bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leading with local solutions to keep Yarrabah safe: a grounded theory study of an Aboriginal community-controlled health organisation’s response to COVID-19
Authors: McCalman Janya , Longbottom Marlene , Fagan Sara , Fagan Ruth , Andrews Suzanne , Miller Adrian 
Published: July 2021

Abstract
Background
Pandemics such as COVID-19 are a serious public health risk for Australian Aboriginal and Torres Strait Islander communities, yet primary healthcare systems are not well resourced to respond to such urgent events. At the start of the COVID-19 pandemic, a federal government advisory group recommended a rapid, tailored Indigenous response to prevent predicted high morbidity and mortality rates. This paper examines the efforts of one ACCHO, which in the absence of dedicated funding, pivoted its operations in response to COVID-19. Gurriny Yealamucka Health Service (Gurriny) is the only primary healthcare service in the discrete Indigenous community of Yarrabah, Far North Queensland.

Methods
The research was conducted at the request of the Chief Executive Officer of Gurriny. Using grounded theory methods, thirteen Gurriny staff and five Yarrabah and government leaders and community members were interviewed, transcripts of these interviews and 59 documents were imported into NVIVO-12 and coded, and key concepts were compared, organised into higher order constructs, then structured into a theoretical framework.

Results
Gurriny responded to COVID-19 by leading with local solutions to keep Yarrabah safe. Four key strategies were implemented: managing the health service operations, realigning services, educating and supporting community, and working across agencies. These strategies were enabled or hindered by five conditions: the governance and leadership capacity of Gurriny, relying on the health taskforce, locking the door, “copping it”, and (not) having resources. A year after the first case was experienced in Australia and on the eve of vaccine rollout to Indigenous communities, there have been no COVID-19 cases in Yarrabah.

Discussion
The success of the locally led, holistic, comprehensive and culturally safe response of Gurriny suggests that such tailored place-based approaches to pandemics (and other health issues) are appropriate, but require dedicated resourcing. Key challenges were the fragmented and rapidly changing government processes, poorly coordinated communication and resource allocation channels, and bottlenecks in hierarchical funding approval processes.

Conclusions
The COVID-19 response in Yarrabah demonstrates the need for governance reform towards greater resourcing and support for local decision making by Aboriginal community-controlled health organisations.
Combined effects of lung disease history, environmental exposures, and family history of lung cancer to susceptibility of lung cancer in Chinese non-smokers
Authors: Yu Fanglin , Xiao Rendong , Li Xu , Hu Zhijian , Cai Lin , He Fei 
Published: July 2021

Abstract
Background
Although cigarette smoking is a major risk factor for lung cancer, the incidence rate of lung cancer among non-smokers is notable. The etiology and potential mechanism of non-smoker lung cancer are worthy of further research. This study was designed to explore the collective effects of environmental factors and the relationship between environmental exposure index (EEI) and lung cancer among non-smokers by evaluating the joint effects among lung disease history, environmental factors, and family history of lung cancer without smoking confounders.

Methods
A total of 767 never-smoked lung cancer cases and 767 sex- and age-matched controls were selected from the department of Thoracic Surgery and Respiratory Medicine of three hospitals in Fujian, China. We used two methods to develop the EEI according to 12 statistically significant environmental risk factors. Restricted cubic spline (RCS) was applied to analyze the non-linear relationship between EEI and lung cancer in non-smokers. Combined effects, additive interaction, and multiplicative interaction were assessed among lung disease history, EEI, and family history of lung cancer to estimate susceptibility to develop lung cancer.

Results
Lung disease history, especially asthma, was significantly associated with an increased risk of lung cancer with an odds ratio (OR) for asthma history of 14.720 (95% CI: 1.877–115.449). Family history of lung cancer was related to susceptibility of lung cancer (OR = 3.347, 95% CI: 1.930–5.806). According to type of relatives and cancer, a parental or children’s history and a sibling’s history of lung cancer were significantly associated with an increased risk of lung cancer. The positive association between EEI and lung cancer was apparently stronger in those with lung disease history or family lung cancer history. Furthermore, there was a addictive interaction between EEI and lung disease history, and a possibly addictive interaction between EEI and family lung cancer history on development of lung cancer.

Conclusions
There were combined effects among lung disease history, environmental exposures, and family history of lung cancer toward susceptibility to lung cancer in Chinese non-smokers. Non-smokers who had a family history of lung cancer were at higher risk of lung cancer than non-smokers who had lung disease history. Non-smokers with family cancer history may obtain benefits from removal of environmental exposures and active treatment of lung disease.
Design and heterologous expression of a novel dimeric LL37 variant in Pichia pastoris
Authors: Zhan Na , Zhang Licong , Yang Hong , Zheng Yalan , Wei Xinke , Wang Jiajun , Shan Anshan 
Published: July 2021

Abstract
Background
The antimicrobial peptide LL37 is produced by white blood cells (mainly neutrophils) and various epithelial cells, and has the outstanding advantages of participating in immune regulation, causing chemotaxis of immune cells and promoting wound healing. However, the central domain of LL37 needs to be improved in terms of antimicrobial activity.

Results
In this study, the amino acid substitution method was used to improve the antimicrobial activity of the LL37 active center, and a dimeric design with a better selection index was selected. A flexible linker was selected and combined with the 6 × His-SUMO tag and LG was successfully expressed using Pichia pastoris as a host. Recombinant LG displayed strong antimicrobial activity by destroying the cell membrane of bacteria but had low hemolytic activity. In addition, compared with monomeric peptide FR, rLG had improved ability to tolerate salt ions.

Conclusion
This research provides new ideas for the production of modified AMPs in microbial systems and their application in industrial production.
In vitro-in vivo correlations of pulmonary inflammogenicity and genotoxicity of MWCNT
Authors: Di Ianni Emilio , Erdem Johanna Samulin , Møller Peter , Sahlgren Nicklas Mønster , Poulsen Sarah Søs , Knudsen Kristina Bram , Zienolddiny Shan , Saber Anne Thoustrup , Wallin Håkan , Vogel Ulla , Jacobsen Nicklas Raun 
Published: July 2021

Abstract
Background
Multi-walled carbon nanotubes (MWCNT) have received attention due to extraordinary properties, resulting in concerns for occupational health and safety. Costs and ethical concerns of animal testing drive a need for in vitro models with predictive power in respiratory toxicity. The aim of this study was to assess pro-inflammatory response (Interleukin-8 expression, IL-8) and genotoxicity (DNA strand breaks) caused by MWCNT with different physicochemical properties in different pulmonary cell models and correlate these to previously published in vivo data. Seven MWCNT were selected; two long/thick (NRCWE-006/Mitsui-7 and NM-401), two short/thin (NM-400 and NM-403), a pristine (NRCWE-040) and two surface modified; hydroxylated (NRCWE-041) and carboxylated (NRCWE-042). Carbon black Printex90 (CB) was included as benchmark material. Human alveolar epithelial cells (A549) and monocyte-derived macrophages (THP-1a) were exposed to nanomaterials (NM) in submerged conditions, and two materials (NM-400 and NM-401) in co-cultures of A549/THP-1a and lung fibroblasts (WI-38) in an air-liquid interface (ALI) system. Effective doses were quantified by thermo-gravimetric-mass spectrometry analysis (TGA-MS). To compare genotoxicity in vitro and in vivo, we developed a scoring system based on a categorization of effects into standard deviation (SD) units (< 1, 1, 2, 3 or 4 standard deviation increases) for the increasing genotoxicity.

Results
Effective doses were shown to be 25 to 53%, and 21 to 57% of the doses administered to A549 and THP-1a, respectively. In submerged conditions (A549 and THP-1a cells), all NM induced dose-dependent IL-8 expression. NM-401 and NRCWE-006 caused the strongest pro-inflammatory response. In the ALI-exposed co-culture, only NM-401 caused increased IL-8 expression, and no DNA strand breaks were observed. Strong correlations were found between in vitro and in vivo inflammation when doses were normalized by surface area (also proxy for diameter and length). Significantly increased DNA damage was found for all MWCNT in THP-1a cells, and for short MWCNT in A549 cells. A concordance in genotoxicity of 83% was obtained between THP-1a cells and broncho-alveolar lavaged (BAL) cells.

Conclusion
This study shows correlations of pro-inflammatory potential in A549 and THP-1a cells with neutrophil influx in mice, and concordance in genotoxic response between THP-1a cells and BAL cells, for seven MWCNT.
The LORIS MyeliNeuroGene rare disease database for natural history studies and clinical trial readiness
Authors: Spahr Aaron , Rosli Zaliqa , Legault Mélanie , Tran Luan T. , Fournier Simon , Toutounchi Helia , Darbelli Lama , Madjar Cécile , Lucia Cassandra , St-Jean Marie-Lou , Das Samir , Evans Alan C. , Bernard Geneviève 
Published: July 2021

Abstract
Background
Rare diseases are estimated to affect 150–350 million people worldwide. With advances in next generation sequencing, the number of known disease-causing genes has increased significantly, opening the door for therapy development. Rare disease research has therefore pivoted from gene discovery to the exploration of potential therapies. With impending clinical trials on the horizon, researchers are in urgent need of natural history studies to help them identify surrogate markers, validate outcome measures, define historical control patients, and design therapeutic trials.

Results
We customized a browser-accessible multi-modal (e.g. genetics, imaging, behavioral, patient-determined outcomes) database to increase cohort sizes, identify surrogate markers, and foster international collaborations. Ninety data entry forms were developed including family, perinatal, developmental history, clinical examinations, diagnostic investigations, neurological evaluations (i.e. spasticity, dystonia, ataxia, etc.), disability measures, parental stress, and quality of life. A customizable clinical letter generator was created to assist in continuity of patient care.

Conclusions
Small cohorts and underpowered studies are a major challenge for rare disease research. This online, rare disease database will be accessible from all over the world, making it easier to share and disseminate data. We have outlined the methodology to become Title 21 Code of Federal Regulations Part 11 Compliant, which is a requirement to use electronic records as historical controls in clinical trials in the United States. Food and Drug Administration compliant databases will be life-changing for patients and families when historical control data is used for emerging clinical trials. Future work will leverage these tools to delineate the natural history of several rare diseases and we are confident that this database will be used on a larger scale to improve care for patients affected with rare diseases.
Plaque-associated human microglia accumulate lipid droplets in a chimeric model of Alzheimer’s disease
Authors: Claes Christel , Danhash Emma Pascal , Hasselmann Jonathan , Chadarevian Jean Paul , Shabestari Sepideh Kiani , England Whitney E. , Lim Tau En , Hidalgo Jorge Luis Silva , Spitale Robert C. , Davtyan Hayk , Blurton-Jones Mathew 
Published: July 2021

Abstract
Background
Disease-associated microglia (DAMs), that surround beta-amyloid plaques, represent a transcriptionally-distinct microglial profile in Alzheimer’s disease (AD). Activation of DAMs is dependent on triggering receptor expressed on myeloid cells 2 (TREM2) in mouse models and the AD TREM2-R47H risk variant reduces microglial activation and plaque association in human carriers. Interestingly, TREM2 has also been identified as a microglial lipid-sensor, and recent data indicates lipid droplet accumulation in aged microglia, that is in turn associated with a dysfunctional proinflammatory phenotype. However, whether lipid droplets (LDs) are present in human microglia in AD and how the R47H mutation affects this remains unknown.

Methods
To determine the impact of the TREM2 R47H mutation on human microglial function in vivo, we transplanted wild-type and isogenic TREM2-R47H iPSC-derived microglial progenitors into our recently developed chimeric Alzheimer mouse model. At 7 months of age scRNA-seq and histological analyses were performed.

Results
Here we report that the transcriptome of human wild-type TREM2 and isogenic TREM2-R47H DAM xenografted microglia (xMGs), isolated from chimeric AD mice, closely resembles that of human atherosclerotic foam cells. In addition, much like foam cells, plaque-bound xMGs are highly enriched in lipid droplets. Somewhat surprisingly and in contrast to a recent in vitro study, TREM2-R47H mutant xMGs exhibit an overall reduction in the accumulation of lipid droplets in vivo. Notably, TREM2-R47H xMGs also show overall reduced reactivity to plaques, including diminished plaque-proximity, reduced CD9 expression, and lower secretion of plaque-associated APOE.

Conclusions
Altogether, these results indicate lipid droplet accumulation occurs in human DAM xMGs in AD, but is reduced in TREM2-R47H DAM xMGs, as it occurs secondary to TREM2-mediated changes in plaque proximity and reactivity.
Biological knowledge-slanted random forest approach for the classification of calcified aortic valve stenosis
Authors: Cantor Erika , Salas Rodrigo , Rosas Harvey , Guauque-Olarte Sandra 
Published: July 2021

Abstract
Background
Calcific aortic valve stenosis (CAVS) is a fatal disease and there is no pharmacological treatment to prevent the progression of CAVS. This study aims to identify genes potentially implicated with CAVS in patients with congenital bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) in comparison with patients having normal valves, using a knowledge-slanted random forest (RF).

Results
This study implemented a knowledge-slanted random forest (RF) using information extracted from a protein-protein interactions network to rank genes in order to modify their selection probability to draw the candidate split-variables. A total of 15,191 genes were assessed in 19 valves with CAVS (BAV, n = 10; TAV, n = 9) and 8 normal valves. The performance of the model was evaluated using accuracy, sensitivity, and specificity to discriminate cases with CAVS. A comparison with conventional RF was also performed. The performance of this proposed approach reported improved accuracy in comparison with conventional RF to classify cases separately with BAV and TAV (Slanted RF: 59.3% versus 40.7%). When patients with BAV and TAV were grouped against patients with normal valves, the addition of prior biological information was not relevant with an accuracy of 92.6%.

Conclusion
The knowledge-slanted RF approach reflected prior biological knowledge, leading to better precision in distinguishing between cases with BAV, TAV, and normal valves. The results of this study suggest that the integration of biological knowledge can be useful during difficult classification tasks.
One health pathogen surveillance demonstrated the dissemination of gut pathogens within the two coastal regions associated with intensive farming
Authors: Wang Qingyao , Zhang Yixiang , Yang Qian , Fu Songzhe , Qu Baocheng , Defoirdt Tom 
Published: July 2021

Abstract
Background
Intensive aquaculture farming has caused significant degradation of coastal wetlands and has been proposed as a reservoir for pathogenic Vibrio spp.

Results
Gut pathogens including Vibrio spp., Salmonella spp., and Klebsiella spp. were isolated from bird feces, shrimp and wetland water in two typical coastal regions of China in 2015 and 2017 and were subsequently subjected to whole-genome sequencing. Meanwhile, local patient isolates were also selected to confirm the epidemiological links. Bacterial community composition analyses of the sediments that were sampled in 2015 and 2017 were conducted by the hypervariable region 4 of the 16S rRNA gene. Together with the local clinical isolates, we observed highly related Vibrio isolates from waterbirds, wetlands and shrimp. Phylogenetic genome comparisons also demonstrated that sequence types ST3 and ST2414 Vibrio parahaemolyticus isolates obtained from aquatic animals were clonally related to patient isolates. Likewise, three Salmonella typhimurium isolates were also genomically related to one clinical strain. The results showed that farming activities significantly altered the community composition and resulted in the emergence of several pathogens, including Acinetobacter, Mycobacterium and Legionella.

Conclusions
In conclusion, our results demonstrated that intensive shrimp farming in wetlands has two devastating impacts: pathogen dissemination from aquatic animals into migratory birds and transmission of foodborne pathogens into local communities.
Identification of molecular biomarkers associated with disease progression in the testis of bulls infected with Besnoitia besnoiti
Authors: González-Barrio David , Diezma-Díaz Carlos , Gutiérrez-Expósito Daniel , Tabanera Enrique , Jiménez-Meléndez Alejandro , Pizarro Manuel , González-Huecas Marta , Ferre Ignacio , Ortega-Mora Luis M. , Álvarez-García Gema 
Published: July 2021

AbstractBreeding bulls infected with Besnoitia besnoiti may develop sterility during either acute or chronic infection. The aim of this study was to investigate the molecular pathogenesis of B. besnoiti infection with prognosis value in bull sterility. Accordingly, five well-characterized groups of naturally and experimentally infected males were selected for the study based on clinical signs and lesions compatible with B. besnoiti infection, serological results and parasite detection. A broad panel of molecular markers representative of endothelial activation and fibrosis was investigated and complemented with a histopathological approach that included conventional histology and immunohistochemistry. The results indicated the predominance of an intense inflammatory infiltrate composed mainly of resident and recruited circulating macrophages and to a lesser extent of CD3+ cells in infected bulls. In addition, a few biomarkers were associated with acute, chronic or subclinical bovine besnoitiosis. The testicular parenchyma showed a higher number of differentially expressed genes in natural infections (acute and chronic infections) versus scrotal skin in experimental infections (subclinical infection). In subclinical infections, most genes were downregulated except for the CCL24 and CXCL2 genes, which were upregulated. In contrast, the acute phase was mainly characterized by the upregulation of IL-1α, IL-6 and TIMP1, whereas in the chronic phase, the upregulation of ICAM and the downregulation of MMP13, PLAT and IL-1α were the most relevant findings. Macrophages could be responsible for the highest level of gene regulation in the testicular parenchyma of severely affected and sterile bulls, and all these genes could be prognostic markers of sterility.
Non-convex proximal pair and relatively nonexpansive maps with respect to orbits
Authors: Shanjit Laishram , Rohen Yumnam 
Published: July 2021

AbstractEvery non-convex pair $(C, D)$
(
C
,
D
)
may not have proximal normal structure even in a Hilbert space. In this article, we use cyclic relatively nonexpansive maps with respect to orbits to show the presence of best proximity points in $C\cup D$
C
∪
D
, where $C\cup D$
C
∪
D
is a cyclic T-regular set and $(C, D)$
(
C
,
D
)
is a non-empty, non-convex proximal pair in a real Hilbert space. Moreover, we show the presence of best proximity points and fixed points for non-cyclic relatively nonexpansive maps with respect to orbits defined on $C\cup D$
C
∪
D
, where C and D are T-regular sets in a uniformly convex Banach space satisfying $T(C)\subseteq C$
T
(
C
)
⊆
C
, $T(D)\subseteq D$
T
(
D
)
⊆
D
wherein the convergence of Kranoselskii’s iteration process is also discussed.
Sex differences in adaptation to intermittent post-exercise sauna bathing in trained middle-distance runners
Authors: Kirby Nathalie V. , Lucas Samuel J. E. , Cable Thomas G. , Armstrong Oliver J. , Weaver Samuel R. , Lucas Rebekah A. I. 
Published: July 2021

Abstract
Background
The purpose of this study was to investigate the effect of sex on the efficacy of intermittent post-exercise sauna bathing to induce heat acclimation and improve markers of temperate exercise performance in trained athletes.

Methods
Twenty-six trained runners (16 female; mean ± SD, age 19 ± 1 years, V̇O2max F: 52.6 ± 6.9 mL⋅kg−1⋅min−1, M: 64.6 ± 2.4 mL⋅kg−1⋅min−1) performed a running heat tolerance test (30 min, 9 km⋅h−1/2% gradient, 40 °C/40%RH; HTT) and temperate (18 °C) exercise tests (maximal aerobic capacity [V̇O2max] and lactate profile) pre and post 3 weeks of normal exercise training plus 29 ± 1 min post-exercise sauna bathing (101–108 °C) 3 ± 1 times per week.

Results
Females and males exhibited similar reductions (interactions p > 0.05) in peak rectal temperature (− 0.3 °C; p < 0.001), skin temperature (− 0.9 °C; p < 0.001) and heart rate (− 9 beats·min−1; p = 0.001) during the HTT at post- vs pre-intervention. Only females exhibited an increase in active sweat glands on the forearm (measured via modified iodine technique; F: + 57%, p < 0.001; M: + 1%, p = 0.47). Conversely, only males increased forearm blood flow (measured via venous occlusion plethysmography; F: + 31%, p = 0.61; M: + 123%; p < 0.001). Females and males showed similar (interactions p > 0.05) improvements in V̇O2max (+ 5%; p = 0.02) and running speed at 4 mmol·L−1 blood lactate concentration (+ 0.4 km·h−1; p = 0.001).

Conclusions
Three weeks of post-exercise sauna bathing effectively induces heat acclimation in females and males, though possibly amid different thermoeffector adaptations. Post-exercise sauna bathing is also an effective ergogenic aid for both sexes.