bluuebunny/crossref_metadata_2025 huggingface dataset:
3D printing technology to produce intraoral stents for head and neck radiotherapy: A scoping review
Authors: Mota Maria Emília , Schroter Gabriella Torres , Moreira Maria Stella , Alves Fábio Abreu , Jaguar Graziella Chagas , Lopes Rodrigo Nascimento
Published: November 2023

Introduction

Radiotherapy remains one of the main treatments for head and neck cancer; however, it is accompanied by acute and chronic adverse effects. Use of three‐dimensional (3D) oral stents to modulate radiation intensity to specific target areas have been developed to minimize these adverse effects. This study aimed to present a scoping review of studies published on 3D printing of oral stents and their clinical applicability.

Methods

MEDLINE/Pubmed, Scopus, Web of Science and CENTRAL Cochrane data bases were searched, studies selected, and data collected by three independent reviewers up to December 2022. The review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta‐analysis—Extension for Scoping Reviews (PRISMA‐ScR).

Results

The search resulted in 404 studies and 5 articles fulfilled the eligibility criteria and were considered for this review. Three‐dimensional printed intraoral stents were produced for 56 patients with indication for radiotherapy. 3D‐printed stents were well‐tolerated by all tested patients and demonstrated great reproducibility of maxillomandibular relation, required less time for production and lower cost to manufacture. Two studies showed great protection of healthy tissues with 3D‐printed stents during radiotherapy.

Conclusions

Three‐dimensional printing is promising for production of intraoral stents, however, more studies are needed to improve the technique and further investigate the safety and prevention of oral toxicities from radiotherapy.
Categoria de Propriedade Ancestral nas Decisões da Corte Interamericana de Direitos Humanos Acerca de Contenciosos Relativos a Terras Indígenas no Paraguai
Authors: Amorim Vieira Marcello , Ribeiro Júnior Humberto
Published: November 2023

O presente artigo analisa a categoria de propriedade ancestral, explorando-se as sentenças dos casos Comunidade Indígena Yakye Axa vs. Paraguai, Comunidade Indígena Sawhoyamaxa vs. Paraguai e Xákmok Kásek vs. Paraguai na Corte Interamericana de Direitos Humanos (CIDH). A partir do aporte dos estudos decoloniais, utilizando-se ideias legadas por Aníbal Quijano, Boaventura de Sousa Santos, Catherine Walsh, Enrique Dussel e Santiago Castro-Gómez, buscou-se problematizar a dinâmica de trabalho das instituições jurídicas paraguaias, que reproduziam camadas do chamado pensamento abissal, bem como confrontar o modelo de interpretação nacionalista com a tendência internacionalista construída pela CIDH. Tal investigação levou a resultados que refletem a necessidade de incorporação no âmbito estatal dos mecanismos plurais de interpretação normativa, bem como da consideração de precedentes em patamar de igualdade com o conteúdo positivado em âmbito de direito interno, elucidando também os desafios ainda existentes para se vislumbrar práticas sociais interculturais no que tange à participação indígena nas decisões referentes às suas demandas.
PALAVRAS-CHAVE: Propriedade ancestral; Corte Interamericana de Direitos Humanos; Direitos Indígenas; Paraguai; Decolonialidade
Domestic work and health on trial:
Authors: Fonseca Maria Hemília , De Quintana Figueiredo Pasqualeto Olívia , Lopes Scodro Catharina
Published: November 2023

In Brazil, domestic workers had an unfavorable legal treatment in relation to other workers for a long time. This legal inequality was mitigated with Constitutional Amendment (EC) 72/2013 – which extended rights related to workers’ health for the group – and Complementary Law (LC) 150/2015 – focused on, above all, on rights related to working hours. This research investigated the recognition of domestic workers’ health rights in the Brazilian labor Judiciary, by using judicial decisions related to domestic work and health, considering the period of COVID-19 pandemic. The investigation used a qualitative approach and an inductive reasoning, with a bibliographic and documental study, based on the analysis of judicial decisions.
The Essential in Essential Facilities
Authors: Cabral Pires Alves Camila , Da Rocha Diandra Carolina , Pontual Ribeiro Eduardo , Pondé João Luiz , Delorme Prado Luiz Carlos , Puccioni de Oliveira Lyra Marcos
Published: November 2023

The paper examines the applicability of the Essential Facilities Doctrine (EFD) in the context of competition policy in digital platform markets. It begins by comparing this doctrine with the traditional antitrust approach to anti-competitive practices such as tying and raising rivals' costs. It demonstrates that both approaches aim to address antitrust harm resulting from the extension of market power into additional competitive environments. However, the EFD also considers specific conditions that warrant non-discriminatory access obligations and potential regulatory intervention. This comparative analysis of similarities and differences is employed to address antitrust issues in digital platform markets, given the existence of bottlenecks and gatekeepers that can exploit market power. The paper uses the Buscapé v. Google (Google Shopping) case, which was examined by Brazilian antitrust authority in 2019, as an illustrative example to highlight the possible approaches to these antitrust concerns.
KEYWORDS: Essential Facilities Doctrine; Refuse to Deal; Market Power Leveraging; Digital Platforms, Antitrust Policy.
Direito Do Trabalho e Configurações Institucionais: Um Balanço Sobre Normas, Práticas e Concepções em Disputa
Authors: Grillo Sayonara , Artur Karen , Casteli Nunzia
Published: November 2023

O artigo visa contribuir com as reflexões contemporâneas que articulam Direito do Trabalho e Mudança, em especial mapear os debates sobre (a) reformas e contrarreformas trabalhistas, (b) as demandas por novos horizontes nas regulações laborais em diferentes espaços normativos, (c) atuação das instituições do sistema trabalhista e sua contribuição para a efetividade e eficácia dos direitos trabalhistas, (d) bem como sobre as disputas sobre as políticas públicas para combater o trabalho precário, reduzir a informalidade e regular novas formas de trabalho e modos de trabalhar que são impulsionados pela natureza cambiante da organização produtiva no capitalismo e regulados por diferentes opções políticas. Para alcançar esse objetivo, apresenta o “Dossiê Direito do Trabalho e Configurações Institucionais: normas, práticas e concepções em disputa”. O dossiê pretendeu problematizar os processos de mudança produtiva, reformas institucionais, alterações legislativas, mutações constitucionais, giros hermenêuticos e jurisprudenciais tanto os que contribuem para a erosão e desgaste dos eixos estruturantes do Direito do Trabalho, reduzindo a eficácia e a efetividade de suas normas, bem como aqueles que, em contrapartida, buscam reforçar os propósitos de um ramo jurídico voltado para as necessidades de proteção dos direitos dos trabalhadores, do controle do poder econômico e dos poderes empregatício e algorítmico e de afirmação dos direitos humanos de todas as pessoas que trabalham. Assim, o artigo dialoga com os estudos do dossiê, que são focados em debates nacionais e internacionais em torno das construções e sentidos de uma regulação laboral comprometida com a democracia e com o regime de direitos. Como resultado, tem-se a afirmação da regulação pública, engajada em valores de justiça social e solidariedade.

PALAVRAS-CHAVE: Direito do Trabalho; Regulação Pública do Trabalho; Instituições trabalhistas; Reformas Trabalhistas; Capitalismo de Plataforma.
Role of brain‐derived neurotrophic factor in endotoxaemia‐induced acute lung injury
Authors: Shi Jinye , Song Shuang , Wu Kaixuan , Liang Gui , Wang Aizhong , Xu Xiaotao
Published: November 2023

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), which is a pulmonary manifestation of a systemic reactive inflammatory syndrome, is a serious disease with high mortality, and sepsis is an important risk factor in the development of ALI. Brain‐derived neurotrophic factor (BDNF) is a member of the nerve growth factor family. It plays an essential role in the regulation of the modification of synaptic efficacy and brain metabolic activity and enhances neuronal survival. However, the role and underlying mechanism of BDNF in sepsis‐induced ALI remain unclear. Here, we sought to observe the expression of BDNF in the lung tissues of mice. C57BL/6J mice were divided randomly into two groups: saline (n = 4) and lipopolysaccharide (LPS) (n = 4). We found that BDNF expression was elevated in the lung tissues of septic mice. Furthermore, we found that BDNF colocalized with aquaporin 5, a marker for type I alveolar epithelial cells, by immunofluorescence staining. In addition, we also found that tropomyosin‐related kinase B, the specific receptor of BDNF, colocalized with surfactant protein C, a marker for type II alveolar epithelial cells, by immunofluorescence staining. Finally, the present study indicated that BDNF may alleviate excessive LPS‐induced autophagy in alveolar epithelial cells. Overall, we hypothesize that BDNF expression increases in the lung tissues of septic mice as a compensatory mechanism to ameliorate sepsis‐induced ALI by inhibiting excessive alveolar epithelial cell autophagy.
Reconstruction Algorithm for Complex Dexel Models Based on Composite Block Partition
Authors: Yu Haiwen , Wu Dianliang , Xu Hanzhong
Published: November 2023

In machining simulations, dexel models are often used to represent objects to achieve high accuracy and real-time performance. However, this approach leads to the loss of original surface information and topological relationships, thereby affecting the visualization effect of simulations. Furthermore, existing reconstruction methods have the drawbacks of generalization or redundancy. To reconstruct the surface of dexel models efficiently and accurately, this paper proposes an algorithm based on “composite block” partition, which converts the dexel model into a polyhedral model. The algorithm begins by partitioning the entire dexel model within the grids into several composite blocks based on the “Connectivity Principle” and generating their end faces. Subsequently, the transitional zone’s surface is reconstructed based on the connectivity relationships of the boundaries of composite blocks. Finally, an optimization process refines the boundaries to generate smoother side faces at a low computational cost. The paper first validates the algorithm’s reconstruction capability and the effectiveness of edge refinement through the reconstruction of various dexel models with different precision levels. It is observed that edge refinement does not introduce excessive additional computation, doubling the overall efficiency compared to existing algorithms. Furthermore, by changing model volumes and performing separate reconstructions, it’s noted that as the volume increases, the incremental growth in conversion time gradually decreases. This makes the algorithm particularly suitable for reconstructing large-scale complex dexel models. Finally, the application of this algorithm in virtual-real simulation systems and industrial digital twin systems is briefly introduced.
Design Space Exploration and Evaluation Using Margin-Based Trade-Offs
Authors: Al Handawi Khalil , Brahma Arindam , Wynn David C. , Kokkolaras Michael , Isaksson Ola
Published: November 2023

Design space exploration and margin analysis can inform critical decisions early in engineering design, helping to handle the uncertainties of early design while ensuring design performance. In practice, the complexity of many products makes such decision-making challenging. This paper addresses the challenge with a new design framework that relies on the margin value method to evaluate sets of concepts that are combinatorially generated from an enhanced function-means tree. The basis for concept comparison is the margin value in each design alternative. The margin value method is expanded to address a broad class of design problems by using surrogate models and novel metrics for evaluating different conceptual alternatives. Visualization tools are introduced to support the evaluations. The efficacy of the framework is demonstrated using the design of a structural aero-engine component involving simulation models and uncertain load specifications. Overall, this paper shows how design concepts can be compared objectively and distilled to a set of alternatives that would retain their values throughout product development.
Structural Designs of Novel Deployable Polyhedral Grippers for Noncontact Capturing Missions
Authors: Tang Ruijie , Meng Qizhi , Xie Fugui , Liu Xin-Jun , Wang Jinsong
Published: November 2023

Deployable polyhedral grippers have attracted increasing attention for their priority in noncontact capturing missions. Enrichment of these grippers may benefit the conduction of various capturing tasks. In this paper, novel deployable polyhedral grippers are presented. A design flow is proposed for the structural designs of diverse grippers. The core problem during the construction is reducible to the structural designs and combination of multiple synchronously deployable modules. Each module, containing three faces connected by two revolute joints, can realize one-degree-of-freedom deployment. Type synthesis of synchronously deployable modules adopting different layouts of revolute joints is conducted. The mobility and kinematics of these modules are analyzed to verify the achieved motion. As examples, four deployable polyhedral grippers based on different polyhedrons and deployment diagrams are presented. The deployment performance of the prototype proves the validity of the proposed design method and exhibits the potential of these deployable polyhedral grippers for diverse capturing missions.
RANKL/RANK is required for cytokine-induced beta cell death; osteoprotegerin, a RANKL inhibitor, reverses rodent type 1 diabetes
Authors: Kondegowda Nagesha Guthalu , Filipowska Joanna , Do Jeong-su , Leon-Rivera Nancy , Li Rosemary , Hampton Rollie , Ogyaadu Selassie , Levister Camilla , Penninger Josef M. , Reijonen Helena , Levy Carol J. , Vasavada Rupangi C.
Published: November 2023

Treatment for type 1 diabetes (T1D) requires stimulation of functional β cell regeneration and survival under stress. Previously, we showed that inhibition of the RANKL/RANK [receptor activator of nuclear factor kappa Β (NF-κB) ligand] pathway, by osteoprotegerin and the anti-osteoporotic drug denosumab, induces rodent and human β cell proliferation. We demonstrate that the RANK pathway mediates cytokine-induced rodent and human β cell death through RANK-TRAF6 interaction and induction of NF-κB activation. Osteoprotegerin and denosumab protected β cells against this cytotoxicity. In human immune cells, osteoprotegerin and denosumab reduce proinflammatory cytokines in activated T-cells by inhibiting RANKL-induced activation of monocytes. In vivo, osteoprotegerin reversed recent-onset T1D in nonobese diabetic/Ltj mice, reduced insulitis, improved glucose homeostasis, and increased plasma insulin, β cell proliferation, and mass in these mice. Serum from T1D subjects induced human β cell death and dysfunction, but not α cell death. Osteoprotegerin and denosumab reduced T1D serum–induced β cell cytotoxicity and dysfunction. Inhibiting RANKL/RANK could have therapeutic potential.
Severe acute malnutrition promotes bacterial binding over proinflammatory cytokine secretion by circulating innate immune cells
Authors: Phiri Tracy N. , Mutasa Kuda , Rukobo Sandra , Govha Margaret , Mushayanembwa Patience , Mwakamui Simutanyi , Haider Tafhima , Zyambo Kanekwa , Dumbura Cherlynn , Tome Joice , Runodamoto Thompson , Chidamba Leah , Majo Florence D. , Ngosa Deophine , Chandwe Kanta , Kapoma Chanda , Mwapenya Benjamin , Mufukari Wadzanai , Sturgeon Jonathan P. , Robertson Ruairi C. , Smuk Melanie , Ntozini Robert , Nathoo Kusum , Amadi Beatrice , Kelly Paul , Bwakura-Dangarembizi Mutsa , Prendergast Andrew J. , Bourke Claire D.
Published: November 2023

Children with severe acute malnutrition (SAM) have high infectious mortality and morbidity, implicating defects in their immune defenses. We hypothesized that circulating innate immune cells from children (0 to 59 months) hospitalized with SAM in Zambia and Zimbabwe (
n
= 141) have distinct capacity to respond to bacteria relative to adequately nourished healthy controls (
n
= 92). SAM inpatients had higher neutrophil and monocyte
Escherichia coli
binding capacity but lower monocyte activation and proinflammatory mediator secretion in response to lipopolysaccharide or heat-killed
Salmonella typhimurium
than controls. Among SAM cases, wasting severity was negatively associated with cytokine secretion, children with HIV had lower monocyte activation, and the youngest children released the least myeloperoxidase upon stimulation. Inpatient bacterial binding capacity and monocyte activation were associated with higher odds of persistent SAM at discharge, a risk factor for subsequent mortality. Thus, SAM shifts innate immune cell function, favoring bacterial containment over proinflammatory activation, which may contribute to health deficits after discharge.
Valley-conserved topological integrated antenna for 100-Gbps THz 6G wireless
Authors: Jia Ridong , Kumar Sonu , Tan Thomas Caiwei , Kumar Abhishek , Tan Yi Ji , Gupta Manoj , Szriftgiser Pascal , Alphones Arokiaswami , Ducournau Guillaume , Singh Ranjan
Published: November 2023

The topological phase revolutionized wave transport, enabling integrated photonic interconnects with sharp light bending on a chip. However, the persistent challenge of momentum mismatch during intermedium topological mode transitions due to material impedance inconsistency remains. We present a 100-Gbps topological wireless communication link using integrated photonic devices that conserve valley momentum. The valley-conserved silicon topological waveguide antenna achieves a 12.2-dBi gain, constant group delay across a 30-GHz bandwidth and enables active beam steering within a 36° angular range. The complementary metal oxide semiconductor–compatible valley-conserved devices represent a major milestone in hybrid electronic-photonic-based topological wireless communications, enabling terabit-per-second backhaul communication, high throughput, and intermedium transport of information carriers, vital for the future of communication from the sixth to X generation.
Shifting the trajectory of therapeutic development for neurological and psychiatric disorders
Authors: Krainc Dimitri , Martin William J. , Casey Bradford , Jensen Frances E. , Tishkoff Sarah , Potter William Z. , Hyman Steven E.
Published: November 2023

Clinical trials for central nervous system disorders often enroll patients with unrecognized heterogeneous diseases, leading to costly trials that have high failure rates. Here, we discuss the potential of emerging technologies and datasets to elucidate disease mechanisms and identify biomarkers to improve patient stratification and monitoring of disease progression in clinical trials for neuropsychiatric disorders. Greater efforts must be centered on rigorously standardizing data collection and sharing of methods, datasets, and analytical tools across sectors. To address health care disparities in clinical trials, diversity of genetic ancestries and environmental exposures of research participants and associated biological samples must be prioritized.
Involvement of endoplasmic reticulum and histone proteins in immunomodulation by TLR4-interacting SPA4 peptide against
Escherichia coli
Authors: Awasthi Shanjana , Singh Bhupinder , Ramani Vijay , Godbole Nachiket M. , King Catherine
Published: November 2023

Pulmonary host defense is critical for the control of lung infection and inflammation. An increased expression and activity of Toll-like receptor 4 (TLR4) induce phagocytic uptake/clearance and inflammation against Gram-negative bacteria. In this study, we addressed the mechanistic aspect of the immunomodulatory activity of the TLR4-interacting SPA4 peptide (amino acid sequence GDFRYSDGTPVNYTNWYRGE) against
Escherichia coli
. Binding of the SPA4 peptide to bacteria and direct anti-bacterial effects were investigated using flow cytometric, microscopic, and bacteriological methods. The bacterial uptake and inflammatory cytokine response were studied in dendritic cells expressing endogenous basal level of TLR4 or overexpressing TLR4. The subcellular distribution and co-localization of TLR4 and bacteria were investigated by immunocytochemistry. Furthermore, we studied the cellular expression and co-localization of endoplasmic reticulum (ER) molecules (calnexin and ER membrane protein complex subunit 1; EMC1) with lysosomal-associated membrane protein 1 (LAMP1) in cells infected with
E. coli
and treated with the SPA4 peptide. Simultaneously, the expression of histone H2A protein was quantitated by immunoblotting. Our results demonstrate no binding or direct killing of the bacteria by SPA4 peptide. Instead, it induces the uptake and localization of
E. coli
in the phagolysosomes for lysis and simultaneously suppresses the secreted levels of TNF-α. Overexpression of TLR4 further augments the pro-phagocytic and anti-inflammatory activity of SPA4 peptide. A time-dependent change in subcellular distribution of TLR4 and an increased co-localization of TLR4 with
E. coli
in SPA4 peptide-treated cells suggest an enhanced recognition and internalization of bacteria in conjugation with TLR4. Furthermore, an increased co-localization of calnexin and EMC1 with LAMP1 indicates the involvement of ER in pro-phagocytic activity of SPA4 peptide. Simultaneous reduction in secreted amounts of TNF-α coincides with suppressed histone H2A protein expression in the SPA4 peptide-treated cells. These results provide initial insights into the plausible role of ER and histones in the TLR4-immunomodulatory activity of SPA4 peptide against Gram-negative bacteria.
Pathogenesis of
Achromobacter xylosoxidans
respiratory infections: colonization, persistence, and transcriptome profiling in synthetic cystic fibrosis sputum medium
Authors: Billiot Caitlin E. , Novak Lea , McDaniel Melissa S. , Lindgren Natalie R. , Swords W. Edward
Published: November 2023

Cystic fibrosis (CF) is a genetic disease affecting epithelial ion transport, resulting in thickened mucus and impaired mucociliary clearance. Persons with CF (pwCF) experience life-long infections of the respiratory mucosa caused by a diverse array of opportunists, which are leading causes of morbidity and mortality. In recent years, there has been increased appreciation for the range and diversity of microbes causing CF-related respiratory infections. The introduction of new therapeutics and improved detection methodology has revealed CF-related opportunists such as
Achromobacter xylosoxidans
(
Ax
).
Ax
is a Gram-negative bacterial species which is widely distributed in environmental sources and has been increasingly observed in sputa and other samples from pwCF, typically in patients in later stages of CF disease. In this study, we characterized CF clinical isolates of
Ax
and tested colonization and persistence of
Ax
in respiratory infection using immortalized human CF respiratory epithelial cells and BALB/c mice. Genomic analyses of clinical
Ax
isolates showed homologs for factors including flagellar synthesis, antibiotic resistance, and toxin secretion systems.
Ax
isolates adhered to polarized cultures of CFBE41o- human immortalized CF bronchial epithelial cells and caused significant cytotoxicity and depolarization of cell layers.
Ax
colonized and persisted in mouse lungs for up to 72 h post infection, with inflammatory consequences that include increased neutrophil influx in the lung, lung damage, cytokine production, and mortality. We also identified genes that are differentially expressed in synthetic CF sputum media. Based on these results, we conclude that
Ax
is an opportunistic pathogen of significance in CF.
miR-155 facilitates the synergistic replication between avian leukosis virus subgroup J and reticuloendotheliosis virus by targeting a dual pathway
Authors: Xue Jingwen , Zhou Defang , Zhou Jing , Du Xusheng , Zhang Xinyue , Liu Xiaoyang , Ding Longying , Cheng Ziqiang
Published: November 2023

Co-infection of avian leukosis virus subgroup J (ALV-J) and reticuloendotheliosis virus (REV) in poultry flocks induces synergistic replication, which worsens immunosuppression, growth inhibition, and increased mortality. However, the synergistic replication mechanism between ALV-J and REV is still not fully understood. We showed that microRNA-155 (miR-155) targets a dual pathway, PRKCI-MAPK8 and TIMP3-MMP2, which interacts with the U3 region of ALV-J and REV to promote synergistic replication between ALV-J and REV. Initially, we found that the RNA levels of ALV-J and REV increased significantly in ALV-J and REV co-infected cells and tissues compared with mono-infected cells and tissues. Next, miRNAomics showed that ALV-J and REV synergistically increased miR-155 levels. In co-infected cells, miR-155 promoted synergistic replication of ALV-J and REV. All structural proteins of the two viruses activated the expression of miR-155, especially gag proteins, rather than insertional activation. Proteomic study of cells co-infected with ALV-J and REV and transfected with miR-155 indicated that miR-155 directly suppressed PRKCI and TIMP3 and that PRKCI directly prevented MAPK8 expression, while TIMP3 directly interfered MMP2 expression. We also found that MAPK8 and MMP2 co-interacted with ALV-J and REV’s U3 to enhance synergistic replication. In conclusion, ALV-J and REV synergistically activate miR-155, facilitating the synergistic replication of ALV-J and REV by PRKCI-MAPK8 and TIMP3-MMP2 dual-pathway interaction with the U3 region of ALV-J and REV. This discovery will assist in explaining how two retroviruses replicate synergistically.

IMPORTANCE

The synergy of two oncogenic retroviruses is an essential phenomenon in nature. The synergistic replication of ALV-J and REV in poultry flocks increases immunosuppression and pathogenicity, extends the tumor spectrum, and accelerates viral evolution, causing substantial economic losses to the poultry industry. However, the mechanism of synergistic replication between ALV-J and REV is still incompletely elusive. We observed that microRNA-155 targets a dual pathway, PRKCI-MAPK8 and TIMP3-MMP2, interacting with the U3 region of ALV-J and REV, enabling synergistic replication. This work gives us new targets to modulate ALV-J and REV’s synergistic replication, guiding future research on the mechanism.
Hypoxia and HIF-1α promote lytic
de novo
KSHV infection
Authors: Lee See-Chi , Naik Nenavath Gopal , Tombácz Dóra , Gulyás Gábor , Kakuk Balázs , Boldogkői Zsolt , Hall Kevin , Papp Bernadett , Boulant Steeve , Toth Zsolt
Published: November 2023

The impact of different stress conditions on the oncogenic Kaposi’s sarcoma-associated herpesvirus (KSHV) primary infection that can occur
in vivo
remains largely unknown. We hypothesized that KSHV can establish a latency or lytic cycle following
de novo
infection, depending on the conditions of the cellular environment. Previous studies showed that hypoxia is a natural stress condition that promotes lytic reactivation and contributes to KSHV pathogenesis, but its effect on
de novo
KSHV infection is unknown. To test the effect of hypoxia on KSHV infection, we infected cells under normoxia and hypoxia, performed a comparative analysis of viral gene expression and viral replication, and tested chromatinization of the KSHV genome during infection. We found that hypoxia induces viral lytic gene expression and viral replication following
de novo
infection in several biologically relevant cell types, in which the virus normally establishes latency under normoxia. We also found that hypoxia reduces the level of repressive heterochromatin and promotes the formation of a transcriptionally permissive chromatin on the incoming viral DNA during infection. We demonstrate that silencing hypoxia-inducible factor-1α (HIF-1α) during hypoxia abrogates lytic KSHV infection, while the overexpression of HIF-1α under normoxia is sufficient to drive lytic KSHV infection. Also, we determined that the DNA-binding domain and the N-terminal but not the C-terminal transactivation domain of HIF-1α are required for HIF-1α-induced lytic gene expression. Altogether, our data indicate that HIF-1α accumulation, which can be induced by hypoxia, prevents the establishment of latency and promotes lytic KSHV infection following primary infection.

IMPORTANCE

The current view is that the default pathway of Kaposi’s sarcoma-associated herpesvirus (KSHV) infection is the establishment of latency, which is a prerequisite for lifelong infection and viral oncogenesis. This view about KSHV infection is supported by the observations that KSHV latently infects most of the cell lines cultured
in vitro
in the absence of any environmental stresses that may occur
in vivo
. The goal of this study was to determine the effect of hypoxia, a natural stress stimulus, on primary KSHV infection. Our data indicate that hypoxia promotes euchromatin formation on the KSHV genome following infection and supports lytic
de novo
KSHV infection. We also discovered that hypoxia-inducible factor-1α is required and sufficient for allowing lytic KSHV infection. Based on our results, we propose that hypoxia promotes lytic
de novo
infection in cells that otherwise support latent infection under normoxia; that is, the environmental conditions can determine the outcome of KSHV primary infection.
Complete mitochondrial genome sequence of the Agaricomycetes brown rot fungus
Fomitopsis pinicola
isolate FBCC1181
Authors: Österman-Udd Janina , Lundell Taina Kristina
Published: November 2023

The mitochondrial genome of the brown rot fungus
Fomitopsis pinicola
isolate FBCC 1181 is a 66.5 kbp circular chromosome. It contains 64 predicted genes, including a set typical for Basidiomycota Agaricomycetes mitogenomes. Introns of
cox
and
cob
genes contain several homing endonucleases of both LAGLIDADG and GIY-YIG types.
Draft genome sequence of multidrug-resistant
Citrobacter portucalensis
BAU_133-2 strain isolated from a domestic duck (
Anas platyrhynchos domesticus
) in Bangladesh
Authors: Ahmed Tarana , Islam Md. Saiful , Nuruzzaman Mohammad , Sadekuzzaman Mohammad , Kabir S. M. Lutful , Rahman Md. Tanvir , Khan Md. Shahidur Rahman
Published: November 2023

We announce the genome sequence of the
Citrobacter portucalensis
BAU_133-2 strain isolated from a domestic duck. Our assembled genome contained a length of 4.8 Mb, 110.0× genome coverage, 51.91% of an average GC content, 1 plasmid, 1 CRISPR array, 8 prophages, 27 antibiotic resistance genes, and 75 virulence factor genes.
Engineered probiotic
Lactobacillus plantarum
WCSF I for monitoring and treatment of
Staphylococcus aureus
infection
Authors: Li Haoran , Jia Minjun , Qi Qingsheng , Wang Qian
Published: November 2023

Lactobacillus plantarum
is one of the most thoroughly researched species of the genus
Lactobacillus
, which possesses the characteristics of easy genetic transformation, high-density growth, and high intestinal tract survival.
L. plantarum
has been proven to play a potential role as a probiotic delivery vector.
Staphylococcus aureus
is a common Gram-positive pathogenic bacterium. It uses an autoinducer peptide (AIP) produced by its Agr quorum-sensing (AgrQS) system to sense the population density. Using the quorum-sensing mechanism exclusive to
S. aureus
, we constructed an AgrQS system in
L. plantarum
WCSF induction and killing modules based on AIP sensing and regulation so that
L. plantarum
could effectively eliminate
S. aureus
when detecting exogenous AIP at nanomolar concentrations. By optimizing the expression strength of the two-component system AgrAC using different
L. plantarum
-derived promoters and replacing the core promoter of the AgrA-activating promoter, the activation strength of AgrQS increased from the initial 1.2-fold to 5.3-fold. By introducing the signal peptide N20-guided lysostaphin aureus protein, engineered
L. plantarum
was able to effectively control the release of lysostaphin aureus protein and inhibit the growth of
S. aureus
. For the first time, engineered
L. plantarum
can detect and treat
S. aureus
infection, laying the groundwork for the future development of engineered probiotics for the monitoring and therapy of intestinal pathogens.

IMPORTANCE

Bacterial infection and the emergence of drug-resistant strains are major problems in clinical treatment.
Staphylococcus aureus
, which typically infects the skin and blood of animals, is also a potential intestinal pathogen that needs to be addressed by the emergence of a new treatment approach. Probiotic therapy is the most likely alternative to antibiotic therapy to solve the problem of bacterial drug resistance in clinical practice. In this study, the engineered
Lactobacillus plantarum
can not only sense the signal AIP to detect
S. aureus
but also kill
S. aureus
by secreting the lysostaphin enzyme. Our strategy employed an Agr quorum-sensing genetic circuit to simultaneously detect and treat pathogenic bacteria, which provided a theoretical possibility for solving practical clinical bacterial infection cases in the future.
The fourth COVID-19 vaccine dose increased the neutralizing antibody response against the SARS-CoV-2 Omicron (B.1.1.529) variant in a diverse Brazilian population
Authors: Pires Farias Jéssica , Andreata-Santos Robert , Dalety da Silva Brito Ruth , Silva Souza Milena , Moreira Costa Fogaça Mayanna , Ramos Pinheiro Josilene , Ferreira da Cruz Edgar , Liang Willian , Simões Rafael da Conceição , Barros Luiz Wilson , Birbrair Alexander , Oliveira Vidal Paloma , Terzi Maricato Juliana , Torres Braconi Carla , Ferreira Luís Carlos de Souza , Ramos Janini Luiz Mário , Amorim Jaime Henrique
Published: November 2023

Most of the original immunization regimens against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were composed of two doses, followed by a subsequent third booster dose to control the Omicron variant and hence coronavirus disease 2019 (COVID-19). However, most data generated regarding the fourth dose were not based on the general population. Therefore, this study aimed to verify the effect of the fourth COVID-19 vaccine dose in a diverse Brazilian population. This retrospective observational study was conducted between May and September 2022. We gathered data on the vaccine regimens and COVID-19 serologic status from 266 healthy volunteers who received three or four vaccine doses, as well as COVID-19 diagnosis and viral genome sequencing from 457 patients with flu-like symptoms. In addition, we conducted immunoinformatic analysis to assess the conserved epitopes in the locally circulating viruses. We showed that the fourth dose did not increase the serum levels of antiviral antibodies, as measured by enzyme-linked immunosorbent assay. However, it significantly increased neutralizing antibody (NAb) titers against the Omicron variant. All viral sequences generated in this study were Omicron subvariants, mainly B.A.5.1. Notably, most NAb epitopes present in the wild-type SARS-CoV-2 were not detected among the circulating Omicron subvariants. None of the volunteers who received the third or fourth doses presented COVID-19 for at least 1 year before the study period. Altogether, these results indicate that the fourth vaccine dose increases the serum levels of NAbs that recognize highly conserved epitopes in Omicron subvariants.

IMPORTANCE

Several additional COVID-19 vaccine doses were administered in the Brazilian population to prevent the disease caused by the B.1.1.529 (Omicron) variant. The efficacy of a third dose as a booster is already well described. However, it is important to clarify the humoral immune response gain induced by a fourth dose. In this study, we evaluate the effect of the fourth COVID-19 vaccine dose in a diverse Brazilian population, considering a real-life context. Our study reveals that the fourth dose of the COVID-19 vaccine increased the neutralizing antibody response against SARS-CoV-2 Omicron and significantly contributed in the reduction of the disease caused by this variant.
High-resolution chronostratigraphy of late Mesozoic sequences in northern North China: Implications for the linkages among intracontinental orogeny, volcanism, Jehol Biota, and Pacific plate subduction
Authors: Ma Qiang , Zhong Yuting , Yin Qingzhu , Huyskens Magdalena H. , Ma Liang , Xia Xiaoping , Meng Qing-Ren , Zhou Zhong-He , Xu Yi-Gang
Published: November 2023

Subduction of the paleo-Pacific plate during the late Mesozoic is thought to have been responsible for the destruction of the North China craton, manifested by intense volcanism, lithospheric deformation, and dramatic changes in surface morphology and terrestrial ecosystems. However, the timing and correlations of these consequential events remain obscure. This issue was addressed here by carrying out a high-resolution geochronologic study on the Upper Jurassic–Lower Cretaceous sequences of the Luanping basin, northern Hebei Province, China. Secondary ion mass spectrometry (SIMS) and chemical abrasion–isotope dilution–isotope ratio mass spectrometry (CA-ID-IRMS) zircon U-Pb ages from samples near the boundaries of the stratigraphic units help to redefine the chronostratigraphic framework of this basin and more importantly reveal that the second phase of the Yanshanian orogeny, representing a tectonic transition from flat to steep subduction of the paleo-Pacific plate, occurred within 0.87 ± 0.10 m.y. between 134.162 ± 0.091 Ma and 133.295 ± 0.043 Ma. Crustal extension then followed and resulted in development of rift basins and vigorous volcanism. The Jehol Biota came into being in Lower Cretaceous successions formed after ca. 130 Ma. The late Mesozoic Luanping basin therefore records how the subduction of the paleo-Pacific plate drove intracontinental orogeny, volcanism, basin development, and ecosystem evolution.
Incidental seromucinous hamartoma of the anterior nasal cavity presenting after episode of vestibular neuritis
Authors: Raviprasad Abheek G , Malaty John , Wynne Brianna , Orlando Frank A
Published: November 2023

A woman in her 70s presented to primary care clinic complaining of acute onset dizziness for 1 day that was initially diagnosed as vestibular neuritis and treated with steroids. The next day, she presented to the emergency department with worsening symptoms. Imaging revealed no intracranial process; however, non-contrast CT imaging revealed a soft-tissue mass in the posterior ethmoid sinus. The vertigo completely resolved before an otolaryngologist surgically removed the nasal mass, which actually originated from the right cribriform plate and extended to the anterior middle turbinate head. The final pathology was consistent with seromucinous hamartoma.
STAREE-Mind Imaging Study: a randomised placebo-controlled trial of atorvastatin for prevention of cerebrovascular decline and neurodegeneration in older individuals
Authors: Harding Ian H , Ryan Joanne , Heritier Stephane , Spark Simone , Flanagan Zachary , McIntyre Richard , Anderson Craig S , Naismith Sharon L , Chong Trevor T-J , O'Sullivan Michael , Egan Gary , Law Meng , Zoungas Sophia
Published: November 2023

Introduction

Cerebrovascular disease and neurodegeneration are causes of cognitive decline and dementia, for which primary prevention options are currently lacking. Statins are well-tolerated and widely available medications that potentially have neuroprotective effects. The STAREE-Mind Imaging Study is a randomised, double-blind, placebo-controlled clinical trial that will investigate the impact of atorvastatin on markers of neurovascular health and brain atrophy in a healthy, older population using MRI. This is a nested substudy of the ‘Statins for Reducing Events in the Elderly’ (STAREE) primary prevention trial.

Methods

Participants aged 70 years or older (n=340) will be randomised to atorvastatin or placebo. Comprehensive brain MRI assessment will be undertaken at baseline and up to 4 years follow-up, including structural, diffusion, perfusion and susceptibility imaging. The primary outcome measures will be change in brain free water fraction (a composite marker of vascular leakage, neuroinflammation and neurodegeneration) and white matter hyperintensity volume (small vessel disease). Secondary outcomes will include change in perivascular space volume (glymphatic drainage), cortical thickness, hippocampal volume, microbleeds and lacunae, prefrontal cerebral perfusion and white matter microstructure.

Ethics and dissemination

Academic publications from this work will address the current uncertainty regarding the impact of statins on brain structure and vascular integrity. This study will inform the utility of repurposing these well-tolerated, inexpensive and widely available drugs for primary prevention of neurological outcomes in older individuals. Ethics approval was given by Monash University Human Research Ethics Committee, Protocol 12206.

Trial registration number

ClinicalTrials.gov Identifier:NCT05586750.
Qualitative study of the perceived experiences and needs coping of primary caregivers of patients with breast cancer during operation in central China
Authors: Li Min , Guo Jun , Gao Jinnan , Wang Linying , Ding Yongxia
Published: November 2023

Purpose

The purpose of this study is to gain an in-depth understanding of the intraoperative waiting period experience and needs response of primary caregivers of patients with breast cancer.

Method

Using a purposive sampling method, 16 primary caregivers of patients with breast cancer admitted to the Department of Breast Surgery of Shanxi Bethune Hospital from January to May 2022 were selected as study subjects. Semistructured in-depth interviews were conducted using a qualitative research method.

Results

Five themes were extracted from the levels of safety and security, information transfer, emotion management, psychological adjustment and role adaptation: safety first and intraoperative care, lack of information and misdirection, negative emotions and tired of coping, ineffective worry and overthinking, and role multiplicity and bearing alone, respectively.

Conclusion

The intraoperative waiting period for primary caregivers of patients with breast cancer felt multidimensional and had less than optimal needs satisfaction. Healthcare professionals should use the existing needs as an entry point to give appropriate interventions to enhance the coping ability of caregivers of patients with breast cancer.
Protocol for validating an algorithm to identify neurocognitive disorders in Canadian Longitudinal Study on Aging participants: an observational study
Authors: Mayhew Alexandra J , Hogan David , Raina Parminder , Wolfson Christina , Costa Andrew P , Jones Aaron , Kirkland Susan , O'Connell Megan , Taler Vanessa , Smith Eric E , Liu-Ambrose Teresa , Ma Jinhui , Thompson Mary , Wu Changbao , Chertkow Howard , Griffith Lauren E
Published: November 2023

Introduction

In population-based research, disease ascertainment algorithms can be as accurate as, and less costly than, performing supplementary clinical examinations on selected participants to confirm a diagnosis of a neurocognitive disorder (NCD), but they require cohort-specific validation. To optimise the use of the Canadian Longitudinal Study on Aging (CLSA) to understand the epidemiology and burden of NCDs, the CLSA Memory Study will validate an NCD ascertainment algorithm to identify CLSA participants with these disorders using routinely acquired study data.

Methods and analysis

Up to 600 CLSA participants with equal numbers of those likely to have no NCD, mild NCD or major NCD based on prior self-reported physician diagnosis of a memory problem or dementia, medication consumption (ie, cholinesterase inhibitors, memantine) and/or self-reported function will be recruited during the follow-up 3 CLSA evaluations (started August 2021). Participants will undergo an assessment by a study clinician who will also review an informant interview and make a preliminary determination of the presence or absence of an NCD. The clinical assessment and available CLSA data will be reviewed by a Central Review Panel who will make a final categorisation of participants as having (1) no NCD, (2) mild NCD or, (3) major NCD (according to fifth version of the Diagnostic and Statistical Manual of Mental Disorders criteria). These will be used as our gold standard diagnosis to determine if the NCD ascertainment algorithm accurately identifies CLSA participants with an NCD. Weighted Kappa statistics will be the primary measure of agreement. Sensitivity, specificity, the C-statistic and the phi coefficient will also be estimated.

Ethics and dissemination

Ethics approval has been received from the institutional research ethics boards for each CLSA Data Collection Site (Université de Sherbrooke, Hamilton Integrated Research Ethics Board, Dalhousie University, Nova Scotia Health Research Ethics Board, University of Manitoba, McGill University, McGill University Health Centre Research Institute, Memorial University of Newfoundland, University of Victoria, Élisabeth Bruyère Research Institute of Ottawa, University of British Columbia, Island Health (Formerly the Vancouver Island Health Authority, Simon Fraser University, Calgary Conjoint Health Research Ethics Board).

The results of this work will be disseminated to public health professionals, researchers, health professionals, administrators and policy-makers through journal publications, conference presentations, publicly available reports and presentations to stakeholder groups.
Examining the health and functioning status of medical laboratory professionals in Ontario, Canada: an exploratory study during the COVID-19 pandemic
Authors: Joncic Genavieve , Jain Mahika , Chattu Vijay Kumar , Gohar Basem , Nowrouzi-Kia Behdin
Published: November 2023

Objectives

This study aims to explore the overall and specific aspects of the functioning of medical laboratory professionals (MLPs) in Ontario, Canada during the COVID-19 pandemic.

Design

A cross-sectional analysis where a questionnaire was used to assess the mental status of MLPs.

Setting

An online questionnaire administered in Ontario, Canada.

Participants

632 MLPs (medical laboratory technologists, technicians and assistants) were included.

Main outcome measures

We employed the WHO Disability Assessment Schedule V.2.0 (WHODAS V.2.0) Questionnaire to assess functioning/disability and Copenhagen Psychosocial Questionnaire, third edition for psychosocial workplace factors. Multiple regression analysis examined the relationship between overall and specific domain functioning scores and psychosocial workplace factors.

Results

Of the total 632 participants, the majority were female gender and Caucasian. It was found that health (β=2.25, p<0.001, CI: 1.77 to 2.73), management of environmental conditions (β=0.65, p<0.001, CI: 0.33 to 0.98), fear of unemployment (β=−0.72, p<0.001, CI: −1.09 to −0.35) and frequency of stress (β=−1.86, p<0.001, CI: −2.33 to −1.40), in addition to bullying exposure (β=0.56, p<0.01, CI: 0.15 to 0.98) and threats of violence exposure (β=0.90, p<0.01, CI: 0.25 to 1.54), significantly decreased functioning overall and within the specific WHODAS V.2.0 functioning domains.

Conclusion

This study provides preliminary evidence of the overall and specific aspects of functioning among the MLPs during the COVID-19 pandemic. Besides, these findings can support and guide the improvement of workplace practices and policies among MLPs in the future.