bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a System for Biosynthesis, Isolation and Purification of the Holoform of Recombinant Human Neuroglobin and Its Characteristics
Authors: Semenova M. A. , Bochkova Z. V. , Smirnova O. M. , Ignatova A. A. , Parshina E. Y. , Ziganshin R. H. , Bocharov E. V. , Brazhe N. A. , Maksimov G. V. , Kirpichnikov M. P. , Dolgikh D. A. , Chertkova R. V.
Published: July 2023

Abstract—

An efficient system for the biosynthesis, isolation and purification of recombinant human neuroglobin has been developed and optimized, which makes it possible to produce protein in quantities sufficient to study its properties. According to UV-visible, IR-, CD-, and NMR spectroscopy data, recombinant neuroglobin is a structured protein in the holoform state. The data of chromato-mass-spectrometric analysis made it possible to conclude that there is a correctly formed disulfide bond in the structure of the oxidized form of the protein. Using Raman and surface-enhanced Raman spectroscopy with laser excitation at 532 nm, it was shown that heme in the reduced and oxidized forms of neuroglobin has vibrational degrees of freedom typical ofb-type hemes, and the iron atom is hexacoordinated. Using Raman spectroscopy with laser excitation at 633 nm, it was found that reduced –SH-groups were present in reduced neuroglobin, while in oxidized neuroglobin a disulfide bridge was formed. The results obtained serve as the basis for detailed studies of the functioning of neuroglobin as a neuroprotector, in particular, during its interaction with oxidized cytochromec, which is released from mitochondria in violation of their functioning and/or morphology.
From Peptides to Receptors
Authors: Tsetlin V. I.
Published: July 2023

Abstract—

In the 1960s and 1970s, the Institute of Chemistry of Natural Compounds developed a topochemical approach for designing new biologically active peptide compounds, the applicability of which to the creation of inhibitors and effective substrates of proteolytic enzymes was shown by the author of this review under the direct supervision of V.T. Ivanov. The next task was to establish the conformation of protein neurotoxins from snake venoms and to study the topography of their binding to the target, the nicotinic acetylcholine receptor (nAChR) from the electric organ of the Torpedo marmorata ray. With selectively labeled derivatives containing one fluorescent or spin label on established amino acid residues, neurotoxin residues in contact with nAChR were identified for the first time. Later, in collaboration with the laboratory of V.T. Ivanov, new analogs of α-conotoxins (peptide neurotoxins from venomous Conus mollusks), were synthesized including their photoactivated derivatives, which showed the participation of all Torpedo nAChR subunits in the binding of α-conotoxins. In the final part, the review briefly presents the recent achievements of the Department of Molecular Neuroimmune Signaling (headed by V.I. Tsetlin) concerning the isolation and synthesis of new peptide and protein neurotoxins and the study of how they work.
Understanding caregiver experiences with disease-modifying therapies for spinal muscular atrophy: a qualitative study
Authors: Xiao Lena , Kang Sohee , Djordjevic Djurdja , Gonorazky Hernan , Chiang Jackie , Ambreen Munazzah , Nigro Elisa , Law Eugenia , Weinstock Lauren , McCradden Melissa , Amin Reshma
Published: July 2023

Objective

Spinal muscular atrophy (SMA) is a neuromuscular disorder that manifests with motor deterioration and respiratory complications. The paradigm of care is shifting as disease-modifying therapies including nusinersen, onasemnogene abeparvovec and risdiplam alter the disease trajectory of SMA. The objective of this study was to explore caregivers’ experiences with disease-modifying therapies for SMA.

Design

Qualitative study including semistructured interviews with caregivers of children with SMA who received disease-modifying therapies. Interviews were audio recorded, transcribed verbatim, coded and analysed using content analysis.

Setting

The Hospital for Sick Children (Toronto, Canada).

Results

Fifteen family caregivers of children with SMA type 1 (n=5), type 2 (n=5) and type 3 (n=5) participated. There were two emerging themes and several subthemes (in parentheses): (1) inequities in access to disease-modifying therapies (variable regulatory approvals, prohibitively expensive therapies and insufficient infrastructure) and (2) patient and family experience with disease-modifying therapies (decision making, hope, fear and uncertainty).

Conclusion

The caregiver experience with SMA has been transformed by the advent of disease-modifying therapies. Consistent and predictable access to disease-modifying therapies is a major concern for caregivers of children with SMA but is influenced by regulatory approvals, funding and eligibility criteria that are heterogenous across jurisdictions. Many caregivers described going to great lengths to access therapies, highlighting issues related to justice, such as equity and access. This diverse population reflects contemporary patients and families with SMA; their broad experiences may inform the healthcare delivery of other emerging orphan drugs.
Rest and exercise early after sport-related concussion: a systematic review and meta-analysis
Authors: Leddy John J , Burma Joel S , Toomey Clodagh M , Hayden Alix , Davis Gavin A , Babl Franz E , Gagnon Isabelle , Giza Christopher C , Kurowski Brad G , Silverberg Noah D , Willer Barry , Ronksley Paul E , Schneider Kathryn J
Published: July 2023

Objective

To synthesise the evidence regarding the risks and benefits of physical activity (PA), prescribed aerobic exercise treatment, rest, cognitive activity and sleep during the first 14 days after sport-related concussion (SRC).

Design

Meta-analysis was performed for PA/prescribed exercise interventions and a narrative synthesis for rest, cognitive activity and sleep. Risk of bias (ROB) was determined using the Scottish Intercollegiate Guidelines Network and quality assessed using Grading of Recommendations, Assessment, Development and Evaluations.

Data sources

MEDLINE, Embase, APA PsycInfo, Cochrane Central Register of Controlled Trials, CINAHL Plus and SPORTDiscus. Searches were conducted in October 2019 and updated in March 2022.

Eligibility criteria

Original research articles with sport-related mechanism of injury in >50% of study sample and that evaluated how PA, prescribed exercise, rest, cognitive activity and/or sleep impact recovery following SRC. Reviews, conference proceedings, commentaries, editorials, case series, animal studies and articles published before 1 January 2001 were excluded.

Results

46 studies were included and 34 had acceptable/low ROB. Prescribed exercise was assessed in 21 studies, PA in 15 studies (6 PA/exercise studies also assessed cognitive activity), 2 assessed cognitive activity only and 9 assessed sleep. In a meta-analysis of seven studies, PA and prescribed exercise improved recovery by a mean of −4.64 days (95% CI −6.69, –2.59). After SRC, early return to light PA (initial 2 days), prescribed aerobic exercise treatment (days 2–14) and reduced screen use (initial 2 days) safely facilitate recovery. Early prescribed aerobic exercise also reduces delayed recovery, and sleep disturbance is associated with slower recovery.

Conclusion

Early PA, prescribed aerobic exercise and reduced screen time are beneficial following SRC. Strict physical rest until symptom resolution is not effective, and sleep disturbance impairs recovery after SRC.

PROSPERO registration number

CRD42020158928.
Criteria to achieve safe antimicrobial intravenous-to-oral switch in hospitalised adult populations: a systematic rapid review
Authors: Harvey Eleanor J , McLeod Monsey , De Brún Caroline , Ashiru-Oredope Diane
Published: July 2023

Objectives

This rapid review aimed to assess and collate intravenous-to-oral switch (IVOS) criteria from the literature to achieve safe and effective antimicrobial IVOS in the hospital inpatient adult population.

Design

The rapid review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.

Data sources

OVID Embase and Medline databases.

Eligibility criteria

Articles of adult populations published globally between 2017 and 2021 were included.

Data extraction and synthesis

An Excel spreadsheet was designed with specific column headings. IVOS criteria from UK hospital IVOS policies informed the framework synthesis.

Results

IVOS criteria from 45/164 (27%) local IVOS policies were categorised into a five-section framework: (1) timing of IV antimicrobial review, (2) clinical signs and symptoms, (3) infection markers, (4) enteral route and (5) infection exclusions. The literature search identified 477 papers, of which 16 were included. The most common timing for review was 48–72 hours from initiation of intravenous antimicrobial (n=5, 30%). Nine studies (56%) stated clinical signs and symptoms must be improving. Temperature was the most frequently mentioned infection marker (n=14, 88%). Endocarditis had the highest mention as an infection exclusion (n=12, 75%). Overall, 33 IVOS criteria were identified to go forward into the Delphi process.

Conclusion

Through the rapid review, 33 IVOS criteria were collated and presented within five distinct and comprehensive sections. The literature highlighted the possibility of reviewing IVOS before 48–72 hours and of presenting heart rate, blood pressure and respiratory rate as a combination early warning score criterion. The criteria identified can serve as a starting point of IVOS criteria review for any institution globally, as no country or region limits were applied. Further research is required to achieve consensus on IVOS criteria from healthcare professionals that manage patients with infections.

PROSPERO registration number

CRD42022320343.
How can we elicit health workers’ preferences for measures to reduce informal payments? A mixed methods approach to developing a discrete choice experiment in Tanzania
Authors: Binyaruka Peter , Angell Blake , McKee Martin , Andreoni Antonio , Mamdani Masuma , Hutchinson Eleanor , Balabanova Dina
Published: July 2023

Objective

While discrete choice experiments (DCEs) have been used in other fields as a means of eliciting respondent preferences, these remain relatively new in studying corrupt practices in the health sector. This study documents and discusses the process of developing a DCE to inform policy measures aimed at addressing informal payments for healthcare in Tanzania.

Design

A mixed methods design was used to systematically develop attributes for the DCE. It involved five stages: a scoping literature review, qualitative interviews, a workshop with health providers and managers, expert review and a pilot study.

Setting

Dar es Salaam and Pwani regions in Tanzania.

Participants

Health workers and health managers.

Results

A large number of factors were identified as driving informal payments in Tanzania and thus represent potential areas for policy intervention. Through iterative process involving different methods (qualitative and quantitative) and seeking consensus views by diverse actors, we derived six attributes for a DCE: mode of payment, supervision at the facility level, opportunity for private practice, awareness and monitoring, disciplinary measures against informal payments and incentive payment for staff if a facility has less informal payments. 12 choice sets were generated and piloted with 15 health workers from 9 health facilities. The pilot study revealed that respondents could easily understand the attributes and levels, answered all the choice sets and appeared to be trading between the attributes. The results from the pilot study had expected signs for all attributes.

Conclusions

We elicited attributes and levels for a DCE to identify the acceptability and preferences of potential policy interventions to address informal payments in Tanzania through a mixed-methods approach. We argue that more attention is needed to the process of defining attributes for the DCE, which needs to be rigorous and transparent in order to derive reliable and policy-relevant findings.
Information provision to caregivers of children with rare dermatological disorders: an international multimethod qualitative study
Authors: Walsh Carleen , Leavey Gerard , McLaughlin Marian
Published: July 2023

Objective

To identify service-provided information needs among dermatological caregivers of patients living with ichthyosis.

Design

This is the first online international qualitative study to explore caregiver-reported service-provided information needs, using transnational focus groups (n=6), individual interviews (n=7) and in-depth emails (n=5). NVivo facilitated the coding process and Framework Analysis was applied.

Setting

Caregivers were recruited through two online ichthyosis support groups and resided across 10 countries and 5 continents (USA, Greece, Netherlands, Ireland, UK, Canada, India, Philippines, Switzerland and Australia).

Participants

A purposive sample of 8 male and 31 female caregivers participated (mean age range 35–44 years). Participants were aged 18 years old or older and fluent in English. Participants cared for a total of 46 children (1:1 ratio for child gender and clinical classification of disease severity). Participants represented all stages along the care continuum, including neonatal intensive care unit and bereavement.

Results

This study advances understanding of how to optimise information-sharing across hospital, community and online settings at three points along the care continuum (screening, active caregiving and survivorship). Timely, personalised and appropriate service-provided information support was considered key in influencing the self-efficacy, coping ability and psychosocial well-being of both the caregiver and their child. The modification of information support, through feedback loops, can result in a different bidirectional psychosocial impact for the caregiver and the affected child.

Conclusion

Our findings provide a novel insight into how existing gaps between caregiver expectations and needs, in terms of information support, can be addressed. As information support is a modifiable factor, improved healthcare education around these themes should become an urgent public health matter to inform future educational and psychosocial interventions.
Protocol for a cluster randomised placebo-controlled trial of adjunctive ivermectin mass drug administration for malaria control on the Bijagós Archipelago of Guinea-Bissau: the MATAMAL trial
Authors: Hutchins Harry , Bradley John , Pretorius Elizabeth , Teixeira da Silva Eunice , Vasileva Hristina , Jones Robert T , Ndiath Mamadou Ousmane , dit Massire Soumare Harouna , Mabey David , Nante Ernesto Jose , Martins Cesario , Logan James G , Slater Hannah , Drakeley Chris , D'Alessandro Umberto , Rodrigues Amabelia , Last Anna R
Published: July 2023

Introduction

As malaria declines, innovative tools are required to further reduce transmission and achieve elimination. Mass drug administration (MDA) of artemisinin-based combination therapy (ACT) is capable of reducing malaria transmission where coverage of control interventions is already high, though the impact is short-lived. Combining ACT with ivermectin, an oral endectocide shown to reduce vector survival, may increase its impact, while also treating ivermectin-sensitive co-endemic diseases and minimising the potential impact of ACT resistance in this context.

Methods and analysis

MATAMAL is a cluster-randomised placebo-controlled trial. The trial is being conducted in 24 clusters on the Bijagós Archipelago, Guinea-Bissau, where the peak prevalence ofPlasmodium falciparum(Pf) parasitaemia is approximately 15%. Clusters have been randomly allocated to receive MDA with dihydroartemisinin–piperaquine and either ivermectin or placebo. The primary objective is to determine whether the addition of ivermectin MDA is more effective than dihydroartemisinin–piperaquine MDA alone in reducing the prevalence ofP. falciparumparasitaemia, measured during peak transmission season after 2 years of seasonal MDA. Secondary objectives include assessing prevalence after 1 year of MDA; malaria incidence monitored through active and passive surveillance; age-adjusted prevalence of serological markers indicating exposure toP. falciparumand anopheline mosquitoes; vector parous rates, species composition, population density and sporozoite rates; prevalence of vector pyrethroid resistance; prevalence of artemisinin resistance inP. falciparumusing genomic markers; ivermectin’s impact on co-endemic diseases; coverage estimates; and the safety of combined MDA.

Ethics and dissemination

The trial has been approved by the London School of Hygiene and Tropical Medicine’s Ethics Committee (UK) (19156) and the Comite Nacional de Eticas de Saude (Guinea-Bissau) (084/CNES/INASA/2020). Results will be disseminated in peer-reviewed publications and in discussion with the Bissau-Guinean Ministry of Public Health and participating communities.

Trial registration number

NCT04844905.
‘You just emotionally break’: understanding COVID-19 narratives through public health humanities
Authors: Saffran Lise , Doobay-Persaud Ashti
Published: July 2023

News reports that feature the experiences of healthcare workers have shaped public conversations about the pandemic from its earliest days. For many, stories of the pandemic have been an introduction to the way public health emergencies intersect with cultural, social, structural, political and spiritual determinants. Such stories often feature clinicians and other providers as characters in pandemic tales of heroism, tragedy and, increasingly, frustration. Examining three common categories of provider-focused news narratives—the clinician as a uniquely vulnerable front-line worker, clinician frustration with vaccine and masking resistance, and the clinician as a hero—the authors argue that the framework of public health humanities offers useful tools to understand and potentially shift public conversation of the pandemic. Close reading of these stories illuminates frames that relate to the role of providers, responsibility for the spread of the virus and how the US health system functions in a global context. Public conversations of the pandemic are shaped by and shape news stories and have important implications for policy. Acknowledging that contemporary health humanities in all its iterations considers how non-clinical factors, such as culture, embodiment and power, impact our understanding of health, illness and healthcare delivery, the authors locate their argument amid critiques that focus on social and structural factors. They argue that it is still possible to shift our understanding of and telling of those stories towards a more population-focused frame.
Correct dosing, adherence and persistence of DOACs in atrial fibrillation and chronic kidney disease: a systematic review and meta-analysis
Authors: Emanuel Subo , Kaba Riyaz A , Delanerolle Gayathri , Field Benjamin C T , Lip Gregory Y H , de Lusignan Simon
Published: July 2023

Background

Chronic kidney disease (CKD) and atrial fibrillation (AF) are increasing in prevalence globally and share common risk factors.

Our aim was to characterise real-world evidence on direct oral anticoagulant (DOAC) prescribing for people with AF and CKD, in terms of adherence, persistence and renal dose titration.

Methods

PubMed, EMBASE and CINAHL were searched from inception to June 2022. Our search terms included a combination of Medical Subject Headings (MeSH) terms and keywords including ‘atrial fibrillation’, ‘chronic kidney disease’, ‘adherence’, ‘persistence’, ‘direct oral anticoagulants’ and ‘dosing’. Data extraction and quality assessment were undertaken by two reviewers independently. Meta-analyses for pooled estimates were performed using DerSimonian and Laird random-effects models. Age, sex, diabetes, hypertension and heart failure were chosen as variables of interest.

Results

From 19 studies, a total of 252 117 patients were included with CKD and AF. Meta-analysis was only possible in seven studies with 128 406 patients, five on DOAC dose titration and two on adherence. There were insufficient studies on persistence. Our meta-analysis of dosing showed that 68% of patients with CKD and AF had correct dosing. There was no evidence to show any association between correct DOAC dosing and variables of interest. Overall, 67% of patients were DOAC adherent.

Conclusion

Adherence and correct dosing of DOACs were suboptimal compared with other medications in the pooled studies with respect to CKD and AF. Thus, further research is required as the lack of generalisation of findings is a rate-limiting factor for improved DOAC management in AF and CKD.

PROSPERO registration number

CRD;42022344491.
Two-dimensional regular string black hole via complete $$\alpha ^{\prime }$$ corrections
Authors: Ying Shuxuan
Published: July 2023

In string theory, an important challenge is to show if the singularity of black holes can be smoothed out by the complete $$\alpha ^{\prime }$$

α
′

corrections. The simplest case is to consider a 2D string black hole or 3D black string. This problem was discussed in a gauged Wess–Zumino–Witten (WZW) model and the results are supposed to be correct to all orders in $$\alpha ^{\prime }$$

α
′

corrections. Based on the recent remarkable progress on classifying all the $$\alpha ^{\prime }$$

α
′

corrections, in this work, we re-study this problem with the low energy effective spacetime action, and provide classes of exact non-perturbative and non-singular solutions of the 2D black hole/3D black string via complete $$\alpha ^{\prime }$$

α
′

corrections.
Study of physical properties of the new inorganic perovskites LiSnX3 (X=Br or I): A DFT approach
Authors: Jabar A. , Labrim H. , Laanab L. , Jaber B. , Bahmad L. , Benyoussef S.
Published: July 2023

This work aims to study the optoelectronic and thermoelectric properties of the new perovskites LiSnX3 (X[Formula: see text]Br or I). This study is carried out by using the density functional theory (DFT) combined with the Boltzmann transport theory. First, the investigation of the structural, electronic and optical properties of such materials, using the Generalized Gradient Approximation (GGA), has been performed. This latter method has been performed under the Perdew–Burke–Ernzerhof (GGA–PBE) approximation applying the exchange correlation potential. It is found that the two compounds exhibit a p-type semiconductor characteristic and interesting optical properties. Moreover, the thermoelectric properties of the studied materials, such as the Seebeck coefficient, electrical conductivity, thermal conductivity, figure of merit and power factor, have been examined. It is found that the Seebeck coefficient takes positive values. This finding reveals and confirms the p-type semiconductor characteristic for two studied compounds. On the other hand, such materials display large values of the figure of merit (ZT) in comparison with the existing thermoelectric materials. Such large values of ZT are found for both small or large temperature values. The obtained results of the optoelectronic and thermoelectric properties show that these materials could be useful both for photovoltaic and thermoelectric applications.
Programming by Example Made Easy
Authors: Wu Jiarong , Wei Lili , Jiang Yanyan , Cheung Shing-Chi , Ren Luyao , Xu Chang
Published: July 2023

Programming by example (PBE) is an emerging programming paradigm that automatically synthesizes programs specified by user-provided input-output examples. Despite the convenience for end-users, implementing PBE tools often requires strong expertise in programming language and synthesis algorithms. Such a level of knowledge is uncommon among software developers. It greatly limits the broad adoption of PBE by the industry. To facilitate the adoption of PBE techniques, we propose a PBE framework called
Bee
, which leverages an “entity-action” model based on relational tables to ease PBE development for a wide but restrained range of domains. Implementing PBE tools with
Bee
only requires adapting domain-specific data entities and user actions to tables, with no need to design a domain-specific language or an efficient synthesis algorithm. The synthesis algorithm of
Bee
exploits bidirectional searching and constraint-solving techniques to address the challenge of value computation nested in table transformation. We evaluated
Bee
’s effectiveness on 64 PBE tasks from three different domains and usability with a human study of 12 participants. Evaluation results show that
Bee
is easier to learn and use than the state-of-the-art PBE framework, and the bidirectional algorithm achieves comparable performance to domain-specifically optimized synthesizers.
FASTSync: A FAST Delta Sync Scheme for Encrypted Cloud Storage in High-bandwidth Network Environments
Authors: Wu Suzhen , Tu Zhanhong , Zhou Yuxuan , Wang Zuocheng , Shen Zhirong , Chen Wei , Wang Wei , Wang Weichun , Mao Bo
Published: July 2023

More and more data are stored in cloud storage, which brings two major challenges. First, the modified files in the cloud should be quickly synchronized to ensure data consistency, e.g., delta synchronization (sync) achieves efficient cloud sync by synchronizing only the updated part of the file. Second, the huge data in the cloud needs to be deduplicated and encrypted, e.g., Message-Locked Encryption (MLE) implements data deduplication by encrypting the content among different users. However, when combined, a few updates in the content can cause large sync traffic amplification for both keys and ciphertext in the MLE-based cloud storage, significantly degrading the cloud sync efficiency. A feature-based encryption sync scheme, FeatureSync, is proposed to address the delta amplification problem. However, with further improvement of the network bandwidth, the performance of FeatureSync stagnates. In our preliminary experimental evaluations, we find that the bottleneck of the computational overhead in the high-bandwidth network environments is the main bottleneck in FeatureSync. In this article, we propose an enhanced feature-based encryption sync scheme FASTSync to optimize the performance of FeatureSync in high-bandwidth network environments. The performance evaluations on a lightweight prototype implementation of FASTSync show that FASTSync reduces the cloud sync time by 70.3% and the encryption time by 37.3%, on average, compared with FeatureSync.
Highly Efficient Electrochemical Oxidation of Carbamazepine Using a Novel Graphene Nanoplatelet-doped PbO2 Electrode: Characteristics, Efficiency, and Mechanism
Authors: Wu Duoer , He Cong , Feng Yang , Ding Yangcheng , Yan Yan , Ma Xiangjuan , Feng Huajun , Xia Yijing
Published: July 2023

A novel graphene nanoplatelet (GN)-doped PbO2 electrode was fabricated and utilized to pulse electrochemical oxidize carbamazepine (CBZ) in aquesous solution. The GN-PbO2 electrode differed from a pure PbO2 electrode in that it exhibited higher surface roughness, smaller particle size, larger specific surface area, greater oxidation peak current, smaller charge transfer resistance, and higher oxygen evolution potential. After electrolysis for 90 min, 94.74% of CBZ and 45.15% of chemical oxygen demand could be removed at an initial pH of 3, pulsed frequency of 3000 Hz, current density of 20 mA cm−2, and pulsed duty cycle of 50%. Additionally, the primary electrochemical oxidation mechanism at the GN-PbO2 anode was indirect radical oxidation and the degradation pathway of CBZ in pulsed electrochemical oxidation was investigated and clarified considering the identified intermediate products and theoretical computations. The results demonstrate that pulsed electrochemical oxidation based on GN-PbO2 electrodes is a promising approach to increasing the viability of pharmaceutical wastewater treatment by electrochemical technologies.
Dielectric Properties of Cellulose/Graphene Nano-Platelet/Polypyrrole Composites
Authors: Haroun Ahmed A. , El nahrawy Amany M. , Kamel Samir
Published: July 2023

Cellulose (Cel)/graphene nano-platelet (GNP) and/or polypyrrole (PPy) composites were prepared via emulsion in combination with a sonication strategy technique, in the presence of sodium dodecyl sulphate (SDS) and ceric ammonium nitrate as emulsifies, with a ratio (1:1:1). The resulting composites were characterized using different analytical tools such as Fourier transform infrared spectroscopy (FTIR), transmitting electron microscope (TEM), and particle size distribution analysis using DLS technique. The results indicated that GNP could be successfully coated on cellulosic fibers in the presence of PPy as conducting polymer. Besides, GNP was dispersed in cluster shape inside the cellulose fibers with a particle size of about 155 d.nm, but after adsorption of PPy, the size was increased to around 429–460 d.nm. The results also exhibited that the addition of GNP increases the thermal stability of the cellulose/polypyrrole composite. Furthermore, dielectric properties, including dielectric constants (e′), dielectric losses (e″), loss tangent (tan δ), and AC conductivity of the prepared composites, were investigated over a frequency range from 42 Hz to 5 MHz. The results showed that the area of the DC conductivity increasing to 104 Hz as the temperature increases.
Nonmyocytes as electrophysiological contributors to cardiac excitation and conduction
Authors: Simon-Chica Ana , Wülfers Eike M. , Kohl Peter
Published: July 2023

Although cardiac action potential (AP) generation and propagation have traditionally been attributed exclusively to cardiomyocytes (CM), other cell types in the heart are also capable of forming electrically conducting junctions. Interactions between CM and nonmyocytes (NM) enable and modulate each other’s activity. This review provides an overview of the current understanding of heterocellular electrical communication in the heart. Although cardiac fibroblasts were initially thought to be electrical insulators, recent studies have demonstrated that they form functional electrical connections with CM in situ. Other NM, such as macrophages, have also been recognized as contributing to cardiac electrophysiology and arrhythmogenesis. Novel experimental tools have enabled the investigation of cell-specific activity patterns in native cardiac tissue, which is expected to yield exciting new insights into the development of novel or improved diagnostic and therapeutic strategies.
Extrinsic and intrinsic modulators of inflammation-resolution signaling in heart failure
Authors: Rao Archana , Gupta Akul , Kain Vasundhara , Halade Ganesh V.
Published: July 2023

Chronic and uncleared inflammation is the root cause of various cardiovascular diseases. Fundamentally, acute inflammation is supportive when overlapping with safe clearance of inflammation termed resolution; however, if the lifestyle-directed extrinsic factors such as diet, sleep, exercise, or physical activity are misaligned, that results in unresolved inflammation. Although genetics play a critical role in cardiovascular health, four extrinsic risk factors—unhealthy processed diet, sleep disruption or fragmentation, sedentary lifestyle, thereby, subsequent stress—have been identified as heterogeneous and polygenic triggers of heart failure (HF), which can result in several complications with indications of chronic inflammation. Extrinsic risk factors directly impact endogenous intrinsic factors, such as using fatty acids by immune-responsive enzymes [lipoxygenases (LOXs)/cyclooxygenases (COXs)/cytochromes-P450 (CYP450)] to form resolution mediators that activate specific resolution receptors. Thus, the balance of extrinsic factors such as diet, sleep, and physical activity feed-forward the coordination of intrinsic factors such as fatty acids-enzymes-bioactive lipid receptors that modulates the immune defense, metabolic health, inflammation-resolution signaling, and cardiac health. Future research on lifestyle- and aging-associated molecular patterns is warranted in the context of intrinsic and extrinsic factors, immune fitness, inflammation-resolution signaling, and cardiac health.
Alcoholic Off-Flavor Disorders in Fresh Fruits
Authors: Ali Maratab , Batool Sara , Khalid Nauman , Manzoor Muhammad Faisal , Zhao Xiuming , Li Xiaoan , Li Fujun , Xinhua Zhang , Aadil Rana Muhammad
Published: July 2023

The off-flavor disorder is one of the most quality deteriorating and undesirable postharvest physiological disorders in fresh fruits. Over-biosynthesis and accumulation of ethanol metabolism-related metabolites such as acetaldehyde and ethanol have been associated with an alcoholic off-flavor disorder in various fresh fruits at both pre- and postharvest stages. Correspondingly, many studies have reported the association of such off-flavor disorders with several inducing factors, including anaerobic respiration, low O2 stress, high CO2 stress, and storage temperature stress, that upregulate ethanol metabolism in fruits. Furthermore, numerous metabolic and physiological mechanisms that govern ethanol metabolism under such factors are subsequently addressed. These mechanisms include the γ-aminobutyric acid (GABA) shunt pathway, mitochondrial energy metabolism, glycolysis, Krebs or TCA cycle, cytosolic malate metabolism, and starch and sugar metabolism. To summarize the relevant findings, the current paper reviews the literature on alcoholic off-flavor disorder, focusing on the role of significant underlying causes and key metabolic and physiological mechanisms in boosting ethanol metabolism in fresh fruits. In addition, recent measures that have been already taken or are in progress to control the higher activity of ethanol metabolism that may eventually result in limiting the alcoholic off-flavor disorder in harvested fresh fruits have also been discussed. Moreover, functions of metabolic mechanisms, including respiratory mechanisms, and other factors such as fruit genetic makeup, degree of maturity, and postharvest handling and storage conditions, are needed to be investigated in future work at both physiological and transcriptomics levels to reveal the additional relation to alcoholic off-flavor disorders in fresh fruits during ripening and storage.
Adaptive Sensitive Information Recognition Based on Multimodal Information Inference in Social Networks
Authors: Ji Peiyu , Shan Fangfang , Li Fuyang , Sun Huifang , Wang Mengyi , Shan Dalong
Published: July 2023

With the advent of the multimedia era, the identification of sensitive information in social data of online social network users has become critical for maintaining the security of network community information. Currently, traditional sensitive information identification techniques in online social networks cannot acquire the full semantic knowledge of multimodal data and cannot learn cross-information between data modalities. Therefore, it is urgent to study a new multimodal deep learning model that considers semantic relationships. This paper presents an improved multimodal dual-channel reasoning mechanism (MDR), which deeply mines semantic information and implicit association relationships between modalities based on the consideration of multimodal data fusion. In addition, we propose a multimodal adaptive spatial attention mechanism (MAA) to improve the accuracy and flexibility of the decoder. We manually annotated real social data of 50 users to train and test our model. The experimental results show that the proposed method significantly outperforms simple multimodal fusion deep learning models in terms of sensitive information prediction accuracy and adaptability and verifies the feasibility and effectiveness of a multimodal deep model considering semantic strategies in social network sensitive information identification.
Supplementary Table S7 from Activin A–Mediated Polarization of Cancer-Associated Fibroblasts and Macrophages Confers Resistance to Checkpoint Immunotherapy in Skin Cancer
Authors: Pich-Bavastro Christine , Yerly Laura , Di Domizio Jeremy , Tissot-Renaud Stéphanie , Gilliet Michel , Kuonen François
Published: July 2023

Supplementary Table S7. Clinical response annotation of the scRNAseq dataset obtained from melanomas treated with ICI.
Supplementary Figure S8 from Activin A–Mediated Polarization of Cancer-Associated Fibroblasts and Macrophages Confers Resistance to Checkpoint Immunotherapy in Skin Cancer
Authors: Pich-Bavastro Christine , Yerly Laura , Di Domizio Jeremy , Tissot-Renaud Stéphanie , Gilliet Michel , Kuonen François
Published: July 2023

Supplementary Figure S8: Activin A exposure in Fibroblasts and Macrophages clusters.
Supplementary Figure S2 from Activin A–Mediated Polarization of Cancer-Associated Fibroblasts and Macrophages Confers Resistance to Checkpoint Immunotherapy in Skin Cancer
Authors: Pich-Bavastro Christine , Yerly Laura , Di Domizio Jeremy , Tissot-Renaud Stéphanie , Gilliet Michel , Kuonen François
Published: July 2023

Supplementary Figure S2: Establishment of spatial transcriptional signatures for TMEs with distinct immune profiles.
Supplementary Figure S11 from Activin A–Mediated Polarization of Cancer-Associated Fibroblasts and Macrophages Confers Resistance to Checkpoint Immunotherapy in Skin Cancer
Authors: Pich-Bavastro Christine , Yerly Laura , Di Domizio Jeremy , Tissot-Renaud Stéphanie , Gilliet Michel , Kuonen François
Published: July 2023

Supplementary Figure S11: ICI-resistant BCCs harbor higher levels of TME2-like CAFs and myeloid cells.
Data from Activin A-mediated polarization of cancer-associated fibroblasts and macrophages confers resistance to checkpoint immunotherapy in skin cancer
Authors: Pich-Bavastro Christine , Yerly Laura , Di Domizio Jeremy , Tissot-Renaud Stéphanie , Gilliet Michel , Kuonen François
Published: July 2023

Abstract
Purpose: Cemiplimab is approved for the treatment of locally advanced basal cell carcinomas (BCCs), however with mitigated results. We sought to interrogate the cellular and molecular transcriptional reprogramming underlying BCC resistance to immunotherapy. Experimental Design: Here, we combined spatial and single-cell transcriptomics to deconvolute the spatial heterogeneity of the tumor microenvironment in regard with response to immunotherapy, in a cohort of both naive and resistant BCCs. Results: We identified subsets of intermingled cancer-associated fibroblasts (CAFs) and macrophages contributing the most to CD8 T cells exclusion and immunosuppression. Within this spatially-resolved peritumoral immunosuppressive niche, CAFs and adjacent macrophages were found to display Activin A-mediated transcriptional reprogramming towards extracellular matrix remodeling, suggesting active participation to CD8 T cells exclusion. In independent datasets of human skin cancers, Activin A-conditioned CAFs and macrophages were associated with resistance to immune checkpoint inhibitors (ICI). Conclusions: Altogether, our data identify the cellular and molecular plasticity of TME and the pivotal role of Activin A in polarizing the TME towards immune suppression and ICI resistance.
Data from Activin A–Mediated Polarization of Cancer-Associated Fibroblasts and Macrophages Confers Resistance to Checkpoint Immunotherapy in Skin Cancer
Authors: Pich-Bavastro Christine , Yerly Laura , Di Domizio Jeremy , Tissot-Renaud Stéphanie , Gilliet Michel , Kuonen François
Published: July 2023

AbstractPurpose:
Cemiplimab is approved for the treatment of locally advanced basal cell carcinomas (BCC), although with mitigated results. We sought to interrogate the cellular and molecular transcriptional reprogramming underlying BCC resistance to immunotherapy.
Experimental Design:
Here, we combined spatial and single-cell transcriptomics to deconvolute the spatial heterogeneity of the tumor microenvironment in regard with response to immunotherapy, in a cohort of both naïve and resistant BCCs.
Results:
We identified subsets of intermingled cancer-associated fibroblasts (CAF) and macrophages contributing the most to CD8 T-cell exclusion and immunosuppression. Within this spatially resolved peritumoral immunosuppressive niche, CAFs and adjacent macrophages were found to display Activin A–mediated transcriptional reprogramming towards extracellular matrix remodeling, suggesting active participation to CD8 T-cell exclusion. In independent datasets of human skin cancers, Activin A–conditioned CAFs and macrophages were associated with resistance to immune checkpoint inhibitors (ICI).
Conclusions:
Altogether, our data identify the cellular and molecular plasticity of tumor microenvironment (TME) and the pivotal role of Activin A in polarizing the TME towards immune suppression and ICI resistance.
A Prognostic Model Based on Residual Cancer Burden and Tumor-Infiltrating Lymphocytes on Residual Disease after Neoadjuvant Therapy in HER2+ Breast Cancer
Authors: Miglietta Federica , Ragazzi Moira , Fernandes Bethania , Griguolo Gaia , Massa Davide , Girardi Fabio , Bottosso Michele , Bisagni Alessandra , Zarrilli Giovanni , Porra Francesca , Iannaccone Daniela , Dore Leocadia , Gaudio Mariangela , Santandrea Giacomo , Fassan Matteo , Lo Mele Marcello , De Sanctis Rita , Zambelli Alberto , Bisagni Giancarlo , Guarneri Valentina , Dieci Maria Vittoria
Published: July 2023

Purpose:

We aim to evaluate the prognostic significance of tumor-infiltrating lymphocyte on residual disease (RD-TIL) in HER2+ patients with breast cancer who failed to achieve pathologic complete response (pCR) after anti-HER2+ chemotherapy (CT)-based neoadjuvant treatment (NAT). We assessed the feasibility of combining the prognostic information provided by residual cancer burden (RCB) and RD-TILs into a composite score (RCB+TIL).

Experimental Design:

HER2+ patients with breast cancer treated with CT+anti-HER2-based NAT at three institutions were retrospectively included. RCB and TIL levels were evaluated on hematoxylin and eosin–stained slides from surgical samples according to available recommendations. Overall survival (OS) was used as an outcome measure.

Results:

A total of 295 patients were included, of whom 195 had RD. RCB was significantly associated with OS. Higher RD-TILs were significantly associated with poorer OS as compared with lower RD-TILs (15% cutoff). In multivariate analysis, both RCB and RD-TIL maintained their independent prognostic value. A combined score, RCB+TIL, was calculated from the estimated coefficient of RD-TILs and the RCB index in a bivariate logistic model for OS. The RCB+TIL score was significantly associated with OS. The C-index for OS of the RCB+TIL score was numerically higher than that of RCB and significantly higher than that of RD-TILs.

Conclusions:

We have reported an independent prognostic impact of RD-TILs after anti-HER2+CT NAT, which might underlie an imbalance of the RD microenvironment towards immunosuppressive features. We provided a new composite prognostic score based on RCB+TIL, which was significantly associated with OS and proved to be more informative than the isolated evaluation of RCB and RD-TILs.
Supplementary Fig. 3 from Disruption of the MYC Superenhancer Complex by Dual Targeting of FLT3 and LSD1 in Acute Myeloid Leukemia
Authors: Yashar William M. , Curtiss Brittany M. , Coleman Daniel J. , VanCampen Jake , Kong Garth , Macaraeg Jommel , Estabrook Joseph , Demir Emek , Long Nicola , Bottomly Daniel , McWeeney Shannon K. , Tyner Jeffrey W. , Druker Brian J. , Maxson Julia E. , Braun Theodore P.
Published: July 2023

Epigenetic impact of dual FLT3/LSD1 inhibition.
Supplementary Fig. 2 from Disruption of the MYC Superenhancer Complex by Dual Targeting of FLT3 and LSD1 in Acute Myeloid Leukemia
Authors: Yashar William M. , Curtiss Brittany M. , Coleman Daniel J. , VanCampen Jake , Kong Garth , Macaraeg Jommel , Estabrook Joseph , Demir Emek , Long Nicola , Bottomly Daniel , McWeeney Shannon K. , Tyner Jeffrey W. , Druker Brian J. , Maxson Julia E. , Braun Theodore P.
Published: July 2023

Efficacy of dual FLT3/LSD1 inhibition in MOLM13 cells.
Supplementary Fig. 12 from Disruption of the MYC Superenhancer Complex by Dual Targeting of FLT3 and LSD1 in Acute Myeloid Leukemia
Authors: Yashar William M. , Curtiss Brittany M. , Coleman Daniel J. , VanCampen Jake , Kong Garth , Macaraeg Jommel , Estabrook Joseph , Demir Emek , Long Nicola , Bottomly Daniel , McWeeney Shannon K. , Tyner Jeffrey W. , Druker Brian J. , Maxson Julia E. , Braun Theodore P.
Published: July 2023

Dual FLT3/LSD1 inhibition disrupts LSC clonogenicity.
Supplemental Table S2 from Cost-effectiveness of p16/Ki-67 Dual-Stained Cytology Reflex Following Co-testing with hrHPV Genotyping for Cervical Cancer Screening
Authors: Harper Diane M. , Anderson Rye J. , Baker Ed , Yu Tiffany M.
Published: July 2023

Supplemental Table S2 shows the distribution of patient attributes in the prevalent US population of women eligible for cervical cancer screening
Supplementary Table S6 from Early Infiltration of Innate Immune Cells to the Liver Depletes HNF4α and Promotes Extrahepatic Carcinogenesis
Authors: Goldman Omer , Adler Lital N. , Hajaj Emma , Croese Tommaso , Darzi Naama , Galai Sivan , Tishler Hila , Ariav Yarden , Lavie Dor , Fellus-Alyagor Liat , Oren Roni , Kuznetsov Yuri , David Eyal , Jaschek Rami , Stossel Chani , Singer Oded , Malitsky Sergey , Barak Renana , Seger Rony , Erez Neta , Amit Ido , Tanay Amos , Saada Ann , Golan Talia , Rubinek Tamar , Sang Lee Joo , Ben-Shachar Shay , Wolf Ido , Erez Ayelet
Published: July 2023

Supplementary Table S6 lists the genes regulated by HNF4a
Supplementary Table S4 from Early Infiltration of Innate Immune Cells to the Liver Depletes HNF4α and Promotes Extrahepatic Carcinogenesis
Authors: Goldman Omer , Adler Lital N. , Hajaj Emma , Croese Tommaso , Darzi Naama , Galai Sivan , Tishler Hila , Ariav Yarden , Lavie Dor , Fellus-Alyagor Liat , Oren Roni , Kuznetsov Yuri , David Eyal , Jaschek Rami , Stossel Chani , Singer Oded , Malitsky Sergey , Barak Renana , Seger Rony , Erez Neta , Amit Ido , Tanay Amos , Saada Ann , Golan Talia , Rubinek Tamar , Sang Lee Joo , Ben-Shachar Shay , Wolf Ido , Erez Ayelet
Published: July 2023

Supplementary Table S4 lists the antibodies used for FACS
Supplementary Figure S5 from Early Infiltration of Innate Immune Cells to the Liver Depletes HNF4α and Promotes Extrahepatic Carcinogenesis
Authors: Goldman Omer , Adler Lital N. , Hajaj Emma , Croese Tommaso , Darzi Naama , Galai Sivan , Tishler Hila , Ariav Yarden , Lavie Dor , Fellus-Alyagor Liat , Oren Roni , Kuznetsov Yuri , David Eyal , Jaschek Rami , Stossel Chani , Singer Oded , Malitsky Sergey , Barak Renana , Seger Rony , Erez Neta , Amit Ido , Tanay Amos , Saada Ann , Golan Talia , Rubinek Tamar , Sang Lee Joo , Ben-Shachar Shay , Wolf Ido , Erez Ayelet
Published: July 2023

Supplementary Figure S5 demonstrate the significance of our liver score in predicting outcomes of BC and PDAC patients
Supplementary Table S4 from C/EBPα Confers Dependence to Fatty Acid Anabolic Pathways and Vulnerability to Lipid Oxidative Stress–Induced Ferroptosis in FLT3-Mutant Leukemia
Authors: Sabatier Marie , Birsen Rudy , Lauture Laura , Mouche Sarah , Angelino Paolo , Dehairs Jonas , Goupille Léa , Boussaid Ismael , Heiblig Maël , Boet Emeline , Sahal Ambrine , Saland Estelle , Santos Juliana C. , Armengol Marc , Fernández-Serrano Miranda , Farge Thomas , Cognet Guillaume , Simonetta Federico , Pignon Corentin , Graffeuil Antoine , Mazzotti Céline , Avet-Loiseau Hervé , Delos Océane , Bertrand-Michel Justine , Chedru Amélie , Dembitz Vilma , Gallipoli Paolo , Anstee Natasha S. , Loo Sun , Wei Andrew H. , Carroll Martin , Goubard Armelle , Castellano Rémy , Collette Yves , Vergez François , Mansat-De Mas Véronique , Bertoli Sarah , Tavitian Suzanne , Picard Muriel , Récher Christian , Bourges-Abella Nathalie , Granat Fanny , Kosmider Olivier , Sujobert Pierre , Colsch Benoit , Joffre Carine , Stuani Lucille , Swinnen Johannes V. , Guillou Hervé , Roué Gael , Hakim Nawad , Dejean Anne S. , Tsantoulis Petros , Larrue Clément , Bouscary Didier , Tamburini Jerome , Sarry Jean-Emmanuel
Published: July 2023

Table S4: GSEA results in FLT3-ITD PDX AML cells ex vivo-treated with QUIZ or Veh.