bluuebunny/crossref_metadata_2025 huggingface dataset:
SR45a plays a key role in enhancing cotton resistance to Verticillium dahliae by alternative splicing of immunity genes
Authors: Liu Fujie , Cai Sheng , Dai Lingjun , Ai Nijiang , Feng Guoli , Wang Ningshan , Zhang Wenli , Liu Kang , Zhou Baoliang
Published: April 2024

Alternative splicing (AS) of pre‐mRNAs increases the diversity of transcriptome and proteome and plays fundamental roles in plant development and stress responses. However, the prevalent changes in AS events and the regulating mechanisms of plants in response to pathogens remain largely unknown. Here, we show that AS changes are an important mechanism conferring cotton immunity to Verticillium dahliae (Vd). GauSR45a, encoding a serine/arginine‐rich RNA binding protein, was upregulated expression and underwent AS in response to Vd infection in Gossypium australe, a wild diploid cotton species highly resistant to Vd. Silencing GauSR45a substantially reduced the splicing ratio of Vd‐induced immune‐associated genes, including GauBAK1 (BRI1‐associated kinase 1) and GauCERK1 (chitin elicitor receptor kinase 1). GauSR45a binds to the GAAGA motif that is commonly found in the pre‐mRNA of genes essential for PTI, ETI, and defense. The binding between GauSR45a and the GAAGA motif in the pre‐mRNA of BAK1 was enhanced by two splicing factors of GauU2AF35B and GauU1‐70 K, thereby facilitating exon splicing; silencing either AtU2AF35B or AtU1‐70 K decreased the resistance to Vd in transgenic GauSR45a Arabidopsis. Overexpressing the short splicing variant of BAK1GauBAK1.1 resulted in enhanced Verticillium wilt resistance rather than the long one GauBAK1.2. Vd‐induced far more AS events were in G. barbadense (resistant tetraploid cotton) than those in G. hirsutum (susceptible tetraploid cotton) during Vd infection, indicating resistance divergence in immune responses at a genome‐wide scale. We provided evidence showing a fundamental mechanism by which GauSR45a enhances cotton resistance to Vd through global regulation of AS of immunity genes.
Young guard cells function dynamically despite low mechanical anisotropy but gain efficiency during stomatal maturation in Arabidopsis thaliana
Authors: Jaafar Leila , Chen Yintong , Keynia Sedighe , Turner Joseph A. , Anderson Charles T.
Published: April 2024

Stomata are pores at the leaf surface that enable gas exchange and transpiration. The signaling pathways that regulate the differentiation of stomatal guard cells and the mechanisms of stomatal pore formation have been characterized in Arabidopsis thaliana. However, the process by which stomatal complexes develop after pore formation into fully mature complexes is poorly understood. We tracked the morphogenesis of young stomatal complexes over time to establish characteristic geometric milestones along the path of stomatal maturation. Using 3D‐nanoindentation coupled with finite element modeling of young and mature stomata, we found that despite having thicker cell walls than young guard cells, mature guard cells are more energy efficient with respect to stomatal opening, potentially attributable to the increased mechanical anisotropy of their cell walls and smaller changes in turgor pressure between the closed and open states. Comparing geometric changes in young and mature guard cells of wild‐type and cellulose‐deficient plants revealed that although cellulose is required for normal stomatal maturation, mechanical anisotropy appears to be achieved by the collective influence of cellulose and additional wall components. Together, these data elucidate the dynamic geometric and biomechanical mechanisms underlying the development process of stomatal maturation.
Presumed post‐traumatic subdural hygroma in a 2.5‐year‐old spayed female Chihuahua
Authors: Frouin Maxime , Cavalerie Robin , Piazza Stéphanie , Baudin‐Tréhiou Clément , Blond Laurent
Published: April 2024

A 2.5‐year‐old spayed female Chihuahua dog was presented with chronic cervical pain and exhibited a “prayer‐like position” following a history of a 4‐meter fall. CT and MRI revealed a moderate right‐sided enlargement of the subdural space with cerebrospinal fluid, consistent with a subdural hygroma, appearing connected to a quadrigeminal cistern dilation. Percutaneous transfontanellar external drainage of the subdural fluid accumulation did not prevent its re‐accumulation, and the dog was managed medically, leading to the complete resolution of clinical signs. The subdural hygroma was suspected to be secondary to the previous trauma.
The Use of Multimedia in Newspapers: A Study on the Websites of Emirati Newspapers
Authors: Abdallah Rania , Abokhoza Reneh , Aissani Rahima
Published: April 2024

The competition faced by journalistic websites has imposed the necessity of taking advantage of the capabilities offered by the Internet so that it can provide more distinguished journalistic services, to attract the largest number of users, as the strength of a newspaper website is measured by the number of people browsing it on the one hand, and the period that the user spends on it, The research problem is to monitor the use of multimedia websites of Emirati newspapers (Al-Ittihad, Al-Bayan, Al-Khaleej).The study aimed to determine the extent to which Emirati newspapers use multimedia in their websites during the study period (January - March 2023), and the key elements they used to present and publish their news to the audience. This study used the descriptive analytical approach for 14 issues of each newspaper on their websites, and several results were obtained, the most important of which are: The newspapers sampled for the study relied mainly on pictures, using them in 1272 out of 1632 media, with a percentage of 77.9%. The use of audio clips ranked second, with 218 clips out of 1632 media and a percentage of 13.3%. Al-Khaleej newspaper ranked first with 212 clips out of the total clips used, with a large margin of 97.25%, as it distinguished itself by using audio clips in every news story and alongside every video as an additional feature. Al-Ittihad newspaper only used 6 audio blogs, with a percentage of 2.75% out of 218 clips, followed by videos in third place with 100 videos out of the total media used, with a percentage of 6.1%. Infographics came in fourth place in terms of using multimedia, with 42 infographics, accounting for 2.7% of the total multimedia used.
Post-modernization Paradigm on the Modern Cultural Communication Research: A Literature Review
Authors: Razali Geofakta
Published: April 2024

The aim of this research study was to examine the patterns of cultural communication in the modern era and analyze its impact from a post-modernization paradigm. A rapid review approach employing the keywords “communication” AND “culture” AND “modern” was used to identify relevant articles published between 2019 and 2023. The reveiw which followed the PRISMA guidelines selected 35 articles that were grouped by type, function and purpose of communication (communication, identity, perception, education and entertainment) using the NVivo 12 Pro program. Most articles (n=13) were published in 2022 by predominantly authors from Russia. Modernization gives rise to cultural evolution and changes in ethnic and symbolic identities which drive post-modernists to advocate for the return of cultural identity that relies on various forms of communication. Modernization in cultural communication must be balanced with the post-modernization paradigm so that limitations in the generalization of communication design are in alignment with the subjective needs of each individual. The current study also acknowledged its methodological limitaons and potential biases for transparency and scientific rigor.
Path integrals and p$p$‐adic L$L$‐functions
Authors: Carlson Magnus , Chung Hee‐Joong , Kim Dohyeong , Kim Minhyong , Park Jeehoon , Yoo Hwajong
Published: April 2024

We prove an arithmetic ‘path integral’ formula for the inverse ‐adic absolute values of Kubota–Leopoldt ‐adic ‐functions at roots of unity.
A Constitutive Law Modeling the Mixed Hardening Behavior of Particle-Reinforced Composites
Authors: Zhang R. J. , Liu Yan
Published: April 2024

A homogenized elasto-plastic constitutive law (including both constitutive equations and inversed constitutive equations) is proposed in an incremental form for the particle-reinforced composites based on the flow theory of plasticity and the asymptotic homogenization method. The constitutive law can be used to predict the mixed hardening behavior of particle-reinforced composites under arbitrary loading conditions if the uniaxial tension test curve of matrix materials is known. It is found that the constitutive law of particle-reinforced composites is similar in form to the law of matrix materials. There is a simple proportional relationship between the yield stress, the plastic modulus, and the deviatoric back stress of particle-reinforced composites and the corresponding parameters of matrix materials, which is equal to the ratio of the shear modulus of composites to the shear modulus of matrix materials. The tangent modulus of particle-reinforced composites can be calculated using a simple arithmetic formula according to the tangent modulus of matrix materials. A numerical algorithm is suggested.
Parents on the Concept of Physical Literacy: What Do They Know, What Do They Do, and What Do They Want?
Authors: Simpson Aaron , Jackson Ben , Thornton Ashleigh L. , Rosenberg Michael , Ward Brodie , Roberts Peter , Derbyshire Amanda , Budden Timothy
Published: April 2024

Physical literacy development in early childhood, viewed by many as the foundation for lifelong physical activity engagement, is significantly influenced by parents. Our aim was to explore parents’ understanding of physical literacy and gain insight into their perspectives on physical literacy promotion. We recruited 18 parents of children between 5 and 8 years old in Australia. Using semistructured interviews and thematic analysis, we identified several key issues regarding parents’ understanding and implementation of physical literacy. Parents expressed interest in improving their implementation of physical literacy practices and had (often unintentionally) provided support for physical literacy subcomponents in the past. However, they described difficulties prioritizing physical literacy above other parental demands and expressed conflicting perceptions regarding where the responsibility should lie for developing their child’s physical literacy (e.g., at home or at school). To ensure that the physical literacy “message” reaches parents, we encourage physical literacy promoters to consider the target (e.g., responsibility, priorities, and awareness) of their promotional strategies. Further investigation into the influence of sociocultural and economic factors on parents’ understanding and application of physical literacy is warranted.
Persistent and responsive collective motion with adaptive time delay
Authors: Chen Zhihan , Zheng Yuebing
Published: April 2024

It is beneficial for collective structures to simultaneously have high persistence to environmental noise and high responsivity to nontrivial external stimuli. However, without the ability to differentiate useful information from noise, there is always a tradeoff between persistence and responsivity within the collective structures. To address this, we propose adaptive time delay inspired by the adaptive behavior observed in the school of fish. This strategy is tested using particles powered by optothermal fields coupled with an optical feedback-control system. By applying the adaptive time delay with a proper threshold, we experimentally observe the responsivity of the collective structures enhanced by approximately 1.6 times without sacrificing persistence. Furthermore, we integrate adaptive time delay with long-distance transportation and obstacle-avoidance capabilities to prototype adaptive swarm microrobots. This research demonstrates the potential of adaptive time delay to address the persistence-responsivity tradeoff and lays the foundation for intelligent swarm micro/nanorobots operating in complex environments.
ER-export and ARFRP1/AP-1–dependent delivery of SARS-CoV-2 Envelope to lysosomes controls late stages of viral replication
Authors: Pearson Guy J. , Mears Harriet V. , Broncel Malgorzata , Snijders Ambrosius P. , Bauer David L. V. , Carlton Jeremy G.
Published: April 2024

The β-coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the global COVID-19 pandemic. Coronaviral Envelope (E) proteins are pentameric viroporins that play essential roles in assembly, release, and pathogenesis. We developed a nondisruptive tagging strategy for SARS-CoV-2 E and find that, at steady state, it localizes to the Golgi and to lysosomes. We identify sequences in E, conserved across
Coronaviridae
, responsible for endoplasmic reticulum–to–Golgi export, and relate this activity to interaction with COP-II via SEC24. Using proximity biotinylation, we identify an ADP ribosylation factor 1/adaptor protein–1 (ARFRP1/AP-1)–dependent pathway allowing Golgi-to-lysosome trafficking of E. We identify sequences in E that bind AP-1, are conserved across β-coronaviruses, and allow E to be trafficked from Golgi to lysosomes. We show that E acts to deacidify lysosomes and, by developing a trans-complementation assay for SARS-CoV-2 structural proteins, that lysosomal delivery of E and its viroporin activity is necessary for efficient viral replication and release.
Genomic analyses correspond with deep persistence of peoples of Blackfoot Confederacy from glacial times
Authors: Rider Dorothy First , Wolf Annabel Crop Eared , Murray John , de Flamingh Alida , dos Santos Andre Luiz Campelo , Lanoë François , Zedeño Maria N. , DeGiorgio Michael , Lindo John , Malhi Ripan S.
Published: April 2024

Mutually beneficial partnerships between genomics researchers and North American Indigenous Nations are rare yet becoming more common. Here, we present one such partnership that provides insight into the peopling of the Americas and furnishes another line of evidence that can be used to further treaty and Indigenous rights. We show that the genomics of sampled individuals from the Blackfoot Confederacy belong to a previously undescribed ancient lineage that diverged from other genomic lineages in the Americas in Late Pleistocene times. Using multiple complementary forms of knowledge, we provide a scenario for Blackfoot population history that fits with oral tradition and provides a plausible model for the evolutionary process of the peopling of the Americas.
Pathogenic
TNNI1
variants disrupt sarcomere contractility resulting in hypo- and hypercontractile muscle disease
Authors: Donkervoort Sandra , van de Locht Martijn , Ronchi Dario , Reunert Janine , McLean Catriona A. , Zaki Maha , Orbach Rotem , de Winter Josine M. , Conijn Stefan , Hoomoedt Daan , Neto Osorio Lopes Abath , Magri Francesca , Viaene Angela N. , Foley A. Reghan , Gorokhova Svetlana , Bolduc Véronique , Hu Ying , Acquaye Nicole , Napoli Laura , Park Julien H. , Immadisetty Kalyan , Miles Lee B. , Essawi Mona , McModie Salar , Ferreira Leonardo F. , Zanotti Simona , Neuhaus Sarah B. , Medne Livija , ElBagoury Nagham , Johnson Kory R. , Zhang Yong , Laing Nigel G. , Davis Mark R. , Bryson-Richardson Robert J. , Hwee Darren T. , Hartman James J. , Malik Fady I. , Kekenes-Huskey Peter M. , Comi Giacomo Pietro , Sharaf-Eldin Wessam , Marquardt Thorsten , Ravenscroft Gianina , Bönnemann Carsten G. , Ottenheijm Coen A. C.
Published: April 2024

Troponin I (TnI) regulates thin filament activation and muscle contraction. Two isoforms, TnI-fast (
TNNI2
) and TnI-slow (
TNNI1
), are predominantly expressed in fast- and slow-twitch myofibers, respectively.
TNNI2
variants are a rare cause of arthrogryposis, whereas
TNNI1
variants have not been conclusively established to cause skeletal myopathy. We identified recessive loss-of-function
TNNI1
variants as well as dominant gain-of-function
TNNI1
variants as a cause of muscle disease, each with distinct physiological consequences and disease mechanisms. We identified three families with biallelic
TNNI1
variants (F1: p.R14H/c.190-9G>A, F2 and F3: homozygous p.R14C), resulting in loss of function, manifesting with early-onset progressive muscle weakness and rod formation on histology. We also identified two families with a dominantly acting heterozygous
TNNI1
variant (F4: p.R174Q and F5: p.K176del), resulting in gain of function, manifesting with muscle cramping, myalgias, and rod formation in F5. In zebrafish, TnI proteins with either of the missense variants (p.R14H; p.R174Q) incorporated into thin filaments. Molecular dynamics simulations suggested that the loss-of-function p.R14H variant decouples TnI from TnC, which was supported by functional studies showing a reduced force response of sarcomeres to submaximal [Ca
2+
] in patient myofibers. This contractile deficit could be reversed by a slow skeletal muscle troponin activator. In contrast, patient myofibers with the gain-of-function p.R174Q variant showed an increased force to submaximal [Ca
2+
], which was reversed by the small-molecule drug mavacamten. Our findings demonstrated that
TNNI1
variants can cause muscle disease with variant-specific pathomechanisms, manifesting as either a hypo- or a hypercontractile phenotype, suggesting rational therapeutic strategies for each mechanism.
Antibody-mediated targeting of human microglial leukocyte Ig-like receptor B4 attenuates amyloid pathology in a mouse model
Authors: Hou Jinchao , Chen Yun , Cai Zhangying , Heo Gyu Seong , Yuede Carla M. , Wang Zuoxu , Lin Kent , Saadi Fareeha , Trsan Tihana , Nguyen Aivi T. , Constantopoulos Eleni , Larsen Rachel A. , Zhu Yiyang , Wagner Nicole D. , McLaughlin Nolan , Kuang Xinyi Cynthia , Barrow Alexander D. , Li Dian , Zhou Yingyue , Wang Shoutang , Gilfillan Susan , Gross Michael L. , Brioschi Simone , Liu Yongjian , Holtzman David M. , Colonna Marco
Published: April 2024

Microglia help limit the progression of Alzheimer’s disease (AD) by constraining amyloid-β (Aβ) pathology, effected through a balance of activating and inhibitory intracellular signals delivered by distinct cell surface receptors. Human leukocyte Ig-like receptor B4 (LILRB4) is an inhibitory receptor of the immunoglobulin (Ig) superfamily that is expressed on myeloid cells and recognizes apolipoprotein E (ApoE) among other ligands. Here, we find that LILRB4 is highly expressed in the microglia of patients with AD. Using mice that accumulate Aβ and carry a transgene encompassing a portion of the
LILR
region that includes
LILRB4
, we corroborated abundant LILRB4 expression in microglia wrapping around Aβ plaques. Systemic treatment of these mice with an anti-human LILRB4 monoclonal antibody (mAb) reduced Aβ load, mitigated some Aβ-related behavioral abnormalities, enhanced microglia activity, and attenuated expression of interferon-induced genes. In vitro binding experiments established that human LILRB4 binds both human and mouse ApoE and that anti-human LILRB4 mAb blocks such interaction. In silico modeling, biochemical, and mutagenesis analyses identified a loop between the two extracellular Ig domains of LILRB4 required for interaction with mouse ApoE and further indicated that anti-LILRB4 mAb may block LILRB4-mApoE by directly binding this loop. Thus, targeting LILRB4 may be a potential therapeutic avenue for AD.
pH-dependent regulation of an acidophilic
O
-acetylhomoserine sulfhydrylase from
Lactobacillus plantarum
Authors: Matoba Yasuyuki , Oda Kosuke , Wataeda Maho , Kanemori Hina , Matsuo Koichi
Published: April 2024

Bacteria have two routes for the
l
-methionine biosynthesis. In one route called the direct sulfuration pathway, acetylated
l
-homoserine is directly converted into
l
-homocysteine. The reaction using H
2
S as the second substrate is catalyzed by a pyridoxal 5ʹ-phosphate-dependent enzyme,
O
-acetylhomoserine sulfhydrylase (OAHS). In the present study, we determined the enzymatic functions and the structures of OAHS from
Lactobacillus plantarum
(
Lp
OAHS). The
Lp
OAHS enzyme exhibited the highest catalytic activity under the weak acidic pH condition. In addition, crystallographic analysis revealed that the enzyme takes two distinct structures, open and closed forms. In the closed form, two acidic residues are sterically clustered. The proximity may cause the electrostatic repulsion, inhibiting the formation of the closed form under the neutral to the basic pH conditions. We concluded that the pH-dependent regulation mechanism using the two acidic residues contributes to the acidophilic feature of the enzyme.

IMPORTANCE

In the present study, we can elucidate the pH-dependent regulation mechanism of the acidophilic OAHS. The acidophilic feature of the enzyme is caused by the introduction of an acidic residue to the neighborhood of the key acidic residue acting as a switch for the structural interconversion. The strategy may be useful in the field of protein engineering to change the optimal pH of the enzymes. In addition, this study may be useful for the development of antibacterial drugs because the
l
-methionine synthesis essential for bacteria is inhibited by the OAHS inhibitors. The compounds that can inhibit the interconversion between the open and closed forms of OAHS may become antibacterial drugs.
Bulky malignant peripheral nerve sheath tumour of the left thigh in a pregnant woman presenting with a pathological fracture of the proximal femur
Authors: Catelas Diogo , Sousa Duarte , Rodrigues Ana Patrícia , Cardoso Pedro
Published: April 2024

Malignant peripheral nerve sheath tumour (MPNST) is an aggressive soft tissue sarcoma with a poor prognosis, affecting most commonly the extremities. The lungs constitute the most frequent location for distant metastases. Half of all MPNSTs arise in patients with neurofibromatosis type 1, while approximately 10% are radiation induced and the rest are sporadic.

The authors present a pregnant woman in her 40s with a sporadic MPNST of the lower limb and with lung metastases at diagnosis. Treatment consisted of interilioabdominal amputation, followed by adjuvant chemotherapy. Partial response and disease stabilisation were achieved with chemotherapy.

Surgical resection with negative margins is the only potentially curative therapy, while radiation therapy and chemotherapy might be useful in the neoadjuvant or adjuvant setting, but their advantage in survival is not demonstrated. In the reported case, chemotherapy permitted the achievement of partial response and stabilisation of the disease.
Aggressive precursor B cell ALL of cervix with obstructive uropathy
Authors: Bahadur Anupama , Mundhra Rajlaxmi , Gill Poonam , Singh Ashok
Published: April 2024

Involvement of the cervix with acute lymphoblastic leukaemia (ALL) is extremely rare. In this case report, we discuss an unmarried woman in her early 20s, who presented in the emergency with lower abdominal pain and irregular vaginal bleeding for 1 month. Clinical examination and imaging revealed a large cervical mass probably neoplastic with obstructive uropathy. On evaluation, she was diagnosed incidentally with CALLA-positive precursor B cell ALL in peripheral blood flow cytometry. Involvement of B cell ALL in cervical mass was confirmed by histopathological examination of cervical biopsy and immunohistochemistry markers. Her history was not suggestive of signs and symptoms pertaining to leukaemia. Literature is sparse with only a few cases reporting cervical leukaemic infiltration. The present case report is a rarest case where the primary/initial presentation of precursor B cell ALL was seen with cervical involvement and obstructive uropathy mimicking characteristics of advanced cervical malignancy.
Acute kidney failure reveals primary renal non-Hodgkin lymphoma
Authors: Klaus Martin , Sitter Thomas , Hoppe John Michael
Published: April 2024

A male patient in his 60s was admitted to our hospital with symptoms of dyspnoea, asthenia, diaphoresis and acute kidney failure. No tumour or infection was detected in initial screening. However, laboratory examination suggested that the acute kidney failure was due to an intrarenal cause, exhibiting a tubular injury pattern and indications of tumour lysis syndrome. Initial hydration therapy, paired with intravenous rasburicase, rapidly improved the kidney function. Unfortunately, the kidney function deteriorated once again, prompting a kidney biopsy that revealed an aggressive diffuse large B-cell non-Hodgkin lymphoma of the kidney. The chemotherapy, comprised of R-CHOP scheme, led to a full recovery of the kidney function and complete remission of the lymphoma. Primary renal non-Hodgkin lymphoma without nodal manifestation is rare, and its pathophysiology is poorly understood. Therapy schemes can vary significantly between cases, relying primarily on non-renal-specific haemato-oncological guidelines. Therefore, further studies are needed to develop the best therapeutic approaches.
Under-5 mortality surveillance in low-income and middle-income countries: insights from two Health and Demographic Surveillance Systems in rural Gambia
Authors: Wutor Baleng Mahama , Osei Isaac , Sarwar Golam , Adefila Williams Oluwatosin , Galega Lobga Babila , Hossain Ilias , Abdulsalam Yusuf , Lamin Keita Modou , Baldeh Alhagie Muya , Barry Basiru , Ezeani Esu , Mackenzie Grant
Published: April 2024

Without complete data on under-5 mortality, tracking progress towards achieving Sustainable Development Goal 3.2 will be challenging. Such data are also needed to ensure proper planning and prioritisation of scarce resources in low-income and middle-income countries. However, most low-income and middle-income countries have weak Civil Registration and Vital Statistics (CRVS) systems, leaving a critical gap in understanding under-5 mortality dynamics. This paper outlines a community-based approach to enhance under-5 mortality surveillance in low-income countries, using The Gambia as a case study. The methodology involves Health and Demographic Surveillance Systems (HDSSs) in Basse and Fuladu West, employing unique identification numbers, periodical household visits and collaboration with communities, village reporters and project field workers to ensure comprehensive data collection. Verbal autopsies (VAs) are conducted by trained field workers, and causes of death are determined using the physician-certified VA method. Between 1 September 2019 and 1 September 2023, 1333 deaths were detected, for which causes of death were determined for 97.1% (1294 of 1333). The most common causes of death detected were acute respiratory infections including pneumonia, sepsis, diarrhoeal diseases and birth asphyxia. Challenges include the cost of maintaining the HDSSs, poor road infrastructure, Electronic Data Capture transition challenges, and the need for national integration of HDSS data into the CRVS system. The success of this model highlights its potential for scalable and adaptable under-5 mortality surveillance in resource-limited settings.
Association of prepregnancy body mass index and gestational weight gain trajectory with adverse pregnancy outcomes—a prospective cohort study in Shanghai
Authors: Ma Ziwen , Chu Liming , Zhang Zhiping , Hu Yifan , Zhu Yun , Wu Fei , Zhang Yan
Published: April 2024

Objectives

The objective was to investigate the associations of maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) trajectories with adverse pregnancy outcomes (APOs).

Design

This was a prospective cohort study.

Setting

This study was conducted in Shanghai Pudong New Area Health Care Hospital for Women and Children, Shanghai, China.

Primary and secondary outcome measures

A cohort study involving a total of 2174 pregnant women was conducted. Each participant was followed to record weekly weight gain and pregnancy outcomes. The Institute of Medicine classification was used to categorise prepregnancy BMI, and four GWG trajectories were identified using a latent class growth model.

Results

The adjusted ORs for the risks of large for gestational age (LGA), macrosomia, gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) were significantly greater for women with prepregnancy overweight/obesity (OR=1.77, 2.13, 1.95 and 4.24; 95% CI 1.3 to 2.42, 1.32 to 3.46, 1.43 to 2.66 and 2.01 to 8.93, respectively) and lower for those who were underweight than for those with normal weight (excluding HDP) (OR=0.35, 0.27 and 0.59; 95% CI 0.22 to 0.53, 0.11 to 0.66 and 0.36 to 0.89, respectively). The risk of small for gestational age (SGA) and low birth weight (LBW) was significantly increased in the underweight group (OR=3.11, 2.20; 95% CI 1.63 to 5.92, 1.10 to 4.41; respectively) compared with the normal-weight group; however, the risk did not decrease in the overweight/obese group (p=0.942, 0.697, respectively). GWG was divided into four trajectories, accounting for 16.6%, 41.4%, 31.7% and 10.3% of the participants, respectively. After adjustment for confounding factors, the risk of LGA was 1.54 times greater for women in the slow GWG trajectory group than for those in the extremely slow GWG trajectory group (95% CI 1.07 to 2.21); the risk of SGA and LBW was 0.37 times and 0.46 times lower for women in the moderate GWG trajectory group and 0.14 times and 0.15 times lower for women in the rapid GWG trajectory group, respectively; the risk of macrosomia and LGA was 2.65 times and 2.70 times greater for women in the moderate GWG trajectory group and 3.53 times and 4.36 times greater for women in the rapid GWG trajectory group, respectively; and the women in the other three trajectory groups had a lower risk of GDM than did those in the extremely slow GWG trajectory group, but there was not much variation in the ORs. Notably, different GWG trajectories did not affect the risk of HDP.

Conclusions

As independent risk factors, excessively high and low prepregnancy BMI and GWG can increase the risk of APOs.
Internet-delivered transdiagnostic psychological treatments for individuals with depression, anxiety or both: a systematic review with meta-analysis of randomised controlled trials
Authors: Kolaas Karoline , Berman Anne H , Hedman-Lagerlöf Erik , Lindsäter Elin , Hybelius Jonna , Axelsson Erland
Published: April 2024

Objective

Depression and anxiety are major public health problems. This study evaluated the effects of internet-delivered transdiagnostic psychological treatments for individuals with depression, anxiety, or both.

Design

Systematic review with meta-analysis.

Data sources

Medline (Ovid), Cochrane Library (Wiley), the Web of Science Core Collection (Clarivate), and PsycInfo (EBSCO) were searched on 24 May 2021, with an update on 6 February 2023.

Eligibility criteria

Randomised controlled trials of internet-delivered transdiagnostic psychological treatments, open to both participants with primary depression and participants with primary anxiety. This review concerned all treatment frameworks, both guided and unguided formats and all age groups.

Data extraction and synthesis

In random-effects meta-analysis, we estimated pooled effects on depression symptoms and anxiety in terms of Hedges’gwith 95% CIs. Absolute and relative heterogeneity was quantified as the τ2andI2.

Results

We included 57 trials with 21 795 participants. Nine trials (16%) recruited exclusively from routine care, and three (5%) delivered treatment via video. For adults, large within-group reductions were seen in depression (g=0.90; 95% CI 0.81 to 0.99) and anxiety (g=0.87; 95% CI 0.78 to 0.96). Compared with rudimentary passive controls, the added effects were moderate (depression:g=0.52; 95% CI 0.42 to 0.63; anxiety:g=0.45; 95% CI 0.34 to 0.56) and larger in trials that required all participants to meet full diagnostic criteria for depression or an anxiety disorder. Compared with attention/engagement controls, the added effects were small (depression:g=0.30; 95% CI 0.07 to 0.53; anxiety:g=0.21; 95% CI 0.01 to 0.42). Heterogeneity was substantial, and the certainty of the evidence was very low. Two trials concerned adolescents and reported mixed results. One trial concerned older adults and reported promising results.

Conclusion

Internet-delivered transdiagnostic treatments for depression and anxiety show small-to-moderate added effects, varying by control condition. Research is needed regarding routine care, the video format, children and adolescents and older adults.

PROSPERO registration number

CRD42021243172.
Efficacy of electro-acupuncture versus sham acupuncture for diabetic peripheral neuropathy: study protocol for a three-armed randomised controlled trial
Authors: Zhuang Rong , Xiong Zhiyi , Yan Shiyan , Zhang Haoran , Dong Qi , Liu Weiai , Miao Jinling , Zhuo Yuanyuan , Fan Xiaohong , Zhang Weiliang , Wang Xiaomei , Liu Lian , Cao Jianan , Zhang Tiansheng , Hao Chongyao , Huang Xingxian , Jiang Lijiao
Published: April 2024

Introduction

Specific treatment for diabetic peripheral neuropathy (DPN) is still lacking, and acupuncture may relieve the symptoms. We intend to investigate the efficacy and safety of electro-acupuncture (EA) in alleviating symptoms associated with DPN in diabetes.

Methods and analysis

This multicentre, three-armed, participant- and assessor-blind, randomised, sham-controlled trial will recruit 240 eligible participants from four hospitals in China and will randomly assign (1:1:1) them to EA, sham acupuncture (SA) or usual care (UC) group. Participants in the EA and SA groups willl receive either 24-session EA or SA treatment over 8 weeks, followed by an 8-week follow-up period, while participants in the UC group will be followed up for 16 weeks. The primary outcome of this trial is the change in DPN symptoms from baseline to week 8, as rated by using the Total Symptom Score. The scale assesses four symptoms: pain, burning, paraesthesia and numbness, by evaluating the frequency and severity of each. All results will be analysed with the intention-to-treat population.

Ethics and dissemination

The protocol has been approved by the Ethics Committee of the Beijing University of Chinese Medicine (Identifier: 2022BZYLL0509). Every participant will be informed of detailed information about the study before signing informed consent. The results of this trial will be published in a peer-reviewed journal.

Trial registration number

ChiCTR2200061408.
Implementation of an intervention aimed at deprescribing benzodiazepines in a large US healthcare system using patient education materials: a pre/post-observational study with a control group
Authors: Le Tammy M , Campbell Scott , Andraos Alexa , Ahlmark Pedro , Hoang Ha , Isserman Sean , Goldzweig Caroline L , Mays Allison M , Bradley Kristin , Keller Michelle S
Published: April 2024

Objectives

Long-term benzodiazepine use is common despite known risks. In the original Eliminating Medications Through Patient Ownership of End Results (EMPOWER) Study set in Canada, patient education led to increased rates of benzodiazepine cessation. We aimed to determine the effectiveness of implementing an adapted EMPOWER quality improvement (QI) initiative in a US-based healthcare system.

Design

We used a pre–post design with a non-randomised control group.

Setting

A network of primary care clinics.

Participants

Patients with ≥60 days’ supply of benzodiazepines in 6 months and ≥1 risk factor (≥65 years of age, a concurrent high-risk medication prescribed or a diazepam equivalent daily dose ≥10) were eligible.

Intervention

In March 2022, we engaged 22 primary care physicians (PCPs), and 308 of their patients were mailed an educational brochure, physician letter and flyer detailing benzodiazepine risks; the control group included 4 PCPs and 291 of their patients.

Primary and secondary measures

The primary measure was benzodiazepine cessation by 9 months. We used logistic regression and a generalised estimating equations approach to control for clustering by PCP, adjusting for demographics, frailty, number of risk factors, and diagnoses of arthritis, depression, diabetes, falls, and pain.

Results

Patients in the intervention and control groups were comparable across most covariates; however, a greater proportion of intervention patients had pain-related diagnoses and depression. By 9 months, 26% of intervention patients (81 of 308) had discontinued benzodiazepines, compared with 17% (49 of 291) of control patients. Intervention patients had 1.73 greater odds of benzodiazepine discontinuation compared with controls (95% CI: 1.09, 2.75, p=0.02). The unadjusted number needed to treat was 10.5 (95% CI: 6.30, 34.92) and the absolute risk reduction was 0.095 (95% CI: 0.03 to 0.16).

Conclusions

Results from this non-randomised QI initiative indicate that patient education programmes using the EMPOWER brochures have the potential to promote cessation of benzodiazepines in primary care.
Prospective cohort study of genomic newborn screening: BabyScreen+ pilot study protocol
Authors: Lunke Sebastian , Bouffler Sophie E , Downie Lilian , Caruana Jade , Amor David J , Archibald Alison , Bombard Yvonne , Christodoulou John , Clausen Marc , De Fazio Paul , Greaves Ronda F , Hollizeck Sebastian , Kanga-Parabia Anaita , Lang Nitzan , Lynch Fiona , Peters Riccarda , Sadedin Simon , Tutty Erin , Eggers Stefanie , Lee Crystle , Wall Meaghan , Yeung Alison , Gaff Clara , Gyngell Christopher , Vears Danya F , Best Stephanie , Goranitis Ilias , Stark Zornitza
Published: April 2024

Introduction

Newborn bloodspot screening (NBS) is a highly successful public health programme that uses biochemical and other assays to screen for severe but treatable childhood-onset conditions. Introducing genomic sequencing into NBS programmes increases the range of detectable conditions but raises practical and ethical issues. Evidence from prospectively ascertained cohorts is required to guide policy and future implementation. This study aims to develop, implement and evaluate a genomic NBS (gNBS) pilot programme.

Methods and analysis

The BabyScreen+ study will pilot gNBS in three phases. In the preimplementation phase, study materials, including education resources, decision support and data collection tools, will be designed. Focus groups and key informant interviews will also be undertaken to inform delivery of the study and future gNBS programmes. During the implementation phase, we will prospectively recruit birth parents in Victoria, Australia, to screen 1000 newborns for over 600 severe, treatable, childhood-onset conditions. Clinically accredited whole genome sequencing will be performed following standard NBS using the same sample. High chance results will be returned by genetic healthcare professionals, with follow-on genetic and other confirmatory testing and referral to specialist services as required. The postimplementation phase will evaluate the feasibility of gNBS as the primary aim, and assess ethical, implementation, psychosocial and health economic factors to inform future service delivery.

Ethics and dissemination

This project received ethics approval from the Royal Children’s Hospital Melbourne Research Ethics Committee: HREC/91500/RCHM-2023, HREC/90929/RCHM-2022 and HREC/91392/RCHM-2022. Findings will be disseminated to policy-makers, and through peer-reviewed journals and conferences.
Protocol for a construct and clinical validation study of MyCog Mobile: a remote smartphone-based cognitive screener for older adults
Authors: Young Stephanie Ruth , McManus Dworak Elizabeth , Byrne Greg J , Jones Callie Madison , Yoshino Benavente Julia , Yao Lihua , Curtis Laura M , Varela Diaz Maria , Gershon Richard , Wolf Michael , Nowinski Cindy
Published: April 2024

Introduction

Annual cognitive screening in older adults is essential for early detection of cognitive impairment, yet primary care settings face time constraints that present barriers to routine screening. A remote cognitive screener completed on a patient’s personal smartphone before a visit has the potential to save primary care clinics time, encourage broader screening practices and increase early detection of cognitive decline. MyCog Mobile is a promising new remote smartphone-based cognitive screening app for primary care settings. We propose a combined construct and clinical validation study of MyCog Mobile.

Methods and analysis

We will recruit a total sample of 300 adult participants aged 65 years and older. A subsample of 200 healthy adult participants and a subsample of 100 adults with a cognitive impairment diagnosis (ie, dementia, mild cognitive impairment, cognitive deficits or other memory loss) will be recruited from the general population and specialty memory care centres, respectively. To evaluate the construct validity of MyCog Mobile, the healthy control sample will self-administer MyCog Mobile on study-provided smartphones and be administered a battery of gold-standard neuropsychological assessments. We will compare correlations between performance on MyCog Mobile and measures of similar and dissimilar constructs to evaluate convergent and discriminant validity. To assess clinical validity, participants in the clinical sample will self-administer MyCog Mobile on a smartphone and be administered a Mini-Cog screener and these data will be combined with the healthy control sample. We will then apply several supervised model types to determine the best predictors of cognitive impairment within the sample. Area under the receiver operating characteristic curve, accuracy, sensitivity and specificity will be the primary performance metrics for clinical validity.

Ethics and dissemination

The Institutional Review Board at Northwestern University (STU00214921) approved this study protocol. Results will be published in peer-reviewed journals and summaries provided to the study’s funders.
Using Blood Wisely: lessons learnt in establishing a national implementation programme to reduce inappropriate red blood cell transfusion
Authors: Lin Yulia , Levinson Wendy , Day Doreen , Lett Ryan , Petraszko Tanya , Huynh Tai , Patey Andrea M
Published: April 2024

Background

Up to 50% of blood is transfused inappropriately despite best evidence. In 2020, Choosing Wisely Canada launched a major national programme, ‘Using Blood Wisely’, the aim was to engage hospitals to audit their red blood cell transfusion use against national benchmarks and participate in a programme to decrease inappropriate use.

Study design

Using Blood Wisely is a quality improvement programme including national benchmarks, an audit tool, recommended evidence-based effective interventions and a designation to reward success. Hospital engagement was measured using the number of hospitals signing up, performing a baseline audit, submitting the planning survey, entering two or more audits and achieving hospital designation. Barriers to implementation were collected.

Results

From 1 September 2020 to 31 December 2022, 229 individual hospitals signed up over time to participate. Their results are reported as 159 hospitals and hospital groups. Collectively, this accounts for 72% of the blood used in Canada. Overall, 147 (92%) performed a baseline audit, 10 (6%) submitted a planning survey and 130 (82%) entered two or more audits. At baseline (time of enrolment), 75 (51%) met both benchmarks. The designation was awarded to 62 (39%) hospital groups (a total of 105 individual hospitals) that met and sustained benchmarks. Barriers to implementation included human resource shortages, lack of local expertise to advise the team, need for more education of transfusion prescribers and competing priorities.

Conclusion

In its initial phase, Using Blood Wisely engaged a substantial number of hospitals in transfusion quality improvement work and maintained that engagement. This large-scale engagement across a big country was more successful than anticipated. Additional efforts are needed to rigorously evaluate the programme’s impact on utilisation.
Paediatricians’ perspectives in treating lower urinary tract symptoms: a qualitative exploratory needs assessment study
Authors: Spinzi Stav , Agrawal Gunjan , Sharma Aditi , Venkatapuram Pranaya , Sharma Kritika , Brown-Johnson Cati , Kan Kathleen M
Published: April 2024

Background

Paediatric lower urinary tract symptoms (LUTS) are common experiences among school-aged children, with prevalence rates reaching as high as 20%. Paediatricians are often first-line stakeholders in providing treatment for these bothersome symptoms, yet there is no formal resource to support them with the treatment of LUTS. Evaluating paediatricians’ experiences is an important step in informing health promotion efforts to improve health outcomes in children. This study aims to explore paediatricians’ knowledge, beliefs, practice patterns, and perceived barriers and facilitators in providing LUTS care.

Methods

In this qualitative study, we conducted semistructured focus groups of paediatricians within California. Focus groups were conducted via Zoom, and participants were enrolled until thematic saturation was reached. Participants were asked about their current practices, knowledge and beliefs, barriers and facilitators to care, training and education, and responsibility for behaviour and action. Thematic analysis was performed using deductive and inductive approaches; themes were mapped through an iterative, team-based process.

Results

15 paediatricians, aged 30–69 years, with 13 (86.7%) women, were interviewed. Most (11, 73.3%) practised in general outpatient settings. Interviewed paediatricians recognised paediatric LUTS as a common problem that can significantly impact children’s well-being. In practice, paediatricians did not actively screen for LUTS beyond the potty-training milestone due to short visit duration and competing healthcare demands. Lack of guidelines, parental mistrust and inadequate clinical education were barriers identified by paediatricians.

Conclusions

Paediatricians expressed a willingness to help patients but indicated several limitations to providing adequate LUTS care. Future professional development work can emphasise guideline development, early screening strategies to support timely intervention and better education for clinicians.
Twenty-four-hour blood pressure trajectories and clinical outcomes in patients who had an acute ischaemic stroke
Authors: Wang Ruirui , Liu Yang , Zhang Qilu , Zhang Jing , Peng Hao , Shi Mengyao , Peng Yanbo , Xu Tian , Wang Aili , Xu Tan , Chen Jing , Zhang Yonghong , He Jiang
Published: April 2024

Objective

The management of blood pressure (BP) in acute ischaemic stroke remains a subject of controversy. This investigation aimed to explore the relationship between 24-hour BP patterns following ischaemic stroke and clinical outcomes.

Methods

A cohort of 4069 patients who had an acute ischaemic stroke from 26 hospitals was examined. Five systolic BP trajectories were identified by using latent mixture modelling: trajectory category 5 (190–170 mm Hg), trajectory category 4 (180–140 mm Hg), trajectory category 3 (170–160 mm Hg), trajectory category 2 (155–145 mm Hg) and trajectory category 1 (150–130 mm Hg). The primary outcome was a composite outcome of death and major disability at 3 months poststroke.

Results

Patients with trajectory category 5 exhibited the highest risk, while those with trajectory category 1 had the lowest risk of adverse outcomes at 3-month follow-up. Compared with the patients in the trajectory category 5, adjusted ORs (95% CIs) for the primary outcome were 0.79 (0.58 to 1.10), 0.70 (0.53 to 0.93), 0.64 (0.47 to 0.86) and 0.47 (0.33 to 0.66) among patients in trajectory category 4, trajectory category 3, trajectory category 2 and trajectory category 1, respectively. Similar trends were observed for death, vascular events and the composite outcome of death and vascular events.

Conclusion

Patients with persistently high BP at 180 mm Hg within 24 hours of ischaemic stroke onset had the highest risk, while those maintaining stable BP at a moderate-low level (150 mm Hg) or even a low level (137 mm Hg) had more favourable outcomes.