bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contribution of macrophages to neural survival and intracochlear tissue remodeling responses following cochlear implantation
Authors: Rahman Muhammad Taifur , Mostaert Brian J. , Hunger Bryce , Saha Utsow , Claussen Alexander D. , Razu Ibrahim , Nasrin Farjana , Khan Nashwaan Ali , Eckard Peter , Coleman Sarah , Oleson Jacob , Kirk Jonathon R. , Hirose Keiko , Hansen Marlan R. 
Published: November 2023

Abstract
Background
Cochlear implants (CIs) restore hearing to deafened patients. The foreign body response (FBR) following cochlear implantation (post-CI) comprises an infiltration of macrophages, other immune and non-immune cells, and fibrosis into the scala tympani, a space that is normally devoid of cells. This FBR is associated with negative effects on CI outcomes including increased electrode impedances and loss of residual acoustic hearing. This study investigates the extent to which macrophage depletion by an orally administered CSF-1R specific kinase (c-FMS) inhibitor, PLX-5622, modulates the tissue response to CI and neural health.

Main text
10- to 12-week-old CX3CR1 + /GFP Thy1 + /YFP mice on C57BL/6J/B6 background was fed chow containing 1200 mg/kg PLX5622 or control chow for the duration of the study. 7 days after starting the diet, 3-channel cochlear implants were implanted in the ear via the round window. Serial impedance and neural response telemetry (NRT) measurements were acquired throughout the study. Electric stimulation began 7 days post-CI until 28 days post-CI for 5 h/day, 5 days/week, with programming guided by NRT and behavioral responses. Cochleae harvested at 10, 28 or 56 days post-CI were cryosectioned and labeled with an antibody against α-smooth muscle actin (α-SMA) to identify myofibroblasts and quantify the fibrotic response. Using IMARIS image analysis software, the outlines of scala tympani, Rosenthal canal, modiolus, and lateral wall for each turn were traced manually to measure region volume. The density of nuclei, CX3CR1 + macrophages, Thy1 + spiral ganglion neuron (SGN) numbers, and the ratio of the α-SMA + volume/scala tympani volume were calculated. Cochlear implantation in control diet subjects caused infiltration of cells, including macrophages, into the cochlea. Fibrosis was evident in the scala tympani adjacent to the electrode array. Mice fed PLX5622 chow showed reduced macrophage infiltration throughout the implanted cochleae across all time points. However, scala tympani fibrosis was not reduced relative to control diet subjects. Further, mice treated with PLX5622 showed increased electrode impedances compared to controls. Finally, treatment with PLX5622 decreased SGN survival in implanted and contralateral cochleae.

Conclusion
The data suggest that macrophages play an important role in modulating the intracochlear tissue response following CI and neural survival.
“They try to suppress us, but we should be louder”: a qualitative exploration of intimidation in tobacco control
Authors: Matthes Britta K , Alebshehy Raouf , Gilmore Anna B 
Published: November 2023

Abstract
Background
Tobacco control advocates and researchers face powerful opponents who go to great lengths to protect their interests. While threats and attacks are documented in the grey literature, research into intimidation remains scarce. Building on previous exploratory research, this study seeks to offer in-depth insights into experiences of intimidation in the global tobacco control community.

Methods
Using qualitative description, we conducted a focus group and semi-structured interviews with tobacco control advocates and researchers to explore their experiences, including forms of, and responses to, intimidation, and ways forward. Data were analysed using qualitative content analysis.

Results
Twenty-nine individuals from across the globe participated in the study. They reported several forms of intimidation including attacks in the media; online harassment; legal threats; non-legal threats, including death threats; Freedom of Information requests; perceived or actual surveillance; as well as burglary and theft. Responses included non-action (i.e. ignoring attacks); withdrawal (i.e. abandoning a project, area or field); defensive adaptation, for example through self-censorship; and offensive measures, including exposing attacks or filing complaints. Responses were shaped by several factors, including type and level of support from within internal and external networks; as well as an individual’s mindset, skills and experiences; and state-civil society relations. Participants suggested several measures that could help address intimidation: 1) report and monitor intimidation; 2) (better) prepare individuals through awareness raising and training (e.g. IT security, legal); 3) support those in need through legal advice, a peer-support network and involvement in response; and 4) look beyond tobacco control to learn and build connections.

Conclusion
Intimidation is a significant challenge to tobacco control that needs urgent attention. This study suggests measures to address intimidation that require commitment from, and collaboration amongst, multiple actors including governments, international organisations, funders, researchers and civil society. Moreover, collective action beyond tobacco control is needed to not only manage but move beyond intimidation.
Consideration of vaping products as an alternative to adult smoking: a narrative review
Authors: Foster Jane A. 
Published: November 2023

AbstractTobacco harm reduction is a public health approach to reduce the impact of cigarette smoking on individuals. Non-combustible alternatives to cigarettes, such as electronic cigarettes (e-cigarettes), deliver nicotine to the user in the absence of combustion. The absence of combustion in e-cigarettes reduces the level of harmful or potentially harmful chemicals in the aerosol generated. This narrative review examines the published literature that studied the chemistry of e-cigarette aerosols, the related toxicology in cell culture and animal models, as well as clinical studies that investigated short- and long-term changes in biomarkers of smoke exposure after switching to e-cigarettes. In the context of the literature reviewed, the evidence supports the harm reduction potential for adult smokers who switch to e-cigarettes.
Wolfram syndrome type 1: a case series
Authors: Du Danyang , Tuhuti Aihemaitijiang , Ma Yanrong , Abuduniyimu Munila , Li Suli , Ma Guoying , Zynat Jazyra , Guo Yanying 
Published: November 2023

Abstract
Background
Wolfram syndrome (WS) is a rare autosomal recessive multisystem neurodegenerative disease characterized by non-autoimmune insulin-dependent diabetes mellitus, optic atrophy, sensorineural deafness, and diabetes as the main features. Owing to clinical phenotypic heterogeneity, the misdiagnosis rate is high. However, early accurate diagnosis and comprehensive management are key to improving quality of life and prolonging life.

Results
Eleven patients from seven WS pedigrees with 10 mutation sites (c.1314_1317delCTTT, c.C529T, c.C529A, c.G2105A, c.C1885T, c.1859_1860del, c.G2020A, c.C529A, c.G2105A, and c.G1393C) in the WFS1 gene were included. We conducted further expert department analysis to clarify the diagnosis and analyze the correlation between genes and phenotypes.

Conclusions
The genotypes of these patients were closely associated with their phenotypes. The clinical data of the patients were analyzed to provide a basis for the diagnosis and clinical management of the disease.
Multi-modal proteomic characterization of lysosomal function and proteostasis in progranulin-deficient neurons
Authors: Hasan Saadia , Fernandopulle Michael S. , Humble Stewart W. , Frankenfield Ashley M. , Li Haorong , Prestil Ryan , Johnson Kory R. , Ryan Brent J. , Wade-Martins Richard , Ward Michael E. , Hao Ling 
Published: November 2023

Abstract
Background
Progranulin (PGRN) is a lysosomal glycoprotein implicated in various neurodegenerative diseases, including frontotemporal dementia and neuronal ceroid lipofuscinosis. Over 70 mutations discovered in the GRN gene all result in reduced expression of the PGRN protein. Genetic and functional studies point toward a regulatory role for PGRN in lysosome functions. However, the detailed molecular function of PGRN within lysosomes and the impact of PGRN deficiency on lysosomes remain unclear.

Methods
We developed multifaceted proteomic techniques to characterize the dynamic lysosomal biology in living human neurons and fixed mouse brain tissues. Using lysosome proximity labeling and immuno-purification of intact lysosomes, we characterized lysosome compositions and interactome in both human induced pluripotent stem cell (iPSC)-derived glutamatergic neurons (i3Neurons) and mouse brains. Using dynamic stable isotope labeling by amino acids in cell culture (dSILAC) proteomics, we measured global protein half-lives in human i3Neurons for the first time.

Results
Leveraging the multi-modal proteomics and live-cell imaging techniques, we comprehensively characterized how PGRN deficiency changes the molecular and functional landscape of neuronal lysosomes. We found that PGRN loss impairs the lysosome’s degradative capacity with increased levels of v-ATPase subunits on the lysosome membrane, increased hydrolases within the lysosome, altered protein regulations related to lysosomal transport, and elevated lysosomal pH. Consistent with impairments in lysosomal function, GRN-null i3Neurons and frontotemporal dementia patient-derived i3Neurons carrying GRN mutation showed pronounced alterations in protein turnover, such as cathepsins and proteins related to supramolecular polymerization and inherited neurodegenerative diseases.

Conclusion
This study suggested PGRN as a critical regulator of lysosomal pH and degradative capacity, which influences global proteostasis in neurons. Beyond the study of progranulin deficiency, these newly developed proteomic methods in neurons and brain tissues provided useful tools and data resources for the field to study the highly dynamic neuronal lysosome biology.

Graphical Abstract
Invasive FoxM1 phosphorylated by PLK1 induces the polarization of tumor-associated macrophages to promote immune escape and metastasis, amplified by IFITM1
Authors: Xu Rong , Lee Young-Joo , Kim Chang-Hyeon , Min Ga-Hong , Kim Yeo-Bin , Park Jung-Won , Kim Dae-Hoon , Kim Jung-Hyun , Yim Hyungshin 
Published: November 2023

Abstract
Background
Understanding the mechanism behind immune cell plasticity in cancer metastasis is crucial for identifying key regulators. Previously we found that mitotic factors regulate epithelial-mesenchymal transition, but how these factors convert to metastatic players in the tumor microenvironment (TME) is not fully understood.

Methods
The clinical importance of mitotic factors was analyzed by heatmap analysis, a KM plot, and immunohistochemistry in lung adenocarcinoma (LUAD) patients. Immunoprecipitation, LC–MS/MS, kinase assay, and site-directed mutagenesis were performed for the interaction and phosphorylation. A tail-vein injection mouse model, Transwell-based 3D culture, microarray analysis, coculture with monocytes, and chromatin immunoprecipitation assays were used to elucidate the function of phosphorylated FoxM1 in metastasis of TME.

Results
The phosphorylated FoxM1 at Ser25 by PLK1 acquires the reprogramming ability to stimulate the invasive traits in cancer and influence immune cell plasticity. This invasive form of p-FoxM1 upregulates the expression of IL1A/1B, VEGFA, and IL6 by direct activation, recruiting monocytes and promoting the polarization of M2d-like tumor-associated macrophages (TAMs). Upregulation of PD-L1 in LUAD having phosphomimetic FoxM1 facilitates immune evasion. In invasive LUAD with phosphomimetic FoxM1, IFITM1 is the most highly expressed through the activation of the STING-TBK1-IRF3 signaling, which enhances FoxM1-mediated signaling. Clinically, higher expression of FOXM1, PLK1, and IFITM1 is inversely correlated with the survival rate of advanced LUAD patients, providing a promising therapeutic strategy for the treatment of LUAD.

Conclusion
FoxM1-based therapy would be a potential therapeutic strategy for LUAD to reduce TAM polarization, immune escape, and metastasis, since FoxM1 functions as a genetic reprogramming factor reinforcing LUAD malignancy in the TME.
Protocol for a randomized controlled trial to reduce pediatric anesthesia emergence delirium by titration of sevoflurane anesthesia using brain function monitoring
Authors: Suzuki Yasuyuki , Miyasaka Kiyoyuki W. , Hayashi Kuniyoshi , Takahashi Osamu , Nagasaka Yasuko 
Published: November 2023

Abstract
Background
Emergence agitation or emergence delirium is a common complication of unknown etiology in pediatric anesthesia. Pediatric anesthesia emergence delirium (PAED) has been reported most commonly in younger children and may occur in about 30% of children up to 5–6 years old. Exposure to anesthetic agents may contribute to PAED, and we hypothesized that a management strategy to minimize exposure to volatile anesthetics may reduce PAED. Electroencephalography (EEG) signatures captured and displayed by brain function monitors during anesthesia change with concentration of sevoflurane and level of unconsciousness, and these EEG signatures may be used to inform titration of anesthetics.

Methods
A single-center, parallel-group, two-arm, superiority trial with a 1:1 allocation ratio will be performed to compare the incidence of PAED following standard sevoflurane anesthesia (maintained at 1.0MAC) and EEG-guided anesthesia (minimum concentration to sustain surgical anesthesia as determined by monitoring of EEG signatures). Participants between 1 and 6 years of age undergoing surgical procedures involving minimal postoperative pain will be randomly assigned to receive standard (n = 90) or EEG-guided (n = 90) anesthesia. PAED score will be assessed by a blinded observer in the PACU on arrival and after 5, 10, 15, and 30 min.

Discussion
Anesthesia management with proactive use of brain function monitoring is expected to reduce exposure to sevoflurane without compromising surgical anesthesia. We expect this reduced exposure should help prevent PAED. Routinely administering what may be considered standard levels of anesthetic such as 1.0 MAC sevoflurane may be excessive and potentially associated with unfavorable sequelae such as PAED.

Trial registration
Japan Registry of Clinical Trials (jRCT) jRCTs032210248. Prospectively registered on 17 August 2021.
The role of Culex territans mosquitoes in the transmission of Batrachochytrium dendrobatidis to amphibian hosts
Authors: Reinhold Joanna M. , Halbert Ella , Roark Megan , Smith Sierra N. , Stroh Katherine M. , Siler Cameron D. , McLeod David S. , Lahondère Chloé 
Published: November 2023

Abstract
Background
Mosquitoes are the deadliest organisms in the world, killing an estimated 750,000 people per year due to the pathogens they can transmit. Mosquitoes also pose a major threat to other vertebrate animals. Culex territans is a mosquito species found in temperate zones worldwide that feeds almost exclusively on amphibians and can transmit parasites; however, little is known about its ability to transmit other pathogens, including fungi. Batrachochytrium dendrobatidis (Bd) is a topical pathogenic fungus that spreads through contact. With amphibian populations around the world experiencing mass die-offs and extinctions due to this pathogen, it is critical to study all potential modes of transmission. Because Cx. territans mosquitoes are in contact with their hosts for long periods of time while blood-feeding, we hypothesize that they can transmit and pick up Bd.

Methods
In this study, we first assessed Cx. territans ability to transfer the fungus from an infected surface to a clean one under laboratory conditions. We also conducted a surveillance study of Bd infections in frogs and mosquitoes in the field (Mountain Lake Biological station, VA, USA). In parallel, we determined Cx. territans host preference via blood meal analysis of field caught mosquitoes.

Results
We found that this mosquito species can carry the fungus to an uninfected surface, implying that they may have the ability to transmit Bd to their amphibian hosts. We also found that Cx. territans feed primarily on green frogs (Rana clamitans) and bullfrogs (Rana catesbeiana) and that the prevalence of Bd within the frog population at our field site varied between years.

Conclusions
This study provides critical insights into understanding the role of amphibian-biting mosquitoes in transmitting pathogens, which can be applied to disease ecology of susceptible amphibian populations worldwide.

Graphical Abstract
Efficacy of nano encapsulated herbal extracts in the treatment of induced wounds in animal models: a systematic review protocol
Authors: Namuga Catherine , Ocan Moses , Kinengyere Alison A. , Richard Ssenono , Namisango Eve , Muwonge Haruna , Kirabira John Baptist , Lawrence Mugisha , Obuku Ekwaro A. 
Published: November 2023

Abstract
Background
Wounds inflict pain and affect human health causing high expenditure on treatment and management. Herbal crude extracts are used in traditional medicine as a treatment for wounds and other illnesses. However, the progress in the use of plants has been deterred due to their poor solubility and poor bioavailability requiring administration at high doses. It has been established that nanoencapsulation of herbal products in nanocarriers (size 1 nm to 100 nm) such as nanofibers, nanoparticles, nanospheres, and nanoliposomes greatly improves their efficacy. Due to their small and large surface area, nanocarriers are more biologically active, improve bioavailability, protect the drug from deterioration, and release it to the targeted site in a sustainable manner.

Aim
The review aims to collate and appraise evidence on the efficacy of nano encapsulated herbal extracts in the treatment of induced wounds in animal models.

Methods
The review will be protocol-driven and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis for Protocols (PRISMA-P) and protocol guidelines for systematic review and meta-analysis for animal intervention studies. The final review will be conducted and reported with reference to PRISMA 2020 statement. Studies will be searched in Pub Med, ProQuest, Web of Science, Medline Ovid, EMBASE, and Google Scholar. The PRISMA flow criteria will be followed in screening the articles for inclusion. Data extraction form will be designed in Excel spreadsheet 2013 and data extracted based on the primary and secondary outcomes. Risk of bias assessment will be done using SYRCLE’s risk of bias tool for animal studies. Data analysis will be done using narrative and quantitative synthesis.

Expected results
We hope to make meaningful comparisons between the effectiveness of the herb-loaded nanomaterials and other interventions (controls) in the selected studies, based on the primary and secondary outcome measures. We expect that these findings to inform clinical practice on whether preclinical studies show enough quality evidence on the efficacy and safety of herbal-loaded nanomaterials that can be translated into clinical trials and further research.

Systemic review registration
PROSPERO 330330. The protocol was submitted on the 11th of May 2022.
Serum growth differentiation factor-15 (GDF-15) is a biomarker of cardiac manifestations in children with COVID-19
Authors: Ishak Sally Raafat , Ganzoury Mona Mostafa El , Fouda Eman Mahmoud , Anwar Maha Ahmad , Kamal Amany Moustafa , Hamza Heba Mostafa , Bakry Nehad Ahmed 
Published: November 2023

Abstract
Background
COVID-19 leads to severe overwhelming inflammation in some patients mediated by various cytokines (cytokine storm) that usually leads to severe illness accompanied by cardiovascular manifestations. Growth differentiation factor-15 is a cytokine induced by stress and is associated with inflammatory processes in the lung and heart. This study aimed to measure the level of serum growth differentiation factor (GDF-15) in children with COVID-19 and to correlate it with the disease severity, cardiac affection, and the outcome of COVID-19.

Methods
A cross-sectional study was conducted on 144 children; 72 children diagnosed with COVID-19, and 72 healthy children. The severity of COVID-19 was assessed clinically, laboratory, and radiologically. Echocardiography was done within 48 h of admission for COVID-19 patients. Serum GDF-15 was measured by ELISA for both patients and controls.

Results
Serum GDF-15 level was significantly higher in patients with COVID-19 than in controls (p < 0.01). In COVID-19 patients with severe clinical grading, those who were hospitalized in the PICU, and those who died, serum GDF-15 levels were greater. individuals with cardiac manifestations exhibited significantly higher serum GDF-15 levels than individuals without them. In children with COVID-19, increased GDF-15 was correlated to poorer ejection fraction and higher INR using multivariate linear regression analysis.

Conclusion
Serum GDF-15 is a promising biomarker of COVID-19, it can be used as a predictor of cardiac manifestations in children with COVID-19 and severe disease.
Ultrasound guidance practices used for the placement of vascular accesses in intensive care units: an observational multicentre study
Authors: van der Mee-Marquet Nathalie , Valentin Anne-Sophie , Duflot Isabelle , Farizon Mathilde , Petiteau Agnès ,   the collaboration group SPIADI, Allaire Alexandra , Sovic Elise Balestrat , Barbut Frédéric , Barthelemy Patrick , Berger Pierre , Betti Marie-Camille , Blanié Mathilde , Cattaneo Isabelle , Cecille Agnès , Chakaroun Hiba , Cholley Anne-Clémence , David Marion , Davy Aude , Delhomme Joël , Duval Catherine , Edouard Stéphanie , Gabriele Laure , Gallais Séverine , Gerbier Colette , Manquat Gilles , Goldstein Valérie , Gourdon Florence , Joron Sylvie , Kayoulou-Bour Anne-Marie , Laethem Gratienne , Lemann Florence , Lemenager Martine , Lier Marie-Laure , Mesnil Malcie , Mertel Nadine , Morange Virginie , Mottet Benoit , Niot Stella , Ouzani Souad , Perdrix Christophe , Renaud Amélie , Richaud Clémence , Rougier Catherine , Tarsac Maryline , Venelle Myriam , Vidal Isabelle 
Published: November 2023

Abstract
Background
Central catheters expose ICU patients at risk of catheter-related bloodstream infections. A mechanism by which these infections occur is the contamination of the catheter during its insertion if aseptic techniques are not strictly applied. Recent studies suggest that the use of ultrasound guidance (USG) may increase the risk of catheter contamination during insertion. We assessed current practices regarding the use of USG during catheter insertion, with a focus on identifying breaches of the surgical asepsis required for this invasive procedure.

Methods
In 26 intensive care units, we evaluated the use of USG during catheter insertion, using a questionnaire addressed to intensivists and direct observation of their practices.

Results
We analyzed 111 questionnaires and 36 observations of intensivists placing catheters. The questionnaires revealed that 88% of intensivists used USG for catheter insertion. Among those using USG, 56% had received specific training, 17% benefited from specific recommendations, 76% marked the insertion site before skin antisepsis, and during catheter insertion, 96% used sterile gel and 100% used a sterile sheath and sterile gloves. We identified potential deviations from strict aseptic technique, including contact between the sheath and the needle (19.4%), handling of the US system during catheter insertion (2.8%), and use of sterile devices, where they were not yet necessary (during the marking site or skin antisepsis), resulting in their contamination at the time of catheter insertion.

Conclusions
Interventions aimed at ensuring compliance with measures to prevent CRBs should be organized to prevent an increase in infections associated with US-guided catheter insertion.