bluuebunny/crossref_metadata_2025 huggingface dataset:
MiR-497-5p down-regulates CDCA4 to restrains lung squamous cell carcinoma progression
Authors: Hu Jiangwei , Xiang Xinqin , Guan Wei , Lou Weihua , He Junming , Chen Jian , Fu Yin , Lou Guoliang
Published: November 2021

Background

So far, few have concerned miR-497-5p in lung squamous cell carcinoma (LUSC).

Methods

MiR-497-5p expression in LUSC was measured by qRT-PCR. Its impacts on tumor-related cell behaviors were investigated by CCK8 assay, scratch healing assay, flow cytometry and Transwell invasion methods. In addition, interaction between miR-497-5p and CDCA4 in LUSC was also elucidated through rescue experiment, western blot, dual-luciferase, and bioinformatics analysis.

Results

Low level of miR-497-5p was confirmed in LUSC tissue and cells. Overexpressed miR-497-5p markedly inhibited cancer progression. miR-497-5p restrained CDCA4 expression. Rescue assay showed that overexpressing miR-497-5p eliminated effect of overexpressed CDCA4.

Conclusion

By targeting CDCA4, miR-497-5p restrained development of LUSC.
Improving phenylalanine and micronutrients status of children with phenylketonuria: a pilot randomized study
Authors: Zamani Reza , Karimi-Shahanjarini Akram , Tapak Leili , Moeini Babak
Published: November 2021

Background

Children with Phenylketonuria (PKU) need a special diet to avoid a variety of physical and psychological complications. The aim of this study was to compare and assess the effects of two interventions on and levels of phenylalanine and micronutrients in children with PKU.

Methods

Forty-six children with PKU (ages 1–12 years) and their caregivers were randomly assigned to one of two 10-week interventions: a caregiver educational intervention based on the Integrative Model of Behvioral Prediction (IMBP) and supplementary low-protein-modified foods. Outcomes consisted of Children's plasma phenylalanine and micronutrients (i.e., vitamin B12, vitamin D3, and zinc) and hemoglobin levels. To assess the sustainability of outcomes, we also compared the children’s phenylalanine level at five-time points including baseline and 10-week, 6 months, 12 months, and 24 months follow-ups. In addition, caregivers of both groups were asked to complete a questionnaire to assess how well the interventions were implemented as well as satisfaction with interventions.

Results

While a large percentage of children had phenylalanine levels out of range indicating non-adherence (69.6% and 81% in the educational and food items group, respectively), micronutrient deficiencies were not prevalent in the patient cohort. The levels of phenylalanine in both groups decreased significantly over time. However, conducting a repeated-measures ANOVA to evaluating the change in groups across five-time points, revealed a significant difference between groups (F = 4.68, p = 0.03). That is, the educational intervention was more effective in lowering the children's phenylalanine level. At 24-month follow-up, the percentage of children with a normal range of phenylalanine level in the educational and food items groups increased to 73.9 and 57.1 percent, respectively, from 26 and 38 percent at baseline. There were no significant changes in children's micronutrients level following the interventions, except in the hemoglobin. In this way, at 10-week follow-up, the mean hemoglobin of children in the educational group reduced significantly (P = 0.041). However, there was no significant difference between the two groups. In general, all caregivers completed the process evaluation checklist, the feedback was largely positive.

Conclusions

The results of this study demonstrated that both educational and providing food item interventions resulted in a significant reduction in phenylalanine levels. Empowering caregivers of patients, creating and fortifying social networks, providing favorable social supports, and providing access to special food items may be effective in controlling PKU.

Clinical trial registration: Iranian Registry of Clinical Trials (IRCT20180506039548N1). Registered 6th Jun 2018, https://www.irct.ir/trial/30977.
The impact of Mediterranean diet on coronary plaque vulnerability, microvascular function, inflammation and microbiome after an acute coronary syndrome: study protocol for the MEDIMACS randomized, controlled, mechanistic clinical trial
Authors: Fernández Ana I. , Bermejo Javier , Yotti Raquel , Martínez-Gonzalez Miguel Ángel , Mira Alex , Gophna Uri , Karlsson Roger , Al-Daccak Reem , Martín-Demiguel Irene , Gutiérrez-Ibanes Enrique , Charron Dominique , Fernández-Avilés Francisco ,   on behalf of the MEDIMACS research team, Fernández Ana I. , Bermejo Javier , Yotti Raquel , Gutierrez-Ibanes Enrique , Gabaldón-Badiola Álvaro , Martín-Demiguel Irene , Sanz Ricardo , Martínez-Legazpi Pablo , Elízaga Jaime , Fernández-Avilés Francisco , Jurado Elena , Martínez-Gonzalez Miguel Ángel , Razquin Cristina , Vázquez-Ruiz Zenaida , Mira Alex , López Aránzazu , Ferrer Maria D. , Gophna Uri , Reshef Leah , Karlsson Roger , Moore Edward , Karlsson Göran , Winqvist Anna , Al-Daccak Reem , Charron Dominique
Published: November 2021

Background

Primary prevention trials have demonstrated that the traditional Mediterranean diet is associated with a reduction in cardiovascular mortality and morbidity. However, this benefit has not been proven for secondary prevention after an acute coronary syndrome (ACS). We hypothesized that a high-intensity Mediterranean diet intervention after an ACS decreases the vulnerability of atherosclerotic plaques by complex interactions between anti-inflammatory effects, microbiota changes and modulation of gene expression.

Methods

The MEDIMACS project is an academically funded, prospective, randomized, controlled and mechanistic clinical trial designed to address the effects of an active randomized intervention with the Mediterranean diet on atherosclerotic plaque vulnerability, coronary endothelial dysfunction and other mechanistic endpoints. One hundred patients with ACS are randomized 1:1 to a monitored high-intensity Mediterranean diet intervention or to a standard-of-care arm. Adherence to diet is assessed in both arms using food frequency questionnaires and biomarkers of compliance. The primary endpoint is the change (from baseline to 12 months) in the thickness of the fibrous cap of a non-significant atherosclerotic plaque in a non-culprit vessel, as assessed by repeated optical coherence tomography intracoronary imaging. Indices of coronary vascular physiology and changes in gastrointestinal microbiota, immunological status and protein and metabolite profiles will be evaluated as secondary endpoints.

Discussion

The results of this trial will address the key effects of dietary habits on atherosclerotic risk and will provide initial data on the complex interplay of immunological, microbiome-, proteome- and metabolome-related mechanisms by which non-pharmacological factors may impact the progression of coronary atherosclerosis after an ACS.

Trial registration

ClinicalTrials.govNCT03842319. Registered on 13 May 2019
Partial oral antibiotic treatment for bacterial brain abscess: an open-label randomized non-inferiority trial (ORAL)
Authors: Bodilsen Jacob , Brouwer Matthijs C. , van de Beek Diederik , Tattevin Pierre , Tong Steven , Naucler Pontus , Nielsen Henrik
Published: November 2021

Background

The advised standard treatment for bacterial brain abscess following surgery is 6 to 8 weeks of intravenous (IV) antibiotic treatment, but an early switch to oral antibiotic treatment has been suggested to be equally effective.

Methods

This investigator-initiated, international, multi-center, parallel group, open-label, randomized (1:1 allocation) controlled trial will examine if oral treatment after 2 weeks of IV antibiotic therapy is non-inferior to standard 6–8 weeks of IV antibiotics for bacterial brain abscess in adults (≥ 18 years of age). The study will be conducted at hospitals across Denmark, the Netherlands, France, Australia, and Sweden. Exclusion criteria are severe immunocompromise or impaired gastro-intestinal absorption, pregnancy, device-related brain abscesses, and brain abscess caused by nocardia, tuberculosis, or Pseudomonas spp. The primary objective is a composite endpoint at 6 months after randomization consisting of all-cause mortality, intraventricular rupture of brain abscess, unplanned re-aspiration or excision of brain abscess, relapse, or recurrence. The primary endpoint will be adjudicated by an independent blinded endpoint committee. Secondary outcomes include extended Glasgow Outcome Scale scores and all-cause mortality at end of treatment as well as 3, 6, and 12 months since randomization, completion of assigned treatment, IV catheter associated complications, durations of admission and antibiotic treatment, severe adverse events, quality of life scores, and cognitive evaluations. The planned sample size is 450 patients for a one-sided alpha of 0.025 and a power of 90% to exclude a difference in favor of standard treatment of more than 10%. Date of initiation of first study center was November 3, 2020, with active recruitment for 3 years and follow-up for 1 year of all patients.

Discussion

The results of this study may guide future recommendations for treatment of bacterial brain abscess. If early transition to oral antibiotics proves non-inferior to standard IV treatment, this will provide considerable health and costs benefits.

Trial registration

ClinicalTrials.gov NCT04140903, first registered 28.10.2019. EudraCT number: 2019-002845-39, first registered 03.07.2019
The invasive Korean bush mosquito Aedes koreicus (Diptera: Culicidae) in Germany as of 2020
Authors: Hohmeister Nicolas , Werner Doreen , Kampen Helge
Published: November 2021

Background

The Korean bush mosquito Aedes koreicus was recently reported to have established a population in western Germany (Wiesbaden) in 2016. The species is difficult to distinguish morphologically from its close relative, the invasive Japanese bush mosquito Ae. japonicus, which is already widely distributed in many parts of Germany, including the area colonised by Ae. koreicus. Genetic confirmation of morphologically identified “Ae. japonicus” collection material, however, had only been done exceptionally before the German Ae. koreicus population became known.

Methods

Dried archived “Ae. japonicus” specimens both from the municipality of Wiesbaden and from deliberately and randomly selected distribution sites all over Germany were re-examined morphologically and genetically for admixture by Ae. koreicus. Moreover, cemeteries in the greater Wiesbaden area were sampled in 2019 and 2020 to check for Ae. koreicus spread. Korean and Japanese bush mosquitoes submitted to the German citizen science mosquito monitoring scheme “Mueckenatlas” in 2019 and 2020 were also subjected to particularly thorough species identification. The ND4 DNA sequences generated in this study in the context of species identification were phylogenetically compared to respective GenBank entries of Ae. koreicus. As a by-product, several genetic markers were evaluated for their suitability to identify Ae. koreicus.

Results

Aedes koreicus specimens could be identified in mosquito collection material and submissions from Wiesbaden from 2015 onwards, suggesting establishment to have happened in the same year as Ae. japonicus establishment. Detections of Ae. koreicus from 2019 and 2020 in Wiesbaden indicate a negligible enlargement of the populated area as described for 2018. Two Ae. koreicus specimens were also submitted from the city of Munich, southern Germany, in 2019 but further specimens could not be identified during immediate local inspections. Comparison of ND4 sequences generated in this and other studies demonstrate a high degree of homology, suggesting that this DNA region is not informative enough for clarification of origins and relationships of Ae. koreicus populations. For genetic identification of Ae. koreicus, PCR primers used for classical CO1 barcoding were found to lead to mismatches and produce no or incorrect amplicons. Alternative CO1 primers or a validated ND4 marker should be used instead.

Conclusions

Aedes koreicus is probably introduced into Germany every now and then but rarely succeeds in becoming established. As with most European populations, the German population is characterised by a limited expansion tendency. Since Ae. koreicus is a potential vector, however, Asian bush mosquitoes found at new places should be examined quite carefully and known distribution areas of Ae. japonicus regularly checked for the presence of Ae. koreicus.

Graphical Abstract
In vivo human molecular neuroimaging of dopaminergic vulnerability along the Alzheimer’s disease phases
Authors: Sala Arianna , Caminiti Silvia Paola , Presotto Luca , Pilotto Andrea , Liguori Claudio , Chiaravalloti Agostino , Garibotto Valentina , Frisoni Giovanni Battista , D’Amelio Marcello , Paghera Barbara , Schillaci Orazio , Mercuri Nicola , Padovani Alessandro , Perani Daniela
Published: November 2021

Background

Preclinical and pathology evidence suggests an involvement of brain dopamine (DA) circuitry in Alzheimer’s disease (AD). We in vivo investigated if, when, and in which target regions [123I]FP-CIT-SPECT regional binding and molecular connectivity are damaged along the AD course.

Methods

We retrospectively selected 16 amyloid-positive subjects with mild cognitive impairment due to AD (AD-MCI), 22 amyloid-positive patients with probable AD dementia (AD-D), and 74 healthy controls, all with available [123I]FP-CIT-SPECT imaging. We tested whether nigrostriatal vs. mesocorticolimbic dopaminergic targets present binding potential loss, via MANCOVA, and alterations in molecular connectivity, via partial correlation analysis. Results were deemed significant at p < 0.05, after Bonferroni correction for multiple comparisons.

Results

We found significant reductions of [123I]FP-CIT binding in both AD-MCI and AD-D compared to controls. Binding reductions were prominent in the major targets of the ventrotegmental-mesocorticolimbic pathway, namely the ventral striatum and the hippocampus, in both clinical groups, and in the cingulate gyrus, in patients with dementia only. Within the nigrostriatal projections, only the dorsal caudate nucleus showed reduced [123I]FP-CIT binding, in both groups. Molecular connectivity assessment revealed a widespread loss of inter-connections among subcortical and cortical targets of the mesocorticolimbic network only (poor overlap with the control group as expressed by a Dice coefficient ≤ 0.25) and no alterations of the nigrostriatal network (high overlap with controls, Dice coefficient = 1).

Conclusion

Local- and system-level alterations of the mesocorticolimbic dopaminergic circuitry characterize AD, already in prodromal disease phases. These results might foster new therapeutic strategies for AD. The clinical correlates of these findings deserve to be carefully considered within the emergence of both neuropsychiatric symptoms and cognitive deficits.
Feasibility of utilizing ultra-low-dose contrast medium for pancreatic artery depiction using the combination of advanced virtual monoenergetic imaging and high-concentration contrast medium: an intra-patient study
Authors: Li Juan , Wang Yu-hong , Zheng Fu-ling , Chen Xin-yue , Lin Yun , Zhu Cai-rong , Wu Yi-fan , Xu Qiang , Jin Zheng-yu , Xue Hua-dan
Published: November 2021

Objectives

The least amount of contrast medium (CM) should be used under the premise of adequate diagnosis. The purpose of this study is to evaluate the feasibility of utilizing ultra-low-dose (224 mgI/kg) CM for pancreatic artery depiction using the combination of advanced virtual monoenergetic imaging (VMI+) and high-concentration (400 mgI/mL) CM.

Materials and methods

41 patients who underwent both normal dose CM (ND-CM, 320 mgI/kg) and low dose CM (LD-CM, 224 mgI/kg) thoracoabdominal enhanced CT for tumor follow-up were prospectively included. The VMI+ at the energy level of 40-kev for LD-CM images was reconstructed. CT attenuation, signal-to-noise ratios (SNRs), and contrast-to-noise ratios (CNRs) of the abdominal artery, celiac artery, and superior mesenteric artery (SMA) and qualitative scores of pancreatic arteries depiction were recorded and compared among the three groups (ND-CM, LD-CM, and VMI+ LD-CM images). ANOVA and Friedman tests were used for statistical analysis.

Results

All quantitative and qualitative parameters on LD-CM images were lower than that on ND-CM images (all p < 0.01). There were no significant differences of all arteries’ qualitative scores between ND-CM and VMI+ LD-CM images (all p > 0.05). VMI+ LD-CM images had the highest mean CT and CNR values of all arteries (all p < 0.0001). The CM volume was 52.6 ± 9.4 mL for the ND-CM group and 37.0 ± 6.7 mL for the LD-CM group.

Conclusion

Ultra-low-dose CM (224 mgI/kg) was feasible for depicting pancreatic arteries. Inferior angiographic image quality could be successfully compensated by VMI+ and high-concentration CM.
Pneumatosis intestinalis associated with lenvatinib during thyroid cancer treatment: a case report
Authors: Toda Soji , Iwasaki Hiroyuki , Murayama Daisuke , Isoda Maya , Nakayama Hirotaka , Suganuma Nobuyasu , Masudo Katsuhiko
Published: November 2021

Background

Pneumatosis intestinalis is a rare disease characterized by gas-filled cysts within the submucosa or serosa of the intestinal tract. In recent years, pneumatosis intestinalis was reported in patients undergoing cancer treatment, and some case reports exist that report that pneumatosis intestinalis occurs during administration of vascular endothelial growth factor inhibitors, such as bevacizumab and sunitinib. Here, we report the first case of pneumatosis intestinalis during lenvatinib treatment.

Case presentation

A 77-year-old Japanese man presented to our hospital with a chief complaint of numbness in the right leg and weakness of the lower limbs 9 years after right thyroid lobectomy. Computed tomography showed a tumor 90 mm in size from the lumbar spine to the sacrum, causing spinal cord compression. Blood tests showed that the patient’s thyroglobulin level was increased to 11,600 ng/ml. We diagnosed him with thyroid cancer with bone metastases. External beam radiotherapy (39 Gy/13 Fr) was performed on the bone metastases, followed by total thyroidectomy and radioactive iodine therapy. Four months after radioactive iodine therapy, lenvatinib was introduced because the symptoms of numbness and weakness recurred. Lenvatinib was introduced at dose of 24 mg, and then it was reduced to 14 mg owing to Common Terminology Criteria for Adverse Event grade 3 paronychia of the right foot. Although no further significant adverse events occurred, a scheduled computed tomography image showed pneumatosis intestinalis of the ascending colon 14 weeks after the introduction of lenvatinib. No abdominal or digestive symptoms were observed; therefore, we selected conservative treatment. We discontinued lenvatinib for a week, but we were required to restart lenvatinib as the numbness in the right leg worsened after withdrawal. Since the introduction of lenvatinib, 3 years and 5 months passed; we continued lenvatinib treatment, and the therapeutic effect remains partial response. There has been no recurrence of pneumatosis intestinalis.

Conclusions

Although rare, it is important to recognize that pneumatosis intestinalis can occur in association with lenvatinib and should be differentiated from intestinal perforation. Pneumatosis intestinalis association with lenvatinib can be improved by withdrawal.
Immune response to allogeneic equine mesenchymal stromal cells
Authors: Kamm J. Lacy , Riley Christopher B. , Parlane Natalie A. , Gee Erica K. , McIlwraith C. Wayne
Published: November 2021

Background

Mesenchymal stromal cells (MSCs) are believed to be hypoimmunogeneic with potential use for allogeneic administration.

Methods

Bone marrow was harvested from Connemara (n = 1), Standardbred (n = 6), and Thoroughbred (n = 3) horses. MSCs were grouped by their level of expression of major histocompatibility factor II (MHC II). MSCs were then sub-grouped by those MSCs derived from universal blood donor horses. MSCs were isolated and cultured using media containing fetal bovine serum until adequate numbers were acquired. The MSCs were cultured in xenogen-free media for 48 h prior to use and during all assays. Autologous and allogeneic MSCs were then directly co-cultured with responder leukocytes from the Connemara horse in varying concentrations of MSCs to leukocytes (1:1, 1:10, and 1:100). MSCs were also cultured with complement present and heat-inactivated complement to determine whether complement alone would decrease MSC viability. MSCs underwent haplotyping of their equine leukocyte antigen (ELA) to determine whether the MHC factors were matched or mismatched between the donor MSCs and the responder leukocytes.

Results

All allogeneic MSCs were found to be ELA mismatched with the responder leukocytes. MHC II-low and universal blood donor MSCs caused no peripheral blood mononuclear cell (PBMC) proliferation, no increase in B cells, and no activation of CD8 lymphocytes. Universal blood donor MSCs stimulated a significant increase in the number of T regulatory cells. Neutrophil interaction with MSCs showed that universal blood donor and MHC II-high allogeneic MSCs at the 6 h time point in co-culture caused greater neutrophil activation than the other co-culture groups. Complement-mediated cytotoxicity did not consistently cause MSC death in cultures with active complement as compared to those with inactivated complement. Gene expression assays revealed that the universal blood donor group and the MHC II-low MSCs were more metabolically active both in the anabolic and catabolic gene categories when cultured with allogeneic lymphocytes as compared to the other co-cultures. These upregulated genes included CD59, FGF-2, HGF, IDO, IL-10, IL-RA, IL-2, SOX2, TGF-β1, ADAMSTS-4, ADAMSTS-5, CCL2, CXCLB/IL-8, IFNγ, IL-1β, and TNFα.

Conclusions

MHC II-low MSCs are the most appropriate type of allogeneic MSC to prevent activation of the innate and cell-mediated component of the adaptive immune systems and have increased gene expression as compared to other allogeneic MSCs.
DrugEx v2: de novo design of drug molecules by Pareto-based multi-objective reinforcement learning in polypharmacology
Authors: Liu Xuhan , Ye Kai , van Vlijmen Herman W. T. , Emmerich Michael T. M. , IJzerman Adriaan P. , van Westen Gerard J. P.
Published: November 2021

In polypharmacology drugs are required to bind to multiple specific targets, for example to enhance efficacy or to reduce resistance formation. Although deep learning has achieved a breakthrough in de novo design in drug discovery, most of its applications only focus on a single drug target to generate drug-like active molecules. However, in reality drug molecules often interact with more than one target which can have desired (polypharmacology) or undesired (toxicity) effects. In a previous study we proposed a new method named DrugEx that integrates an exploration strategy into RNN-based reinforcement learning to improve the diversity of the generated molecules. Here, we extended our DrugEx algorithm with multi-objective optimization to generate drug-like molecules towards multiple targets or one specific target while avoiding off-targets (the two adenosine receptors, A1AR and A2AAR, and the potassium ion channel hERG in this study). In our model, we applied an RNN as the agent and machine learning predictors as the environment. Both the agent and the environment were pre-trained in advance and then interplayed under a reinforcement learning framework. The concept of evolutionary algorithms was merged into our method such that crossover and mutation operations were implemented by the same deep learning model as the agent. During the training loop, the agent generates a batch of SMILES-based molecules. Subsequently scores for all objectives provided by the environment are used to construct Pareto ranks of the generated molecules. For this ranking a non-dominated sorting algorithm and a Tanimoto-based crowding distance algorithm using chemical fingerprints are applied. Here, we adopted GPU acceleration to speed up the process of Pareto optimization. The final reward of each molecule is calculated based on the Pareto ranking with the ranking selection algorithm. The agent is trained under the guidance of the reward to make sure it can generate desired molecules after convergence of the training process. All in all we demonstrate generation of compounds with a diverse predicted selectivity profile towards multiple targets, offering the potential of high efficacy and low toxicity.
Volcanic hazard assessment for tephra fallout in Martinique
Authors: Michaud-Dubuy Audrey , Carazzo Guillaume , Kaminski Edouard
Published: November 2021

Mount Pelée (Martinique) is one of the most active volcanoes in the Lesser Antilles arc with more than 34 magmatic events in the last 24,000 years, including the deadliest eruption of the 20th century. The current volcanic hazard map used in the civil security plan puts the emphasis on the volcanic hazard close to the volcano. This map is however based on an incomplete eruptive history and does not take into account the variability of the expected source conditions (mass eruption rate, total erupted mass, and grain-size distribution) or the wind effect on ash dispersal. We propose here to refine the volcanic hazard map for tephra fallout by using the 2-D model of ash dispersal HAZMAP. We first simulate the maximum expected eruptive scenario at Mount Pelée (i.e., the P3 eruption) using a seasonal wind profile. Building upon the good agreement with field data, we compute probability maps based on this maximum expected scenario, which show that tephra fallout hazard could threaten not only areas close to the volcano but also the southern part of Martinique. We then use a comprehensive approach based on 16 eruptive scenarios that include new field constraints obtained in the recent years on the past Plinian eruptions of Mount Pelée volcano. Each eruptive scenario considers different values of total erupted mass and mass eruption rate, and is characterized by a given probability of occurrence estimated from the refined eruptive history of the volcano. The 1979-2019 meteorological ERA-5 database is used to further take into account the daily variability of winds. These new probability maps show that the area of probable total destruction is wider when considering the 16 scenarios compared to the maximum expected scenario. The southern part of Martinique, although less threatened than when considering the maximum expected scenario, would still be impacted both by tephra fallout and by its high dependence on the water and electrical network carried from the northern part of the island. Finally, we show that key infrastructures in Martinique (such as the international airport) have a non-negligible probability of being impacted by a future Plinian eruption of the Mount Pelée. These results provide strong arguments for and will support significant and timely reconceiving of the emergency procedures as the local authorities have now placed Mount Pelée volcano on alert level yellow (vigilance) based on increased seismicity and tremor-type signals.
Peer support for smoking cessation: a protocol of systematic review and meta-analysis
Authors: Seo Hyun-Ju , Kim Soo Young , Park Dongah , Sheen Seung-Soo , Choi Miyoung , Jang Bo-Hyoung , Lee Su Jung , Cha Youngju
Published: November 2021

Background

Peer-support programs are a useful social support strategy for populations trying to quit smoking who are willing to maintain smoking abstinence. This study is a protocol for a systematic review and meta-analysis to assess the effectiveness of peer support for smoking cessation.

Methods

This protocol will be conducted in accordance with the Cochrane Handbook of Systematic Reviews of Interventions 6.2. We will conduct a comprehensive search in the Cochrane Central Register of Controlled Trials, ovidEmbase, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature, ovidMEDLINE, Google Scholar, and Open Grey, as well as the Trials Register of Promoting Health Interventions in EPPI-Centre, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, and reference lists of included papers. The review will include randomized controlled trials of peer support interventions aimed to stop smoking in any population. Two reviewers will independently screen and select relevant studies. Version 2 of the Cochrane tool that assesses risk of bias in randomized trials will be used to assess the risk of bias in the included studies. The primary outcomes will be defined as the tobacco abstinence rate and adverse events. If a quantitative synthesis is not appropriate, a synthesis without meta-analysis will be undertaken.

Discussion

This review will provide the best available evidence regarding the effects of peer support interventions to quit smoking. The results from this study will help to inform healthcare providers on the optimal peer support intervention modalities such as intensity, delivery methods, type of support provider, and duration of the intervention.

Systematic review registration

PROSPERO CRD42020196288
From research to practice: a model for clinical implementation of evidence-based outpatient interventions for eating disorders
Authors: Anderson Kristen E. , Desai Sara G. , Zalaznik Rodie , Zielinski Natalia , Loeb Katharine L.
Published: November 2021

Background

A question frequently raised in the field is whether evidence-based interventions have adequate translational capacity for delivery in real-world settings where patients are presumed to be more complex, clinicians less specialized, and multidisciplinary teams less coordinated. The dual purpose of this article is to (a) outline a model for implementing evidence-driven, outpatient treatments for eating disorders in a non-academic clinical setting, and (b) report indicators of feasibility and quality of care.

Main Body

Since our inception (2015), we have completed nearly 1000 phone intakes, with first-quarter 2021 data suggesting an increase in the context of COVID-19. Our caseload for the practice currently consists of approximately 200 active patients ranging from 6 to 66 years of age. While the center serves a transdiagnostic and trans-developmental eating disorder population, modal concerns for which we receive inquiries are Anorexia Nervosa and Avoidant Restrictive Food Intake Disorder, with the most common age range for prospective patients spanning childhood through late adolescence/emerging adulthood; correspondingly, the modal intervention employed is Family-based treatment. Our team for each case consists, at a minimum, of a primary internal therapist and a physician external to the center.

Short Conclusion

We will describe our processes of recruiting, training and coordinating team members, of ensuring ongoing fidelity to evidence-based interventions, and of training the next generation of clinicians. Future research will focus on a formal assessment of patient outcomes, with comparison to benchmark outcomes from randomized controlled trials.
Nanopore sequencing for the screening of myeloid and lymphoid neoplasms with eosinophilia and rearrangement of PDGFRα, PDGFRβ, FGFR1 or PCM1-JAK2
Authors: Romagnoli Simone , Bartalucci Niccolò , Gesullo Francesca , Balliu Manjola , Bonifacio Stefania , Fernandez Anair Graciela Lema , Mannelli Francesco , Bolognini Davide , Pelo Elisabetta , Mecucci Cristina , Guglielmelli Paola , Vannucchi Alessandro Maria
Published: November 2021

Eosinophilia represents a group of diseases with heterogeneous pathobiology and clinical phenotypes. Among the alterations found in primary Eosinophilia, gene fusions involving PDGFRα, PDGFRβ, FGFR1 or JAK2 represent the biomarkers of WHO-defined “myeloid and lymphoid neoplasms with eosinophilia”. The heterogeneous nature of genomic aberrations and the promiscuity of fusion partners, may limit the diagnostic accuracy of current cytogenetics approaches. To address such technical challenges, we exploited a nanopore-based sequencing assay to screen patients with primary Eosinophilia. The comprehensive sequencing approach described here enables the identification of genomic fusion in 60 h, starting from DNA purified from whole blood.
Prevalence and incidence of idiopathic subglottic stenosis in southern and central Alberta: A retrospective cohort study
Authors: Chan Ryan K. , Ahrens Beau , MacEachern Paul , Bosch J. Douglas , Randall Derrick R.
Published: November 2021

Background

Subglottic stenosis (SGS) is a reportedly rare disease that causes recurrent severe airway obstruction. Etiologies reported for SGS include idiopathic, iatrogenic, autoimmune, congenital, and traumatic, with variable ratios among different centres. From empiric observation, southern and central Alberta was hypothesized to have a disproportionate distribution of SGS driven by increased idiopathic SGS (iSGS) compared to previous literature. Identification of causative agents of iSGS will help understand and guide future management options, so this study aimed to characterize the demographics of SGS subtypes, define prevalence and incidence rates of iSGS in southern Alberta, and geographically analyze for clustering of iSGS prevalence.

Methods

SGS patients from Alberta census divisions No. 1–9 and 15 were retrospectively reviewed. Patients were subtyped according to etiology of SGS and characterized. Idiopathic SGS prevalence and incidence was assessed; prevalence was further geographically segregated by census division and forward sortation area (FSA). Significant clustering patterns were assessed for using a Global Moran's I analysis.

Results

From 2010 to 2019 we identified 250 SGS patients, who were substantially overrepresented by idiopathic patients (80.4%) compared to autoimmune (10.0%), iatrogenic (7.6%), congenital (1.2%), and traumatic (0.8%). The total iSGS prevalence was 9.28/100,000 with a mean annual incidence rate of 0.71/100,000 per year. Significant clustering was observed (Moran's index 0.125; z-score 2.832; p = 0.0046) and the highest rates of prevalence were observed in southern Alberta and in rural communities heterogeneously dispersed around Calgary FSAs.

Conclusion

In southern and central Alberta, iSGS patients were disproportionately over-represented in contrast to other subtypes with the highest prevalence in southern Alberta. There was a three-fold higher annual incidence compared to previous literature demonstrating the highest rates of disease reported worldwide. Future research aims to expand the geographical scope and to assess for demographic or environmental differences within significant clusters that may contribute to disease pathophysiology.

Level of evidence

III.

Graphical Abstract
Discerning the painter’s hand: machine learning on surface topography
Authors: Ji F. , McMaster M. S. , Schwab S. , Singh G. , Smith L. N. , Adhikari S. , O’Dwyer M. , Sayed F. , Ingrisano A. , Yoder D. , Bolman E. S. , Martin I. T. , Hinczewski M. , Singer K. D.
Published: November 2021

Attribution of paintings is a critical problem in art history. This study extends machine learning analysis to surface topography of painted works. A controlled study of positive attribution was designed with paintings produced by a class of art students. The paintings were scanned using a chromatic confocal optical profilometer to produce surface height data. The surface data were divided into virtual patches and used to train an ensemble of convolutional neural networks (CNNs) for attribution. Over a range of square patch sizes from 0.5 to 60 mm, the resulting attribution was found to be 60–96% accurate, and, when comparing regions of different color, was nearly twice as accurate as CNNs using color images of the paintings. Remarkably, short length scales, even as small as a bristle diameter, were the key to reliably distinguishing among artists. These results show promise for real-world attribution, particularly in the case of workshop practice.
Influence of macrophage polarization on the effectiveness of surgical therapy of peri-implantitis
Authors: Galarraga-Vinueza Maria Elisa , Obreja Karina , Khoury Chantal , Begic Amira , Ramanauskaite Ausra , Sculean Anton , Schwarz Frank
Published: November 2021

Purpose

To evaluate the influence of macrophage expression and polarization on the effectiveness of surgical therapy of peri-implantitis over a 6 month follow-up.

Methods

A total of fourteen patients (n = 14 implants) diagnosed with peri-implantitis underwent access flap surgery, granulation tissue removal, implantoplasty, and augmentation at intra-bony components using a natural derived bone mineral and application of a native collagen membrane during a standardized surgical procedure. Granulation tissue biopsies were prepared for immunohistochemical characterization and macrophage polarization assessment. M1 and M2 phenotype expression was identified and quantified through immunohistochemical markers and histomorphometrical analyses. Clinical evaluation and data collection were performed initially and after a healing period of 6 months. Statistical analyses were performed to associate infiltrated area, macrophage, and M1/M2 phenotype influence on peri-implant tissue healing parameters after a 6-month follow-up.

Results

Mean infiltrated compartment (ICT) values occupied a total percentage of 70.3% ± 13.0 in the analyzed granulation tissue biopsies. Macrophages occupied a mean area of 15.3% ± 7.0. M1 and M2 phenotypes were present in 7.1 ± 4.1% and 5.5 ± 3.7%, respectively. No statistically significant difference was observed between M1 and M2% expression (p = 0.16). The mean M1/ M2 ratio amounted to 1.5 ± 0.8. Surgical therapy was associated with statistically significant reductions in mean bleeding on probing (BOP), probing depth (PD) and suppuration (SUPP) scores at 6 months (p < 0.05). Linear regression analyses revealed a significant correlation between macrophage expression (CD68%) and changes in PD scores and M1 (%) expression and changes in mucosal recession (MR) scores at 6 months.

Conclusions

The present data suggest that macrophages might influence peri-implant tissue healing mechanisms following surgical therapy of peri-implantitis over a short-term period. Particularly, changes in PD and MR scores were statistically significantly associated with macrophage expression and phenotype.

Graphical Abstract
Treatment of perioperative swelling by rest, ice, compression, and elevation (RICE) without and with additional application of negative pressure (RICE+) in patients with a unilateral ankle fracture: study protocol for a monocentric, evaluator-blinded randomized controlled pilot trial
Authors: Fischer Dagmar-C , Sckell Axel , Garkisch Angelina , Dresing Klaus , Eisenhauer Anton , Valentini Luzia , Mittlmeier Thomas
Published: November 2021

Background

Edema is commonly seen after surgical fixation of ankle fractures. Rest, ice, compression, and elevation (RICE) is an established combination to prevent swelling but hardly able to stimulate lymphatic resorption. Recently, an epicutaneously applied negative pressure suction apparatus (LymphaTouch®) has been introduced to stimulate lymphatic flow. While postoperative recovery, soft tissue, and osseous healing as well as functional outcome are probably linked to the amount of postoperative swelling, estimates on this relative to prevention (RICE) or prevention + stimulated resorption (RICE+) of fluid are scarce.

Methods and analysis

This is a single-center, evaluator-blinded randomized pilot trial to investigate postoperative swelling in adults requiring surgical fixation of a closed unilateral ankle fracture. A total of 50 patients will be recruited and randomly assigned to RICE or RICE+ prior to surgery. All patients will undergo evaluator-blinded measurements of the ankle volume the day before surgery and subsequently from the evening of the 2nd postoperative day every 24 h until discharge. RICE will be initiated right after surgery and continued until discharge from the hospital in all patients. Additional application of negative pressure therapy (RICE+) will be initiated on the morning of the 2nd postoperative day and repeated every 24 h until the time of discharge from the hospital. Outcome measures are (i) the relative amount and the time course of the postoperative swelling, (ii) the demand for analgesic therapy (type and amount) together with the perception of pain, (iii) the rate of complications, and (iv) mobility of the ankle joint and the recovery of walking abilities during a 12-weeks follow-up period. Serum and urine samples taken prior to sugery and during postoperative recovery will allow to evaluate the ratio of naturally occurring stable calcium isotopes (δ44/42Ca) as a marker of skeletal calcium accrual.

Ethics and dissemination

The protocol was approved by the institutional Ethics Committee (Rostock University Medical Center, Rostock, Germany) in accordance with the Declaration of Helsinki (approval number: A 2020-0092). The results of this study will be actively disseminated through scientific publications and conference presentations.

Trial registration

DRKS, DRKS00023739. Registered on 14 December 2020
Context Matters: Social Psychological Factors That Underlie Academic Performance across Seven Institutions
Authors: Salehi S. , Berk S. A. , Brunelli R. , Cotner S. , Creech C. , Drake A. G. , Fagbodun S. , Hall C. , Hebert S. , Hewlett J. , James A. C. , Shuster M. , St. Juliana J. R. , Stovall D. B. , Whittington R. , Zhong M. , Ballen C. J.
Published: November 2021

Findings presented here demonstrate that institutional context plays an important role in the mechanisms underlying performance gaps in undergraduate biology and may affect how social psychological interventions impact performance across different learning environments.
Adaptive Gaussian mixture model and convolution autoencoder clustering for unsupervised seismic waveform analysis
Authors: Zhu Donglin , Cui Jingbin , Li Yan , Wan Zhonghong , Li Lei
Published: November 2021

Seismic facies analysis can effectively estimate reservoir properties, and seismic waveform clustering is a useful tool for facies analysis. We have developed a deep-learning-based clustering approach called the modified deep convolutional embedded clustering with adaptive Gaussian mixture model (AGMM-MDCEC) for seismic waveform clustering. Trainable feature extraction and clustering layers in AGMM-MDCEC are implemented using neural networks. We fuse the two independent processes of feature extraction and clustering, such that the extracted features are modified simultaneously with the results of clustering. We use a convolutional autoencoder for extracting features from seismic data and to reduce data redundancy in the algorithm. At the same time, weights of clustering network are fine-tuned through iteration to obtain state-of-the-art clustering results. We apply our new classification algorithm to a data volume acquired in western China to map architectural elements of a complex fluvial depositional system. Our method obtains superior results over those provided by traditional K-means, Gaussian mixture model, and some machine-learning methods, and it improves the mapping of the extent of the distributary system.
Breast Magnetic Resonance Image Analysis for Surgeons Using Virtual Reality: A Comparative Study
Authors: El Beheiry Mohamed , Gaillard Thomas , Girard Noémie , Darrigues Lauren , Osdoit Marie , Feron Jean-Guillaume , Sabaila Anne , Laas Enora , Fourchotte Virginie , Laki Fatima , Lecuru Fabrice , Couturaud Benoit , Binder Jean-Philippe , Masson Jean-Baptiste , Reyal Fabien , Malhaire Caroline
Published: November 2021

PURPOSE

The treatment of breast cancer, the leading cause of cancer and cancer mortality among women worldwide, is mainly on the basis of surgery. In this study, we describe the use of a medical image visualization tool on the basis of virtual reality (VR), entitled DIVA, in the context of breast cancer tumor localization among surgeons. The aim of this study was to evaluate the speed and accuracy of surgeons using DIVA for medical image analysis of breast magnetic resonance image (MRI) scans relative to standard image slice-based visualization tools.

MATERIALS AND METHODS

In our study, residents and practicing surgeons used two breast MRI reading modalities: the common slice-based radiology interface and the DIVA system in its VR mode. Metrics measured were compared in relation to postoperative anatomical-pathologic reports.

RESULTS

Eighteen breast surgeons from the Institut Curie performed all the analysis presented. The MRI analysis time was significantly lower with the DIVA system than with the slice-based visualization for residents, practitioners, and subsequently the entire group ( P < .001). The accuracy of determination of which breast contained the lesion significantly increased with DIVA for residents ( P = .003) and practitioners ( P = .04). There was little difference between the DIVA and slice-based visualization for the determination of the number of lesions. The accuracy of quadrant determination was significantly improved by DIVA for practicing surgeons ( P = .01) but not significantly for residents ( P = .49).

CONCLUSION

This study indicates that the VR visualization of medical images systematically improves surgeons' analysis of preoperative breast MRI scans across several different metrics irrespective of surgeon seniority.
Automated Text-Based Symptom Monitoring With Rapid Clinician Triage for Patients With Cancer and Suspected or Confirmed COVID-19
Authors: Cotner Cody E. , Balachandran Mohan , Do David , Ferrell Will , Khan Neda , Kopinsky Michael , McGettigan Suzanne , Morgan Anna U. , Zinck Lindsey , Schuchter Lynn M. , Shulman Lawrence N. , Asch David A. , Manz Christopher R. , Parikh Ravi B.
Published: November 2021

PURPOSE

Patients with cancer are at greater risk of developing severe symptoms from COVID-19 than the general population. We developed and tested an automated text-based remote symptom-monitoring program to facilitate early detection of worsening symptoms and rapid assessment for patients with cancer and suspected or confirmed COVID-19.

METHODS

We conducted a feasibility study of Cancer COVID Watch, an automated COVID-19 symptom-monitoring program with oncology nurse practitioner (NP)-led triage among patients with cancer between April 23 and June 30, 2020. Twenty-six patients with cancer and suspected or confirmed COVID-19 were enrolled. Enrolled patients received twice daily automated text messages over 14 days that asked “How are you feeling compared to 12 hours ago? Better, worse, or the same?” and, if worse, “Is it harder than usual for you to breathe?” Patients who responded worse and yes were contacted within 1 hour by an oncology NP.

RESULTS

Mean age of patients was 62.5 years. Seventeen (65%) were female, 10 (38%) Black, and 15 (58%) White. Twenty-five (96%) patients responded to ≥ 1 symptom check-in, and overall response rate was 78%. Four (15%) patients were escalated to the triage line: one was advised to present to the emergency department (ED), and three were managed in the outpatient setting. Median time from escalation to triage call was 11.5 minutes. Four (15%) patients presented to the ED without first escalating their care via our program. Participant satisfaction was high (Net Promoter Score: 100, n = 4).

CONCLUSION

Implementation of an intensive remote symptom monitoring and rapid NP triage program for outpatients with cancer and suspected or confirmed COVID-19 infection is possible. Similar tools may facilitate more rapid triage for patients with cancer in future pandemics.