bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of high-intensity versus low-intensity psychoanalytically oriented long-term treatments and determinants of outcome: individual participant data Meta-analysis of Long-term Analytic treatment Studies (MeLAS)
Authors: Krakau Lina , Leuzinger-Bohleber Marianne , Brähler Elmar , Schmidt Peter , Rost Felicitas , Huber Dorothea , Klug Guenther , Löffler-Stastka Henriette , Rössler-Schülein Hemma , Leichsenring Falk , Salzer Simone , Brockmann Josef , Jakobsen Thorsten , Ernst Mareike , Beutel Manfred E
Published: July 2023

Introduction

Long-term psychodynamic/psychoanalytic psychotherapy (LTPP) is a prevalent treatment option for complex mental disorders. Yet, little is known about the role of treatment intensity in LTPP. We present a study protocol for a systematic review and individual participant data (IPD) meta-analysis aggregating and analysing individual data from randomised and quasi-experimental trials by meta-analysis. The purpose is to (1) determine the treatment effectiveness of LTPP with low versus high intensity (up to 2 weekly sessions vs three or more), (2) compare their joint effectiveness to shorter therapies and treatments as usual, (3) identify predictors and moderators of treatment outcomes and (4) determine reciprocal relationships between different outcome domains (symptomatic and structural/personality change) over the courses of LTPP.

Methods and analysis

We include studies from (randomised controlled trial, RCT) and quasi-experimental trials, where at least one condition was LTPP of high or low frequency. Long-term treatment is defined as ≥1 year or ≥50 sessions. To be eligible studies must include a standardised outcome measure of symptoms (global or disorder specific) with at least one proof of reliability. The primary outcome is symptom reduction (global or specific), secondary outcome criteria are reliable change, remission, functional capacities, personality, personality functioning and interpersonal pathology. Relevant studies will mainly be identified by searching relevant databases: PubMed, PsycINFO (via EBSCO), Web of Science (via Elsevier), Chochrane’s Central Register of Controlled Trials (via Wiley). Risk of bias will be evaluated in line with the Cochrane assessments tools for quasi-experimental trials and RCTs, respectively.

Ethics and dissemination

Aggregation of data from primary trials collected based on ethics votes. Dissemination into clinical practice via open access publications of findings.

PROSPERO registration number

CRD42022304982; Pre-results.
Manchester Intermittent and Daily diet Type 1 Diabetes App Study (MIDDAS-Type 1): protocol for a randomised feasibility trial of an intermittent and continuous low-energy diet in patients with type 1 diabetes and overweight and obesity
Authors: McDiarmid Sarah , Harvie Michelle , Aglan Azza , Winterbottom Hannah , Mubita Womba , Hulme Amanda , Davies Jane , Yates James , Krizak Suzanne , Perry Diane , Issa Basil G
Published: July 2023

Introduction

Rising levels of overweight and obesity among people with type 1 diabetes (T1D) contribute to insulin resistance, dyslipidaemia, retinopathy, cardiometabolic complications and psychological morbidity. Continuous low-energy diets (CLED) providing approximately 800 kcal (3347 kJ)/day can produce significant weight loss in type 2 diabetes, and intermittent low-energy diets (ILED) may be an alternative. The Manchester Intermittent and Daily diet Type 1 Diabetes App Study (MIDDAS-Type 1) aims to assess the safety, acceptability and feasibility of remotely delivered ILED and CLED programmes for people with T1D and overweight and obesity.

Methods and analysis

Twelve participants with T1D and body mass index ≥27.5 kg/m2(≥25 kg/m2in high-risk ethnic minorities) recruited from an National Health Service (NHS) trust and research register in England will be randomised to a remotely delivered CLED (n=6) or ILED (n=6) for 12 weeks. The CLED includes a daily Optifast 850 kcal (3556 kJ) 75 g carbohydrate formula diet. The ILED includes 2 days/week of Optifast and 5 days of a portion-controlled Mediterranean diet (170–250 g carbohydrate/day). Both groups will receive matched high-frequency remote support from a dietitian, nurse and psychologist via telephone and/or the Oviva app. The primary outcome will assess safety (occurrence of severe hypoglycaemia, ketonaemia, ketoacidosis and time above and below target blood glucose). Secondary outcomes include study uptake, retention, dietary adherence, acceptability, intervention delivery fidelity and potential efficacy in relation to change in weight, insulin requirements, glycated haemoglobin, lipids, insulin resistance (estimated glucose disposal rate) and quality of life. Participants will be invited for optional repeat measurements at 52 weeks.

Ethics and dissemination

The trial protocol (V4.0/08.06.2022) was granted ethical approval by Cambridge East Research Ethics Committee (Ref: 21/EE/0014). The study will inform progression to a full-scale randomised controlled trial to test the efficacy of these programmes for patients with T1D and overweight and obesity.

Trial registration number

NCT04674384; Pre-results.
Unequal access? Use of sickness absence benefits by precariously employed workers with common mental disorders: a register-based cohort study in Sweden
Authors: Hernando-Rodriguez Julio C , Matilla-Santander Nuria , Murley Chantelle , Blindow Katrina , Kvart Signild , Almroth Melody , Kreshpaj Bertina , Thern Emelie , Badarin Kathryn , Muntaner Carles , Gunn Virginia , Padrosa Eva , Julià Mireia , Bodin Theo
Published: July 2023

Objective

This study compares the use of sickness absence benefits (SABs) due to a common mental disorder (CMD) between precariously employed and non-precariously employed workers with CMDs.

Design

Register-based cohort study.

Participants

The study included 78 215 Swedish workers aged 27–61 who experienced CMDs in 2017, indicated by a new treatment with selective serotonin reuptake inhibitors (SSRIs). Excluded were those who emigrated or immigrated, were self-employed, had an annual employment-based income <100 Swedish Krona, had >90 days of unemployment per year, had student status, had SABs due to CMDs during the exposure measurement (2016) and the two previous years, had an SSRI prescription 1 year or less before the start of the SSRI prescription in 2017, had packs of >100 pills of SSRI medication, had a disability pension before 2017, were not entitled to SABs due to CMDs in 2016, and had no information about the exposure.

Outcome

The first incidence of SABs due to CMDs in 2017.

Results

The use of SABs due to a CMD was slightly lower among precariously employed workers compared with those in standard employment (adjusted OR [aOR] 0.92, 95% CI 0.81 to 1.05). Particularly, women with three consecutive years in precarious employment had reduced SABs use (aOR 0.48, 95% CI 0.26 to 0.89), while men in precarious employment showed weaker evidence of association. Those in standard employment with high income also showed a lower use of SABs (aOR 0.74, 95% CI 0.67 to 0.81). Low unionisation and both low and high-income levels were associated with lower use of SABs, particularly among women.

Conclusions

The study indicates that workers with CMDs in precarious employment may use SABs to a lower extent. Accordingly, there is a need for (1) guaranteeing access to SABs for people in precarious employment and/or (2) reducing involuntary forms of presenteeism.
Adolescent childbirth and mobility disability among women ages 15–49: an analysis of population health surveys from 14 low-income and middle-income countries
Authors: Peck Katherine E , Bassani Diego G , Camara Saionara MA , Domingues Marlos R , Sentell Tetine , Velez Maria P , Pirkle Catherine M
Published: July 2023

Objectives

Adolescent childbirth is associated with older adult adverse health outcomes that negatively affect mobility function, but these associations have not been studied globally in large samples of reproductive-age women. This study examines the association between age at first childbirth and mobility disability in national surveys from low-income and middle-income countries, and hypotheses that adolescent childbirth is associated with mobility disability.

Design

Cross-sectional analysis.

Setting

Population health surveys from 2013 to 2018 containing mobility disability measures among ever-pregnant women ages 15–49. These included 13 Demographic Health Surveys from Haiti, Pakistan, Uganda, Cambodia, Colombia, South Africa, Timor-Leste, Albania, Gambia, Maldives, Peru, Senegal and Yemen and 1 Maternal Health Survey from Ghana.

Participants

The sample included 157 988 women ages 15–49 years.

Primary outcome measure

Adolescent childbirth was defined as 10–19 years of age. Poisson regression models were used to estimate prevalence ratios (PRs) of mobility disability among women who first gave birth during adolescence and in adult life (ages 20–45 years) in each country and across the whole sample. Countries were also analysed according to the use of standard and non-standard mobility disability measures. Covariates included current age, urban/rural residence, education and household wealth.

Results

Prevalence of adolescent childbirth (17.5%–66.2%) and mobility disability (0.32%–21.45%) varied widely across countries. Adolescent childbirth was significantly (p<0.05) associated with greater mobility disability in six of eight countries using standard disability measures. Among the six countries that did not use standard disability measures, none showed a statistically significant association between adolescent childbirth and mobility disability. Considering the whole sample and adjusting for all covariates, women who gave birth during adolescence had greater prevalence of mobility disability (pooled PR 1.19, 95% CI 1.06–1.31).

Conclusions

This analysis suggests a moderate and consistent association of adolescent childbearing with subsequent mobility disability.
Oral health surveys of Traditional Peoples and Communities in Brazil: a scoping review protocol
Authors: Raymundo Maria Letícia Barbosa , Araújo Elza Cristina Farias de , Silva Rênnis Oliveira da , Santiago Bianca Marques , Vieira Thiago Isidro , Sousa Simone Alves , Lucena Edson Hilan Gomes de , Cavalcanti Yuri Wanderley
Published: July 2023

Objective

The objective of this review protocol is to map the available evidence regarding all the oral health surveys of Traditional Peoples and Communities (TPCs) in Brazil.

Methods and analysis

The review question of the protocol is: ‘What evidence is available on the oral health surveys of Traditional Peoples and Communities in Brazil?’. Observational studies that report oral health surveys of TPC in Brazil will be included. The protocol considered the Problem, Concept and Context strategy to guide data collection, as established by the Joanna Briggs Institute. The search strategy will consider Medical Subject Headings terms, synonyms and relevant free terms about epidemiological surveys in oral health and TPC in Brazil, with no limits to data, language, subject or search type, in the databases Medical Literature Analysis and Retrieval System Online (MEDLINE/PubMed), Literatura Latino-americana e do Caribe em Ciências da Saúde (LILACS), Scopus, Web of Science and Embase. Bibliographic searches will be updated until June 2023. The selection will be carried out by two independent, blinded reviewers, following the eligibility criteria, based on the title and abstract identified in the initial search. Potentially eligible studies will be fully read to confirm eligibility and collect relevant information. The categorisation of the studies will consider the author and year of publication, the traditional group studied, the study design, geographic location, age group, sample size, data collection method and the main oral health problem evaluated and its outcome. The data obtained and extracted will be presented in table format and text and presented using the visualisation of similarities method.

Ethics and dissemination

The present study does not need ethical approval. The protocol title was registered in the Open Science Framework (DOI 10.17605/OSF.IO/BQ5J3). A final article will be prepared presenting the results of the scoping review, and will be submitted for publication in a peer-reviewed journal. The findings of this review will be presented at national conferences and scientific meetings.
TeleRehabilitation with Aims to Improve Lower extremity recovery in community-dwelling individuals who have had a stroke: protocol for a multisite, parallel group, assessor-blinded, randomised attention-controlled trial
Authors: Sakakibara Brodie M , Wiley Elise , Barclay Ruth , Bayley Mark , Davis Jennifer C , Eng Janice J , Harris Anne , Inness Elizabeth L , MacKay-Lyons Marilyn , Monaghan Jennifer , Pollock Courtney , Pooyania Sepideh , Schneeberg Amy , Teasell Robert , Yao Jennifer , Tang Ada
Published: July 2023

Introduction

Telerehabilitation is an accessible service delivery model that may support innovative lower extremity rehabilitation programmes that extend the stroke recovery continuum into the community. Unfortunately, there is limited evidence on the provision of exercises for lower extremity recovery after stroke delivered using telerehabilitation. In response, we developed the TeleRehabilitation with Aims to Improve Lower extremity recovery poststroke (TRAIL) programme, a 4-week progressive exercise and self-management intervention delivered synchronously using video-conferencing technology. Our primary hypothesis is that individual within 1-year poststroke who participate in TRAIL will experience significantly greater improvements in functional mobility than individuals in an attention-controlled education programme (EDUCATION).

Methods and analysis

In this multisite, parallel group, assessor-blinded randomised attention-controlled trial, 96 community-living stroke survivors within 1-year poststroke will be recruited from five sites (Vancouver, Winnipeg, Toronto, London and Halifax, Canada) from the CanStroke Recovery Trials Platform which is a network of Canadian hospital sites that are affiliated with academic institutions to facilitate participant recruitment and quality trial practices. Participants will be randomised on a 1:1 basis to TRAIL or EDUCATION. Participants randomised to TRAIL will receive eight telerehabilitation sessions where they will perform exercises and receive self-management support to improve lower extremity recovery from a TRAIL physical therapist. The primary outcome will be measured using the Timed Up and Go. Secondary outcomes include lower extremity muscle strength, functional balance, motor impairment, balance self-efficacy, health-related quality of life and health service use for our economic evaluation. Measurements will be taken at baseline, immediately after the intervention, 3-month and 6-month postintervention.

Ethics and dissemination

Ethics approval for this research has been obtained by all participating sites. All study participants will provide their informed consent prior to enrolling them in the study. Findings from this trial will be disseminated in peer-reviewed journals and presentations at international scientific meetings.

Trial registration number

ClinicalTrials.gov,NCT04908241.
Geometrically induced spectral properties of soft quantum waveguides and layers
Authors: Exner Pavel
Published: July 2023

We present a review of recent results about a class of Schrödinger operators usually called soft quantum waveguides, with the focus on relations between their spectral properties and the geometry of the confinement. We also mention a number of open problems in this area.
Lower bounds on the energy of the Bose gas
Authors: Fournais Søren , Girardot Theotime , Junge Lukas , Morin Leo , Olivieri Marco
Published: July 2023

We present an overview of the approach to establish a lower bound to the ground state energy for the dilute, interacting Bose gas in a periodic box. In this paper, the size of the box is larger than the Gross–Pitaevskii length scale. The presentation includes both the two- and three-dimensional cases, and catches the second-order correction, i.e. the Lee–Huang–Yang term. The calculation on a box of this length scale is the main step to calculate the energy in the thermodynamic limit. However, the periodic boundary condition simplifies many steps of the argument considerably compared to the localized problem coming from the thermodynamic case.
HPV42, a “Low-Risk” Type, and Digital Papillary Adenocarcinoma
Authors: Starrett Gabriel J. , Schiller John T. , Lowy Douglas R.
Published: July 2023

Chronic infection by several “high-risk” human papillomavirus (HPV) types has been causally implicated in several forms of anogenital and oropharyngeal cancers. Now, HPV42, which is usually classified as a “low-risk” type, can be listed as the main cause of digital papillary adenocarcinoma, an uncommon malignant tumor of the fingers and toes.

See related article by Leiendecker et al., p. 70 (3).
Fetal Thyrotoxicosis due to Maternal TSH Receptor Stimulating Antibodies Causes Infant Central Hypothyroidism
Authors: van Hulsteijn Leonie T. , Prins Jelmer R. , Scheffer-Rath Mirjam E.A. , van Trotsenburg A.S. Paul , Links Thera P. , Dullaart Robin P.F.
Published: July 2023

Introduction: Women with a current diagnosis or past history of Graves’ disease (GD) are at risk of developing fetal thyrotoxicosis (FT) during pregnancy when they are inadequately treated, or because of placental passage of TSH receptor antibodies (TRAb). It is known that FT induced by high maternal thyroid hormone concentrations may result in infant (central) hypothyroidism. Case Presentation: In a euthyroid woman with a history of GD treated with radioactive iodide (I131), persistently high levels of maternal TRAb resulted in recurrent FT during two separate pregnancies, followed by neonatal hyperthyroidism and infant central hypothyroidism. Discussion: This case demonstrates the novel insight that FT due to high fetal thyroid hormone concentrations stimulated by high maternal TRAb levels might also result in (central) hypothyroidism, requiring long-term evaluation of the hypothalamus-pituitary-thyroid axis in these children.
Tissue Glue-Based Sealing Patch for the in vivo Prevention of Iatrogenic Prelabor Preterm Rupture of Fetal Membranes
Authors: Devaud Yannick R , Avilla-Royo Eva , Lionetti Leonardo , Tronnier Helena , Seehusen Frauke , Monné Rodriguez Josep M. , Moehrlen Ueli , Weisskopf Miriam , Vonzun Ladina , Strübing Nele , Ochsenbein-Kölble Nicole , Ehrbar Martin
Published: July 2023

Introduction: One of the main concerns for all fetal surgeries is the risk of preterm delivery due to the preterm prelabor rupture of the fetal membranes (iPPROM). Clinical approaches to seal fetal membrane (FM) defects are missing due to the lack of appropriate strategies to apply sealing biomaterials at the defect site. Methods: Here, we test the performance of a previously developed strategy to seal FM defects with cyanoacrylate-based sealing patches in an ovine model up to 24 days after application. Results: Patches sealed tightly the fetoscopy-induced FM defects and remained firmly attached to the defect over 10 days. At 10 days after treatment, 100% (13/13) of the patches were attached to the FMs, and 24 days after treatment 25% (1/4) of the patches placed in CO2 insufflation, and 33% (1/3) in NaCl infusion remained. However, all successfully applied patches (20/24) led to a watertight sealing at 10 or 24 days after treatment. Histological analysis indicated that cyanoacrylates induced a moderate immune response and disrupted the FM epithelium. Conclusion: Together, these data show the feasibility of minimally invasive sealing of FM defects by locally gathering tissue adhesive. Further development to combine this technology with refined tissue glues or healing-inducing materials holds great promise for future clinical translation.
Usefulness of Preoperative Predictors of Pathological Complicated Appendicitis
Authors: Shiihara Masahiro , Sudo Yasuhiro , Matsushita Norimasa , Kubota Takeshi , Hibi Yasuhiro , Osugi Harushi , Inoue Tatsuo
Published: July 2023

Introduction: Complicated appendicitis (CA) is often indicated for emergency surgery; however, preoperative predictors of pathological CA (pCA) remain unclear. Furthermore, characteristics of CA that can be treated conservatively have not yet been established. Methods: 305 consecutive patients diagnosed with acute appendicitis were reviewed. The patients were divided into two groups: an emergency surgery and a conservative treatment group. The emergency surgery group was pathologically classified as having uncomplicated appendicitis (pUA) and pCA, and the preoperative predictors of pCA were retrospectively assessed. Based on the preoperative pCA predictors, a predictive nomogram whether conservative treatment would be successful or not was created. The predictors were applied to the conservative treatment group, and the outcomes were investigated. Results: In the multiple logistic regression analysis of the factors contributing to pCA, C-reactive protein ≥3.5 mg/dL, ascites, appendiceal wall defect, and periappendiceal fluid collection were independent risk factors. Over 90% of cases without any of the above four preoperative pCA predictors were pUA. The accuracy of the nomogram was 0.938. Conclusion: Our preoperative predictors and nomogram are useful to aid in distinguishing pCA and pUA and to predict whether or not conservative treatment will be successful. Some CA can be treated with conservative treatment.
Estimating Glomerular Filtration Rate in China: Is the European Kidney Function Consortium (EKFC) Equation the Solution?
Authors: Delanaye pierre , Pottel Hans
Published: July 2023

The new European Kidney Function Consortium (EKFC) creatinine-based equation has been developed to be applicable over the entire age range (from 2 to 100 years) without any loss of performance in young adults and without loss of continuity in estimating glomerular filtration rate (GFR) between adolescents and adults. This goal is obtained by better taking into account the relationship between serum creatinine (SCr) and age in the estimating GFR model. This is accomplished by rescaling SCr, namely, dividing SCr by so-called Q value which is the median normal value of SCr concentration in a given healthy population. The better performance of the EKFC equation, compared to the current equations, has been shown in large European and African cohorts. Such good results are also suggested in cohorts from China, including in the current issue of Nephron. The good performance of the EKFC equation is observed, especially when the authors used a specific Q value for their populations notwithstanding GFR was measured by a controversial method. Using a population-specific Q value could make the EFKC equation universally applicable.
Morphological and molecular characterization of Travassosinema viatorum n. sp. (Nematoda: Oxyuridomorpha: Travassosinematidae) from the invasive millipede Chamberlinius hualienensis Wang, 1956 (Diplopoda: Polydesmida: Paradoxosomatidae) in Okinawa, Japan
Authors: MORFFE JANS , GARCÍA NAYLA , HASEGAWA KOICHI
Published: July 2023

Travassosinema viatorum n. sp. (Nematoda: Oxyuridomorpha: Travassosinematidae) is described from the invasive millipede Chamberlinius hualienensis Wang, 1956 (Diplopoda: Polydesmida: Paradoxosomatidae) in Okinawa, Japan. Females of T. viatorum n. sp. resemble T. claudiae Morffe & Hasegawa, 2017; T. thyropygi Hunt, 1996 and T. travassosi Rao, 1958 by lacking both lateral alae and a contraction posterior to the vulva. The body length of T. viatorum n. sp. is shorter than the aforementioned species. It differs from T. claudiae and T. thyropygi by its comparatively longer oesophagus, more posterior vulva, lack of cuticular ribs in the alae of the umbraculum and in the position of the nerve ring and excretory pore. Travassosinema viatorum n. sp. can be differentiated from T. travassosi by the extension of the cephalic umbraculum and the smaller eggs. The phylogeny of T. viatorum n. sp. is inferred by the D2–D3 domains of the 28S rDNA. The new species is located in a monophyletic clade with other sequences of Travassosinema from millipedes. The comparison of the phylogenies of Travassosinema and their hosts points to host switching rather than coevolution as a mechanism to explain the host-nematode relationships. This constitutes the second species of the genus Travassosinema described from the Japanese archipelago and the first oxyuridomorph nematodes found in C. hualienensis.
Identification of the susceptible genes and mechanism underlying the comorbid presence of coronary artery disease and rheumatoid arthritis: a network modularization analysis
Authors: Zhang Siqi , Niu Qikai , Tong Lin , Liu Sihong , Wang Pengqian , Xu Haiyu , Li Bing , Zhang Huamin
Published: July 2023

Objective

The comorbidities of coronary artery disease (CAD) and rheumatoid arthritis (RA) are mutual risk factors, which lead to higher mortality, but the biological mechanisms connecting the two remain unclear. Here, we aimed to identify the risk genes for the comorbid presence of these two complex diseases using a network modularization approach, to offer insights into clinical therapy and drug development for these diseases.

Method

The expression profile data of patients CAD with and without RA were obtained from the GEO database (GSE110008). Based on the differentially expressed genes (DEGs), weighted gene co-expression network analysis (WGCNA) was used to construct a gene network, detect co-expression modules, and explore their relation to clinical traits. The Zsummary index, gene significance (GS), and module membership (MM) were utilized to screen the important differentiated modules and hub genes. The GO and KEGG pathway enrichment analysis were applied to analyze potential mechanisms.

Result

Based on the 278 DEGs obtained, 41 modules were identified, of which 17 and 24 modules were positively and negatively correlated with the comorbid occurrence of CAD and RA (CAD&RA), respectively. Thirteen modules with Zsummary < 2 were found to be the underlying modules, which may be related to CAD&RA. With GS ≥ 0.5 and MM ≥ 0.8, 49 hub genes were identified, such as ADO, ABCA11P, POT1, ZNF141, GPATCH8, ATF6 and MIA3, etc. The area under the curve values of the representative seven hub genes under the three models (LR, KNN, SVM) were greater than 0.88. Enrichment analysis revealed that the biological functions of the targeted modules were mainly involved in cAMP-dependent protein kinase activity, demethylase activity, regulation of calcium ion import, positive regulation of tyrosine, phosphorylation of STAT protein, and tissue migration, etc.

Conclusion

Thirteen characteristic modules and 49 susceptibility hub genes were identified, and their corresponding molecular functions may reflect the underlying mechanism of CAD&RA, hence providing insights into the development of clinical therapies against these diseases.
‘Drive the doctor’ for endovascular thrombectomy in a rural area: a simulation study
Authors: Maas Willemijn J. , van der Zee Durk-Jouke , Lahr Maarten M.H. , Bouma Marc , Buskens Erik , Uyttenboogaart Maarten
Published: July 2023

Background

Patients who present in a primary stroke center (PSC) with ischemic stroke are usually transferred to a comprehensive stroke center (CSC) in case of a large vessel occlusion (LVO) for endovascular thrombectomy (EVT) treatment, the so-called ‘drip-and-ship’ (DS) model. The ‘drive-the-doctor’ (DD) model modifies the DS model by allowing mobile interventionalists (MIs) to transfer to an upgraded PSC acting as a thrombectomy capable stroke center (TSC), instead of transferring patients to a CSC. Using simulation we estimated time savings and impact on clinical outcome of DD in a rural region.

Methods

Data from EVT patients in northern Netherlands was prospectively collected in the MR CLEAN Registry between July 2014 - November 2017. A Monte Carlo simulation model of DS patients served as baseline model. Scenarios included regional spread of TSCs, pre-hospital patient routing to ‘the nearest PSC’ or ‘nearest TSC’, MI’s notification after LVO confirmation or earlier prehospital, and MI’s transport modalities. Primary outcomes are onset to groin puncture (OTG) and predicted probability of favorable outcome (PPFO) (mRS 0–2).

Results

Combining all scenarios OTG would be reduced by 28–58 min and PPFO would be increased by 3.4-7.1%. Best performing and acceptable scenario was a combination of 3 TSCs, prehospital patient routing based on the RACE scale, MI notification after LVO confirmation and MI’s transfer by ambulance. OTG would reduce by 48 min and PPFO would increase by 5.9%.

Conclusions

A DD model is a feasible scenario to optimize acute stroke services for EVT eligible patients in rural regions. Key design decisions in implementing the DD model for a specific region are regional spread of TSCs, patient routing strategy, and MI’s notification moment and transport modality.
Prognostic factors for persistent symptoms in adults with mild traumatic brain injury: an overview of systematic reviews
Authors: Déry Julien , Ouellet Béatrice , de Guise Élaine , Bussières Ève-Line , Lamontagne Marie-Eve
Published: July 2023

Background

Mild traumatic brain injury (mTBI) is an increasing public health problem, because of its persistent symptoms and several functional consequences. Understanding the prognosis of a condition is an important component of clinical decision-making and can help to guide the prevention of persistent symptoms following mTBI. The prognosis of mTBI has stimulated several empirical primary research papers and many systematic reviews leading to the identification of a wide range of factors. We aim to synthesize these factors to get a better understanding of their breadth and scope.

Methods

We conducted an overview of systematic reviews. We searched in databases systematic reviews synthesizing evidence about the prognosis of persistent symptoms after mTBI in the adult population. Two reviewers independently screened all references and selected eligible reviews based on eligibility criteria. They extracted relevant information using an extraction grid. They also rated independently the risk of bias using the ROBIS tool. We synthesized evidence into a comprehensive conceptual map to facilitate the understanding of prognostic factors that have an impact on persistent post-concussion symptoms.

Results

From the 3857 references retrieved in a database search, we included 25 systematic reviews integrating the results of 312 primary articles published between 1957 and 2019. We examined 35 prognostic factors from the systematics reviews. No single prognostic factor demonstrated convincing and conclusive results. However, age, sex, and multiple concussions showed an affirmatory association with persistent post-concussion outcomes in systematic reviews.

Conclusion

We highlighted the need for a comprehensive picture of prognostic factors related to persistent post-concussion symptoms. We believe that these prognostic factors would guide clinical decisions and research related to prevention and intervention regarding persistent post-concussion symptoms.

Systematic review registration

PROSPERO CRD42020176676
A distributional regression approach to modeling the impact of structural and intermediary social determinants on communities burdened by tuberculosis in Eastern Amazonia – Brazil
Authors: Giacomet Clóvis Luciano , Ramos Antônio Carlos Vieira , Moura Heriederson Sávio Dias , Berra Thaís Zamboni , Alves Yan Mathias , Delpino Felipe Mendes , Farley Jason E. , Reynolds Nancy R. , Alonso Jonas Bodini , Teibo Titilade Kehinde Ayandeyi , Arcêncio Ricardo Alexandre
Published: July 2023

Background

Tuberculosis (TB) is a disease that is influenced by social determinants of health. However, the specific structural and intermediary determinants of TB in Eastern Amazonia remain unclear. Despite being rich in natural resources, the region faces significant challenges related to poverty, inequality, and neglected diseases. The objective of this study was to use mathematical modeling to evaluate the influence of structural and intermediary determinants of health on TB in Eastern Amazonia, Brazil.

Methods

This cross-sectional included all TB cases diagnosed and registered in the Notifiable Diseases Information System (SINAN) from 2001 to 2017. Data on social determinants were collected at the census tract level. The generalized additive model for location, scale, and shape (GAMLSS) framework was employed to identify the effect of social determinants on communities with a high TB prevalence. The Double Poisson distribution (DPO) was chosen, and inclusion of quadratic effects was tested.

Results

A total of 1730 individuals were diagnosed with TB and reported in SINAN during the analyzed period. The majority were female (59.3%), aged 31 to 59 years (47.6%), identified as blacks (67.9%), and had incomplete elementary education (46.6%). The prevalence of alcoholism was 8.6% and mental illness was 0.7%. GAMLSS analyses demonstrated that the risk of community incidence of TB is associated with the proportion of the population lacking basic sanitation, as well as with the age groups of 16–31 years and > 61 years.

Conclusions

The study highlights the strategic utility of GAMLSS in identifying high-risk areas for TB. Models should encompass a broader range of social determinants to inform policies aimed at reducing inequality and achieving the goals of the End TB strategy.
Designing and psychometric analysis of an instrument to assess learning process in a virtual environment
Authors: Ahmady Soleiman , Kohan Noushin , Mirmoghtadaie Zohreh Sadat , Hamidi Hadi , Sabet Divshali Babak , Rakhshani Tayebeh , Khani Jeihooni Ali
Published: July 2023

Background

Today, methods that enable students to benefit from online programs to the fullest and learn independently and self-directed are of critical importance. Many scales have been developed to measure self-directed learning in the physical classroom. This study was conducted to design and assess the psychometric properties of an instrument to assess learning process in a virtual environment.

Materials and methods

A questionnaire for assessing s learning process in a virtual environment was developed following six steps. The process began with a systematic search for related articles. A qualitative study was then conducted to identify self-directed learning strategies and processes in virtual environments. The identified strategies were then compared with those from a literature review, and the scale items were developed accordingly. Expert validation, exploratory factor analysis, and reliability analysis were conducted to ensure questionnaire validity and reliability. This study included online postgraduate students from Iranian medical science universities in 2019.

Results

The scale consisted of 5 factors and 44 items. In exploratory factor analysis, five subscales explained 90% of the total variance. Cronbach’s alpha was 0.91 for the total scale. The interclass correlation coefficient between the test and retest was 0.77.

Conclusion

A questionnaire designed to assess learning process in a virtual environment for postgraduate virtual students has reasonable psychometric properties, including reasonable internal reliability and construct validity.
Strong coupling in plasmonic metal nanoparticles
Authors: Lee Yoon-Min , Kim Seong-Eun , Park Jeong-Eun
Published: July 2023

The study of strong coupling between light and matter has gained significant attention in recent years due to its potential applications in diverse fields, including artificial light harvesting, ultraefficient polariton lasing, and quantum information processing. Plasmonic cavities are a compelling alternative of conventional photonic resonators, enabling ultracompact polaritonic systems to operate at room temperature. This review focuses on colloidal metal nanoparticles, highlighting their advantages as plasmonic cavities in terms of their facile synthesis, tunable plasmonic properties, and easy integration with excitonic materials. We explore recent examples of strong coupling in single nanoparticles, dimers, nanoparticle-on-a-mirror configurations, and other types of nanoparticle-based resonators. These systems are coupled with an array of excitonic materials, including atomic emitters, semiconductor quantum dots, two-dimensional materials, and perovskites. In the concluding section, we offer perspectives on the future of strong coupling research in nanoparticle systems, emphasizing the challenges and potentials that lie ahead. By offering a thorough understanding of the current state of research in this field, we aim to inspire further investigations and advances in the study of strongly coupled nanoparticle systems, ultimately unlocking new avenues in nanophotonic applications.
Fluid management strategies and their interaction with mechanical ventilation: from experimental studies to clinical practice
Authors: de Carvalho Eduardo Butturini , Battaglini Denise , Robba Chiara , Malbrain Manu L. N. G. , Pelosi Paolo , Rocco Patricia Rieken Macedo , Silva Pedro Leme
Published: July 2023

Patients on mechanical ventilation may receive intravenous fluids via restrictive or liberal fluid management. A clear and objective differentiation between restrictive and liberal fluid management strategies is lacking in the literature. The liberal approach has been described as involving fluid rates ranging from 1.2 to 12 times higher than the restrictive approach. A restrictive fluid management may lead to hypoperfusion and distal organ damage, and a liberal fluid strategy may result in endothelial shear stress and glycocalyx damage, cardiovascular complications, lung edema, and distal organ dysfunction. The association between fluid and mechanical ventilation strategies and how they interact toward ventilator-induced lung injury (VILI) could potentiate the damage. For instance, the combination of a liberal fluids and pressure-support ventilation, but not pressure control ventilation, may lead to further lung damage in experimental models of acute lung injury. Moreover, under liberal fluid management, the application of high positive end-expiratory pressure (PEEP) or an abrupt decrease in PEEP yielded higher endothelial cell damage in the lungs. Nevertheless, the translational aspects of these findings are scarce. The aim of this narrative review is to provide better understanding of the interaction between different fluid and ventilation strategies and how these interactions may affect lung and distal organs. The weaning phase of mechanical ventilation and the deresuscitation phase are not explored in this review.
Does human milk composition predict later risk of obesity? A systematic review
Authors: Vieira Queiroz De Paula Mayara , Grant Maude , Lanigan Julie , Singhal Atul
Published: July 2023

Background

Possible mechanisms behind the association of breastfeeding with a lower risk of later obesity are unknown but one possibility is the unique composition of human milk. Here, we systematically reviewed the evidence linking breast-milk macronutrient and hormonal composition with later obesity.

Methods

We searched 7 databases for studies that included infants predominantly breast-fed for the first 3 months and which analysed associations between a measure of breast-milk composition and later (> 6 months) measures of obesity or body composition.

Results

47 publications were identified for full-text screening, of which 10 were eligible and only 3 found significant associations. Higher leptin concentration in breast milk at age 1 month was associated with lower infant BMI at 12, 18 and 24 months of age (1 study). Higher breast-milk adiponectin concentration at 6 weeks and 4 months were associated with adiposity at age 12 and 24 months (1 study). In 1 study, breast-milk carbohydrate content was positively associated, and fat content negatively associated, with adiposity at age 12 months. No significant associations were found between other hormones or macronutrients in human milk and later risk of obesity or body composition.

Conclusions

The evidence linking breast-milk composition with later obesity was inconsistent and confined to single, individual studies. Our review highlights the methodological limitations of previous studies and the need for further research in this area.
G9a inactivation in progenitor cells with Isl1-Cre with reduced recombinase activity models aspects of Dandy-Walker complex
Authors: Chi Lijun , Zhong Ling , Lee Dorothy , Yu Xinwen , Caballero Amalia , Nieman Brian , Delgado-Olguin Paul
Published: July 2023

G9a, also known as EHMT2, is essential for embryogenesis and has specific functions in multiple developmental processes. G9a inactivation affects development of the nervous system, which is formed with contribution of descendants of progenitor cells expressing the transcription factor Isl1. However, the function of G9a in Isl1-expressing progenitors is unknown. Here, we show that G9a is required for proper development of multiple structures formed with contribution of Isl1-expressing progenitors. A Cre-dependent GFP reporter revealed that the recombinase activity of the Isl1-Cre used in this study to inactivate G9a was reduced to a subset of Isl1-expressing progenitor cells. G9a mutants reached endpoint by 7 weeks of age with cardiac hypertrophy, hydrocephalus, underdeveloped cerebellum and hind limb paralysis, modeling aspects of Dandy-Walker complex. Moreover, neuroepithelium of the lateral ventricle derived from Isl1-expressing progenitors was thinner and disorganized, potentially compromising cerebrospinal fluid dynamics in G9a mutants. Micro-computed tomography after iodine staining revealed increased volume of the heart, eye lens and brain structures in G9a mutant fetuses. Thus, altered development of descendants of the second heart field and the neural crest could contribute to multicomponent malformation like Dandy-Walker.
A functional sgRNA-CRISPR screening method for generating murine RET and NTRK1 rearranged oncogenes
Authors: Schubert Laura , Le Anh T. , Hinz Trista K. , Navarro Andre C. , Nelson-Taylor Sarah K. , Nemenoff Raphael A. , Heasley Lynn E. , Doebele Robert C.
Published: July 2023

CRISPR/Cas9 gene editing represents a powerful tool for investigating fusion oncogenes in cancer biology. Successful experiments require that sgRNAs correctly associate with their target sequence and initiate double stranded breaks which are subsequently repaired by endogenous DNA repair systems yielding fusion chromosomes. Simple tests to ensure sgRNAs are functional are not generally available and often require single cell cloning to identify successful CRISPR-editing events. Here, we describe a novel method relying on acquisition of IL3-independence in Ba/F3 cells to identify sgRNA pairs that generate oncogenic gene rearrangements of the Ret and Ntrk1 tyrosine kinases. The rearrangements were confirmed with PCR, RT-PCR and sequencing and Ba/F3 cells harboring Ret or Ntrk1 rearrangements acquired sensitivity to RET and TRK inhibitors, respectively. Adenoviruses encoding Cas9 and sgRNA pairs inducing the Kif5b-Ret and Trim24-Ret rearrangements were intratracheally instilled into mice and yielded lung adenocarcinomas. A cell line (TR.1) established from a Trim24-Ret positive tumor exhibited high in vitro sensitivity to the RET inhibitors LOXO-292 and BLU-667 and orthotopic TR.1 cell-derived tumors underwent marked shrinkage upon LOXO-292 treatment. Thus, the method offers an efficient means to validate sgRNAs that successfully target their intended loci for the generation of novel, syngeneic murine oncogene-driven tumor models.
Flat mount preparation for whole-mount fluorescent imaging of zebrafish embryos
Authors: Frommelt Joseph , Liu Emily , Bhaidani Afraz , Hu Bo , Gao Yuanyuan , Ye Ding , Lin Fang
Published: July 2023

The zebrafish is a widely used model organism for biomedical research due to its ease of maintenance, external fertilization of embryos, rapid embryonic development, and availability of established genetic tools. One notable advantage of using zebrafish is the transparency of the embryos, which enables high-resolution imaging of specific cells, tissues, and structures through the use of transgenic and knock-in lines. However, as the embryo develops, multiple layers of tissue wrap around the lipid-enriched yolk, which can create a challenge to image tissues located deep within the embryo. While various methods are available, such as two-photon imaging, cryosectioning, vibratome sectioning, and micro-surgery, each of these has limitations. In this study, we present a novel deyolking method that allows for high-quality imaging of tissues that are obscured by other tissues and the yolk. Embryos are lightly fixed in 1% PFA to remove the yolk without damaging embryonic tissues and are then refixed in 4% PFA and mounted on custom-made bridged slides. This method offers a simple way to prepare imaging samples that can be subjected to further preparation, such as immunostaining. Furthermore, the bridged slides described in this study can be used for imaging tissue and organ preparations from various model organisms.
All ions must serve: The role of various regimes of data acquisition in joint classifier for intraoperative mass spectrometry-based glial tumour identification
Authors: Pekov Stanislav I. , Zavorotnyuk Denis S. , Sorokin Anatoly A. , Bormotov Denis S. , Derkach Mariya M. , Starkov Dmitrii N. , Popov Igor A.
Published: July 2023

Background: Ambient ionisation mass spectrometry, in combination with machine learning techniques, provides a promising tool for rapid intraoperative tumour tissue identification. However, deficiency of non-tumour control samples leads to the classifiers overfitting, especially in neurosurgical applications. Ensemble learning approaches based on the analysis of multimodal mass spectrometry data are able to overcome the overfitting problem through the extended time of data acquisition. In this work, the contribution of each regime of the data acquisition and the requirements for the metrics for further mass spectrometry set-up optimisation are evaluated.

Methods: Two independent datasets of the multimodal molecular profiles, a total of 81 glial tumour and non-tumour pathological tissues, were analysed in a cross-validation set-up. The XGboost algorithm was used to build classifiers, and their performance was evaluated using different testing and validating sets. The individual classifiers for each mass spectrometry regime were aggregated into joint classifiers. The impact of each regime was evaluated by the exclusion of specific regimes from the aggregation.

Results: The aggregated classifiers with excluded regimes show lower accuracy for most, but not all, excluded regimes. False positive rates have been found to be increased in most cases proving the strong effect of the ensemble learning approach on the overcoming of the “small sample size” problem.

Conclusions: The impact of each group of regimes – with different ion polarity, resolution or mass range of spectra was found to be non-linear. It might be attributed to biochemical reasons as well as to the physical limitation of mass analysers. The required metrics for the evaluation of each regime contribution to the classification efficiency should be a numerical estimation of how the classifier depends on any given regime and could not be estimated only by excluding any group of regimes at all.