bluuebunny/crossref_metadata_2025 huggingface dataset:
Paroxysmal dystonia and psychotic exacerbations in chronic psychosis: Diagnostic dilemmas and preliminary treatment approaches
Authors: Mishra Biswa Ranjan , Biswas Tathagata , Sreeraj Vanteemar S. , Nath Santanu , Mohapatra Debadatta , Maiti Rituparna
Published: May 2023

Patients with chronic psychosis on prolonged antipsychotic therapy may present with paroxysmal dystonia along with an exacerbation of their psychotic symptoms: paroxysmal dystonia and psychotic exacerbations (PDPE). The interindividual variability in the clinical presentations of PDPE can pose challenges in its diagnosis and treatment. The objectives of this work are to (i) discuss this rare phenomenon through a series of 10 patients and a relevant literature review, (ii) conceptualize its neurobiological underpinnings, and (iii) explore the preliminary treatment approaches for its management. Acute stress and/or a dysfunctional gamma‐aminobutyric acid (GABA) ergic or dopaminergic system may be implicated in the pathogenesis of PDPE. The episodes respond acutely to parenteral benzodiazepines, while long‐term management can be achieved by reducing antipsychotic doses, switching to clozapine or using central GABA enhancers. This article is the first attempt at conceptualizing and exploring treatment options for the rare condition PDPE and intends to guide future research in this regard.
The impact of the COVID‐19 pandemic on antibiotic consumption and prevalence of pathogens in primary and secondary healthcare settings in Northern Ireland
Authors: Aldeyab Mamoon A. , Crowe William , Karasneh Reema A. , Patterson Lynsey , Sartaj Muhammad , Ewing Judith , Lattyak William J. , Al‐Azzam Sayer , Araydah Mohammad , Darwish Elhajji Feras , Kabbaha Suad , Conway Barbara R. , Conlon‐Bingham Geraldine , Farren David , Scott Michael
Published: May 2023

Aim

To evaluate the impact of the COVID‐19 pandemic on the patterns of antimicrobial use and the incidence of pathogens in primary and secondary healthcare settings in Northern Ireland.

Methods

Data were collected on antibiotic use and Gram‐positive and Gram‐negative pathogens from primary and secondary healthcare settings in Northern Ireland for the period before (January 2015‐March 2020) and during (April 2020‐December 2021) the pandemic. Time series intervention analysis methods were utilized.

Results

In the hospital setting, the mean total hospital antibiotic consumption during the pandemic was 1864.5 defined daily doses (DDDs) per 1000 occupied‐bed days (OBD), showing no significant change from pre‐pandemic (P = .7365). During the pandemic, the use of second‐generation cephalosporins, third‐generation cephalosporins, co‐amoxiclav and levofloxacin increased, there was a decrease in the percentage use of the hospital Access group (P = .0083) and an increase in the percentage use of Watch group (P = .0040), and the number of hospital Klebsiella oxytoca and methicillin‐susceptible Staphylococcus aureus cases increased. In primary care, the mean total antibiotic consumption during the COVID‐19 pandemic was 20.53 DDDs per 1000 inhabitants per day (DID), compared to 25.56 DID before the COVID‐19 pandemic (P = .0071). During the pandemic, there was a decrease in the use of several antibiotic classes, an increase in the percentage use of the Reserve group (P = .0032) and an increase in the number of community‐onset Pseudomonas aeruginosa cases.

Conclusion

This study provides details of both changes in antibiotic consumption and the prevalence of infections in hospitals and primary care before and during the COVID‐19 pandemic that emphasize the importance of antimicrobial stewardship in pandemic situations.
Guiding future paediatric drug studies based on existing pharmacokinetic and efficacy data: Cardiovascular drugs as a proof of concept
Authors: Smeets Nori J. L. , Raaijmakers Lieke P. M. , van der Zanden Tjitske M. , Male Christoph , de Wildt Saskia N.
Published: May 2023

Introduction

Off‐label drug use in the paediatric population is common, and the lack of high‐quality efficacy studies poses patients at risk for failing pharmacotherapy. Next to efficacy studies, pharmacokinetic (PK) studies are increasingly used to inform paediatric dose selection. As resources for paediatric trials are limited, we aimed to summarize existing PK and efficacy studies to identify knowledge gaps in available evidence supporting paediatric dosing recommendations, thereby taking paediatric cardiovascular drugs as proof of concept.

Methods

For each cardiovascular drug, paediatric indication and prespecified age group, together comprising one record, the authorized state was assessed. Next, for off‐label records, the highest level of evidence was scored. High‐quality efficacy studies were defined as meta‐analysis or randomized controlled trials. Other comparative research, noncomparative research or consensus‐based expert opinions were considered low quality. The level of evidence for PK studies was scored per drug and per age group, but regardless of indication.

Results

A total of 58 drugs included 417 records, of which 279 (67%) were off‐label. Of all off‐label records, the majority (81%) were not supported by high‐quality efficacy studies, but for 140 of these records (62%) high‐quality PK studies were available.

Conclusion

We demonstrated that for the majority of off‐label cardiovascular drugs, only low‐quality efficacy studies were available. However, high‐quality PK studies were frequently available. Combining these PK data with extrapolation of efficacy data from adults may help to close the current information gap and prioritize the drugs for which clinical studies and safety data are urgently needed.
Discussion of the special issue on cognitive load theory
Authors: Sweller John
Published: May 2023

Background

The present Special Issue contains 9 papers exploring novel cognitive load theory research questions.

Aim

To provide a discussion of the 9 articles in this Special Issue of the Journal and to highlight the strengths and weaknesses of the papers and indicate opportunities for future studies.

Procedure

Briefly summarizes cognitive load theory in its current version followed by the discussion of the 9 individual papers.
In the arena: contesting disaster creation in cities
Authors: Cheek Wesley Webb , Chmutina Ksenia , von Meding Jason
Published: May 2023

Space is a feature of all disasters, and it is through decisions on how space is developed, used, and reproduced that disasters manifest themselves. Critical urban theory sees urban space—cities—as an arena of contestation expressed through the relationship between people, power, and the built environment. Cities allow for an unpacking of this process of contestation through the interpretation of various temporal, spatial, social, and physical elements that together create complex issues and ‘wicked problems’. In these urban spaces in all their complexity, disasters reveal both the worst injustices and inequalities present in a society. By drawing on three well‐known cases—Hurricane Katrina in 2010; the Haiti earthquake in 2010; and the Great East Japan Earthquake and Tsunami in 2011—this paper not only explores the opportunities that critical urban theory presents for gaining a deeper understanding of disaster risk creation, but also it encourages disaster scholars to engage with it.
What outcomes do disabled children and their caregivers value most?
Authors: Geboers Jessica
Published: May 2023

This commentary is on the original article by Heydenrijk‐Kikkert et al. on pages 1493–1500 of this issue.
Use of underwater contactless ultrasonography to elucidate the internal anatomy and reproductive activity of manta and devil rays (family: Mobulidae)
Authors: Froman Niv , Genain Marie‐Aude , Stevens Guy M. W. , Pearce Gareth P.
Published: May 2023

The ability to visualise the internal anatomical structures of fish provides important information on their reproductive status and body condition and has made important contributions to many areas of fish biology. Obtaining information on the internal anatomy of fish has traditionally required euthanasia and dissection. Although ultrasonography is now increasingly used to study internal fish anatomy without the need for euthanasia, traditional techniques still require restraint and contact with the animal, both of which are known to cause stress. This has prompted the development of waterproof, contactless and portable equipment to allow ultrasonographic examinations to be carried out in free‐swimming individuals, which also facilitates the application of this tool in wild populations of endangered species. This study reports the validation of this equipment using anatomical examinations of nine manta and devil ray (Mobulidae) specimens landed at fish markets in Sri Lanka. The species studied were Mobula kuhlii (n = 3), Mobula thurstoni (n = 1), Mobula mobular (n = 1), Mobula tarapacana (n = 1) and Mobula birostris (n = 3). The use of this equipment was further validated with ultrasonographic examinations in 55 free‐swimming reef manta rays Mobula alfredi, which enabled maturity status to be quantified in 32 females. Structures successfully identified in free‐swimming individuals were the liver, spleen, gallbladder, gastrointestinal tract, skeletal structures, developing follicles and uterus. The study demonstrated that ultrasonography provided a reliable method of determining both sexual maturity and gestational status in free‐swimming M. alfredi. The methodology induced no detectable signs of disturbance to the animals involved and therefore offers a viable and practical alternative to invasive techniques currently used to study anatomical changes in both captive and wild marine organisms.
Satisfaction with injection experience of patients with neuroendocrine tumors enrolled on lanreotide autogel patient support programs: Results from the international HomeLAN survey
Authors: Hernando Jorge , Kolarova Teodora , Verslype Chris , Kaltsas Gregory , Houchard Aude , Gueguen Delphine , De Herder Wouter W.
Published: May 2023

Lanreotide autogel/depot (LAN) is a somatostatin analog used in first‐line treatment for neuroendocrine tumors (NETs). The aim of HomeLAN was to evaluate the satisfaction with injection experience among patients with NETs receiving at‐home LAN injection via patient support programs (PSPs). This was an international, non‐interventional, cross‐sectional, online survey in adults with NETs enrolled in PSPs, receiving LAN injections at home, administered by a healthcare professional (HCP) or administered independently (self or caregiver administering injection). The primary endpoint was satisfaction with the most recent LAN injection. Secondary endpoints included the level of anxiety prior to injection, impact on daily life, and the extents to which participants felt in control of their life and agreed that home administration met their medical needs. In total, 111 participants from Belgium, Greece, the Netherlands, and Spain completed the survey (50.5% male; mean age, 63.6 years; most common primary tumor site was intestine [47.7%]). For 99 participants, their most recent injection was administered by an HCP. Overall, 95.5% of all participants were satisfied with their most recent injection experience (95% confidence interval: 89.89%–98.06%); 67% reported experiencing no anxiety prior to injection, 91.0% reported that home injection had a “great deal” or “quite a bit” of positive impact on their daily life, and 85.6% strongly agreed that the PSP met their medical needs. In the HCP injection subgroup, 71.7% reported that this mode of administration helped them to feel in control of their lives. In this patient survey, satisfaction levels were high among patients with NETs receiving LAN injections at home via a LAN PSP. Most patients did not experience anxiety prior to their most recent injection and acknowledged that thanks to their treatment they had a good quality of life despite their disease. Most strongly agreed that the PSP met their medical needs, which highlights the valuable service that LAN PSPs provide for patients with NETs.
COVID‐19: The disease, the vaccine and the heart
Authors: Turner Christian J
Published: May 2023

Coronavirus SARS‐CoV‐2 has fundamentally affected the health, healthcare delivery and daily life in all populations and age groups in Australia. The aim of this report is to summarise how it has affected the paediatric population with an emphasis on, but not limited to, the cardiac manifestations. A literature review and appraisal of data relating to SARS‐CoV‐2 cardiac manifestations and vaccination in the paediatric population was undertaken.The majority of children with SARS‐CoV‐2 infection recover well. However, a very small proportion may develop severe acute disease. In the sub‐acute phase, children may also develop a Kawasaki like illness, Paediatric Inflammatory Multisystem Syndrome temporally associated with SARS‐CoV‐2. Whilst not directly cardiac in nature, SARS‐CoV‐2 also affected children in other profound ways. Public health measures with widespread lockdowns appeared to disproportionately affect the paediatric population causing physical deconditioning and psychological harm. Vaccination against SARS‐CoV‐2 has proven to be safe and effective, but the small rate of complications did disproportionately affect teenage children with risks of myocarditis and pericarditis. The long term outcomes following myocarditis related to SARS‐Cov‐2 vaccination are yet to be clarified. When treating children in the era of SARS‐CoV‐2, Paediatricians need to be well aware of the risks of infection in the acute and sub‐acute phases, have a good understanding of the well‐established recommendations for vaccination, and also be cognisant of psychological impacts.
Mortality associated with antiarrhythmic medication for atrial fibrillation among patients with left ventricular hypertrophy
Authors: Agdamag Arianne Clare , Westanmo Anders , Gravely Amy , Angsubhakorn Natthapon , Chen Lin Yee , Adabag Selcuk
Published: May 2023

Background

Atrial fibrillation (AF) guidelines recommend amiodarone as the preferred antiarrhythmic medication (AAM) in patients with left ventricular hypertrophy (LVH), due to potential pro‐arrhythmic risk with other AAM. However, there are limited data to support this assertion.

Methods

We retrospectively analyzed the records of 8204 patients who were prescribed AAM for AF and had transthoracic echocardiogram (TTE) at the multicenter, VA Midwest Health Care Network from 2000 to 2021. We excluded patients without LVH (septal or posterior wall dimension ≤1.4 cm). The primary outcome variable was all‐cause mortality during antiarrhythmic therapy or within 6 months after stopping it. Propensity‐stratified analyses were performed between amiodarone versus non‐amiodarone (Vaughan‐Williams Class I and III) AAM.

Results

A total of 1277 patients with LVH (mean age 70.2 ± 9.5 years) were included in the analysis. Of these, 774 (60.6%) were prescribed amiodarone. Baseline characteristics of the two comparison groups were similar after propensity adjustment. After a median 1.40 years of follow‐up, 203 (15.9%) patients died. Incidence rates per 100 patient‐year follow‐up was 9.02 (7.58–10.66) for amiodarone and 4.98 (3.91–62.56) for non‐amiodarone. In propensity‐stratified analysis, amiodarone use was associated with 1.58 times higher risk of mortality (95% CI 1.03–2.44; p = .038). Sub‐group analysis in 336 (26.3%) patients with severe LVH showed no difference in mortality (HR 1.41, 95% CI 0.82–2.43, p = .21).

Conclusion

Among patients with AF and LVH, amiodarone was associated with a significantly higher mortality risk than other AAM.
The chromatic number of Rn$\mathbb {R}^{n}$ with multiple forbidden distances
Authors: Naslund Eric
Published: May 2023

Let be a finite set of distances, and let be the graph with vertex set and edge set , and let . Erdős asked about the growth rate of the m‐distance chromatic number
We improve the best existing lower bound for , and show that
where is an explicit constant. Our full result is more general, and applies to cliques in this graph. Let denote the minimum number of colors needed to color G so that no color contains a ‐clique, and let denote the largest value this takes for any distance set of size m. Using the partition rank method, we show that
A “Think Coach, Think Male” Phenomenon: Women Coaches’ Experiences of Development, Progression, and Retention in Coaching Within the United Kingdom
Authors: Gosai Jyoti , Jowett Sophia , Rhind Daniel J.A.
Published: May 2023

Women coaches have remained underrepresented within sports coaching at all levels. Thus, the purpose of this paper was to describe the factors surrounding the development, progression, and retention of women coaches within the United Kingdom. The study involved semistructured interviews with 15 women coaches who were coaching female athletes in team sports. Content analysis of the qualitative data identified barriers and enablers at individual, interpersonal, organisational, and sociocultural levels. Results indicated that women coaches face several barriers because of their gender, which their men counterparts do not often encounter. Practically, individuals and organisations can both take action to reduce damaging stereotypical ideologies that produce challenging predicaments for women within the coaching landscape.
Calibrating Physical Activity and Sedentary Behavior for Hip-Worn Accelerometry in Older Women With Two Epoch Lengths: The Women’s Health Initiative Objective Physical Activity and Cardiovascular Health Calibration Study
Authors: Evenson Kelly R. , Wen Fang , Moore Christopher C. , LaMonte Michael J. , Lee I-Min , LaCroix Andrea Z. , Di Chongzhi
Published: May 2023

Purpose: The purpose of this study was to develop 60-s epoch accelerometer intensity cut points for vertical axis count and vector magnitude (VM) output from hip-worn triaxial accelerometers among women 60–91 years old. We also compared these cut points against cut points derived by multiplying 15-s epoch cut points by four. Methods: Two hundred apparently healthy women wore an ActiGraph GT3X+ accelerometer on their hip while performing a variety of laboratory-based activities that were sedentary (watching television and assembling a puzzle), low light (washing/drying dishes), high light (laundry and dust mopping), or moderate-to-vigorous physical activity (400-m walk) intensity. Oxygen uptake was measured using an Oxycon portable calorimeter. Sedentary behavior and physical activity intensity cut points for vertical axis and VM counts were derived for 60-s epochs from receiver operating characteristic and by multiplying the 15-s cut points by four; both were compared with oxygen uptake. Results: The median age was 74.5 years (interquartile range 70–83). The 60-s epoch cut points for vertical counts were 0 sedentary, 1–73 low light, 74–578 high light, and ≥579 moderate-to-vigorous physical activity. The 60-s epoch cut points for VM were 0–88 sedentary, 89–663 low light, 664–1,730 high light, and ≥1,731 moderate-to-vigorous physical activity. For both sets of cut points, the receiver operating characteristic approach yielded more accurate estimates than the multiplication approach. Conclusion: The derived 60-s epoch cut points for vertical counts and VM can be applied to epidemiologic studies to define sedentary behavior and physical activity intensities in older adult populations.
Physical Activity and Sitting Time Patterns and Sociodemographic Correlates Among 155,790 South American Adults
Authors: Werneck André O. , Araujo Raphael H.O. , Anza-Ramírez Cecilia , Brazo-Sayavera Javier , García-Witulski Christian , Aguilar-Farias Nicolas , Baldew Se-Sergio , Sadarangani Kabir P. , Ramírez-Vélez Robinson , García-Hermoso Antonio , Ferrari Gerson , Cañete Felicia , Nieto-Martinez Ramfis , Silva Danilo R.
Published: May 2023

Background: To estimate the prevalence of different physical activity (PA) domains and sitting time (ST), and to analyze the association with sociodemographic indicators. Methods: Data from the most recent nationally representative survey from each of the South American countries, comprising 155,790 adults (18–64 y), were used. Data on leisure-time, transport, and occupational PA (all 3 domains as nonzero), total PA (≥150 min/wk), and ST (≥8 h/d) were assessed by specific questionnaires in each survey. Gender, age group (18–34, 35–49, and 50–64 y), and education (quintiles) were used as sociodemographic factors. Random effect meta-analysis of the association between sociodemographic factors and PA and ST were conducted. Results: The prevalence of PA guidelines compliance and elevated ST in South America was 70.3% and 14.1%, respectively. Women were less likely to achieve the recommended levels of total and domain-based PA. Participants in the highest quintile of education were more likely for elevated ST (2.80, 2.08–3.77), lower occupational PA (0.65, 0.44–0.95), but higher leisure-time PA (3.13, 2.31–4.27), in comparison with lowest quintile. Older adults were less likely to participate in total and leisure-time PA. Conclusion: Our findings highlight the urge to tackle the inequalities in PA practice in South America, especially gender and education inequalities, for leisure-time PA.
Functional neuronal circuits promote disease progression in cancer
Authors: Restaino Anthony C. , Walz Austin , Vermeer Samuel J. , Barr Jeffrey , Kovács Attila , Fettig Robin R. , Vermeer Daniel W. , Reavis Hunter , Williamson Caitlin S. , Lucido Christopher T. , Eichwald Tuany , Omran Dalia K. , Jung Euihye , Schwartz Lauren E. , Bell Maria , Muirhead DesiRae M. , Hooper Jody E. , Spanos William C. , Drapkin Ronny , Talbot Sebastien , Vermeer Paola D.
Published: May 2023

The molecular and functional contributions of intratumoral nerves to disease remain largely unknown. We localized synaptic markers within tumors suggesting that these nerves form functional connections. Consistent with this, electrophysiological analysis shows that malignancies harbor significantly higher electrical activity than benign disease or normal tissues. We also demonstrate pharmacologic silencing of tumoral electrical activity. Tumors implanted in transgenic animals lacking nociceptor neurons show reduced electrical activity. These data suggest that intratumoral nerves remain functional at the tumor bed. Immunohistochemical staining demonstrates the presence of the neuropeptide, Substance P (SP), within the tumor space. We show that tumor cells express the SP receptor, NK1R, and that ligand/receptor engagement promotes cellular proliferation and migration. Our findings identify a mechanism whereby intratumoral nerves promote cancer progression.
Single-cell multiomic analysis identifies a HOX-PBX gene network regulating the survival of lymphangioleiomyomatosis cells
Authors: Olatoke Tasnim , Wagner Andrew , Astrinidis Aristotelis , Zhang Erik Y. , Guo Minzhe , Zhang Alan G. , Mattam Ushodaya , Kopras Elizabeth J. , Gupta Nishant , Smith Eric P. , Karbowniczek Magdalena , Markiewski Maciej M. , Wikenheiser-Brokamp Kathryn A. , Whitsett Jeffrey A. , McCormack Francis X. , Xu Yan , Yu Jane J.
Published: May 2023

Lymphangioleiomyomatosis (LAM) is a rare, progressive lung disease that predominantly affects women. LAM cells carry
TSC1/TSC2
mutations, causing mTORC1 hyperactivation and uncontrolled cell growth. mTORC1 inhibitors stabilize lung function; however, sustained efficacy requires long-term administration, and some patients fail to tolerate or respond to therapy. Although the genetic basis of LAM is known, mechanisms underlying LAM pathogenesis remain elusive. We integrated single-cell RNA sequencing and single-nuclei ATAC-seq of LAM lungs to construct a gene regulatory network controlling the transcriptional program of LAM cells. We identified activation of uterine-specific HOX-PBX transcriptional programs in pulmonary LAM
CORE
cells as regulators of cell survival depending upon HOXD11-PBX1 dimerization. Accordingly, blockage of HOXD11-PBX1 dimerization by HXR9 suppressed LAM cell survival in vitro and in vivo. PBX1 regulated STAT1/3, increased the expression of antiapoptotic genes, and promoted LAM cell survival in vitro. The HOX-PBX gene network provides promising targets for treatment of LAM/TSC mTORC1-hyperactive cancers.
A multiyear tropical Pacific cooling response to recent Australian wildfires in CESM2
Authors: Fasullo John T. , Rosenbloom Nan , Buchholz Rebecca
Published: May 2023

The climate response to biomass burning emissions from the 2019–2020 Australian wildfire season is estimated from two 30-member ensembles using CESM2: one of which incorporates observed wildfire emissions and one that does not. In response to the fires, an increase in biomass aerosol burdens across the southern hemisphere is simulated through late 2019 and early 2020, accompanied by an enhancement of cloud albedo, particularly in the southeastern subtropical Pacific Ocean. In turn, the surface cools, the boundary layer dries, and the moist static energy of the low-level flow into the equatorial Pacific is reduced. In response, the intertropical convergence zone migrates northward and sea surface temperature in the Niño3.4 region cools, with coupled feedbacks amplifying the cooling. A subsequent multiyear ensemble mean cooling of the tropical Pacific is simulated through the end of 2021, suggesting an important contribution to the 2020–2022 strong La Niña events.
Nature-inspired catalytic asymmetric rearrangement of cyclopropylcarbinyl cation
Authors: Li Qing-Hua , Zhang Gui-Shan , Wang Feng , Cen Yixin , Liu Xi-Liang , Zhang Jian-Wei , Wang Yu-Hui , Lee Albert W. M. , Gao Dingding , Lin Guo-Qiang , Tian Ping
Published: May 2023

In nature, cyclopropylcarbinyl cation is often involved in cationic cascade reactions catalyzed by natural enzymes to produce a great number of structurally diverse natural substances. However, mimicking this natural process with artificial organic catalysts remains a daunting challenge in synthetic chemistry. We report a small molecule–catalyzed asymmetric rearrangement of cyclopropylcarbinyl cations, leading to a series of chiral homoallylic sulfide products with good to excellent yields and enantioselectivities (up to 99% enantiomeric excess). In the presence of a chiral SPINOL-derived
N
-triflyl phosphoramide catalyst, the dehydration of prochiral cyclopropylcarbinols occurs rapidly to generate symmetrical cyclopropylcarbinyl cations, which are subsequently trapped by thione-containing nucleophiles. A subgram-scale experiment and multiple downstream transformations of the sulfide products are further pursued to demonstrate the synthetic utility. Notably, a few heteroaromatic sulfone derivatives could serve as “covalent warhead” in the enzymatic inhibition of severe acute respiratory syndrome coronavirus 2 main protease.
Combinational Deletions of
MGF110-9L
and
MGF505-7R
Genes from the African Swine Fever Virus Inhibit TBK1 Degradation by an Autophagy Activator PIK3C2B To Promote Type I Interferon Production
Authors: Zhu Guoqiang , Ren Jingjing , Li Dan , Ru Yi , Qin Xiaodong , Feng Tao , Tian Hong , Lu Bingzhou , Shi Dongfang , Shi Zhengwang , Yang Wenping , Zheng Haixue
Published: May 2023

African swine fever (ASF) is a contagious and lethal hemorrhagic disease of pigs caused by the African swine fever virus (ASFV), leading to significant economic consequences for the global pig industry. The development of an effective and safe ASF vaccine has been unsuccessful.
Diversity of Fungal Communities on Diseased and Healthy Cinnamomum burmannii Fruits and Antibacterial Activity of Secondary Metabolites
Authors: Wang Wei , Cai Teng , Yang Yuting , Guo Hui , Shang Zhuo , Shahid Hamza , Zhang Yirong , Qiu Sirun , Zeng Xinnian , Xu Xiaoli , Liu Yi , Fang Ping , Ding Ping , Mao Ziling , Shan Tijiang
Published: May 2023

Powdery fruit disease is a notorious disease of
Cinnamomum burmannii
that causes severe loss in fruit production. Studies on the function of endophytic fungal communities in healthy plant tissues are not new, while little is known about the functional changes of fungal communities in disease-causing plant tissues.
Calibrating the Early Cretaceous Urho Pterosaur Fauna in Junggar Basin and implications for the evolution of the Jehol Biota
Authors: Zheng Daran , Chang Su-Chin , Ramezani Jahandar , Xu Xing , Xu Honghe , Wang He , Pei Rui , Fang Yanan , Wang Jun , Wang Bo , Zhang Haichun
Published: May 2023

Over the past decades, abundant and well-preserved vertebrate fossils, known as the Urho Pterosaur Fauna, have been recovered from the Lower Cretaceous Tugulu Group in Junggar Basin, Xinjiang, NW China. Excavated materials belong to pterosaur, plesiosaur, dinosaur, crocodylomorph, and turtle taxa. As such, they provide key insights into the evolutionary history of several critical vertebrate groups in the Early Cretaceous. The Junggar assemblages have been interpreted as belonging to the Jehol Biota sensu lato, representing its northwesternmost known geographic extent. This research presents a new chemical abrasion−isotope dilution−thermal ionization mass spectrometry U-Pb age of 135.2 ± 0.9 Ma (2σ internal error) from a tuffaceous bed stratigraphically below the fauna-bearing layers, indicating a Valanginian maximum age for the Urho fauna. Combined with available biostratigraphic data, the results bear several important paleobiologic implications for the Early Cretaceous vertebrates. First, the Dsungaripterus pterosaur and Psittacosaurus ornithischian fauna appear to have emerged earlier than previously believed. Second, the data suggest that the oldest carcharodontosaurids in Asia appeared during the Valanginian Stage and extend the age range of basal coelurosaurs and basal crocodyliforms. Our results do not support the notion of the Jehol Biota sensu lato migrating as far west as the Junggar Basin in their later stages. The new information calls into question the temporal and spatial bases for the conventional, three-stage evolutionary theory of the Jehol Biota.
Survival, hospitalisation and surgery in children born with Pierre Robin sequence: a European population-based cohort study
Authors: Santoro Michele , Garne Ester , Coi Alessio , Tan Joachim , Loane Maria , Ballardini Elisa , Cavero-Carbonell Clara , de Walle Hermien EK , Gatt Miriam , Gissler Mika , Jordan Sue , Klungsøyr Kari , Lelong Natalie , Urhoj Stine Kjaer , Wellesley Diana G , Morris Joan K
Published: May 2023

Objective

To evaluate survival, hospitalisations and surgical procedures for children born with Pierre Robin sequence (PRS) across Europe.

Design

Multicentre population-based cohort study.

Setting

Data on 463 live births with PRS from a population of 4 984 793 from 12 EUROCAT congenital anomaly registries.

Methods

Data on children with PRS born 1995–2014 were linked electronically to data on mortality, hospitalisations and surgical procedures up to 10 years of age. Each registry applied a common data model to standardise the linked data and ran common syntax scripts to produce aggregate tables. Results from each registry were pooled using random-effect meta-analyses.

Main outcome measures

Probability of survival, proportion of children hospitalised and undergoing surgery, and median length of hospital stay.

Results

The majority of deaths occurred in the first year of life with a survival rate of 96.0% (95% CI 93.5% to 98.5%); 95.1% (95% CI 92.7% to 97.7%) survived to age 10. In the first year of life, 99.2% (95% CI 95.0% to 99.9%) of children were hospitalised with a median stay of 21.4 days (95% CI 15.6 to 27.2), and 67.6% (95% CI 46.6% to 81.8%) underwent surgery. In the first 5 years of life, 99.2% of children underwent a median of two surgical procedures. Between ages 5 and 9, 58.3% (95% CI 44.7% to 69.7%) were hospitalised with a median annual stay of 0.3 days.

Conclusions

Children with PRS had high mortality and morbidity with long hospital stays in the first year of life, and almost all had surgery before 5 years of age. Survival improved after infancy with fewer hospitalisations after age 5. This study provides reliable estimates of the survival and morbidity of children with PRS for families and healthcare providers.
Training the public health emergency response workforce: a mixed-methods approach to evaluating the virtual reality modality
Authors: Bugli Dante , Dick Leah , Wingate Kaitlin C , Driscoll Scott , Beck Dave , Walsh Bridget , Greiner Ashley Lauren
Published: May 2023

Objectives

To produce and evaluate a novel virtual reality (VR) training for public health emergency responders.

Design

Following a VR training designed to test key public health emergency responder competencies, a prospective cohort of participants completed surveys rating self-assessed skill levels and perceptions of training methods.

Setting

The VR training sessions were administered in a quiet room at the US Centers for Disease Control and Prevention (CDC), Atlanta, Georgia.

Participants

All participants volunteered from a list of CDC emergency international surge responders.

Outcome measures

Perceived impact of the training on responder skills was self-reported via a Likert 5-point scale questionnaire. Assessments were modelled according to the Expanded Technology Acceptance Model measuring participantperceived usefulness ofandintention to usethe new technology. Inductive coding of qualitative feedback resulted in the identification of central themes.

Results

From November 2019 to January 2020, 61 participants were enrolled. Most (98%) participants self-rated above neutral for all skills (mean 4.3; range 1.21–5.00). Regression modelling showed that theperceived ease of use ofthe VR and ability to producedemonstrable resultsas likely drivers of further use. Participants agreed that others would benefit from the training (97%), it was representative of actual response scenarios (72%) and they would use lessons learnt in the field (71%). Open-response feedback highlighted feeling being immersed in the training and its utility for public health responders.

Conclusions

At a time when a trained emergency public health workforce is a critical need, VR may be an option for addressing this gap. Participants’ impressions and feedback, in the setting of their high skill level and experience, highlighted the utility and benefit of using VR to deliver training. Further research is needed to determine skill acquisition through VR training among a pool of future responders with limited to no response experience.
Association between bilirubin levels and risk of stroke: a systematic review and meta-analysis
Authors: Wang Gege , Qiao Luyao , Tang Zhenyu , Zhou Siqi , Min Jun , Li Min
Published: May 2023

Objective

To evaluate the association between bilirubin levels and stroke risk.

Design

Systematic review and meta-analysis, reported in accordance with Meta-analysis Of Observational Studies in Epidemiology guidelines.

Data sources

The PubMed, Embase, Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure Databases were searched from inception up to 27 February 2022.

Eligibility criteria

Cohort studies assessing the dose–response relationship between bilirubin levels and risk of stroke were eligible for inclusion. There were no language restrictions.

Data extraction and synthesis

All data from eligible studies were collected and assessed by two independent investigators. We generated pooled relative risks (RRs) with 95% CIs. We used a restricted cubic spline model for the dose–response analyses. Subsequent subgroup analyses were conducted according to stroke outcomes, follow-up duration, geographical area and size of the cohort.

Results

Nine articles including results from 11 cohort studies with 7835 cases of stroke and 263 596 participants met the inclusion criteria. The summarised RR of stroke comparing the highest and lowest bilirubin level was 0.85 (95% CI 0.72 to 0.99). The dose–response analysis indicated that a 15 µmol/L increment of bilirubin level was associated with an 18% lower risk of stroke (RR=0.82, 95% CI 0.67 to 0.99). For ischaemic stroke, the RR was 0.76 (95% CI 0.58 to 0.99). Significant publication bias was not detected.

Conclusions

Elevated bilirubin levels were associated with a decreased risk of stroke among adults.

PROSPERO registration number

CRD42017071497.
Evaluation of health utility in trial-based cost–utility analyses for major cardiovascular disease: protocol for a systematic review
Authors: Nakao Yasuhisa , Kawakami Hiroshi , Miyazaki Shigehiro , Saito Makoto , Luo Yan , Yamamoto Kazumichi , Yamaguchi Osamu
Published: May 2023

Introduction

The global incidence of cardiovascular disease (CVD) is high, and the medical costs associated with its management have been increasing. Cost–utility analyses (CUAs) are essential for understanding the value of healthcare interventions and for decision-making. A majority of the CUAs for CVD are model based and have cited health utilities from previously published data; standard health utilities for the CUAs of CVD have not been established yet. Thus, we aim to identify the standard utilities according to the patients’ condition and disease severity in patients with major CVDs.

Methods and analysis

We will search Medline and Evidence-Based Medicine Reviews for trial-based CUA studies that have reported on quality-adjusted life-years using original health utilities for patients with three major forms of CVD (coronary artery disease, heart failure and atrial fibrillation). Papers on trial-based CUAs will be included, while those on model-based CUAs will be excluded. No restrictions will be made in terms of intervention type. The main outcome comprises the health utilities calculated on a scale of 0–1 (irrespective of the measurement methods) at baseline and after treatment. Two independent investigators will screen the eligibility of articles; they will extract data, including health utilities, from the eligible articles for further analysis. The quality of the included studies will be assessed using the Consolidated Health Economic Evaluation Reporting Standards checklist. We will describe the means and SDs of the health utilities from all the included studies. The mean utility weights for individual studies will be combined through meta-analyses using a random-effects model to obtain the representative health utility value for each disease. Subgroup analyses will be conducted according to the severity and duration of each disease.

Ethics and dissemination

Ethical approval is not required. The review will be submitted to an appropriate peer-reviewed journal.

PROSPERO registration number

CRD42022316278.
Study protocol: how does parental stress measured by clinical scales and voice acoustic stress markers predict children’s response to PTSD trauma-focused therapies?
Authors: Zeghari Radia , Gindt Morgane , König Alexandra , Nachon Ophelie , Lindsay Hali , Robert Philippe , Fernandez Arnaud , Askenazy Florence
Published: May 2023

Introduction

Post-traumatic stress disorder (PTSD) symptoms in youth are influenced by parental anxiety and stress. When parents have high levels of stress or have developed PTSD themselves, children tend to show more anxiety symptoms. Parental stress can affect the severity of children’s PTSD and lower the success of recovery. However, the influence of parental stress on the effectiveness of trauma-focused therapies (eye movement desensitisation and reprocessing and cognitive behavioural therapy) has not yet been investigated to our knowledge. Hence, we will measure parental stress (using both validated scales and vocal acoustic markers) and investigate how it influences children’s PTSD recovery.

Method and analysis

Sixty children between the ages of 7 and 15 years who experienced type 1 trauma will be recruited at the Nice Pediatric Psychotrauma Center in France. We plan to measure stress using two different approaches. We will ask parents to answer validated scales of stress and mood in general. Stress will also be measured using vocal acoustic markers. Parents will be recorded while narrating their child’s trauma and during the narrative of a positive and neutral recall of events. Child participants will have to complete anxiety, PTSD and depression scales before the beginning of the trauma-focused therapy and after 3 months of treatment.

Linear mixed effects models and differential statistics, such as significance testing corrected for multiple testing, will be used to determine the validity of speech features for the proposed hypotheses. Repeated measures analysis of variance will be performed on the clinical scales scores according to parental stress. Correlations will be performed between clinical scales of parents and children according to time of assessment.

Ethics and dissemination

This study was approved by the Committee for the Protection of Individuals of the University of Nice Sophia Antipolis (CERNI) on 21 February 2022, under the number CER2022-015.

All participants will be informed that this is an observational study and their consent taken prior to the experiment. Participants will be informed that they can withdraw from the study at any time and that it would not affect the care provided.

Trial registration number

CER AVIS n° 2022-015.
Epidemiological study on gender bias and low-value practices in primary care: a study protocol
Authors: Carrillo Irene , Lopez-Pineda Adriana , Pérez-Jover Virtudes , Guilabert Mercedes , Vicente María Asunción , Fernández César , Gil-Guillen Vicente F , Orozco-Bletrán Domingo , Chilet-Rosell Elisa , Luzon Oliver Lourdes , Astier-Peña Maria Pilar , Tella Susanna , Carratalá-Munuera Concepción , Mira José Joaquín
Published: May 2023

Introduction

Evidence shows that gender has a substantial impact on health behaviours, access to and use of health systems and health system responses. This study aims to assess gender bias in patients subjected to low-value practices in the primary care setting and to develop recommendations for reducing adverse events that women experience for this reason.

Methods and analysis

A Delphi study will be performed to reach a consensus on the ‘Do Not Do’ recommendations with a possible gender bias. A retrospective cohort study in a random selection of medical records will then be carried out to identify the frequency of adverse events that occur when the selected ‘Do Not Do’ recommendations are ignored. Qualitative research techniques (consensus conference and nominal group) will be carried out to develop recommendations to address any gender bias detected, considering barriers and facilitators in clinical practice.

Ethics and dissemination

The study was approved by the ethics committee of San Juan de Alicante Hospital (San Juan de Alicante, Spain) Reference N. 21/061. We will disseminate the research findings via peer-reviewed articles, presentations at national and international scientific forums and webinars.

Trial registration number

The study was registered at ClinicalTrials.gov (NCT05233852) on 10 February 2022.
Compliance and patient satisfaction with treatment settings recommended by the medical on-call service 116117 in Germany using computer-assisted structured initial assessment: a cross-sectional observational study accompanying the demand intervention
Authors: Schäfer Ingmar , Menzel Agata , Herrmann Tobias , Willms Gerald , Oltrogge Jan Hendrik , Lühmann Dagmar , Scherer Martin
Published: May 2023

Objectives

In order to reduce the use of emergency departments, computer-assisted initial assessment was implemented at the medical on-call service 116117. Our study assessed compliance and patient satisfaction.

Design

Cross-sectional observational postal survey.

Setting

Medical on-call service 116117 by eight Associations of Statutory Health Insurance Physicians in Germany.

Participants

The intervention was observed between January 2020 and March 2021. Minors and patients with invalid contact data were excluded. A random sample of eligible patients received standardised questionnaires by mail.

Outcome measures

We analysed associations of sociodemographic data, health status, previous service use, health literacy, and recommended settings with compliance and patient satisfaction by multivariable, multilevel logistic regression.

Interventions

Based on symptoms and context factors, the computer software suggested service levels. Staff and patient discussed if higher levels were indicated, services were available and self-transport was possible. They then agreed on recommendations for treatment settings.

Results

Of 9473 contacted eligible patients, 1756 patients (18.5%) participated. Median age was 66 years (IQR=50–79), and 986 (59.0%) were women. At least one recommended setting was used by 1397 patients (85.4%). General practitioner (GP) practices were used by 143 patients (68.4%). Generally, better compliance was associated with lower depression levels (OR 1.59, 95% CI 1.17 to 2.17, p=0.003), fewer previous hospital stays (OR 2.02, 95% CI 1.27 to 3.23, p=0.003) and recommendations for any setting other than GP practices (OR 0.13, 95% CI 0.06 to 0.29, p<0001, to OR 0.37, 95% CI 0.19 to 0.72, p=0.003). A total of 606 patients (50.7%) were completely satisfied. Patient satisfaction was associated with higher age (OR 1.30, 95% CI 1.13 to 1.49, p<0.001), better self-rated health (OR 1.30, 95% CI 1.10 to 1.53, p=0.002), not having musculoskeletal disorders (OR 0.68, 95% CI 0.49 to 0.94, p=0.021), better health literacy (OR 0.69, 95% CI 0.54 to 0.89, p=0.005, and OR 0.49, 95% CI 0.36 to 0.67, p<0.001) and receiving no recommendation for GP practices (OR 0.61, 95% CI 0.43 to 0.87, p=0.006).

Conclusions

Most patients were compliant and satisfied. Lowest compliance and satisfaction were found in GP practices, but nonetheless, two of three patients with respective recommendations were willing to use this setting.

Trial registration number

German Clinical Trials Register DRKS00017014.
Polycyclic aromatic hydrocarbons and risk of rheumatoid arthritis: a cross-sectional analysis of the National Health and Nutrition Examination Survey, 2007–2016
Authors: Beidelschies Michelle , Lopez Rocio , Pizzorno Joseph , Le Phuc , Rothberg Michael B , Husni M E , D'Adamo Christopher
Published: May 2023

Objective

While there are several well-established environmental risk factors for rheumatoid arthritis (RA), a paucity of evidence exists linking environmental toxicants with RA prevalence. We aimed to examine the associations between various environmental toxicants and RA among adults in the U.S. general population while adjusting for non-heritable risk factors.

Design

Cross-sectional study.

Setting

National Health and Nutrition Examination Survey conducted from 2007 to 2016.

Participants

The study included 21 987 adult participants (no RA: 20 569; RA: 1418). Participants were excluded (n=7214) if they did not answer questions related to self-reporting of RA, had another or unknown type of arthritis, or did not have interview or biospecimen data.

Primary and secondary outcome measures

Association between individual toxicants and body burden scores for polycyclic aromatic hydrocarbons (PAH), phthalates and plasticisers (PHTHTEs) metabolites or volatile organic compounds (VOCs) and participant self-reported RA based on multivariable logistic regression models while adjusting for age, sex, urine creatinine, body mass index, smoking, race, education, family poverty income ratio, any vigorous or moderate activity and dietary fibre.

Results

While increased prevalence of RA was observed in participants with the highest quartile of various individual PAHs, only 1-hydroxynaphthalene (OR: 1.8 (1.1 to 3.1); p=0.020) remained associated in a fully adjusted model. PAH body burden was found to be associated with RA (Q4 vs Q1, OR: 2.2 (1.09 to 4.2); p=0.028) in a fully adjusted model. Interestingly, after accounting for PAH body burden, smoking was not associated with RA (OR: 1.4 (0.89 to 2.3); p=0.13). A mediation analysis demonstrated that PAH body burden accounted for 90% of the total effect of smoking on RA. PHTHTE and VOC metabolites were not associated with RA in fully adjusted models.

Conclusions and relevance

PAHs are associated with RA prevalence, mediate the majority of the effects of smoking on RA, and are associated with RA independent of smoking status.