bluuebunny/crossref_metadata_2025 huggingface dataset:
Nisin loaded carbopol gel against Pseudomonas aeruginosa infected third‐degree burns: A therapeutic intervention
Authors: Preet Simran , Kaur Jasleen , Raza Kaisar
Published: March 2021

The emergence of multidrug resistant strains of Pseudomonas aeruginosa necessitates the exploration of novel therapeutic intervention (s). The present study aimed to develop a nisin loaded carbopol gel formulation (NLCG) and explore its therapeutic efficacy against P. aeruginosa infected burn wounds. The formulation was prepared using Carbopol 940 as a polymer and characterized in terms of its appearance, stability, pH, rheology, spreadability, release, and permeation profiles. Disc diffusion assay and field emission scanning electron microscopy were carried out to establish in vitro antibacterial activity while the in vitro cytotoxicity was evaluated by hemolytic and trypan blue exclusion assay. Furthermore, in vivo efficacy was investigated by developing P. aeruginosa infected third‐degree murine burn wound model followed by evaluation of parameters like bacterial loads, skin restoration, histopathological architecture, levels of hydroxyproline, myeloperoxidase and cytokines. Our studies yielded a stable formulation with pH, viscosity and drug release flux values as 6.5 ± 0.02, 382.4 p and 160.55 ± 3.64 μg h−1 cm−2, respectively. Approximately, 84.02 ± 1.63% of nisin was found to permeate into murine skin, further, affirmed by confocal microscopic observations. Interestingly, no in vitro cytotoxicity of NLCG (to erythrocytes and/or to peritoneal macrophages) could be observed. The log units decrease (s) in CFUs of Pseudomonas in skin were found to be 1.5137, 4.2257, 6.456 after 12, 24 and 72 h of topical gel therapy, respectively. Percentage wound closure, tensile strength, histological, and scanning electron microscopic studies further provided a healing evidence with skin showing restoration of the epithelium. The gel therapy also led to a significant modulation (p ≤ 0.05) in hydroxyproline content, myeloperoxidase levels, and serum levels of IL‐1, IL‐10, and TNF‐α. Our formulation revealed anti‐Pseudomonas, wound healing, and immunomodulatory efficacy of NLCG. Further investigations are warranted to determine the underlying mechanism (s) of these displayed antibacterial and immunomodulatory effects.
Competencies and scope of practice of nurse practitioners in primary health care: a scoping review protocol
Authors: Schlunegger Margarithe Charlotte , Aeschlimann Simona , Palm Rebecca , Zumstein-Shaha Maya
Published: March 2021

Objective:

The objective of this scoping review is to explore existing literature about nurse practitioners’ competencies and scope of practice in primary health care in order to examine and conceptually map the evidence and identify gaps in the literature.

Introduction:

To meet growing health care needs, current primary health care models have expanded to include nurse practitioners. The integration of nurse practitioners in primary health care is challenging. This is mainly due to the lack of a unified definition of the role, competencies, or clear criteria to determine scope of practice.

Inclusion criteria:

This scoping review will consider studies addressing nurse practitioner practice in primary health care. The focus lies on nurse practitioner competencies (eg, core competencies or practice activities) and scope of practice (eg, areas of responsibility or legally defined professional boundaries). Studies that were conducted in primary health care settings in rural, urban, and suburban regions where nurse practitioners are employed will be included.

Methods:

Studies published in English, German, or French from 1965 to present will be considered. The databases to be searched include PubMed, CINAHL, Web of Science, and PsycINFO. Sources of unpublished studies and gray literature to be searched will include ProQuest Dissertations and Theses, OpenGrey, and websites of national nurse practitioner organizations. Retrieval of full-text studies and data extraction will be performed independently by two reviewers. The extracted data will be presented in tables or graphs, with an accompanying narrative summary.
A Tricky Subject – archaeology in opinion polls on cultural heritage. Recent examples from Poland
Authors: Oniszczuk Agnieszka
Published: March 2021

Understanding the public by analysing the wants, interests and expectations regarding their involvement in archaeology is one of the strategic aims of Europae Archaeologiae Consilium (EAC). Cultural heritage has been the topic of several public opinion polls in Poland over the past few years. In 2011 and 2015, the Narodowy Instytut Dziedzictwa (National Institute of Cultural Heritage) carried out two representative surveys. Subsequent polls focusing on more specific issues or groups of respondents were undertaken in 2015, 2017 and 2018. Other data from Poland come from the 2017 Special Eurobarometer survey on cultural heritage. They can be contrasted with archaeology-orientated opinion polls: a Europe-wide survey carried out within the NEARCH project led by Inrap (French National Institute for Preventive Archaeological Research) and several smaller-scale projects, which might be treated as starting points for more representative research.

The scope of these surveys includes: public perception of cultural heritage and archaeology, subjective value of cultural heritage, attitudes towards archaeology, relevance of archaeology for the present (also in terms of the socio-economic potential of archaeological heritage), people's interaction with archaeology and archaeological heritage, sources of information about archaeological heritage etc.

Comparison of these data will serve to establish the relevance of surveys for archaeological heritage management. The author will also examine if the specific nature of archaeological heritage is reflected in the surveys and how the public feels about its most hidden heritage. Based on the results of her analysis, the author will look at the desired scope of a survey aimed at filling the identified gaps and shaped to fit the needs of evidence-based archaeological heritage management.
Development-Led or 'Preventive' Archaeology in the Grand Duchy of Luxembourg
Authors: Duong Mei
Published: March 2021

The preventive archaeology system in Luxembourg was developed during the 1990s. Archaeological heritage is now managed by the National Archaeological Research Centre/Centre national de recherche archéologique (CNRA), founded in 2011, although there is still no legal framework within which archaeology can be protected. A draft law implementing the principles of the Valletta Convention will provide the structure for the CNRA to assess construction projects and require archaeological investigations. This paper outlines the development of the system, notes the challenges and highlights opportunities to raise public awareness, which are keys to engage the public in local decision making, through the communes.
Qualitative features of a NPZ-Model
Authors: Youssouf Yaya Yaya , Ngom Diene , Sy Mamadou
Published: March 2021

Qualitative study of higher order non linear dynamical systems? is a rewarding experience and a great challenge. This reflective paper is an attempt to deeply analyze interaction features between nutrients, phytoplanktons and zooplanktons by building a so-called NPZ-Model. We used classical methods (of Lyapunov, Hopf, etc.) to examine existence, positivity, boundedness and stability of solutions. Our main contribution is the implementation of a meaningful space parameter that simultaneously guarantees instability of equilibria at the border and? stability of the internal equilibrium. In the case of internal equilibrium instability, we observed the emergence of limit cycle which means the existence of periodical solutions.
Validation of the Critical Strain-Based Methodology for Evaluating the Mechanical Safety of Ball Grid Array Solder Joints in a Launch Random Vibration Environment
Authors: Park Tae-Yong , Oh Hyun-Ung
Published: March 2021

To overcome the limitations of Steinberg's theory for evaluating the mechanical safety of the solder joints of spaceborne electronics in a launch random vibration environment, a critical strain-based methodology was proposed and validated in a previous study. However, in order to apply the critical strain-based methodology to mechanical design of spaceborne electronics with high confidence, its effectiveness must be validated under various conditions of the package mounting locations and the first eigenfrequencies of a printed circuit board (PCB); achieving this validation is the primary objective of this study. For the experimental validation, PCB specimens with ball grid array (BGA) packages mounted on various board locations were fabricated and exposed to a random vibration environment to assess the fatigue life of the solder joint. The effectiveness of the critical strain-based methodology was validated through a comparison of the fatigue life of the packages under test and to the margin of safety, which was estimated using various analytical approaches.
Multiscale Study on Effect of Humidity on Shape Memory Polymers Used in Three-Dimensional Printing
Authors: Livolsi Frank , May Thomas , Caputo Dylan , Fouladi Kamran , Eslami Babak
Published: March 2021

Shape memory polymers (SMP) are used in the three-dimensional (3D) printing field for different applications such as soft robotics or medical devices. Although this technology has expanded the capabilities of additive manufacturing, there still exists fundamental questions regarding the optimum condition for manufacturing these 3D-printed parts. Various factors play a crucial role in the final quality of printed parts, such as deposition orientation, percentage infill, or environmental conditions. In this paper, we study the effect of humidity on commercially available shape memory polymers (SMPs) (NinjaFlex©) at both micro- and macroscale. By performing a 3D computational fluid dynamic model for the printing environment, it is found there are significant temperature and humidity fluctuations around the hot-end and printing bed. Macroscale characterization through ASTM D638 tensile testing shows that for humidity levels higher than 60%, there is a 5–10% reduction in the strength of the material (ultimate strength and tangent modulus). This study is verified by microscale characterization performed with atomic force microscopy on thin films. It is shown that in addition to the effect of humidity on the stiffness of materials, there is an effect on the loss moduli of the matter as well. As humidity increases, these polymers become more viscoelastic. Simultaneously, it is shown higher humidity levels cause increased micro-level surface roughness, which can be the cause for the strength reduction for higher humidities.
Etching with electron beam-generated plasmas: Selectivity versus ion energy in silicon-based films
Authors: Walton S. G. , Boris D. R. , Rosenberg S. G. , Miyazoe H. , Joseph E. A. , Engelmann S. U.
Published: March 2021

In the ideal case, plasma-enhanced atomic layer etching enables the ability to not only remove one monolayer of material but also leave adjacent layers undamaged. This dual mandate requires fine control over the flux of species to ensure efficacy, while maintaining an often arduously low ion energy. Electron beam-generated plasmas are well-suited for etching at low ion energies as they are generally characterized by highly charged particle densities (1010–1011 cm−3) and low electron temperatures (<1.0 eV), which provide the ability to deliver a large flux of ions whose energies are <5 eV. Raising the ion energy with substrate biasing thus enables process control over an energy range that extends down to values commensurate with the bond strength of most material systems. In this work, we discuss silicon nitride etching using pulsed, electron beam-generated plasmas produced in argon-SF6 backgrounds. We pay particular attention to the etch rates and selectivity versus oxidized silicon nitride and polycrystalline silicon as a function of ion energy from a few eV up to 50 eV. We find the blanket etch rate of Si3N4 to be in the range of 1 A/s, with selectivities (versus SiO2 and poly-Si) greater than 10:1 when ion energies are below 30 eV.
Topotactic crystal structure transformation from spinel ferrite to wüstite in epitaxial Fe3O4 films via Kr ion irradiation
Authors: Liu Yang , Hisamatsu Yuki , Sharmin Sonia , Oshima Daiki , Iwata Satoshi , Kato Takeshi , Sekiba Daiichiro , Kita Eiji , Yanagihara Hideto
Published: March 2021

Krypton ion irradiation was carried out on Fe3O4 epitaxial thin films grown on MgO (001) substrates. The spinel structure (Fd3¯m) of Fe3O4 was found to be transformed into another structure as a result of the ion irradiation without any loss of the epitaxial relationship with the MgO substrate. Both total film thickness and, therefore, the composition ratio between Fe and O remained the same even after the ion irradiation process, as confirmed by both cross-sectional transmission electron microscope images and Rutherford backscattering analysis. An x-ray diffraction experiment revealed that the irradiated crystal possessed a rocksalt structure (Fm3¯m), with the lattice constant being approximately half of that of Fe3O4. Ion irradiation, thus, gave rise to a topotactic crystal transformation to wüstite with a composition of Fe0.75O, which is a metastable phase of iron oxides.
How could operational underwater sound from future offshore wind turbines impact marine life?
Authors: Stöber Uwe , Thomsen Frank
Published: March 2021

Offshore wind farms are part of the transition to a sustainable energy supply and both the total numbers and size of wind turbines are rapidly increasing. While the impact of underwater sound related to construction work has been in the focus of research and regulation, few data exist on the potential impact of underwater sound from operational wind farms. Here, we reviewed published sound levels of underwater sound from operational wind farms and found an increase with size of wind turbines expressed in terms of their nominal power. This trend was identified in both broadband and turbine-specific spectral band sound pressure levels (SPLs). For a nominal power of 10 MW, the trends in broadband SPLs and turbine-specific spectral band SPLs yielded source levels of 170 and 177 dB re 1 μPa m, respectively. The shift from using gear boxes to direct drive technology is expected to reduce the sound level by 10 dB. Using the National Oceanic Atmospheric Administration criterion for behavioral disruption for continuous noise (i.e., level B), a single 10 MW direct drive turbine is expected to cause behavioral response in marine mammals up to 1.4 km distance from the turbine, compared to 6.3 km for a turbine with gear box.
Identification and Characterization of Mycobacterium smegmatis and Mycobacterium avium subsp.
paratuberculosis
Zinc Transporters
Authors: Goethe Elke , Gieseke Ayla , Laarmann Kristin , Lührs Janita , Goethe Ralph
Published: March 2021

Zinc is necessary for bacterial growth but is toxic when present in excess. Hence, bacterial cells have developed systems to alter intracellular concentration.
Mechanism of Viral Glycoprotein Targeting by Membrane-Associated RING-CH Proteins
Authors: Lun Cheng Man , Waheed Abdul A. , Majadly Ahlam , Powell Nicole , Freed Eric O.
Published: March 2021

Viral envelope glycoproteins are an important structural component on the surfaces of enveloped viruses that direct virus binding and entry and also serve as targets for the host adaptive immune response. In this study, we investigate the mechanism of action of the MARCH family of cellular proteins that disrupt the trafficking and virion incorporation of viral glycoproteins across several virus families.
Environmental Candida auris and the Global Warming Emergence Hypothesis
Authors: Casadevall Arturo , Kontoyiannis Dimitrios P. , Robert Vincent
Published: March 2021

Global warming was proposed to be a contributing cause for the nearly simultaneous emergence of different clades of
Candida auris
as a nosocomial pathogen in different continents. The global warming emergence hypothesis posits that
C. auris
existed in the environment prior to its clinical recognition and became pathogenic for humans because of thermal adaptation in response to climate change. The isolation of
C. auris
from two sites in the remote Andaman Islands establishes it as an environmental organism, a necessary condition for the hypothesis.
Saccharomyces cerevisiae Requires
CFF1
To Produce 4-Hydroxy-5-Methylfuran-3(2H)-One, a Mimic of the Bacterial Quorum-Sensing Autoinducer AI-2
Authors: Valastyan Julie S. , Kraml Christina M. , Pelczer Istvan , Ferrante Thomas , Bassler Bonnie L.
Published: March 2021

Quorum sensing is a cell-to-cell communication process that bacteria use to monitor local population density. Quorum sensing relies on extracellular signal molecules called autoinducers (AIs).
The Transcription Factor Pdr802 Regulates Titan Cell Formation and Pathogenicity of Cryptococcus neoformans
Authors: Reuwsaat Julia C. V. , Agustinho Daniel P. , Motta Heryk , Chang Andrew L. , Brown Holly , Brent Michael R. , Kmetzsch Livia , Doering Tamara L.
Published: March 2021

The pathogenic yeast
Cryptococcus neoformans
presents a worldwide threat to human health, especially in the context of immunocompromise, and current antifungal therapy is hindered by cost, limited availability, and inadequate efficacy. After the infectious particle is inhaled,
C. neoformans
initiates a complex transcriptional program that integrates cellular responses and enables adaptation to the host lung environment.
Allelic Interference in Prion Replication Is Modulated by the Convertibility of the Interfering PrP
C
and Other Host-Specific Factors
Authors: Espinosa Juan Carlos , Andreoletti Olivier , Marín-Moreno Alba , Lugan Severine , Aguilar-Calvo Patricia , Cassard Hervé , Lorenzo Patricia , Douet Jean-Yves , Villa-Díaz Ana , Aron Naima , Prieto Irene , Huor Alvina , Torres Juan María
Published: March 2021

Prion propagation can be interfered with by the expression of a second prion protein in the host. In the present study, we investigated prion propagation in a host expressing two different prion protein genes.
A PAS Protein Directs Metabolic Reprogramming during Cryptococcal Adaptation to Hypoxia
Authors: Zhao Youbao , Lin Xiaorong
Published: March 2021

C. neoformans
is the main causative agent of fungal meningitis that is responsible for about 15% of all HIV-related deaths. Although an obligate aerobic fungus,
C. neoformans
is well adapted to hypoxia conditions that the fungus could encounter in the host or the environment.
Neck swelling and airway narrowing as an initial manifestation of giant cell arteritis
Authors: Lim Zhen Sheng , Sharp Colin
Published: March 2021

Giant cell arteritis can result in a wide range of symptoms due to the extensive distribution of the external carotid artery. Face and neck swelling and trismus are under-recognised features of giant cell arteritis and can present as the initial symptom prior to the development of classical temporal tenderness and jaw claudication. The lack of awareness of the less common symptoms may result in a late diagnosis of giant cell arteritis, leading to irreversible vision loss. In this paper, we present a case of neck swelling and airway narrowing as the initial manifestation of giant cell arteritis.
Progressive bulbar symptomatology due to vascular brainstem compression
Authors: Younus Osman , Hampton Timothy , Silber Eli , Dervenoulas George
Published: March 2021

Symptomatic brainstem compression from vertebral artery dolichoectasia is rare. There are no recognised diagnostic or treatment criteria to guide management of this disease. We report a case of medullary compression and cerebral ischaemia from an enlarged and tortuous vertebral artery. Our patient developed progressive dysphonia and dysphagia. Cerebral MRI revealed compression of the medulla oblongata by a right ectatic vertebral artery and a right occipital lobe infarct. Other causes of bulbar dysfunction were ruled out. He was treated with anticoagulation and underwent percutaneous endoscopic gastrostomy. We review selected literature on the presentation, diagnosis and management of this rare neurologic condition.
Confounding case of seromucinous hamartoma
Authors: Godse Neal Rajan , Staltari Giuseppe Vittorio , Doeden Katherine , Gillman Grant Shale
Published: March 2021

A 67-year-old man presented with progressive diplopia. On evaluation, he was noted to have bilateral palsies of cranial nerves III, IV and VI as well as a unilateral right true vocal fold paralysis. CT and MRI studies demonstrated a T2-bright left ethmoid mass with no evidence of bony erosion. Direct visualisation demonstrated a polypoid appearing mass of the left sphenoethmoid recess. Operative biopsy was pursued with final pathology demonstrating benign seromucinous hamartoma. Subsequent blood work demonstrated high titres of anti-acetylcholine receptor antibodies consistent with myasthenia gravis. The patient was started on pyridostigmine with improvement in his ocular cranial neuropathies.
Endoscopic treatment of Crohn-related strictures with a self-expandable stent compared with balloon dilation: a prospective, randomised, controlled study
Authors: Hedenström Per , Stotzer Per-Ove
Published: March 2021

Objective

Fibrotic strictures in the gastrointestinal tract are frequent in Crohn’s disease. Endoscopic dilation is a standard treatment. However, recurrence is common after dilation and there are complications such as bleeding or perforation. Endoscopic treatment using self-expandable metal stents has shown diverging results. The aim of this study was to evaluate the outcome of endoscopic treatment with a self-expandable stent in ileocecal Crohn’s disease.

Design/method

Patients with Crohn’s disease and a symptomatic ileocecal stricture were eligible for prospective, consecutive inclusion in a single-centre setting. Patients were randomised to treatment with either 18 mm balloon dilatation (GroupDIL) or stenting (GroupSTENT) using a 20 mm diameter, partially covered Hanarostent NCN. Patients were followed for a minimum of 24 months postendoscopy. Outcomes were technical success, adverse events and clinical success (defined as no need for repeated interventions).

Results

Thirteen patients (GroupDILn=6; GroupSTENT=7) were included with twelve patients (GroupDILn=5; GroupSTENT=7) being eligible for complete follow-up. Technical success was achieved in all cases. Adverse events were border-line significantly more common in the GroupSTENT: 4/7 (57%) (pain: n=3; pain and rectal bleeding: n=1) compared with the GroupDIL: 0/5 (0%), p=0.08, which resulted in preterm termination of the study. The clinical success rate was GroupSTENT: 6/7 (86%) vs GroupDIL: 1/5 (20%), p=0.07.

Conclusion

Patients with strictures related to Crohn’s disease may benefit from treatment with self-expandable metal stents rather than dilatation. However, there seems to be an increased risk for patient pain after stenting, which has to be considered and handled.

Trail registration number

The study was registered at Clinical Trials (NCT04718493).
Evidence of the effectiveness of travel-related measures during the early phase of the COVID-19 pandemic: a rapid systematic review
Authors: Grépin Karen Ann , Ho Tsi-Lok , Liu Zhihan , Marion Summer , Piper Julianne , Worsnop Catherine Z , Lee Kelley
Published: March 2021

Objective

To review the effectiveness of travel measures implemented during the early stages of the COVID-19 pandemic to inform changes on how evidence is incorporated in the International Health Regulations (2005) (IHR).

Design

We used an abbreviated Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols to identify studies that investigated the effectiveness of travel-related measures preprinted or published by 1 June 2020.

Results

We identified 29 studies, of which 26 were modelled. Thirteen studies investigated international measures, while 17 investigated domestic measures (one investigated both). There was a high level of agreement that the adoption of travel measures led to important changes in the dynamics of the early phases of the COVID-19 pandemic: the Wuhan measures reduced the number of cases exported internationally by 70%–80% and led to important reductions in transmission within Mainland China. Additional travel measures, including flight restrictions to and from China, may have led to additional reductions in the number of exported cases. Few studies investigated the effectiveness of measures implemented in other contexts. Early implementation was identified as a determinant of effectiveness. Most studies of international travel measures did not account for domestic travel measures thus likely leading to biased estimates.

Conclusion

Travel measures played an important role in shaping the early transmission dynamics of the COVID-19 pandemic. There is an urgent need to address important evidence gaps and also a need to review how evidence is incorporated in the IHR in the early phases of a novel infectious disease outbreak.
Effect of routinely assessing and addressing depression and diabetes distress using patient-reported outcome measures in improving outcomes among adults with type 2 diabetes: a systematic review protocol
Authors: McMorrow Rita , Hunter Barbara , Hendrieckx Christel , Kwasnicka Dominika , Cussen Leanne , Ho Felicia Ching Siew , Speight Jane , Emery Jon , Manski-Nankervis Jo-Anne
Published: March 2021

Introduction

Type 2 diabetes is a global health priority. People with diabetes are more likely to experience mental health problems relative to people without diabetes. Diabetes guidelines recommend assessment of depression and diabetes distress during diabetes care. This systematic review will examine the effect of routinely assessing and addressing depression and diabetes distress using patient-reported outcome measures in improving outcomes among adults with type 2 diabetes.

Methods and analysis

MEDLINE, Embase, CINAHL Complete, PsycInfo, The Cochrane Library and Cochrane Central Register of Controlled Trials will be searched using a prespecified strategy using a prespecified Population, Intervention, Comparator, Outcomes, Setting and study design strategy. The date range of the search of all databases will be from inception to 3 August 2020. Randomised controlled trials, interrupted time-series studies, prospective and retrospective cohort studies, case–control studies and analytical cross-sectional studies published in peer-reviewed journals in the English language will be included. Two review authors will independently screen abstracts and full texts with disagreements resolved by a third reviewer, if required, using Covidence software. Two reviewers will undertake risk of bias assessment using checklists appropriate to study design. Data will be extracted using prespecified template. A narrative synthesis will be conducted, with a meta-analysis, if appropriate.

Ethics and dissemination

Ethics approval is not required for this review of published studies. Presentation of results will follow the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidance. Findings will be disseminated via peer-reviewed publication and conference presentations.

PROSPERO registration number

CRD42020200246.
Association of adverse childhood experiences with diabetes in adulthood: results of a cross-sectional epidemiological survey in Singapore
Authors: Subramaniam Mythily , Abdin Edimansyah , Vaingankar Janhavi Ajit , Chang Sherilyn , Sambasivam Rajeswari , Jeyagurunathan Anitha , Seow Lee Seng Esmond , Van Dam Rob , Chow Wai Leng , Chong Siow Ann
Published: March 2021

Objectives

Several studies have linked diabetes mellitus to adverse childhood experiences (ACEs). While a number of studies have examined the association between ACEs and diabetes in Western populations, few have done it in Asian populations. The current study aimed to examine (1) the association between ACEs and diabetes, including the association after age stratification, and (2) the association of comorbid depression, resource use and health-related quality of life (HRQoL) among those with diabetes and ACEs in Singapore.

Settings

Participants were surveyed in their homes or any other preferred venue of their choice.

Participants

6126 individuals aged 18 years and above were randomly selected among Singapore residents.

Design

Cross-sectional nationwide epidemiological study.

Results

Exposure to any ACE was not associated with increased odds of diabetes; however, those who had experienced parental separation, death or divorce of a parent had higher odds of diabetes. In addition, we observed significant interaction between age and ACEs in relation to odds of diabetes. ACEs were significantly associated with higher odds of diabetes mainly in the younger age group. The prevalence of major depressive disorder was significantly higher among those with diabetes and ACEs than those with diabetes alone (3.7% and 0.3% respectively).

Conclusions

Efforts to promote regular exercise and healthy lifestyles both in the population and among those with diabetes must continue for the prevention and management of diabetes. The findings emphasise the need to create more awareness of both the prevalence and impact of ACEs among those treating chronic diseases.
Bereaved families’ experiences of end-of-life decision making for general medicine patients
Authors: Moon Felicity , Mooney Christine , McDermott Fiona , Miller Alistair , Poon Peter
Published: March 2021

Background

Family involvement in decision making for hospitalised patients is associated with improved end-of-life care. Yet, these discussions can be challenging for physicians and families and associated with distress, confusion and conflict. There is a need to understand how best to support families involved in decisions regarding the transition from active to palliative treatment in hospital settings.

Aim

To explore bereaved families’ experiences of end-of-life decision making for general medicine patients.

Design

A qualitative exploratory study framed by social constructionism using semistructured interviews and thematic analysis.

Setting and participants

The general medicine units of one large public hospital in Melbourne, Australia. We recruited 28 bereaved family members of patients who had received end-of-life care.

Findings

Patients and families depended on physicians to explain clinical complexity and treatment beneficence; however, trust in medical judgement was mediated by participant’s own interpretations of clinical progress. Families sought to be respected as advocates and experienced distress if physicians disregarded their perspectives and insight concerning patient preferences. Ideally, families supported patients to express their preferences to physicians. Otherwise, families contextualised treatment decisions through their knowledge of patient’s values and quality of life. Families often felt burdened by or excluded from medical decision making and experienced distress and confusion regarding their rights to request or refuse treatment.

Conclusion

Our study highlights how families contribute to decision making to ensure end-of-life care treatments reflect patient preferences. Physicians can ease families’ distress around treatment withdrawal by providing a meaningful explanation of complex clinical issues, clarifying decision-making roles and acknowledge families’ desire to protect and advocate for their loved one.
Clinicopathological characteristic of ciliated muconodular papillary tumour of the lung
Authors: Yang Yong , Xie Xiaofeng , Jiang Gening , Zhang Liping , Liu Hongcheng
Published: March 2021

Aims

Ciliated muconodular papillary tumour (CMPT) is a rare tumour characterised by tripartite cellular components of mucinous cells, ciliated columnar cells and basal cells with a predominantly papillary architecture. Its clinicopathological characteristics and treatment methods have not been fully elucidated.

Methods

Twenty-six patients with CMPT diagnosed and treated in our hospital were retrospectively analysed.

Results

The cohort was composed of 13 males and 13 females, with a mean age of 64.4±5.93 years. The diameter of the primary tumour ranged from 0.3 to 1.4 cm. The lesions appeared as subsolid nodules, ground-glass nodules and cavitary nodules under the CT scan. All the patients underwent surgical treatment and did not receive postoperative adjuvant therapy. All the CMPTs were diagnosed by immunohistochemistry and not by intraoperative frozen sections. Next-generation sequencing detection demonstrated EGFR, KRAS and BRAF mutations and ALK rearrangements in CMPTs. The follow-up duration ranged from 5 to 65 months, and no case of tumour recurrence was observed until the final follow-up.

Conclusions

The incidence of CMPT is low, and the prognosis is good. Immunohistochemistry is helpful for an accurate diagnosis of CMPT, while intraoperative frozen sections cannot fully guide the surgical method. Sublobectomy may be enough without adjuvant treatment. CMPTs exhibited a relatively high rate of driver gene mutations, while the mutation sites were not consistent with those in lung adenocarcinoma.
Real-world biomarker testing rate and positivity rate in NSCLC in Spain: Prospective Central Lung Cancer Biomarker Testing Registry (LungPath) from the Spanish Society of Pathology (SEAP)
Authors: Salas Clara , Martín-López Javier , Martínez-Pozo Antonio , Hernández-Iglesias Teresa , Carcedo David , Ruiz de Alda Lucia , García J Francisco , Rojo Federico
Published: March 2021

Aim

The aim of this study was to describe the testing rate and frequency of molecular alterations observed in the Lung Cancer Biomarker Testing Registry (LungPath).

Methods

A descriptive study of NSCLC biomarker determinations collected from March 2018 to January 2019, from 38 Spanish hospitals, was carried out. Only adenocarcinoma and not otherwise specified histologies were included for epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and programmed death ligand-1 (PD-L1) expression. The testing rate and the positivity rate were calculated. Multivariate logistic regression was used to explore the joint relationship between independent explanatory factors and both testing and positivity rates. Two models were adjusted: one with sample type and histology as independent factors, and the other adding the testing rate or the positivity rate of the other biomarkers.

Results

3226 patient samples were analysed, whereEGFR,ALK,ROS1and PD-L1 information was collected (a total of 12 904 determinations). Overall, 9118 (71.4%) determinations were finally assessed.EGFR(91.4%) andALK(80.1%) were the mainly tested biomarkers. Positivity rates forEGFR,ALK,ROS1and PD-L1 were 13.6%, 3.4%, 2.0% and 49.2%, respectively. Multivariate models showed a lower testing rate for ALK in surgical pieces, fine-needle aspiration or other types of samples versus biopsies.

Conclusions

Despite the high testing rate in EGFR and ALK in NSCLC, the real-world evidence obtained from the LungPath demonstrates that ROS1 and PD-L1 were not determined in a significant portion of patients. LungPath provides crucial information to improve the coverage in molecular testing in lung cancer, to monitor the positivity rate and the introduction of new biomarker testing in clinical practice.
Secondary haemophagocytic lymphohistiocytosis in COVID-19: correlation of the autopsy findings of bone marrow haemophagocytosis with HScore
Authors: Núñez-Torrón Claudia , Ferrer-Gómez Ana , Moreno Moreno Esther , Pérez-Mies Belen , Villarrubia Jesús , Chamorro Sandra , López-Jiménez Javier , Palacios J , Piris-Villaespesa Miguel , García-Cosío Mónica
Published: March 2021

Background

Secondary haemophagocytic lymphohistiocytosis (sHLH) is characterised by a hyper activation of immune system that leads to multiorgan failure. It is suggested that excessive immune response in patients with COVID-19 could mimic this syndrome. Some COVID-19 autopsy studies have revealed the presence of haemophagocytosis images in bone marrow, raising the possibility, along with HScore parameters, of sHLH.

Aim

Our objective is to ascertain the existence of sHLH in some patients with severe COVID-19.

Methods

We report the autopsy histological findings of 16 patients with COVID-19, focusing on the presence of haemophagocytosis in bone marrow, obtained from rib squeeze and integrating these findings with HScore parameters. CD68 immunohistochemical stains were used to highlight histiocytes and haemophagocytic cells. Clinical evolution and laboratory parameters of patients were collected from electronic clinical records.

Results

Eleven patients (68.7%) displayed moderate histiocytic hyperplasia with haemophagocytosis (HHH) in bone marrow, three patients (18.7%) displayed severe HHH and the remainder were mild. All HScore parameters were collected in 10 patients (62.5%). Among the patients in which all parameters were evaluable, eight patients (80%) had an HScore >169. sHLH was not clinically suspected in any case.

Conclusions

Our results support the recommendation of some authors to use the HScore in patients with severe COVID-19 in order to identify those who could benefit from immunosuppressive therapies. The presence of haemophagocytosis in bone marrow tissue, despite not being a specific finding, has proved to be a very useful tool in our study to identify these patients.
Psoriasis Does Not Worsen Outcomes in Patients Admitted for Ischemic Stroke: An Analysis of the National Inpatient Sample
Authors: Edigin Ehizogie , Kaul Subuhi , Eseaton Precious Obehi , Ojemolon Pius Ehiremen , Patel Axi , Manadan Augustine
Published: March 2021

Psoriasis is a chronic inflammatory state associated with an increased risk of cardiometabolic diseases, stroke, and mortality. Although psoriasis increases the risk of ischemic stroke, whether outcomes, including mortality, are adversely affected is unknown.

This study aims to compare inpatient mortality of patients admitted for ischemic stroke with and without psoriasis. The secondary outcome measures were hospital length of stay (LOS), total hospital charges, odds of receiving tissue plasminogen activator (TPA), and mechanical thrombectomy between both groups.

Data were obtained from the National Inpatient Sample (NIS) 2016 and 2017 databases using the International Classification of Diseases, Tenth Revision, Clinical Modification codes. Multivariable logistic and linear regression analysis were used accordingly to account for confounders of the outcomes.

The combined 2016 and 2017 NIS database comprised over 71 million discharges. Of these, ischemic stroke accounted for 525,570 hospitalizations and 2425 (0.5%) had a concomitant diagnosis of psoriasis. Patients hospitalized for ischemic stroke with coexisting psoriasis did not have a difference in inpatient mortality (3.5% vs 5.5%; p=0.285) compared with those without psoriasis. However, psoriasis cohort had shorter LOS (5.0 vs 5.7 days; p=0.029) and lower total hospital charges ($60,471 vs $70,246; p=0.003) compared with the non-psoriasis cohort. The odds of receiving TPA and undergoing mechanical thrombectomy were not different in both groups.

Inpatient mortality, odds of receiving TPA, and undergoing mechanical thrombectomy in patients who had an ischemic stroke with or without psoriasis were not different. However, patients with psoriasis had a significantly shorter LOS and lower hospital charges.
Designed improvement to T-cell immunotherapy by multidimensional single cell profiling
Authors: Bandey Irfan N , Adolacion Jay R T , Romain Gabrielle , Paniagua Melisa Martinez , An Xingyue , Saeedi Arash , Liadi Ivan , You Zheng , Rajanayake Rasindu B , Hwu Patrick , Singh Harjeet , Cooper Laurence JN , Varadarajan Navin
Published: March 2021

Background

Adoptive cell therapy based on the infusion of chimeric antigen receptor (CAR) T cells has shown remarkable efficacy for the treatment of hematologic malignancies. The primary mechanism of action of these infused T cells is the direct killing of tumor cells expressing the cognate antigen. However, understanding why only some T cells are capable of killing, and identifying mechanisms that can improve killing has remained elusive.

Methods

To identify molecular and cellular mechanisms that can improve T-cell killing, we utilized integrated high-throughput single-cell functional profiling by microscopy, followed by robotic retrieval and transcriptional profiling.

Results

With the aid of mathematical modeling we demonstrate that non-killer CAR T cells comprise a heterogeneous population that arise from failure in each of the discrete steps leading to the killing. Differential transcriptional single-cell profiling of killers and non-killers identified CD137 as an inducible costimulatory molecule upregulated on killer T cells. Our single-cell profiling results directly demonstrate that inducible CD137 is feature of killer (and serial killer) T cells and this marks a different subset compared with the CD107apos(degranulating) subset of CAR T cells. Ligation of the induced CD137 with CD137 ligand (CD137L) leads to younger CD19 CAR T cells with sustained killing and lower exhaustion. We genetically modified CAR T cells to co-express CD137L, in trans, and this lead to a profound improvement in anti-tumor efficacy in leukemia and refractory ovarian cancer models in mice.

Conclusions

Broadly, our results illustrate that while non-killer T cells are reflective of population heterogeneity, integrated single-cell profiling can enable identification of mechanisms that can enhance the function/proliferation of killer T cells leading to direct anti-tumor benefit.
MRI data-driven algorithm for the diagnosis of behavioural variant frontotemporal dementia
Authors: Manera Ana L , Dadar Mahsa , Van Swieten John Cornelis , Borroni Barbara , Sanchez-Valle Raquel , Moreno Fermin , Laforce Jr Robert , Graff Caroline , Synofzik Matthis , Galimberti Daniela , Rowe James Benedict , Masellis Mario , Tartaglia Maria Carmela , Finger Elizabeth , Vandenberghe Rik , de Mendonca Alexandre , Tagliavini Fabrizio , Santana Isabel , Butler Christopher R , Gerhard Alex , Danek Adrian , Levin Johannes , Otto Markus , Frisoni Giovanni , Ghidoni Roberta , Sorbi Sandro , Rohrer Jonathan Daniel , Ducharme Simon , Collins D Louis ,   FTLDNI investigators
Published: March 2021

Introduction

Structural brain imaging is paramount for the diagnosis of behavioural variant of frontotemporal dementia (bvFTD), but it has low sensitivity leading to erroneous or late diagnosis.

Methods

A total of 515 subjects from two different bvFTD cohorts (training and independent validation cohorts) were used to perform voxel-wise morphometric analysis to identify regions with significant differences between bvFTD and controls. A random forest classifier was used to individually predict bvFTD from deformation-based morphometry differences in isolation and together with semantic fluency. Tenfold cross validation was used to assess the performance of the classifier within the training cohort. A second held-out cohort of genetically confirmed bvFTD cases was used for additional validation.

Results

Average 10-fold cross-validation accuracy was 89% (82% sensitivity, 93% specificity) using only MRI and 94% (89% sensitivity, 98% specificity) with the addition of semantic fluency. In the separate validation cohort of definite bvFTD, accuracy was 88% (81% sensitivity, 92% specificity) with MRI and 91% (79% sensitivity, 96% specificity) with added semantic fluency scores.

Conclusion

Our results show that structural MRI and semantic fluency can accurately predict bvFTD at the individual subject level within a completely independent validation cohort coming from a different and independent database.
Evaluation of stroke thrombectomy including patients where IV
thrombolysis is contraindicated or has failed: a randomized trial of two
novel thrombectomy devices
Authors: White Philip M , Gregson Barbara , Cora Elena Adela , Dixit Anand , Subramanian Ganesh , Joshi Yogish , Simister Robert , Lakey Rachel , Maiter Ahmed , Ford Gary A
Published: March 2021

Background

Study was a PROBE design phase II randomized controlled trial (RCT).
We assessed trial feasibility and technical efficacy and safety of two
novel thrombectomy devices – ERIC (a retriever device) and SOFIA (a
distal access catheter) – used alone or in combination depending on
operator preference.

Methods

Four UK neuroscience centers enrolled adults with proximal large
artery occlusion (LAO) stroke on imaging where arterial puncture was
achievable within 5.5 hours (8.5 hours for posterior circulation) of
symptom onset; National Institutes of Health Stroke Scale (NIHSS) ≥6
with limited ischemic change on CT imaging. Randomization was 2:1 into
intervention arm (ERIC and/or SOFIA). Patients and core lab were blinded
to allocation. Primary outcome was independent core lab adjudication of
reperfusion (modified Thrombolysis in Cerebral Infarction (mTICI)
scale). Secondary outcomes were modified Rankin score (mRS) at 90 and
365 days (independence and shift analysis), 30-day mortality,
symptomatic intracranial hemorrhage (sICH), procedural complications and
NIHSS change.

Results

Sixty-six patients were enrolled. TICI 2B/3 reperfusion was achieved
in 72% in intervention compared with 90% in control arm on intention to
treat (ITT) analysis (P=0.2) and 78% compared with 86% on per protocol
analysis (P=0.7). Functional independence at 90 days was 40%
(intervention) compared with 43% (control) on ITT analysis (P=1.0). sICH
rates were low at 0% and 5%, respectively (P=0.3). The 30-day mortality
was 9% intervention compared with 14% control (P=0.7).

Conclusions

Study indicated feasibility of a phase II RCT trial approach for
assessing new thrombectomy devices. In a broad LAO stroke population
ERIC and SOFIA were not statistically different from control devices.
Larger trials are needed.
Age-adjusted infarct volume cut-off points improve stroke outcome prognostication beyond modeling with age and infarct volume
Authors: Bouslama Mehdi , Haussen Diogo C , Rodrigues Gabriel Martins , Barreira Clara M , Dehkharghani Seena , Frankel Michael R , Nogueira Raul G
Published: March 2021

Background

Age and infarct volume are among the most powerful predictors of outcome after large vessel occlusion acute strokes (LVOS).

Objective

To study the impact of age-adjusted final infarct volume (FIV) on functional outcomes.

Methods

Review of a prospectively collected thrombectomy database at a tertiary care center between September 2010 and February 2018. Consecutive patients with anterior circulation LVOS who achieved full reperfusion (modified Thrombolysis in Cerebral Infarction 3) were categorized into four age groups: (G1) <60 years, (G2) 60–69, (G3) 70–79, (G4) ≥80 years. The Youden Index was used to identify the optimal FIV cut-off point for good outcome (modified Rankin Scale score 0–2) discrimination in each group and the overall population. The predictive ability of these specific thresholds was evaluated using binary logistic regressions and compared with the non-age-adjusted cut-off point.

Results

516 patients were analyzed (G1: n=171, G2: n=130, G3: n=103, G4: n=112). Patients with poor outcome had a larger FIV in each group (p<0.01 for all). The target FIV cut-off point decreased with increased age: G1: 45.7 mL (sensitivity 56%, specificity 80%); G2: 30.4 mL (sensitivity 63%, specificity 75%); G3: 20.2 mL (sensitivity 76%, specificity 65%); G4: 16.9 mL (sensitivity 68%, specificity 70%). The non-age-adjusted cut-off point was 19.2 mL (sensitivity 70%, specificity 59%).

In multivariate analysis, adjusting for confounders including age and FIV, achieving a FIV less than the age-adjusted threshold was an independent predictor of good outcome (aOR=2.72, 95% CI 1.41 to 5.24, p<0.001). In contrast, a similar model including the non-age-adjusted target cut-off point failed to reveal an association with good outcome (aOR=1.72, 95% CI 0.93 to 3.19, p<0.085). Furthermore, the latter model had a weaker outcome predictive ability as assessed by the Akaike information criterion (409 vs 403).

Conclusions

Age-adjusted infarct volume represents a strong outcome discriminator beyond age and infarct volume in isolation and might help to refine patient selection and improve outcome prognostication in stroke thrombectomy.