bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of immediate dentine sealing and resin coating in reducing dental sensitivity in a child with idiopathic neuropathy and anterior dental attrition: Case report
Authors: Tapia Martinez Akemy Celeste , Vilcapoma Guerra Henry Jesús , Torres Ramos Gilmer
Published: November 2022

Background

Idiopathic neuropathy is a peripheral nervous system disorder of unknown etiology. Patients with this disorder often suffer from bruxism problems. Bruxism is defined as an oral parafunction characterized by occlusal contacts resulting from non‐physiological, repetitive, and involuntary masticatory motor activities. These events can trigger accentuated wear of the tooth structure leading to sensitivity. Tooth sensitivity is the pain arising from the exposed dentin in response to chemical, thermal, tactile, or osmotic stimuli that cannot be explained as the result of any other dental defect or disease. Sensitivity treatment using adhesive systems has a long‐term or permanent effect. Therefore, this article is aimed at describing the management of dental sensitivity, through dentin sealing and resin coating techniques, during the dental restoration process of a child with idiopathic neuropathy and dental attrition in the anterior sector. All of this, with the consideration of using the minimal intervention philosophy.

Case Presentation

A 6‐year‐old male patient diagnosed with idiopathic neuropathy and suffering from multiple dental attritions with dental sensitivity in the upper anterior teeth. With the clinical‐radiographic evaluation, the family history, and the interconsultations with the neuropaediatrics service, the definitive diagnosis of dental sensitivity due to stage‐3 moderate attrition was obtained, for which rehabilitation of the upper anterior sector was planned through the use of immediate dentin sealing (IDS) and resin coating (RC). Conclusion: The use of IDS and RC techniques shows acceptable sensitivity, which is why these techniques are recommended in cases of moderate attrition in early mixed dentition. The immediate rehabilitation along with the stamping technique improved the aesthetic and functional aspects. Therefore, it is advisable to use them immediately after dentin sealing.
Use of serum amyloid A in equine medicine and surgery
Authors: Jacobsen Stine
Published: November 2022

Serum amyloid A (SAA) has become an indispensable part of the management of equine patients in general practice and specialized hospital settings. Although several proteins possess acute phase properties in horses, the usefulness of SAA exceeds that of other acute phase proteins. This is due to the highly desirable kinetics of the equine SAA response. SAA concentrations exhibit a rapid and pronounced increase in response to inflammation and a rapid decline after the resolution of inflammation. This facilitates the detection of inflammatory disease and real‐time monitoring of inflammatory activity. SAA may be used in all stages of patient management: (1) before diagnosis (to rule in/rule out inflammatory disease), (2) at the time of diagnosis (to assess the severity of inflammation and assist in prognostication), and (3) after diagnosis (to monitor changes in inflammatory activity in response to therapy, with relapse of disease, or with infectious/inflammatory complications). By assessing other acute phase reactants in addition to SAA, clinicians can succinctly stage inflammation. White blood cell counts and serum iron concentration change within hours of an inflammatory insult, SAA within a day, and fibrinogen within 2–3 days; the interrelationship of these markers thus indicates the duration and activity of the inflammatory condition. Much research on the equine SAA response and clinical use has been conducted in the last decade. This is the prerequisite for the evidence‐based use of this analyte. However, still today, most published studies involve a fairly low number of horses. To obtain solid evidence for use of SAA, future studies should be designed with larger sample sizes.
Li7P2S8Br0.5I0.5 (LPSBI) solid state electrolyte by XPS
Authors: Strange Lyndi E. , Engelhard Mark H. , Yu Zhaoxin , Lu Dongping
Published: November 2022

There have been increasing surface characterization studies of battery materials specifically in the context of before and after cell operation to determine any chemical changes. Therefore, providing reliable reference spectra of battery-related materials is important. In this paper, survey and high-energy resolution data are reported for the solid-state electrolyte Li7P2S8Br0.5I0.5, which has been synthesized and characterized at Pacific Northwest National Laboratory. The current data present narrow-scan regions of I 3d, I 4d, Br 3d, O 1s, P 2p, S 2p, and C 1s core-level spectra, as well as wide-scan survey data that were obtained using the Al Kα x-ray source with a Thermo Fisher Nexsa instrument.
Homogeneous high In content InxGa1−x N films by supercycle atomic layer deposition
Authors: Hsu Chih-Wei , Martinovic Ivan , Magnusson Roger , Bakhit Babak , Palisaitis Justinas , Persson Per. O. Å. , Rouf Polla , Pedersen Henrik
Published: November 2022

InxGa1−x N is a strategically important material for electronic devices given its tunable bandgap, modulated by the In/Ga ratio. However, current applications are hindered by defects caused by strain relaxation and phase separation in the material. Here, we demonstrate growth of homogeneous InxGa1−x N films with 0.3 < x < 0.8 up to ∼30 nm using atomic layer deposition (ALD) with a supercycle approach, switching between InN and GaN deposition. The composition is uniform along and across the films, without signs of In segregation. The InxGa1−x N films show higher In-content than the value predicted by the supercycle model. A more pronounced reduction of GPCInN than GPCGaN during the growth processes of InN and GaN bilayers is concluded based on our analysis. The intermixing between InN and GaN bilayers is suggested to explain the enhanced overall In-content. Our results show the advantage of ALD to prepare high-quality InxGa1−x N films, particularly with high In-content, which is difficult to achieve with other growth methods.
Stimulus-frequency otoacoustic emissions and middle-ear pressure gains in a finite-element mouse model
Authors: Motallebzadeh Hamid , Puria Sunil
Published: November 2022

For evoked otoacoustic emissions (OAEs), the stimulus and emission signals traverse the middle ear (ME) in forward and reverse directions, respectively. In this study, a fully coupled three-dimensional finite-element model of the mouse ear canal (EC), ME, and cochlea was used to calculate ME pressure gains, impedances, and reflectances at the EC-entrance and stapes-footplate–cochlear-fluid interfaces. The cochlear model incorporates a series of interdigitated Y-shaped structures sandwiched between the basilar membrane and reticular lamina, each comprised of a Deiters' cell, its phalangeal-process extension, and an outer hair cell (OHC). By introducing random perturbations to the OHC gains, stimulation-frequency otoacoustic emissions (SFOAEs) were generated. Raising the perturbation magnitude from 10% to 80% increased the SFOAE magnitude by up to 24 dB in the 10–30 kHz frequency range. Increasing or decreasing the stiffness of the stapes annular ligament and eardrum by a factor of 8 changed the SFOAEs by up to 30 dB, but the round-trip ME gain as measured could not account for this. A modified round-trip ME gain, with reflections removed at the EC-entrance and stapes–cochlea boundaries, eliminated a ±10 dB discrepancy and allowed ME changes to be quantitatively associated with changes in measured OAEs.
Drone noise directivity and psychoacoustic evaluation using a hemispherical microphone array
Authors: Alkmim Mansour , Cardenuto João , Tengan Elisa , Dietzen Thomas , Van Waterschoot Toon , Cuenca Jacques , De Ryck Laurent , Desmet Wim
Published: November 2022

This paper proposes an experimental setup for measuring the sound radiation of a quadrotor drone using a hemispherical microphone array. The measured sound field is decomposed into spherical harmonics, which enables the evaluation of the radiation pattern to non-probed positions. Additionally, the measurement setup allows the assessment of noise emission and psychoacoustic metrics at a wide range of angles. The obtained directivity patterns using a third-order spherical harmonic decomposition (SHD) are shown to exhibit low distortion with respect to the original measurements, therefore, validating the SHD as an adequate representation strategy. Furthermore, the noise emissions are evaluated, and the highest noise emission is observed in the 90° azimuth direction. The exterior spherical acoustic holography description is employed to evaluate psychoacoustic metrics at arbitrary far-field positions and validated on a reference microphone. The estimated psychoacoustic metrics are closely related to the target metrics, which allows for sound quality analysis at any point external to the drone.
Phase-field simulations of morphology development in reactive polymer blending
Authors: Sengupta Rajarshi , Tikekar Mukul D. , Raj James V. , Delaney Kris T. , Villet Michael C. , Fredrickson Glenn H.
Published: November 2022

Reactive blending is an efficient method for synthesizing polymer blends. Industrially, this process is carried out in extruders, where the reacting polymers and the generated copolymer are subjected to high shear stresses. The dynamics of the process, and the resulting morphology is dictated by a coupling of the hydrodynamic forces in the extruder, the thermodynamic interactions between species, and the reaction kinetics on a complex interfacial manifold. We use phase-field simulations to quantify the evolution of the reactive blending process under an external shear flow. Specifically, we consider a model system of two homopolymers of equal length, which react via an end-coupling reaction to form a diblock copolymer of double the length. We compare the morphology development in two different initial geometries of the homopolymers—a cylindrical thread and a drop of one homopolymer in a matrix of the second. We investigate the effect of flow strength, measured by the shear rate, and reaction kinetics, quantified by a Damkohler number, on the progress of the reaction and morphology development. Cylindrical threads are susceptible to breakup via the Rayleigh capillary instability. We demonstrate that this instability can be suppressed by imposing shear along the direction of the thread and increasing the extent of the reaction. The reaction rate in this geometry is unaffected by shear imposed along the cylinder axis. Drops deform significantly under an imposed flow, eventually stretching to long cylindrical threads for sufficient shear rates. In the case of drops, shear stresses enhance the reaction rate by deforming the drop, enabling more homopolymers to come in contact at the expanded interface. We show that shear stresses significantly impact the morphology development and reaction dynamics in reactive polymer blending.
Efficacy and Immune Correlates of OMP-1B and VirB2-4 Vaccines for Protection of Dogs from Tick Transmission of Ehrlichia chaffeensis
Authors: Budachetri Khemraj , Lin Mingqun , Chien Rory C. , Zhang Wenqing , Brock Guy Nathaniel , Rikihisa Yasuko
Published: November 2022

Ehrlichiaare tick-borne pathogens that cause a potentially fatal illness—ehrlichiosis—in animals and humans worldwide. Currently, no vaccine is available for ehrlichiosis, and treatment options are limited.
About the Observational Check of the Mechanism of Gamma Radiation in Soft Gamma Repeaters (SGR)
Authors: Bisnovatyi-Kogan G. S.
Published: November 2022

Soft gamma repeaters (SGR) are identified as single neutron stars (NS) inside the Galaxy, or nearby galaxies, with sporadic transient gamma radiation. A total number of discovered SGR, including relative Anomalous X-ray pulsars (AXP), is few tens of objects. Many of them show periodic radiation, connected with NS rotation, with periods 2–12 s. The slow rotation is accompanied by small rate of loss of rotational energy, which is considerably smaller than the observed sporadic gamma ray luminosity, and is many orders less that the luminosity during giant bursts, observed in 4 SGR. Therefore the energy source is usually connected with annihilation of very strong NS magnetic field. Another model is based on release of a nuclear energy stored in the NS non-equilibrium layer. We suggest here an observational test with could distinguish between these two models.
Ethnic differences and inequities in paediatric healthcare utilisation in the UK: a scoping review
Authors: Zhang Claire X , Quigley Maria A , Bankhead Clare , Bentley Thomas , Otasowie Claire , Carson Claire
Published: November 2022

Background

Despite the increased policy attention on ethnic health inequities since the COVID-19 pandemic, research on ethnicity and healthcare utilisation in children has largely been overlooked.

Objectives

This scoping review aimed to describe and appraise the quantitative evidence on ethnic differences (unequal) and inequities (unequal, unfair and disproportionate to healthcare needs) in paediatric healthcare utilisation in the UK 2001–2021.

Methods

We searched Embase, Medline and grey literature sources and mapped the number of studies that found differences and inequities by ethnic group and healthcare utilisation outcome. We summarised the distribution of studies across various methodological parameters.

Results

The majority of the 61 included studies (n=54, 89%) identified ethnic differences or inequities in paediatric healthcare utilisation, though inequities were examined in fewer than half of studies (n=27, 44%). These studies mostly focused on primary and preventive care, and depending on whether ethnicity data were aggregated or disaggregated, findings were sometimes conflicting. Emergency and outpatient care were understudied, as were health conditions besides mental health and infectious disease. Studies used a range of ethnicity classification systems and lacked the use of theoretical frameworks. Children’s ethnicity was often the explanatory factor of interest while parent/caregiver ethnicity was largely overlooked.

Discussion

While the current evidence base can assist policy makers to identify inequities in paediatric healthcare utilisation among certain ethnic groups, we outline recommendations to improve the validity, generalisability and comparability of research to better understand and thereby act on ethnic inequities in paediatric healthcare.
Hepatitis B virus and other transfusion-transmissible infections in child blood recipients in Lao People’s Democratic Republic: a hospital-based study
Authors: Khounvisith Vilaysone , Saysouligno Sonephet , Souvanlasy Bounpalisone , Billamay Somxay , Mongkhoune Sodaly , Vongphachanh Bounta , Snoeck Chantal J , Black Antony P , Muller Claude P , Hübschen Judith M
Published: November 2022

Introduction

Children requiring multiple blood transfusions are at high risk of transfusion-transmissible infections (TTIs). Lao People’s Democratic Republic is a low-resource setting where donor blood screening faces challenges. This study aimed to determine the burden of TTIs in children in Vientiane Capital.

Methods

300 children with transfusion history and 300 controls were recruited. In addition, 49 newly diagnosed transfusion recipients were followed for up to 12 months. Serum was tested for hepatitis B surface antigen and IgG antibodies against parvovirus B19, hepatitis B, C and E viruses.

Results

The patients had a similar prevalence of anti-hepatitis B core antibodies (56; 18.7%) and hepatitis B surface antigen (8; 2.7%) as the controls (58; 19.3% and 9; 3.0%, respectively). However, there was a higher prevalence of an antibody profile suggestive of hepatitis B vaccination (anti-hepatitis B surface antibody positive/anti-hepatitis B core antibody negative) in the transfused group (140/299; 46.8%) than in controls (77/300; 25.7%, p<0.01). All other markers were similar in the patients and controls or higher in the controls: anti-hepatitis C virus (2.7% and 3.3%, p=0.6), anti-hepatitis E virus (7.5% and 12.7%, p=0.006) and anti-parvovirus B19 (2.4% and 8.5%, p=0.001). The longitudinal cohort did not show an increase in any marker over time.

Conclusion

Our results suggest no significant role of TTIs in Lao children. The higher prevalence of the hepatitis B vaccination profile in transfusion recipients showed that recommendations to vaccinate before commencing transfusions is at least partially implemented, although there is room for improvement.
Updated systematic review of Australian school-based prevention programmes for alcohol and other drugs: a review protocol
Authors: Devine Emma Krogh , Teesson Maree , Debenham Jennifer , Guckel Tara , Stapinski Lexine Ann , Barrett Emma , Champion Katrina Elizabeth , Chapman Cath , Newton Nicola Clare
Published: November 2022

Introduction

Adolescent onset substance use is associated with neurodevelopmental, social and psychological harms. Thus, alcohol and other drug prevention programmes are essential to promote health and well-being during this period. Schools are uniquely positioned to deliver such prevention programmes. The last decade has seen a large expansion of school-based alcohol and drug prevention programmes in Australia, warranting an update of the comprehensive review conducted by Teessonet alin 2012. This proposed review aims to (1) identify school-based substance use prevention programmes that have been trialled in Australia since 2011, (2) evaluate their efficacy and (3) identify intervention components associated with effectiveness. This will assist schools in identifying and adopting effective evidence-based programmes and inform future programme development, evaluation and policy.

Methods and analysis

Studies published from 2011 will be identified by searching the electronic databases PubMed, PsycINFO, Medline, Embase, ProQuest and Cochrane Library in addition to grey literature searches. Eligible studies will be controlled trials (including randomised controlled trials, cluster randomised controlled trials and quasi-experimental trials) of programmes measuring drug and alcohol related outcomes that are conducted in a school setting and have been trialled within Australia. Records will be independently screened for eligibility by two review authors, with disagreements being resolved by consensus or a third review author where necessary. Data extraction, risk of bias and study quality will also be completed independently by two review authors. A qualitative synthesis of all eligible studies will be presented. In addition, if there are sufficient data to combine studies, a random-effects meta-analysis will be conducted.

Ethics and dissemination

This research is exempt from ethics approval as no primary data are collected, with work instead being carried out on published documents. The findings of this proposed review will be disseminated in a peer-reviewed journal and at conferences.

PROSPERO registration number

CRD42021272959.
Effects of insoles adapted in flip-flop sandals for persistent heel pain: a protocol for a sham-controlled randomised trial
Authors: Fagundes Marina Gomes , Teixeira Mendes André Augusto Martines , Barbosa Germanna Medeiros , de Souza Marcelo Cardoso
Published: November 2022

Introduction

Persistent heel pain is a prevalent complaint affecting up to 10% of the population. Insoles adapted in flip-flop sandals are an alternative treatment for pain and function of individuals with persistent heel pain, showing improvement within 12 weeks of treatment. Most studies considered foot posture and biomechanics to prescribe insoles for persistent heel pain, but few verified the effects of a 12-week treatment on pain catastrophising. This study will investigate the effects of insoles adapted in flip-flop sandals on pain intensity, function, functional walking capacity and pain catastrophising of individuals with persistent heel pain.

Methods and analysis

This is a protocol for a sham-controlled randomised trial. Eighty individuals with persistent heel pain will be assessed and randomised into two intervention groups: insoles adapted in flip-flop sandals and flip-flop sandals with sham (ie, flat) insoles. Assessments will be conducted at baseline (T0), after 6 weeks (T6), 12 weeks postintervention (T12) and after a 4-week follow-up (T16). The primary outcome will be the pain intensity, and secondary outcomes will be foot function, functional walking capacity and pain catastrophising. Analysis of variance with mixed design (if normal distribution) or Friedman’s test (if not normal distribution) will verify intergroup and intragroup differences. Bonferroni post hoc tests will be performed in case of significant group or time interaction. Intent-to-treat analysis will be used, and a significance level of 5% and 95% CIs will be considered.

Ethics and dissemination

This study was approved by the research ethics committee of the Federal University of Rio Grande do Norte (registry no. 4,018,821). Results will be disseminated to individuals, submitted to a peer-reviewed journal and disclosed in scientific meetings.

Trial registration number

NCT04784598.
Development of the SPREAD framework to support the scaling of de-implementation strategies: a mixed-methods study
Authors: Kroon Daniëlle , van Dulmen Simone A , Westert Gert P , Jeurissen Patrick P T , Kool Rudolf B
Published: November 2022

Objective

We aimed to increase the understanding of the scaling of de-implementation strategies by identifying the determinants of the process and developing a determinant framework.

Design and methods

This study has a mixed-methods design. First, we performed an integrative review to build a literature-based framework describing the determinants of the scaling of healthcare innovations and interventions. PubMed and EMBASE were searched for relevant studies from 1995 to December 2020. We systematically extracted the determinants of the scaling of interventions and developed a literature-based framework. Subsequently, this framework was discussed in four focus groups with national and international de-implementation experts. The literature-based framework was complemented by the findings of the focus group meetings and adapted for the scaling of de-implementation strategies.

Results

The literature search resulted in 42 articles that discussed the determinants of the scaling of innovations and interventions. No articles described determinants specifically for de-implementation strategies. During the focus groups, all participants agreed on the relevance of the extracted determinants for the scaling of de-implementation strategies. The experts emphasised that while the determinants are relevant for various countries, the implications differ due to different contexts, cultures and histories. The analyses of the focus groups resulted in additional topics and determinants, namely, medical training, professional networks, interests of stakeholders, clinical guidelines and patients’ perspectives. The results of the focus group meetings were combined with the literature framework, which together formed the supporting the scaling of de-implementation strategies (SPREAD) framework. The SPREAD framework includes determinants from four domains: (1) scaling plan, (2) external context, (3) de-implementation strategy and (4) adopters.

Conclusions

The SPREAD framework describes the determinants of the scaling of de-implementation strategies. These determinants are potential targets for various parties to facilitate the scaling of de-implementation strategies. Future research should validate these determinants of the scaling of de-implementation strategies.
Study protocol for locoregional precision treatment of hepatocellular carcinoma with transarterial chemoembolisation (TACTida), a clinical study: idarubicin dose selection, tissue response and survival
Authors: Nyman Sofi Sennefelt , Ahlström Håkan , Creusen Angeliki Dimopoulou , Dahlgren David , Hedeland Mikael , Heindryckx Femke , Johnson Ulf , Khaled Jaafar , Kullenberg Fredrik , Nyman Rickard , Rorsman Fredrik , Sheikhi Reza , Simonsson Ulrika S H , Sjögren Erik , Wanders Alkwin , Lennernäs Hans , Ebeling Barbier Charlotte
Published: November 2022

Introduction

Hepatocellular carcinoma (HCC) is a common cause of cancer-related death, often detected in the intermediate stage. The standard of care for intermediate-stage HCC is transarterial chemoembolisation (TACE), where idarubicin (IDA) is a promising drug. Despite the fact that TACE has been used for several decades, treatment success is unpredictable. This clinical trial has been designed believing that further improvement might be achieved by increasing the understanding of interactions between local pharmacology, tumour targeting, HCC pathophysiology, metabolomics and molecular mechanisms of drug resistance.

Methods and analysis

The study population of this single-centre clinical trial consists of adults with intermediate-stage HCC. Each tumour site will receive TACE with two different IDA doses, 10 and 15 mg, on separate occasions. Before and after each patient’s first TACE blood samples, tissue and liquid biopsies, and positron emission tomography (PET)/MRI will be performed. Blood samples will be used for pharmacokinetics (PK) and liver function evaluation. Tissue biopsies will be used for histopathology analyses, and culturing of primary organoids of tumour and non-tumour tissue to measure cell viability, drug response, multiomics and gene expression. Multiomics analyses will also be performed on liquid biopsies. PET/MRI will be used to evaluate tumour viability and liver metabolism. The two doses of IDA will be compared regarding PK, antitumour effects and safety. Imaging, molecular biology and multiomics data will be used to identify HCC phenotypes and their relation to drug uptake and metabolism, treatment response and survival.

Ethics and dissemination

Participants give informed consent. Personal data are deidentified. A patient will be withdrawn from the study if considered medically necessary, or if it is the wish of the patient. The study has been approved by the Swedish Ethical Review Authority (Dnr. 2021-01928) and by the Medical Product Agency, Uppsala, Sweden.

Trial registration number

EudraCT number: 2021-001257-31.
Cohort profile: Risk and risk factors for female breast cancer after treatment for childhood and adolescent cancer: an internationally pooled cohort
Authors: Wang Yuehan , Kremer Leontien C M , van Leeuwen Flora E , Armstrong Gregory T , Leisenring Wendy , de Vathaire Florent , Hudson Melissa M , Kuehni Claudia E , Arnold Michael A , Haddy Nadia , Demoor-Goldschmidt Charlotte , Diallo Ibrahima , Howell Rebecca M , Ehrhardt Matthew J , Moskowitz Chaya S , Neglia Joseph P , van der Pal Helena J H , Robison Leslie L , Schaapveld Michael , Turcotte Lucie M , Waespe Nicolas , Ronckers Cécile M , Teepen Jop C
Published: November 2022

Purpose

The International Consortium for Pooled Studies on Subsequent Malignancies after Childhood and Adolescent Cancer was established in 2018 to address gaps in knowledge of risk and risk factors for breast cancer subsequent to childhood/adolescent cancer by pooling individual patient data from seven cohorts. Initially, the pooled cohort will focus on three clinically relevant questions regarding treatment-related subsequent breast cancer risk in female survivors, which are the risk related to low-dose radiotherapy exposure to the chest, specific chemotherapy agents and attained age.

Participants

The consortium database includes pooled data on 21 892 female survivors from seven cohorts in North America and Europe with a primary cancer diagnosis at <21 years of age, and survival ≥5 years from diagnosis.

Findings to date

This is a newly established pooled study. The cohort profile summarised the data collected from each included cohort, including childhood cancer diagnosis information and treatment details (ie, radiotherapy fields and cumulative doses, and chemotherapy agents and cumulative doses for each agent). Included cohorts’ follow-up started 1951–1981 and ended 2013–2021, respectively, for a median follow-up duration of 24.3 (IQR 18.0–32.8) years since primary cancer diagnosis. The median age at primary cancer diagnosis was 5.4 (IQR 2.5–11.9) years. And the median attained age at last follow-up was 32.2 (IQR 24.0–40.4) years. In all, 4240 (19.4%) survivors were treated with radiotherapy to the chest and 9308 (42.5%) with anthracyclines. At the end of the follow-up, 835 females developed a first subsequent breast cancer, including 635 invasive breast cancer only, 184 carcinomas in situ only (172 ductal carcinomas in situ and 12 lobular carcinomas in situ), and 16 with both an invasive and in situ diagnosis at the same moment. The cumulative incidences of subsequent breast cancer (both invasive and in situ) 25 and 35 years after primary cancer diagnosis were 2.2% and 6.2%, respectively.

Future plans

The consortium is intended to serve as a model and robust source of childhood/adolescent cancer survivor data for elucidating other knowledge gaps on subsequent breast cancer risk, and risk of other subsequent malignancies (including data on males) in the future.
Review of the utility of routine mortality reviews among deaths on General Internal Medicine wards in a Canadian tertiary care hospital
Authors: Tran Kelvin , Padwal Raj , Hamilton Peter , Ngo Jennifer
Published: November 2022

Background

Hospital morbidity and mortality reviews are common quality assurance activities, intended to uncover latent or unrecognised systemic issues that contribute to preventable adverse events and patient harm. Mortality reviews may be routinely mandated by hospital policy or for accreditation purposes. However, patients under the care of certain specialties, such as general internal medicine (GIM), are affected by a substantial burden of chronic disease, advanced age, frailty or limited life expectancy. Many of their deaths could be viewed as reasonably foreseeable, and unrelated to poor-quality care.

Methods

We sought to determine how frequently postmortem chart reviews for hospitalised GIM patients at our tertiary care centre in Canada would uncover patient safety or quality of care issues that directly led to these patients’ deaths. We reviewed the charts of all patients who died while admitted to the GIM admitting service over a 12-month time period between 1 July 2020 and 30 June 2021.

Results

We found that in only 2% of cases was a clinical adverse event detected that directly contributed to a poor or unexpected outcome for the patient, and of those cases, more than half were related to unfortunate nosocomial transmission of COVID-19 infection.

Conclusion

Due to an overall low yield, we discourage routine mortality chart reviews for general medical patients, and instead suggest that organisations focus on strategies to recognise and capture safety incidents that may not necessarily result in death.
Inhibiting DNA methylation and RNA editing upregulates immunogenic RNA to transform the tumor microenvironment and prolong survival in ovarian cancer
Authors: Gomez Stephanie , Cox Olivia L , Walker Reddick R , Rentia Uzma , Hadley Melissa , Arthofer Elisa , Diab Noor , Grundy Erin E , Kanholm Tomas , McDonald James I , Kobyra Julie , Palmer Erica , Noonepalle Satish , Villagra Alejandro , Leitenberg David , Bollard Catherine M , Saunthararajah Yogen , Chiappinelli Katherine B
Published: November 2022

Background

Novel therapies are urgently needed for ovarian cancer (OC), the fifth deadliest cancer in women. Preclinical work has shown that DNA methyltransferase inhibitors (DNMTis) can reverse the immunosuppressive tumor microenvironment in OC. Inhibiting DNA methyltransferases activate transcription of double-stranded (ds)RNA, including transposable elements. These dsRNAs activate sensors in the cytoplasm and trigger type I interferon (IFN) signaling, recruiting host immune cells to kill the tumor cells. Adenosine deaminase 1 (ADAR1) is induced by IFN signaling and edits mammalian dsRNA with an A-to-I nucleotide change, which is read as an A-to-G change in sequencing data. These edited dsRNAs cannot be sensed by dsRNA sensors, and thus ADAR1 inhibits the type I IFN response in a negative feedback loop. We hypothesized that decreasing ADAR1 editing would enhance the DNMTi-induced immune response.

Methods

Human OC cell lines were treated in vitro with DNMTi and then RNA-sequenced to measure RNA editing. Adar1 was stably knocked down in ID8Trp53-/-mouse OC cells. Control cells (shGFP) or shAdar1 cells were tested with mock or DNMTi treatment. Tumor-infiltrating immune cells were immunophenotyped using flow cytometry and cell culture supernatants were analyzed for secreted chemokines/cytokines. Mice were injected with syngeneic shAdar1 ID8Trp53-/-cells and treated with tetrahydrouridine/DNMTi while given anti-interferon alpha and beta receptor 1, anti-CD8, or anti-NK1.1 antibodies every 3 days.

Results

We show that ADAR1 edits transposable elements in human OC cell lines after DNMTi treatment in vitro. Combining ADAR1 knockdown with DNMTi significantly increases pro-inflammatory cytokine/chemokine production and sensitivity to IFN-β compared with either perturbation alone. Furthermore, DNMTi treatment and Adar1 loss reduces tumor burden and prolongs survival in an immunocompetent mouse model of OC. Combining Adar1 loss and DNMTi elicited the most robust antitumor response and transformed the immune microenvironment with increased recruitment and activation of CD8+ T cells.

Conclusion

In summary, we showed that the survival benefit from DNMTi plus ADAR1 inhibition is dependent on type I IFN signaling. Thus, epigenetically inducing transposable element transcription combined with inhibition of RNA editing is a novel therapeutic strategy to reverse immune evasion in OC, a disease that does not respond to current immunotherapies.
Compartmentalization of the host microbiome: how tumor microbiota shapes checkpoint immunotherapy outcome and offers therapeutic prospects
Authors: Boesch Maximilian , Horvath Lena , Baty Florent , Pircher Andreas , Wolf Dominik , Spahn Stephan , Straussman Ravid , Tilg Herbert , Brutsche Martin H
Published: November 2022

The host microbiome is polymorphic, compartmentalized, and composed of distinctive tissue microbiomes. While research in the field of cancer immunotherapy has provided an improved understanding of the interaction with the gastrointestinal microbiome, the significance of the tumor-associated microbiome has only recently been grasped. This article provides a state-of-the-art review about the tumor-associated microbiome and sheds light on how local tumor microbiota shapes anticancer immunity and influences checkpoint immunotherapy outcome. The direct route of interaction between cancer cells, immune cells, and microbiota in the tumor microenvironment is emphasized and advocates a focus on the tumor-associated microbiome in addition to the spatially separated gut compartment. Since the mechanisms underlying checkpoint immunotherapy modulation by tumor-associated microbiota remain largely elusive, future research should dissect the pathways involved and outline strategies to therapeutically modulate microbes and their products within the tumor microenvironment. A more detailed knowledge about the mechanisms governing the composition and functional quality of the tumor microbiome will improve cancer immunotherapy and advance precision medicine for solid tumors.
Perception of heated tobacco products and support for regulations: a cross-sectional study in Hong Kong
Authors: Wu Yongda Socrates , Cheung Yee Tak Derek , Ho Sai Yin , Tong Henry Sau Chai , Lai Vienna Wai Yin , Lam Tai Hing , Wang Man Ping
Published: November 2022

Background

Hong Kong has proposed banning the sale of heated tobacco products (HTPs). Perceptions of reduced harms and effectiveness for quitting combustible cigarettes (CCs) of HTPs due to their promotions may erode public support for regulations. We assessed the associations between perceptions of HTPs and support for regulations in Hong Kong.

Methods

In two population-based landline surveys conducted in 2018–2019, 1985 respondents (51.4% male; 22.7% aged 60+ years) reported perceived relative harm of HTPs to CCs and effectiveness for quitting CCs, and support for five HTP regulations (ban on promotion and advertisements, use in smoke-free areas, sales to minors, registration before sale, sale licence) and a total ban on sale. Current and former smokers were oversampled due to low prevalence. Descriptive statistics were weighted to the general population. Associations were analysed, adjusting for sociodemographic characteristics, smoking status and ever HTP use.

Results

27.4% (N=515) of respondents perceived HTPs as less harmful, and 18.8% (N=1299) perceived them as effective for quitting CCs. Support was generally high (at least one regulation, 99.1%, N=1959; all five regulations, 66.8%, N=1114; total ban, 63.5%, N=946). Perceptions of reduced harm were associated with lower support for all five regulations (adjusted risk ratio 0.85, 0.75 to 0.96) and a total ban on sale (0.58, 0.51 to 0.66). Results were similar for perceptions of effectiveness for quitting.

Conclusions

Lower support for HTP regulations and a total ban on sale were associated with perceptions of reduced harm and effectiveness for quitting CCs of HTPs in Hong Kong.
Macrophage migration inhibitory factor promotes glucocorticoid resistance of neutrophilic inflammation in a murine model of severe asthma
Authors: Allam Venkata Sita Rama Raju , Pavlidis Stelios , Liu Gang , Kermani Nazanin Zounemat , Simpson Jennifer , To Joyce , Donnelly Sheila , Guo Yi-Ke , Hansbro Philip M , Phipps Simon , Morand Eric F , Djukanovic Ratko , Sterk Peter , Chung Kian Fan , Adcock Ian , Harris James , Sukkar Maria B
Published: November 2022

Background

Severe neutrophilic asthma is resistant to treatment with glucocorticoids. The immunomodulatory protein macrophage migration inhibitory factor (MIF) promotes neutrophil recruitment to the lung and antagonises responses to glucocorticoids. We hypothesised that MIF promotes glucocorticoid resistance of neutrophilic inflammation in severe asthma.

Methods

We examined whether sputum MIF protein correlated with clinical and molecular characteristics of severe neutrophilic asthma in the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. We also investigated whether MIF regulates neutrophilic inflammation and glucocorticoid responsiveness in a murine model of severe asthma in vivo.

Results

MIF protein levels positively correlated with the number of exacerbations in the previous year, sputum neutrophils and oral corticosteroid use across all U-BIOPRED subjects. Further analysis of MIF protein expression according to U-BIOPRED-defined transcriptomic-associated clusters (TACs) revealed increased MIF protein and a corresponding decrease in annexin-A1 protein in TAC2, which is most closely associated with airway neutrophilia and NLRP3 inflammasome activation. In a murine model of severe asthma, treatment with the MIF antagonist ISO-1 significantly inhibited neutrophilic inflammation and increased glucocorticoid responsiveness. Coimmunoprecipitation studies using lung tissue lysates demonstrated that MIF directly interacts with and cleaves annexin-A1, potentially reducing its biological activity.

Conclusion

Our data suggest that MIF promotes glucocorticoid-resistance of neutrophilic inflammation by reducing the biological activity of annexin-A1, a potent glucocorticoid-regulated protein that inhibits neutrophil accumulation at sites of inflammation. This represents a previously unrecognised role for MIF in the regulation of inflammation and points to MIF as a potential therapeutic target for the management of severe neutrophilic asthma.
Genomic analysis of a new type VI secretion system in Vibrio parahaemolyticus and its implications for environmental adaptation in shrimp ponds
Authors: Wang Rui , Xiao Jinzhou , Wang Qingyao , Zhao Wenyu , Liu Xinyue , Liu Ying , Fu Songzhe
Published: November 2022

The type VI secretion system (T6SS) in Vibrio spp. is often used to kill heteroclonal neighbors by direct injection of toxic effectors, but its strategies in aquacultural environments receive limited attention. In this study, we conducted genomic analysis for a T6SS-harboring plasmid in V. parahaemolyticus strain VP157. Coculture assays were further conducted to verify its antibacterial function. The results showed that strain VP157 harbored a 132-kb plasmid, pVP157-1, which consists of two fragments: an 87.8-kb fragment identical to plasmid pTJ114-1 and a 44.2-kb T6SS gene cluster with only 4% DNA identity to T6SS1 in the V. parahaemolyticus reference genome. Gene-by-gene analysis of six genes representing core T6SS components suggested that each gene has distinct evolutionary origins. In vitro experimental evolution revealed that pVP157-1 can excise from the VP157 genome with an excision rate of 4%. A coculture assay suggested that strain VP157 had significantly higher antibacterial activity against Bacillus pumilus and V. cholerae than the strain without pVP157-1(VP157∆T6SS). In contrast, a rapid decline was observed for the proportion of VP157∆ T6SS in a mock microbial community, which decreased from 10.7% to 2.1% in 5 days. The results highlighted that the acquisition of T6SS fostered the fitness of V . parahaemolyticus in a complex environment.
Formula for two-loop divergent part of 4-D Yang–Mills effective action
Authors: Ivanov A. V. , Kharuk N. V.
Published: November 2022

In the paper, we study the two-loop contribution to the effective action of the four-dimensional quantum Yang–Mills theory. We derive a new formula for the contribution in terms of three functions, formed from the Green’s function expansion near the diagonal. This result can be applied to different types of regularization. Therefore, we test it by using the dimensional regularization and cutoff ones and show the consistence with the results, obtained in other works.
Nature and Origin of Operators Entering the Master Equation of an Open Quantum System
Authors: Spaventa Giovanni , Verrucchi Paola
Published: November 2022

By exploiting the peculiarities of a recently introduced formalism for describing open quantum systems (the parametric representation with environmental coherent states) we derive an equation of motion for the reduced density operator of an open quantum system that has the same structure of the celebrated Gorini–Kossakowski–Sudarshan–Lindblad equation, but holds regardless of Markovianity being assumed. The operators in our result have explicit expressions in terms of the Hamiltonian describing the interactions with the environment, and can be computed once a specific model is considered. We find that, instead of a single set of Lindblad operators, in the general (non-Markovian) case there one set of Lindblad-like operators for each and every point of a symplectic manifold associated to the environment. This intricacy disappears under some assumptions (which are related to Markovianity and the classical limit of the environment), under which it is possible to recover the usual master-equation formalism. Finally, we find such Lindblad-like operators for two different models of a qubit in a bosonic environment, and show that in the classical limit of the environment their renown master equations are recovered.
Pulse-transfer function of the intensity-curvature functional: Applications in magnetic resonance angiography of the human brain
Authors: Ciulla Carlo
Published: November 2022

This paper reports additional evidence of the high-pass filtering properties of the intensity-curvature functional (ICF). Magnetic resonance angiography (MRA) of the human brain is used to calculate its ICF. MRA and ICF are direct Z-transformed. The pulsetransfer function (PTF) of the ICF is defined as the inverse Z-transform of the ratio between Z-space of ICF and Z-space of MRA. The image space of PTF is calculated and is direct Z-transformed. MRA is reconstructed through inverse Z-transform of the ratio between Z-space of ICF and Z-space of PTF. MRA reconstruction proves correctness of the approximated approach and adds evidence to the assumption that ICF is a high-pass filter. This research provides two novelties: (1) additional evidence that ICF is a high-pass filter and (2) a medical image processing technique that proves correct that the PTF of a high-pass filter (ICF) can be approximated by the ratio between Z-space of ICF and Z-space of MRA. It follows that MRA can be reconstructed using the inverse Z-transform of the ratio between Z-space of ICF and Z-space of PTF.
Socially Assistive Robots for Parkinson's Disease: Needs, Attitudes and Specific Applications as Identified by Healthcare Professionals
Authors: Bar-On Inbal , Mayo Gili , Levy-Tzedek Shelly
Published: November 2022

To explore how
socially assistive robots (SARs)
may assist the specific needs of
individuals with Parkinson's disease (IwPD)
, we conducted three focus groups with 12 clinicians who treat IwPD. We present a thematic analysis of their perceptions of the needs of the patients, and their own expectations, perceived advantages, disadvantages and concerns regarding the use of SARs for IwPD. Clinicians were positive towards using SARs for IwPD, if used in the patient's home, for motor, communication, emotional, and cognitive needs, especially for practice and for help with activities of daily living. They were concerned that a SAR might be used to replace clinicians’ work, and stressed it should only
augment
the clinicians’ work. They thought a SAR may relieve some of the burden experienced by informal caregivers, and identified specific applications for SARs for PD. We asked 18 stakeholders (nine IwPD, nine family members) to rate their level of agreement with the clinicians’ statements. The greatest divergence between their views and those of the clinicians was on the topic of using a SAR as a companion, or as a feeding assistant, to which they objected. This work may be used as a basis for future studies designing SARs for IwPD.
Serialism and Opacity in Phonological Theory
Authors: Pruitt Kathryn
Published: November 2022

Opacity is a natural language phenomenon where a phonological process is rendered non-surface-true by virtue of its interaction with other processes. Phonologists have long been fascinated with opaque generalizations both from a typological standpoint (What kinds of non-surface-true generalizations are found?) and a theoretical one (Which formal tools permit an analysis of opacity?). This review aims to ( a) discuss the breadth of non-surface-true generalizations in light of phonologists’ (often implicit) working definitions of opacity and ( b) address opacity as a flashpoint in one of the larger debates in generative phonology, between the rule-based serial approach of Chomsky & Halle's Sound Pattern of English and constraint-based parallel Optimality Theory. A conclusion offered here is that the well-known problems Optimality Theory faces with some kinds of opacity are due not to its lack of serialism but to the fact that such processes are input-motivated rather than output-motivated.