bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating the influence of institutions, politics, organizations, and governance on the COVID-19 response in British Columbia, Canada: a jurisdictional case study protocol
Authors: Brubacher Laura Jane , Hasan Md. Zabir , Sriram Veena , Keidar Shelly , Wu Austin , Cheng Michael , Lovato Chris Y. ,   U. B. C. Working Group on Health Systems Response to COVID-19, Berman Peter 
Published: June 2022

AbstractBackgroundResearch on public health responses to COVID-19 globally has largely focused on understanding the virus’ epidemiology, identifying interventions to curb transmission, and assessing the impact of interventions on outcomes. Only recently have studies begun to situate their findings within the institutional, political, or organizational contexts of jurisdictions. Within British Columbia (BC), Canada, the COVID-19 response in early 2020 was deemed highly coordinated and effective overall; however, little is understood as to how these upstream factors influenced policy decisions.MethodsUsing a conceptual framework we developed, we are conducting a multidisciplinary jurisdictional case study to explore the influence of institutional (I), political (P), organizational (O), and governance (G) factors on BC’s COVID-19 public health response in 2020–2021. A document review (e.g. policy documents, media reports) is being used to (1) characterize relevant institutional and political factors in BC, (2) identify key policy decisions in BC’s epidemic progression, (3) create an organizational map of BC’s public health system structure, and (4) identify key informants for interviews. Quantitative data (e.g. COVID-19 case, hospitalization, death counts) from publicly accessible sources will be used to construct BC’s epidemic curve. Key informant interviews (n = 15–20) will explore governance processes in the COVID-19 response and triangulate data from prior procedures. Qualitative data will be analysed using a hybrid deductive–inductive coding approach and framework analysis. By integrating all of the data streams, our aim is to explore decision-making processes, identify how IPOG factors influenced policy decisions, and underscore implications for decision-making in public health crises in the BC context and elsewhere. Knowledge users within the jurisdiction will be consulted to construct recommendations for future planning and preparedness.DiscussionAs the COVID-19 pandemic evolves, governments have initiated retrospective examinations of their policies to identify lessons learned. Our conceptual framework articulates how interrelations between IPOG contextual factors might be applied to such analysis. Through this jurisdictional case study, we aim to contribute findings to strengthen governmental responses and improve preparedness for future health crises. This protocol can be adapted to and applied in other jurisdictions, across subnational jurisdictions, and internationally.
Epstein–Barr virus tegument protein BGLF2 in exosomes released from virus-producing cells facilitates de novo infection
Authors: Sato Yoshitaka , Yaguchi Masahiro , Okuno Yusuke , Ishimaru Hanako , Sagou Ken , Ozaki Somi , Suzuki Takeshi , Inagaki Tomoki , Umeda Miki , Watanabe Takahiro , Fujimuro Masahiro , Murata Takayuki , Kimura Hiroshi 
Published: June 2022

Abstract
Background
Viruses must adapt to the environment of their host cells to establish infection and persist. Diverse mammalian cells, including virus-infected cells, release extracellular vesicles such as exosomes containing proteins and miRNAs, and use these vesicles to mediate intercellular communication. However, the roles of exosomes in viral infection remain unclear.

Results
We screened viral proteins to identify those responsible for the exosome-mediated enhancement of Epstein–Barr virus (EBV) infection. We identified BGLF2 protein encapsulated in exosomes, which were released by EBV-infected cells. BGLF2 protein is a tegument protein that exists in the space between the envelope and nucleocapsid, and it is released into the cytoplasm shortly after infection. BGLF2 protein-containing exosomes enhanced viral gene expression and repressed innate immunity, thereby supporting the EBV infection.

Conclusions
The EBV tegument protein BGLF2 is encapsulated in exosomes and released by infected cells to facilitate the establishment of EBV infection. These findings suggest that tegument proteins support viral infection not only between the envelope and nucleocapsid, as well as in extraviral particles such as exosomes.

Graphical abstract
Blocking TIGIT/CD155 signalling reverses CD8+ T cell exhaustion and enhances the antitumor activity in cervical cancer
Authors: Liu Lu , Wang Aihong , Liu Xiaoli , Han Sai , Sun Yu , Zhang Junhua , Guo Lingyu , Zhang Youzhong 
Published: June 2022

AbstractObjectiveTIGIT/CD155 has attracted widespread attention as a new immune checkpoint and a potential target for cancer immunotherapy. In our study, we evaluated the role of TIGIT/CD155 checkpoints in the progression of cervical cancer.MethodsThe expression of CD155 and TIGIT in cervical cancer tissues was detected using flow cytometry, immunohistochemistry (IHC) and gene expression profiling. In vivo and in vitro experiments have proven that blocking TIGIT/CD155 restores the ability of CD8+T cells to produce cytokines. Changes in the NF-κB and ERK pathways were detected using western blotting (WB) after blocking TIGIT/CD155 signalling.ResultsTIGIT expression was elevated in patients with cervical cancer. High TIGIT expression in CD8+T lymphocytes from patients with cervical cancer promotes the exhaustion of CD8+T lymphocytes. In addition, CD155 is expressed at high levels in cervical cancer tissues and is negatively correlated with the level of infiltrating CD8+T cells. We found that TIGIT, upon binding to CD155 and being phosphorylated, inhibited NF-κB and ERK activation by recruiting SHIP-1, resulting in the downregulation of cytokine production. Blocking TIGIT in activated CD8+T cells attenuates the inhibitory effect of SHIP-1 on CD8+T cells and enhances the activation of NF-κB and ERK. In vivo and in vitro experiments have proven that blocking TIGIT/CD155 restores the ability of CD8+T cells to produce cytokines. Injecting the blocking antibody TIGIT in vivo inhibits tumour growth and enhances CD8+T lymphocyte function. Treatment with a combination of TIGIT and PD-1 inhibitors further increases the efficacy of the TIGIT blocking antibody.ConclusionsOur research shows that TIGIT/CD155 is a potential therapeutic target for cervical cancer.
The treatment of Qibai Pingfei Capsule on chronic obstructive pulmonary disease may be mediated by Th17/Treg balance and gut-lung axis microbiota
Authors: Jia Yu , He Tiantian , Wu Di , Tong Jiabing , Zhu Jie , Li Zegeng , Dong Jingcheng 
Published: June 2022

Abstract
Background
Chronic obstructive pulmonary disease (COPD), a prevalent, progressive respiratory disease, has become the third leading cause of death globally. Increasing evidence suggests that intestinal and pulmonary microbiota dysbiosis is associated with COPD. Researchers have shown that T helper (Th) 17/regulatory T (Treg) imbalance is involved in COPD. Qibai Pingfei Capsule (QBPF) is a traditional Chinese medicine used to treat COPD clinically in China. However, the effects of QBPF intervention on the Th17/Treg balance and microbiota in the gut and lung are still poorly understood.

Methods
This study divided the rats into three groups (n = 8): control, model, and QBPF group. After establishing the model of COPD for four weeks and administering of QBPF for two weeks, Th17 cells, Treg cells, their associated cytokines, transcription factors, and intestinal and pulmonary microbiota of rats were analyzed. Furthermore, the correlations between intestinal and pulmonary microbiota and between bacterial genera and pulmonary function and immune function were measured.

Results
The results revealed that QBPF could improve pulmonary function and contribute to the new balance of Th17/Treg in COPD rats. Meanwhile, QBPF treatment could regulate the composition of intestinal and pulmonary microbiota and improve community structure in COPD rats, suppressing the relative abundance of Coprococcus_2, Prevotella_9, and Blautia in the gut and Mycoplasma in the lung, but accumulating the relative abundance of Prevotellaceae_UCG_003 in the gut and Rikenellaceae_RC9_gut_group in the lung. Additionally, gut–lung axis was confirmed by the significant correlations between the intestinal and pulmonary microbiota. Functional analysis of microbiota showed amino acid metabolism was altered in COPD rats in the gut and lung. Spearman correlation analysis further enriched the relationship between the microbiota in the gut and lung and pulmonary function and immune function in COPD model rats.

Conclusions
Our study indicated that the therapeutic effects of QBPF may be achieved by maintaining the immune cell balance and regulating the gut-lung axis microbiota, providing references to explore the potential biomarkers of COPD and the possible mechanism of QBPF to treat COPD.
Biomechanical effects of interbody cage height on adjacent segments in patients with lumbar degeneration: a 3D finite element study
Authors: Lu Xiao , Li Dachuan , Wang Hongli , Xia Xinlei , Ma Xiaosheng , Lv Feizhou , Zou Fei , Jiang Jianyuan 
Published: June 2022

Abstract
Objective
To investigate the biomechanical effects of interbody cage height on adjacent segments in patients with lumbar degeneration undergoing transforaminal lumbar interbody fusion (TLIF) surgery, so as to provide references for selection of interbody cage.

Methods
The finite element model of normal lower lumbar spine (L3–S1) was built and validated, then constructed three different degenerative segments in L3–L4, and the cages with different height (8, 10, 12, 14 mm) were implanted into L4–L5 disc. All the twelve models were loaded with pure moment of 7.5 N m to produce flexion, extension, lateral bending and axial rotation motions on lumbar spine, and the effects of cage height on range of motion (RoM) and intervertebral pressure in lumbar spine were investigated.

Results
The RoM of adjacent segments and the maximum stress of intervertebral discs increased with the increase in cage height, but this trend was not obvious in mild and moderate degeneration groups. After implantation of four different height cages (8, 10, 12, 14 mm), the RoM of L3/L4 segment reached the maximum during extension. The RoM of mild degeneration group was 2.07°, 2.45°, 2.48°, 2.54°, that of moderate degeneration group was 1.79°, 1.97°, 2.05°, 2.05°, and that of severe degeneration group was 1.43°, 1.66°, 1.74°, 1.74°. The stress of L3–L4 intervertebral disc reached the maximum during flexion. The maximum stress of L3–L4 intervertebral disc was 20.16 MPa, 20.28 MPa, 20.31 MPa and 20.33 MPa in the mild group, 20.58 MPa, 20.66 MPa, 20.71 MPa and 20.75 MPa in the moderate group, and 21.27 MPa, 21.40 MPa, 21.50 MPa and 21.60 MPa in the severe group.

Conclusion
For patients with mild-to-moderate lumbar degenerative disease who need to undergo TLIF surgery, it is recommended that the height of fusion cage should not exceed the original intervertebral space height by 2 mm, while for patients with severe degeneration, a fusion cage close to the original intervertebral height should be selected as far as possible, and the intervertebral space should not be overstretched.
Fluid challenge in critically ill patients receiving haemodynamic monitoring: a systematic review and comparison of two decades
Authors: Messina Antonio , Calabrò Lorenzo , Pugliese Luca , Lulja Aulona , Sopuch Alexandra , Rosalba Daniela , Morenghi Emanuela , Hernandez Glenn , Monnet Xavier , Cecconi Maurizio 
Published: June 2022

AbstractIntroductionFluid challenges are widely adopted in critically ill patients to reverse haemodynamic instability. We reviewed the literature to appraise fluid challenge characteristics in intensive care unit (ICU) patients receiving haemodynamic monitoring and considered two decades: 2000–2010 and 2011–2021.MethodsWe assessed research studies and collected data regarding study setting, patient population, fluid challenge characteristics, and monitoring. MEDLINE, Embase, and Cochrane search engines were used. A fluid challenge was defined as an infusion of a definite quantity of fluid (expressed as a volume in mL or ml/kg) in a fixed time (expressed in minutes), whose outcome was defined as a change in predefined haemodynamic variables above a predetermined threshold.ResultsWe included 124 studies, 32 (25.8%) published in 2000–2010 and 92 (74.2%) in 2011–2021, overall enrolling 6,086 patients, who presented sepsis/septic shock in 50.6% of cases. The fluid challenge usually consisted of 500 mL (76.6%) of crystalloids (56.6%) infused with a rate of 25 mL/min. Fluid responsiveness was usually defined by a cardiac output/index (CO/CI) increase ≥ 15% (70.9%). The infusion time was quicker (15 min vs 30 min), and crystalloids were more frequent in the 2011–2021 compared to the 2000–2010 period.ConclusionsIn the literature, fluid challenges are usually performed by infusing 500 mL of crystalloids bolus in less than 20 min. A positive fluid challenge response, reported in 52% of ICU patients, is generally defined by a CO/CI increase ≥ 15%. Compared to the 2000–2010 decade, in 2011–2021 the infusion time of the fluid challenge was shorter, and crystalloids were more frequently used.
Intensity of insecticide resistance in the major malaria vector Anopheles funestus from Chikwawa, rural Southern Malawi
Authors: Kumala Justin , Koekemoer Lizette L. , Coetzee Maureen , Mzilahowa Themba 
Published: June 2022

Abstract
Background
Malaria vector control using insecticide-based approaches has proven to be an effective strategy. However, widespread insecticide resistance among malaria vector populations across sub-Saharan Africa threatens to derail control efforts. This study was conducted in Chikwawa district, an area in rural southern Malawi characterised by persistent malaria transmission and reports of insecticide resistance in the local mosquito population. The aim of the was to characterise the intensity of insecticide resistance within a population of Anopheles funestus sensu lato (s.l.), a major vector of malaria in this district.

Methods
Live adult females belonging to the An. funestus group were collected from households by indoor aspiration. The CDC bottle assay was used for phenotypic quantification of resistance to deltamethrin, permethrin and alpha-cypermethrin at 1×, 2.5×, 5× and 10× the recommended diagnostic dose for each of these insecticides. WHO tube assays were used to determine susceptibility to bendiocarb, dichlorodiphenyltrichloroethane (DDT) and pirimiphos-methyl insecticides at diagnostic concentrations.

Results
Anopheles funestus s.l. exposed to 10× the recommended diagnostic dose was highly resistant to alpha-cypermethrin (mortality 95.4%); in contrast, mortality was 100% when exposed to both deltamethrin and permethrin at the same dose. Despite showing susceptibility to deltamethrin and permethrin at the 10× concentration, mortality at the 5× concentration was 96.7% and 97.1%, respectively, indicating moderate resistance to these two insecticides. WHO susceptibility assays indicated strong resistance against bendiocarb (mortality 33.8%, n = 93), whereas there was full susceptibility to DDT (mortality 98.9%, n = 103) and pirimiphos-methyl (mortality 100%, n = 103).

Conclusions
Strategies for managing resistance to insecticides, particularly against pyrethroids, must be urgently implemented to maintain the effectiveness of insecticide-based vector control interventions in the area. Such strategies include the wide-scale introduction of third-generation synergist insecticide-treated bed nets (ITNs) and next-generation dual active ingredient ITNs. The use of effective non-pyrethroids, such as pirimiphos-methyl, clothianidin and potentially DDT, could provide a window of opportunity for indoor residual spraying across the district. This strategy would support the current Malawi Insecticide Resistance Management Plan which aims at rotating insecticides to minimise selection pressure and slow down the evolution of resistance to approved insecticides. These actions will help to prevent malaria vector control failure and improve progress towards malaria elimination.

Graphical Abstract
Sensitivity of wMel and wAlbB Wolbachia infections in Aedes aegypti Puducherry (Indian) strains to heat stress during larval development
Authors: Gunasekaran Kasinathan , Sadanandane Candasamy , Panneer Devaraju , Kumar Ashwani , Rahi Manju , Dinesh Sundaram , Vijayakumar Balakrishnan , Krishnaraja Muthuraman , Subbarao Sarala K. , Jambulingam Purushothaman 
Published: June 2022

AbstractBackgroundICMR-Vector Control Research Centre, Puducherry, India, developed two colonies ofAedes aegyptiinfected withwMel andwAlbBWolbaciastrains calledAe. aegypti(Pud) lines for dengue control. The sensitivity ofwMel andwAlbB strains inAe. aegypti(Pud) lines to heat stress was studied.MethodswMel andwAlbB infected and uninfectedAe. aegyptilarvae (first to fourth instars) were reared in the laboratory to adults at 26 °C, 30 °C, 36 °C and 40 °C constant temperatures and also 26–30 °C, 26–36 °C and 26–40 °C diurnal cyclic temperatures. The adults were tested forWolbachiainfection. Experiments were also carried out rearing the larvae under simulated field conditions in summer (April and June) under sunlight using fully open and half open bowls and also under sunlight and natural shade.ResultsAt 36 °C and 40 °C constant temperatures, complete larval mortality was observed. At 30 °C and 26 °C, no larval mortality occurred, butWolbachiadensity was relatively low inwMel infected males compared to control (maintained at 26 ± 1 °C). At diurnal cyclic temperature of 26–40 °C,Wolbachiadensity was reduced in males of both the (Pud) lines, but not in females. At 26–36 °C, reduction inWolbachiadensity was observed inwMel males but not inwAlbB males. At 26–30 °C, no significant reduction inWolbachiadensity was observed withwMel andwAlbB strains. In simulated field conditions (April), under sunlight, the daytime water temperature reached a maximum of 35.7 °C in both full and half open bowls. No larval mortality occurred.Wolbachiafrequency and density was reduced inwMel-infectedAe. aegypti(Pud) males from both type of bowls and in females from full open bowls, and inwAlbB males from half open bowls. In June, rearing of larvae under sunlight, the first-instar larvae experienced a maximum daytime water temperature of > 38 °C that caused complete mortality. No larval mortality was observed in bowls kept under shade (< 32 °C).ConclusionsExposure of larvae to higher rearing temperatures in the laboratory and simulated-field conditions reduced the densities ofwMel andwAlbB strains particularly in males, but the impact was more pronounced forwMel strain. The actual effect of heat stress on the stability of these twoWolbachiastrains needs to be tested under natural field conditions.Graphical Abstract
Myeloid cell-specific deletion of Capns1 prevents macrophage polarization toward the M1 phenotype and reduces interstitial lung disease in the bleomycin model of systemic sclerosis
Authors: Zhang Li , Zheng Dong , Yan Yuemei , Yu Yong , Chen Ruizhen , Li Zheng , Greer Peter A. , Peng Tianqing , Wang Qiang 
Published: June 2022

Abstract
Background
Calpains are a family of calcium-dependent thiol proteases that participate in a wide variety of biological activities. In our recent study, calpain is increased in the sera of scleroderma or systemic sclerosis (SSc). However, the role of calpain in interstitial lung disease (ILD) has not been reported. ILD is a severe complication of SSc, which is the leading cause of death in SSc. The pathogenesis of SSc-related ILD remains incompletely understood. This study investigated the role of myeloid cell calpain in SSc-related ILD.

Methods
A novel line of mice with myeloid cell-specific deletion of Capns1 (Capns1-ko) was created. SSc-related ILD was induced in Capns1-ko mice and their wild-type littermates by injection 0.l mL of bleomycin (0.4 mg/mL) for 4 weeks. In a separate experiment, a pharmacological inhibitor of calpain PD150606 (Biomol, USA, 3 mg/kg/day, i.p.) daily for 30 days was given to mice after bleomycin injection on daily basis. At the end of the experiment, the animals were killed, skin and lung tissues were collected for the following analysis. Inflammation, fibrosis and calpain activity and cytokines were assessed by histological examinations and ELISA, and immunohistochemical analyses, western blot analysis and Flow cytometry analysis.

Results
Calpain activities increased in SSc-mouse lungs. Both deletion of Capns1 and administration of PD150606 attenuated dermal sclerosis as evidenced by a reduction of skin thickness and reduced interstitial fibrosis and inflammation in bleomycin model of SSc mice. These effects of reduced calpain expression or activity were associated with prevention of macrophage polarization toward M1 phenotype and consequent reduced production of pro-inflammatory cytokines including TNF-α, IL-12 and IL-23 in lung tissues of Capns1-ko mice with bleomycin model of SSc. Furthermore, inhibition of calpain correlated with an increase in the protein levels of PI3K and phosphorylated AKT1 in lung tissues of the bleomycin model of SSc mice.

Conclusions
This study for the first time demonstrates that the role of myeloid cell calpain may be promotion of macrophage M1 polarization and pro-inflammatory responses related PI3K/AKT1 signaling. Thus, myeloid cell calpain may be a potential therapeutic target for bleomycin model of SSc-related ILD.
Short- and long-term evaluation of disease-specific symptoms and quality of life following uterine artery embolization of fibroids
Authors: Psilopatis Iason , Fleckenstein Florian Nima , Collettini Federico , Can Elif , Frisch Anne , Gebauer Bernhard , Fehrenbach Uli , Torsello Giovanni Federico , Schnapauff Dirk , David Matthias , Wieners Gero 
Published: June 2022

Abstract
Background
The purpose of this study is to evaluate uterine artery embolization (UAE) for the management of symptomatic uterine leiomyomas regarding changes in quality of life after treatment in a large patient collective. This study retrospectively analyzed prospectively acquired standardized questionnaires of patients treated with UAE. Clinical success was evaluated before and after embolization. Patients were stratified into short- (≤ 7 months) and long-term (> 7 months) follow-up groups depending on the time of completion of the post-interventional questionnaire. Uterine leiomyomas were furthermore divided into small (< 10 cm) and large (≥ 10 cm) tumors based on the diameter of the dominant fibroid.

Results
A total of 245 patients were included into the final data analysis. The Kaplan–Meier analysis showed a cumulative clinical success rate of 75.8% after 70 months until the end of follow-up (9.9 years). All questionnaire subscales showed a highly significant clinical improvement from baseline to short- and long-term follow-up (p < 0.001). Patients with small fibroids showed a significantly better response to UAE in multiple subcategories of the questionnaire than patients with fibroids ≥ 10 cm who had a twofold higher probability of re-intervention in the Cox-regression model.

Conclusions
UAE is an effective treatment method for symptomatic fibroids that leads to quick relief of fibroid-related symptoms with marked improvement of quality of life and is associated with a low risk for re-interventions. Patients with small fibroids tend to show a better response to UAE compared to patients with large fibroids.
Trial registration Charité institutional review board, EA4/167/20. Registered 27 November 2020—Retrospectively registered. https://ethikkommission.charite.de/