Zong Yaxian , Li Huogen
Published: June 2023

The genetic factors underlying growth traits differ over time points or stages. However, most current studies of phenotypes at single time points do not capture all loci or explain the genetic differences underlying growth trajectories. Hybrid Liriodendron exhibits obvious heterosis and is widely cultivated, although its complex genetic mechanism underlying growth traits remains unknown. A genome‐wide association study (GWAS) is an effective method for elucidating the genetic architecture by identifying genetic loci underlying complex quantitative traits. In the present study, using a GWAS, we identified robust loci associated with growth trajectories in hybrid Liriodendron populations. We selected 233 hybrid progenies derived from 25 crosses for resequencing, and measured their tree height (H) and diameter at breast height (DBH) for 11 consecutive years; 192 972 high‐quality single nucleotide polymorphisms (SNPs) were obtained. The dynamics of the multiyear single‐trait GWAS showed that year‐specific SNPs predominated, and only five robust SNPs for DBH were identified in at least three different years. Multitrait GWAS analysis with model parameters as latent variables also revealed 62 SNPs for H and 52 for DBH associated with the growth trajectory, displaying different biomass accumulation patterns, among which four SNPs exerted pleiotropic effects. All identified SNPs also exhibited temporal variations in effect sizes and inheritance patterns potentially related to different growth and developmental stages. The haplotypes resulting from these significant SNPs might pyramid favorable loci, benefitting the selection of superior genotypes. The present study provides insights into the genetic architecture of dynamic growth traits and lays a basis for future molecular‐assisted breeding.
Parallel adaptation to lower altitudes is associated with enhanced plasticity in Heliosperma pusillum (Caryophyllaceae)
Authors: Szukala Aglaia , Bertel Clara , Frajman Božo , Schönswetter Peter , Paun Ovidiu
Published: June 2023

High levels of phenotypic plasticity are thought to be inherently costly in stable or extreme environments, but enhanced plasticity may evolve as a response to new environments and foster novel phenotypes. Heliosperma pusillum forms glabrous alpine and pubescent montane ecotypes that diverged recurrently and polytopically (parallel evolution) and can serve as evolutionary replicates. The specific alpine and montane localities are characterized by distinct temperature conditions, available moisture, and light. Noteworthy, the ecotypes show a home‐site fitness advantage in reciprocal transplantations. To disentangle the relative contribution of constitutive versus plastic gene expression to altitudinal divergence, we analyze the transcriptomic profiles of two parallely evolved ecotype pairs, grown in reciprocal transplantations at native altitudinal sites. In this incipient stage of divergence, only a minor proportion of genes appear constitutively differentially expressed between the ecotypes in both pairs, regardless of the growing environment. Both derived, montane populations bear comparatively higher plasticity of gene expression than the alpine populations. Genes that change expression plastically or constitutively underlie similar ecologically relevant pathways, related to response to drought and trichome formation. Other relevant processes, such as photosynthesis, rely mainly on plastic changes. The enhanced plasticity consistently observed in the montane ecotype likely evolved as a response to the newly colonized, drier, and warmer niche. We report a striking parallelism of directional changes in gene expression plasticity. Thus, plasticity appears to be a key mechanism shaping the initial stages of phenotypic evolution, likely fostering adaptation to novel environments.
Single energy metal artifact reduction performs better than virtual monoenergetic dual‐energy reconstruction in CT of the equine proximal phalanx
Authors: Faulkner Josephine E , Broeckx Bart J G , Martens Ann , Raes Els , Haardt Hanna , Vanderperren Katrien
Published: June 2023

Metal artifacts in CT negatively impact the evaluation of surgical implants and the surrounding tissues. The aim of this prospective experimental study was to evaluate the ability of a single energy metal artifact reduction (SEMAR™, Canon) algorithm and virtual monoenergetic (VM) dual‐energy CT (DECT) scanning techniques to reduce metal artifacts from stainless steel screws surgically inserted into the equine proximal phalanx. Seven acquisitions of 18 cadaver limbs were performed on a Canon Aquilion One Vision CT scanner (Helical +SEMAR, Volume +SEMAR, Standard Helical, Standard Volume and VM DECT at 135, 120, and 105 keV) and reconstructed in a bone kernel. Blinded subjective evaluation performed by three observers indicated a significant effect of acquisition in both adjacent tissues (P < 0.001) and distant tissues (P < 0.001) and the best metal artifact reduction was seen with Helical +SEMAR and Volume +SEMAR. The subjective overall preference of CT acquisition type was (1) Helical +SEMAR, (2) Volume +SEMAR, (3) VM DECT 135 keV, (4) VM DECT 120 keV, (5) VM DECT 105 keV, (6) Standard Helical, (7) Standard Volume (P < 0.001). Unblinded objective evaluation performed by one observer showed that VM DECT 120 keV, Helical +SEMAR, and Volume +SEMAR performed similarly and were objectively the best at reducing blooming artifact. Overall, the best metal artifact reduction was obtained with SEMAR, followed by VM DECT. However, VM DECT performance varies with energy level and was associated with decreased image quality in distant tissues and artifactual overcorrection of metal artifacts at high energy levels.
Arthroscopically guided lag screw fixation of subchondral bone cysts in the medial femoral condyle in Thoroughbred racehorses: description of technique and comparative results
Authors: Young Natalie , Barker Will , Minshall Gaynor , Wright Ian
Published: June 2023

Objective

To describe an arthroscopically guided technique for lag screw placement across subchondral bone cyst (SBC) in the medial femoral condyle (MFC) and to compare postoperative racing performance with corticosteroid injection and cyst debridement.

Study design

Retrospective cohort study.

Animals

One hundred twenty‐three horses with 134 MFC SBCs undergoing treatment at a single referral hospital in the UK between January, 2009, and December, 2020.

Methods

Sex, age, limb affected, radiographic cyst dimensions, preoperative and postoperative lameness, surgical technique (lag screw placement, cyst debridement, intralesional corticosteroid injection), and, where applicable, screw positioning were recorded retrospectively. A ratio was calculated using measurements from preoperative and postoperative radiographs. Outcome was assessed by resolution or improvement in lameness, reduction in cyst size, and starting one race after treatment. Outcome data was compared between treatment groups.

Results

Twenty‐six of 45 (57.8%) horses that underwent transcondylar screw placement raced postoperatively, at a median of 403 days between surgery and first postoperative race. There was no difference between treatment groups with regard to racing or preoperative and postoperative lameness. Cysts treated with transcondylar screw placement had a greater reduction in cyst size and a reduced period of convalescence in comparison with those that underwent debridement; the results were similar to those treated by intralesional corticosteroid injection.

Conclusion

Postoperative racing rates were similar for all techniques. Convalescence was reduced for lag screw placement and corticosteroid injection compared to debridement.

Clinical significance

The arthroscopically guided technique results in radiographically consistent screw placement and cyst engagement and offers a viable alternative to other treatments.
Pengaruh Bahasa Ibunda dalam Pertuturan Murid-Murid Asli Suku Kaum Temuan ketika Pembelajaran Bahasa Melayu
Authors: Nazir Faridah
Published: June 2023

Kajian ini dijalankan untuk meneliti pengaruh bahasa ibunda dalam pertuturan murid- murid suku kaum Temuan di Sekolah Kebangsaan Tekir, Labu, Negeri Sembilan ketika pembelajaran bahasa Melayu dijalankan. Kaedah kajian yang digunakan adalah rakaman spontan dan catatan terhadap pertuturan 11 orang murid di Tahun 6 untuk mengenal pasti pengaruh bahasa ibunda dalam pertuturan murid ketika sesi perbincangan dalam pengajaran dan pembelajaran (PdP) Bahasa Melayu. Kaedah lain yang digunakan adalah borang soal selidik yang diedarkan kepada 24 orang murid di Tahun 2 hingga 6 untuk mengenal pasti aspek-aspek ekstralinguistik yang mempengaruhi penggunaan bahasa ibunda dalam kalangan murid-murid Temuan dalam pertuturan ketika sesi pengajaran dan pembelajaran bahasa Melayu dijalankan. Dapatan kajian menunjukkan terdapat tiga pengaruh bahasa ibunda yang terdapat dalam pertuturan murid, iaitu kelainan bunyi, unsur dialek / bahasa lain dan fenomena campur kod bahasa Temuan dan bahasa Melayu pada peringakat perkataan dan frasa. Aspek-aspek ekstralinguistik yang mempengaruhi penggunaan bahasa ibunda dalam pertuturan murid-murid Temuan pula ialah umur, jantina, kumpulan etnik dan kefasihan murid-murid berbahasa Melayu.
 
This study was conducted to examine the influence of the mother tongue on the speech of students of the Temuan tribe at Tekir Kebangsaan School, Labu, Negeri Sembilan when learning the Malay language. The research method used is the spontaneous recording and notes of the speech of 11 students in Year 6 to identify the influence of the mother tongue in the students' speech during the discussion session in the teaching and learning (PdP) of the Malay language. Another method used was a questionnaire that was distributed to 24 students in years 2 to 6 to identify the extralinguistic aspects that influence the use of the mother tongue among the students. The findings of the study show that there are three influences of the mother tongue found in the student’s speech, namely sound abnormalities, elements of dialects / other languages, and the phenomenon of code-mixing between the Temuan language and the Malay language at the level of words and phrases. Extralinguistic aspects influence the use of the mother tongue in the students' speech. The findings are the age, gender, ethnic group, and fluency of the students in Malay.
The Impact of English Language on Business Communication in Asia: A Scoping Review
Authors: Awangku Ismail Dayangku Aqilah , Pek Lim Seong
Published: June 2023

In the current global era, English is becoming increasingly essential not only as a worldwide language but now widely used as a business language in native and non-native English-speaking countries. Particularly, English language proficiency is mostly required and recognized amongst the countries in the n   continent. Thus, this review emphasises the importance of the English language, the dynamism of ways that may be utilised when teaching the English language and identifying the requirements of English language skills among business workers and students. Hence, the primary goal of this scoping review is to uncover previous research on the impact of the English language on business communication in Asia. This scoping review was reported according to Preferred Reporting Items for Systematic Reviews for Scoping Reviews (PRISMA-ScR) guidelines. Five databases, namely Education Resources Information Center (ERIC), Semantic Scholar, ScienceDirect, Directory of Open Access Journals (DOAJ), and SAGE Journals, were used for data scoping. A total of 10 studies were identified to be eligible for selection.
Persepsi Terhadap Penggunaan Istilah Penyuntingan Berbahasa Melayu dalam Kalangan Pensyarah Bidang Penerbitan
Authors: Suhaimi Mohamad Suhaizi , Sharif Muhammad Ridzwan
Published: June 2023

Penggunaan istilah dalam bidang penyuntingan naskhah sering menimbulkan kekeliruan apabila pengguna bahasa perlu memilih sama ada ingin menggunakan bahasa pinjaman atau bahasa Melayu asli. Oleh itu, kajian ini bertujuan mengenal pasti istilah-istilah penyuntingan dalam bahasa Melayu asli di samping menganalisis persepsi para pensyarah terhadap penggunaan istilah penyuntingan berbahasa Melayu asli. Kajian ini menggunakan kaedah bertanyakan soalan (naming questions) yang bertumpukan kepada persoalan kajian dalam mengkaji persepsi responden terhadap istilah penyuntingan berbahasa Melayu. Selain itu, kajian ini menggunakan kaedah kualitatif serta instrumen soal selidik yang melibatkan empat (4) orang pensyarah universiti sebagai responden yang dipilih melalui persampelan bertujuan (purposive sampling) supaya bertepatan dengan ciri-ciri yang dikehendaki oleh pengkaji. Dapatan kajian mengenai persepsi seperti ‘menggunakan’, ‘menggalakkan’, ‘faham’ dan ‘sikap’ menunjukkan bahawa istilah penyuntingan berbahasa Melayu digunakan sepenuhnya dalam kalangan responden. Selain itu, kecenderungan responden dalam menggunakan istilah-istilah penyuntingan berbahasa Melayu asli juga memaparkan jumlah yang tinggi. Justeru, para pensyarah dalam bidang penyuntingan bahasa Melayu tidak mempunyai persepsi yang negatif terhadap penggunaan istilah penyuntingan berbahasa Melayu asli.
 
Daunting decision in the field of manuscript editing happened when choosing either to use borrowed words or the original Malay language. Therefore, this study aims to identify the terms of editing in the original Malay language as well as to analyse the perceptions of lecturers on the use of editing terms in the original Malay language. This study uses the method of naming questions which focuses on research questions in examining respondents' perceptions of the term Malay language editing. In addition, this study uses qualitative method and questionnaire instruments involving four (4) university lecturers as respondents selected through purposive sampling to coincide with the characteristics desired by the researcher. Findings of the study on perceptions such as ‘use’, ‘encourage’, ‘understand’ and ‘attitude’ show that the term Malay language editing is used fully among the respondents. Besides, their tendency in using original Malay language editing terms also displays a high number. Thus, the lecturers in the field of Malay language editing do not have a negative perception on the use of the term original Malay language editing.
Measurement properties of utility-based health-related quality of life measures in cardiac rehabilitation: a systematic review protocol
Authors: Bulamu Norma B. , Hines Sonia , Gebremichael Lemlem G. , Mpundu-Kaambwa Christine , Pinero de Plaza Maria Alejandra , Dafny Hila A. , Beleigoli Alline , Kaambwa Billingsley , Hendriks Jeroen M. , Clark Robyn A.
Published: June 2023

Objective:

This review will identify and appraise existing evidence on the measurement properties of utility-based health-related quality of life (HRQoL) measures used in cardiac rehabilitation programs. The review will then map the measure domains against the International Classification of Functioning, Disability and Health and the International Consortium of Health Outcome Measures domains for cardiovascular disease.

Introduction:

Improving HRQoL is an international key indicator for delivering high-quality and person-centered secondary prevention programs. Many instruments and measures assess HRQoL in individuals undergoing cardiac rehabilitation. Utility-based measures are suitable for calculating quality-adjusted life years, a required outcome metric in cost–utility analysis. Cost–utility analysis requires the use of utility-based HRQoL measures. However, there is no consensus on which utility-based measure is best for populations undergoing cardiac rehabilitation.

Inclusion criteria:

Eligible studies will include patients aged ≥ 18 years with cardiovascular disease who are undergoing cardiac rehabilitation. Empirical studies that assess quality of life or HRQoL using a utility-based, health-related, patient-reported outcome measure or a measure accompanied by health state utilities will be eligible. Studies must report at least 1 of the following measurement properties: reliability, validity, responsiveness.

Methods:

This review will follow the JBI methodology for systematic reviews of measurement properties. The following databases will be searched from inception to the present: MEDLINE, Emcare, Embase, Scopus, CINAHL, Web of Science Core Collection, Informit, PsyclNFO, REHABDATA, and the Cochrane Library. Studies will be critically appraised using the COSMIN risk of bias checklist. The review will be reported in line with the PRISMA guidelines.

Systematic review registration number:

PROSPERO CRD42022349395
Mites associated with Vitis labrusca (Vitaceae) in southern Brazil: Population dynamics and ecology
Authors: Da Silva Rita Tatiane leão , Berté Amália Luisa Winter , Bizarro Gabriel Lima , Schussler Matheus , Silva Darliane Evangelho , Granich Juliana , Ferla Noeli Juarez
Published: June 2023

Viticulture is one of the main economic activities in Rio Grande do Sul (RS), Brazil, with emphasis on the American grape varieties, Vitis labrusca L. (Vitaceae), used in producing juices and wines. The present work aimed to identify the mite species associated with American grapevines (V. labrusca), their possible natural enemies, and their population fluctuations. The selected varieties were: Bordô (Bd) and Couderc (Cc and Cd) in Dois Lajeados (RS), Bordô (Bi) in Imigrante (RS) and Bordô (Bp), in Putinga (RS). The study was conducted monthly between March 2017 and March 2018, evaluating 20 randomly selected plants from each municipality. We found 5,452 mites belonging to 13 families, distributed across 29 genera and 42 species, or belonging to the suborder Oribatida. Higher mite richness was observed on Cc (12 species) and higher abundance on Cd (2,812 specimens), Cc (868) and Bi (799). Among the predatory mite families, Stigmaeidae had the highest abundance (896 specimens), followed by Phytoseiidae (746). The most abundant species observed were Euseius mesembrinus (Dean), Agistemus riograndensis Johann & Ferla, Tydeus californicus (Banks), Polyphagotars-onemus latus (Banks) and Tarsonemus sp. This is the first study in southern Brazil that evaluates and reports the mite fauna and its ecology on American grape varieties, with high abundance and frequency of predatory mites. This work is important to assist in implementing management techniques that promote the maintenance of predatory mite species in these vineyards.
Auxiliary superfield method for statistical predictions of complex, structural acoustics systems: Saddle point approximation for the mean field
Authors: Photiadis Douglas M. , Villa Mauricio , Dey Saikat
Published: June 2023

The auxiliary superfield approach is proposed as a method to obtain statistical predictions of the acoustic response of complex elastic structures. The potential advantage of the method is the full retention of interference and resonance effects associated with the degrees of freedom being averaged over. It is not known whether this approach leads to tractable problems for structural acoustics systems, however. We have applied the method to the idealized case of an infinite, thin plate with attached oscillators to obtain the mean Green's function. The oscillators are assumed to have an uncorrelated, Gaussian distributed mass and stiffness distribution representing a simple form of complex internal structure. Using the auxiliary superfield approach, the mean Green's functions are expressed exactly as a functional integral. For relatively small disorder, the integral may be estimated by a saddle point approximation which leads to coupled integral equations for effective mass and stiffness matrices that can be solved numerically for a given spatial distribution of the disorder. With the solutions for these matrices, one obtains a self-consistently determined, generalized fuzzy structure model. We give analytical solutions for the simple case of a uniform spatial distribution. The results are promising for the application of the method to more challenging geometries.
Integrating modeled environmental variability into neural network training for underwater source localization
Authors: Diniz Pedro , Calazan Rogério
Published: June 2023

Supervised machine learning (ML) is a powerful tool that has been applied to many fields of underwater acoustics, including acoustic inversion. ML algorithms depend on the existence of extensive labeled datasets, which are difficult to obtain for the task of underwater source localization. A feed-forward neural network (FNN) trained on imbalanced or biased data may end up suffering from a problem analogous to model mismatch in matched field processing (MFP), that is, producing incorrect results due to a difference between the environment sampled by the training data and the actual environment. To overcome this issue, physical and numerical propagation models can act as data augmentation tools to compensate for the lack of comprehensive acoustic data. This paper examines how modeled data can be effectively used for training FNNs. Mismatch tests compare the output from a FNN and MFP and show that the network becomes more robust to various kinds of mismatches when trained on diverse environments. A systematic analysis of how the training dataset's variability impacts a FNN's localization performance on experimental data is carried out. Results show that networks trained with synthetic data achieve better and more robust performance than regular MFP when environment variability is taken into account.
The structure of acoustic voice variation in bilingual speech
Authors: Johnson Khia A. , Babel Molly
Published: June 2023

When a bilingual switches languages, do they switch their voice? Using a conversational corpus of speech from early Cantonese-English bilinguals (n = 34), this paper examines the talker-specific acoustic signatures of bilingual voices. Following the psychoacoustic model of voice, 24 filter and source-based acoustic measurements are estimated. The analysis summarizes mean differences for these dimensions and identifies the underlying structure of each talker's voice across languages with principal component analyses. Canonical redundancy analyses demonstrate that while talkers vary in the degree to which they have the same voice across languages, all talkers show strong similarity with themselves, suggesting an individual's voice remains relatively constant across languages. Voice variability is sensitive to sample size, and we establish the required sample to settle on a consistent impression of one's voice. These results have implications for human and machine voice recognition for bilinguals and monolinguals and speak to the substance of voice prototypes.
Bilirubin is produced nonenzymatically in plants to maintain chloroplast redox status
Authors: Ishikawa Kazuya , Xie Xiaonan , Osaki Yasuhide , Miyawaki Atsushi , Numata Keiji , Kodama Yutaka
Published: June 2023

Bilirubin, a potent antioxidant, is a product of heme catabolism in heterotrophs. Heterotrophs mitigate oxidative stress resulting from free heme by catabolism into bilirubin via biliverdin. Although plants also convert heme to biliverdin, they are generally thought to be incapable of producing bilirubin because they lack biliverdin reductase, the enzyme responsible for bilirubin biosynthesis in heterotrophs. Here, we demonstrate that bilirubin is produced in plant chloroplasts. Live-cell imaging using the bilirubin-dependent fluorescent protein UnaG revealed that bilirubin accumulated in chloroplasts. In vitro, bilirubin was produced nonenzymatically through a reaction between biliverdin and reduced form of nicotinamide adenine dinucleotide phosphate at concentrations comparable to those in chloroplasts. In addition, increased bilirubin production led to lower reactive oxygen species levels in chloroplasts. Our data refute the generally accepted pathway of heme degradation in plants and suggest that bilirubin contributes to the maintenance of redox status in chloroplasts.
Human SAMD9 is a poxvirus-activatable anticodon nuclease inhibiting codon-specific protein synthesis
Authors: Zhang Fushun , Ji Quanquan , Chaturvedi Juhi , Morales Marisol , Mao Yuanhui , Meng Xiangzhi , Dong Leiming , Deng Junpeng , Qian Shu-Bing , Xiang Yan
Published: June 2023

As a defense strategy against viruses or competitors, some microbes use anticodon nucleases (ACNases) to deplete essential tRNAs, effectively halting global protein synthesis. However, this mechanism has not been observed in multicellular eukaryotes. Here, we report that human SAMD9 is an ACNase that specifically cleaves phenylalanine tRNA (tRNA
Phe
), resulting in codon-specific ribosomal pausing and stress signaling. While SAMD9 ACNase activity is normally latent in cells, it can be activated by poxvirus infection or rendered constitutively active by SAMD9 mutations associated with various human disorders, revealing tRNA
Phe
depletion as an antiviral mechanism and a pathogenic condition in SAMD9 disorders. We identified the N-terminal effector domain of SAMD9 as the ACNase, with substrate specificity primarily determined by a eukaryotic tRNA
Phe
–specific 2′-
O
-methylation at the wobble position, making virtually all eukaryotic tRNA
Phe
susceptible to SAMD9 cleavage. Notably, the structure and substrate specificity of SAMD9 ACNase differ from known microbial ACNases, suggesting convergent evolution of a common immune defense strategy targeting tRNAs.
Chronic airway epithelial hypoxia exacerbates injury in muco-obstructive lung disease through mucus hyperconcentration
Authors: Mikami Yu , Grubb Barbara R. , Rogers Troy D. , Dang Hong , Asakura Takanori , Kota Pradeep , Gilmore Rodney C. , Okuda Kenichi , Morton Lisa C. , Sun Ling , Chen Gang , Wykoff Jason A. , Ehre Camille , Vilar Juan , van Heusden Catharina , Livraghi-Butrico Alessandra , Gentzsch Martina , Button Brian , Stutts M. Jackson , Randell Scott H. , O’Neal Wanda K. , Boucher Richard C.
Published: June 2023

Unlike solid organs, human airway epithelia derive their oxygen from inspired air rather than the vasculature. Many pulmonary diseases are associated with intraluminal airway obstruction caused by aspirated foreign bodies, virus infection, tumors, or mucus plugs intrinsic to airway disease, including cystic fibrosis (CF). Consistent with requirements for luminal O
2
, airway epithelia surrounding mucus plugs in chronic obstructive pulmonary disease (COPD) lungs are hypoxic. Despite these observations, the effects of chronic hypoxia (CH) on airway epithelial host defense functions relevant to pulmonary disease have not been investigated. Molecular characterization of resected human lungs from individuals with a spectrum of muco-obstructive lung diseases (MOLDs) or COVID-19 identified molecular features of chronic hypoxia, including increased
EGLN3
expression, in epithelia lining mucus-obstructed airways. In vitro experiments using cultured chronically hypoxic airway epithelia revealed conversion to a glycolytic metabolic state with maintenance of cellular architecture. Chronically hypoxic airway epithelia unexpectedly exhibited increased MUC5B mucin production and increased transepithelial Na
+
and fluid absorption mediated by HIF1α/HIF2α-dependent up-regulation of β and γENaC (epithelial Na
+
channel) subunit expression. The combination of increased Na
+
absorption and MUC5B production generated hyperconcentrated mucus predicted to perpetuate obstruction. Single-cell and bulk RNA sequencing analyses of chronically hypoxic cultured airway epithelia revealed transcriptional changes involved in airway wall remodeling, destruction, and angiogenesis. These results were confirmed by RNA–in situ hybridization studies of lungs from individuals with MOLD. Our data suggest that chronic airway epithelial hypoxia may be central to the pathogenesis of persistent mucus accumulation in MOLDs and associated airway wall damage.
Measles, mumps, and rubella vaccine at age 6 months and hospitalisation for infection before age 12 months: randomised controlled trial
Authors: Zimakoff Anne Cathrine , Jensen Andreas , Vittrup Dorthe Maria , Herlufsen Emma Hoppe , Sørensen Jesper Kiehn , Malon Michelle , Svensson Jannet , Stensballe Lone Graff
Published: June 2023

Objective

To test for potential non-specific effects of an additional, early measles, mumps, and rubella (MMR) vaccine at age 5-7 months on risk of infection related hospitalisation before age 12 months.

Design

Randomised, double blinded, placebo controlled trial.

Setting

Denmark, a high income setting with low exposure to MMR.

Participants

6540 Danish infants aged 5 to 7 months.

Interventions

Infants were randomly allocated 1:1 to intramuscular injection with standard titre MMR vaccine (M-M-R VaxPro) or placebo (solvent only).

Main outcome measures

Hospitalisations for infection, defined as all hospital contacts of infants referred from primary care for hospital evaluation and with an infection diagnosed, analysed as recurrent events, from randomisation to 12 months of age. In secondary analyses implications of censoring for date of subsequent diphtheria, tetanus, pertussis, polio,
Haemophilus influenzae
type B, and immunisation with pneumococci conjugate vaccine (DTaP-IPV-Hib+PCV), potential effect modification by sex, prematurity (<37 weeks’ gestation), season, and age at randomisation were tested, and the secondary outcomes of hospitalisations ≥12 hours and antibiotic use were evaluated.

Results

6536 infants were included in the intention-to-treat analysis. 3264 infants randomised to MMR vaccine experienced 786 hospitalisations for infection before age 12 months compared with 762 for the 3272 infants randomised to placebo. In the intention-to-treat analysis the rate of hospitalisations for infection did not differ between the MMR vaccine and placebo groups (hazard ratio 1.03, 95% confidence interval 0.91 to 1.18). For infants randomised to MMR vaccine compared with those randomised to placebo, the hazard ratio of hospitalisations for infection with a duration of at least 12 hours was 1.25 (0.88 to 1.77), and for prescriptions of antibiotics was 1.04 (0.88 to 1.23). No significant effect modifications were found by sex, prematurity, age at randomisation, or season. The estimate did not change when censoring at the date infants received DTaP-IPV-Hib+PCV after randomisation (1.02, 0.90 to 1.16).

Conclusion

Findings of this trial conducted in Denmark, a high income setting, do not support the hypothesis that live attenuated MMR vaccine administered early to infants aged 5-7 months decreases the rate of hospitalisations for non-targeted infection before age 12 months.

Trial registration

EU Clinical Trials Registry EudraCT 2016-001901-18 and ClinicalTrials.gov
NCT03780179
.
Relationship between job stress and work-related quality of life among emergency medical technicians: a cross-sectional study
Authors: Hashemi Shima , Ghazanfari Firoozeh , Merzah Mohammed , Rezaei Mehdi , Astaraki Peyman , Birjandi Mehdi
Published: June 2023

Objective

This study was aimed to determine the relationship between job stress and work-related quality of life (WRQoL) among emergency medical technicians (EMTs) in Lorestan province, Western Iran.

Design

This was a cross-sectional study.

Methods

Totally 430 EMTs who had been engaged in their respective units for more than 6 months from all emergency facilities in Lorestan province were selected using single stage cluster sampling method. Data were collected from April to July 2019 using two standard questionnaires: job stress (Health and Safety Executive (HSE)) and WRQoL. The OR with 95% CI was used to declare the statistical association (p≤0.05).

Results

All participants were exclusively males, with a mean age of 32±6.87 years. The overall average score of job stress using the HSE scale was 2.69±0.43; while the overall quality of working life score was 2.48±1.01. The type of working shift was found to have a significant impact on the HSE-average score (F(3,417)=5.26, p=0.01); and on the WRQoL-average score (F(3,417)=6.89, p<0.01).

Conclusion

Two-thirds of EMTs working in governmental hospitals had job stress and a low quality of work-related life. Additionally, work shift was statistically significant associated with EMTs’ job stress and WRQoL.
Novel sequential treatment strategy for patients with muscle-invasive bladder cancer (MIBC): intravesical recombinant BCG, followed by neoadjuvant chemoimmunotherapy, radical cystectomy plus pelvic lymphadenectomy and adjuvant immunotherapy – protocol of a multicentre, single arm phase 2 trial (SAKK 06/19)
Authors: Petrausch Ulf , Spahn Martin , Schneider Martina , Hayoz Stefanie , Rentsch Cyrill A , Rothschild Sacha , Omlin Aurelius , Cathomas Richard
Published: June 2023

Introduction

The combination of checkpoint inhibition and cisplatin-based chemotherapy is investigated in muscle invasive bladder cancer (MIBC) and results from phase 2 trials have been presented. Intravesical BCG has been used for non-MIBC (NMIBC) in patients with carcinoma in situ and high-grade Ta/T1 tumours. BCG induces innate and adapted immune response and upregulation of PD-L1 in preclinical models. The proposed trial is intended to implement a new immuno-immuno-chemotherapy induction therapy for MIBC. The combination of BCG and checkpoint inhibition with chemotherapy aims at higher intravesical responses and better local and systemic control of disease.

Methods and analysis

SAKK 06/19 is an open-label single-arm phase II trial for patients with resectable MIBC T2-T4a cN0-1. Intravesical recombinant BCG (rBCG: VPM1002BC) is applied weekly for three instillations followed by four cycles of neoadjuvant cisplatin/gemcitabine every 3 weeks. Atezolizumab 1200 mg every 3 weeks is started together with rBCG and given for four cycles. All patients then undergo restaging and radical cystectomy and pelvic lymphadenectomy. Atezolizumab is continued as maintenance therapy after surgery every 3 weeks for 13 cycles. Pathological complete remission is the primary endpoint. Secondary endpoints include pathological response rate (<ypT2 N0), event-free survival, recurrence-free survival, overall survival, feasibility and toxicity. An interim safety analysis will be performed after the first 12 patients have completed neoadjuvant treatment specifically assessing toxicity possibly associated with intravesical rBCG application.

The study has received approval by ethical committee Zurich, Switzerland, BASEC-No. 2021–01872. Results will be made available by publication.

Trial registration number

NCT04630730.
Protocol for improving the costs and outcomes of assistive reproductive technology fertility care pathways: a study using cost measurement and process mining
Authors: Leusder Maura , van Elten Hilco J , Ahaus Kees , Hilders Carina G J M , van Santbrink Evert J P
Published: June 2023

Introduction

Value-based healthcare suggests that care outcomes should be evaluated in relation to the costs of delivering that care from the perspective of the provider. However, few providers achieve this because measuring cost is considered complex and elaborate and, further, studies routinely omit cost estimates from ‘value’ assessments due to lacking data. Consequently, providers are currently unable to steer towards increased value despite financial and performance pressures. This protocol describes the design, methodology and data collection process of a value measurement and process improvement study in fertility care featuring complex care paths with both long and non-linear patient journeys.

Methods and analysis

We employ a sequential study design to calculate total costs of care for patients undergoing non-surgical fertility care treatments. In doing so, we identify process improvement opportunities and cost predictors and will reflect on the benefits of the information generated for medical leaders. Time-to-pregnancy will be viewed in relation to total costs to determine value. By combining time-driven, activity-based costing with observations and process mining, we trial a method for measuring care costs for large cohorts using electronic health record data. To support this method, we create activity and process maps for all relevant treatments: ovulation induction, intrauterine insemination, in vitro fertilisation (IVF), IVF with intracytoplasmic sperm injection and frozen embryo transfer after IVF. Our study design, by showing how different sources of data can be combined to enable cost and outcome measurements, can be of value to researchers and practitioners looking to measure costs for care paths or entire patient journeys in complex care settings.

Ethics and dissemination

This study was approved by the ESHPM Research Ethics Review Committee (ETH122-0355) and the Reinier de Graaf Hospital (2022–032). Results will be disseminated through seminars, conferences and peer-reviewed publications.
Tolerability of bedtime diuretics: a prospective cohort analysis
Authors: Garrison Scott R , Kelmer Michael , Korownyk Tina , Kolber Michael R , Allan Gary Michael , Bakal Jeffrey , Singer Alexander , Katz Alan , Mcalister Finlay , Padwal Raj S , Lewanczuk Richard , Hill Michael D , McGrail Kimberlyn , O’Neill Braden , Greiver Michelle , Manca Donna P , Mangin Dee , Wong Sabrina T , Kirkwood Jessica E M , McCormack James P , Yeung Jack M S , Green Lee
Published: June 2023

Objectives

We sought to validate, or refute, the common belief that bedtime diuretics are poorly tolerated due to nocturia.

Design

Prespecified prospective cohort analysis embedded within the randomised BedMed trial, in which hypertensive participants are randomised to morning versus bedtime antihypertensive administration.

Setting

352 community family practices across 4 Canadian provinces between March 2017 and September 2020.

Participants

552 hypertensive patients (65.6 years old, 57.4% female) already established on a single once-daily morning antihypertensive and randomised to switch that antihypertensive to bedtime. Of these, 203 used diuretics (27.1% thiazide alone, 70.0% thiazide/non-diuretic combinations) and 349 used non-diuretics.

Intervention

Switching the established antihypertensive from morning to bedtime, and comparing the experience of diuretic and non-diuretic users.

Primary and secondary outcome measures

Primary outcome: Adherence to bedtime allocation time at 6 months (defined as the willingness to continue with bedtime use, not an assessment of missed doses). Secondary 6-month outcomes: (1) nocturia considered to be a major burden and (2) increase in overnight urinations/week. All outcomes were self-reported and additionally collected at 6 weeks.

Results

At 6 months: Adherence to bedtime allocation time was lower in diuretic users than non-diuretic users (77.3% vs 89.8%; difference 12.6%; 95% CI 5.8% to 19.8%; p<0.0001; NNH 8.0), and more diuretic users considered nocturia a major burden (15.6% vs 1.3%; difference 14.2%; 95% CI 8.9% to 20.6%; p<0.0001; NNH 7.0). Compared with baseline, diuretic users experienced 1.0 more overnight urinations/week (95% CI 0.0 to 1.75; p=0.01). Results did not differ between sexes.

Conclusions

Switching diuretics to bedtime did promote nocturia, but only 15.6% found nocturia a major burden. At 6 months, 77.3% of diuretic users were adherent to bedtime dosing. Bedtime diuretic use is viable for many hypertensive patients, should it ever become clinically indicated.

Trial registration number

NCT02990663.
Self-harm among unaccompanied asylum seekers and refugee minors: protocol for a global systematic review of prevalence, methods and characteristics
Authors: Hedrick Kyli , Borschmann Rohan
Published: June 2023

Introduction

Asylum seekers and refugees are at an elevated risk of self-harm, with younger age and traumatic experiences found to further increase such risk. Despite this, evidence regarding self-harm among unaccompanied asylum seekers and refugee minors has not been synthesised. As self-harm among minors is a risk factor for a range of adverse clinical and social outcomes, including suicide, such information may help to inform evidence-based prevention strategies among these vulnerable populations. This systematic review will synthesise findings from the literature regarding the prevalence, methods and characteristics of self-harm, including risk and protective factors, among unaccompanied asylum seekers and refugee minors internationally.

Methods and analysis

We searched key electronic databases (PsycINFO, Scopus, PubMed and Ovid MEDLINE) and grey literature for relevant studies published in English from database inception to 10 February 2023. Our primary outcome is self-harm among unaccompanied asylum seekers and/or refugee minors. With the exception of single-case studies, clinical trials and case-control studies, we will include all types of study design that examine the prevalence of self-harm in unaccompanied asylum seekers and/or refugee minors. We will exclude dissertations, conference abstracts, letters, book chapters, editorials, study registrations, registered protocols and qualitative studies. Only studies reporting on participants aged <18 years will be eligible for inclusion. The Methodological Standard for Epidemiological Research Scale will be used to assess the quality of included studies. If there are sufficient studies and homogeneity between them, we will conduct meta-analyses to calculate pooled estimates of self-harm rates, as well as comparisons between subgroups of relevance. If the studies do not report sufficient data, or there is substantial heterogeneity, we will provide a narrative synthesis of the findings.

Ethics and dissemination

This review is exempt from ethics approval. Our findings will be disseminated through peer-reviewed publications and conference presentations.

PROSPERO registration number

CRD42021292709.
Protocol for a qualitative study exploring the lived experience of hearing loss and patient reported experience in the UK: the HeLP study
Authors: Pryce Helen , Smith Sian Karen , Burns-O'Connell Georgina , Shaw Rachel , Hussain Saira , Banks Jonathan , Hall Amanda , Knibb Rebecca , Greenwood Rosemary , Straus Jean
Published: June 2023

Introduction

Worldwide, hearing loss is a significant public health issue and one of the most common chronic health conditions experienced by older adults. Hearing loss is associated with communication difficulties, social withdrawal, isolation and lower quality of life. Although hearing aid technology has improved significantly, the workload of managing hearing aids has increased. The aim of this qualitative study is to develop a novel theory of people’s lived experience of hearing loss across the lifespan.

Methods

Eligible participants will be young people and adults aged 16 years and above who have a hearing loss and carers/family members of people with a hearing loss. This study will use individual, in-depth face-to-face or online interviews. With participants’ permission, interviews will be audio-recorded and transcribed verbatim. A grounded theory approach to concurrent data gathering and analysis will develop grouped codes and categories and link these to provide a novel theory to describe the experience of hearing loss.

Ethics and dissemination

The study was approved by the West of Scotland Research Ethics Service (approval date: 6 May 2022 ref: 22/WS/0057) and the Health Research Authority and Health and Care Research Wales Approval (approval date: 14 June 2022; IRAS project ID: 308816). The research will inform the development of a Patient Reported Experience Measure to improve the information and support given to patients. Findings will be disseminated through peer-reviewed articles and at academic conferences, as well as to our patient and public involvement groups, healthcare professionals, audiology services and local commissioners.
Burden of mental health problems among pregnant and postpartum women in sub-Saharan Africa: systematic review and meta-analysis protocol
Authors: Awini Elizabeth , Agyepong Irene Akua , Owiredu David , Gyimah Leveana , Ashinyo Mary Eyram , Yevoo Linda Lucy , Aye Sorre Grace Emmanuelle Victoire , Abbas Shazra , Cronin de Chavez Anna , Kane Sumit , Mirzoev Tolib , Danso-Appiah Anthony
Published: June 2023

Introduction

Pregnancy and postpartum-related mental health problems pose serious public health threat to the society, but worryingly, neglected in sub-Saharan Africa (SSA). This review will assess the burden and distribution of maternal mental health (MMH) problems in SSA, with the aim to inform the implementation of context sensitive interventions and policies.

Methods and analysis

All relevant databases, grey literature and non-database sources will be searched. PubMed, LILAC, CINAHL, SCOPUS and PsycINFO, Google Scholar, African Index Medicus, HINARI,African Journals Onlineand IMSEAR will be searched from inception to 31 May 2023, without language restriction. The reference lists of articles will be reviewed, and experts contacted for additional studies missed by our searches. Study selection, data extraction and risk of bias assessment will be done independently by at least two reviewers and any discrepancies will be resolved through discussion between the reviewers. Binary outcomes (prevalence and incidence) of MMH problems will be assessed using pooled proportions, OR or risk ratio and mean difference for continuous outcomes; all will be presented with their 95% CIs. Heterogeneity will be investigated graphically for overlapping CIs and statistically using the I2statistic and where necessary subgroup analyses will be performed. Random-effects model meta-analysis will be conducted when heterogeneity is appreciable, otherwise fixed-effect model will be used. The overall level of evidence will be assessed using Grading of Recommendations Assessment, Development and Evaluation.

Ethics and dissemination

Although no ethical clearance or exemption is needed for a systematic review, this review is part of a larger study on maternal mental health which has received ethical clearance from the Ethics Review Committee of the Ghana Health Service (GHS-ERC 012/03/20). Findings of this study will be disseminated through stakeholder forums, conferences and peer review publications.

PROSPERO registration number

CRD42021269528.