bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autism spectrum disorders and atopic dermatitis: a new perspective from country-based prevalence data
Authors: Tonacci Alessandro , Pioggia Giovanni , Gangemi Sebastiano 
Published: December 2021

AbstractRecently, a continuous growth for both neurodevelopmental and atopic diseases’ incidence was seen throughout the world. Notably, autism spectrum disorders (ASD) and atopic dermatitis (AD) attracted the attention of clinicians and scientists for their impact on the quality of life of patients, starting during childhood. Despite a number of hypotheses about common pathogenesis between the two disorders, uncertainty is still present, and data coming from various parts of the world are contradictory. Fortunately, works recently published have brought useful material for comparative analysis to the benefit of the scientific community, making large scale, country-based perspectives methodologically viable. In light of that, the present study took into account uniform data, available from country-based registries or related publications, dealing with the prevalence of the two conditions around the world, and tried to setup a simple correlation analysis between the two. According to such data, the growth of AD and ASD prevalence appear uncorrelated, leading to hypothesise that, if a common etiopathological pathway exists between the two conditions, they are likely to interact to each other due to a complex interplay of co-morbidities, genes and environmental players not enough explained by a simple correlation analysis. Such facts are worth investigation in future research.
Carbon nanotube biocompatibility in plants is determined by their surface chemistry
Authors: González-Grandío Eduardo , Demirer Gözde S. , Jackson Christopher T. , Yang Darwin , Ebert Sophia , Molawi Kian , Keller Harald , Landry Markita P. 
Published: December 2021

Abstract
Background
Agriculture faces significant global challenges including climate change and an increasing food demand due to a growing population. Addressing these challenges will require the adoption of transformative innovations into biotechnology practice, such as nanotechnology. Recently, nanomaterials have emerged as unmatched tools for their use as biosensors, or as biomolecule delivery vehicles. Despite their increasingly prolific use, plant-nanomaterial interactions remain poorly characterized, drawing into question the breadth of their utility and their broader environmental compatibility.

Results
Herein, we characterize the response of Arabidopsis thaliana to single walled carbon nanotube (SWNT) exposure with two different surface chemistries commonly used for biosensing and nucleic acid delivery: oligonucleotide adsorbed-pristine SWNTs, and polyethyleneimine-SWNTs loaded with plasmid DNA (PEI-SWNTs), both introduced by leaf infiltration. We observed that pristine SWNTs elicit a mild stress response almost undistinguishable from the infiltration process, indicating that these nanomaterials are well-tolerated by the plant. However, PEI-SWNTs induce a much larger transcriptional reprogramming that involves stress, immunity, and senescence responses. PEI-SWNT-induced transcriptional profile is very similar to that of mutant plants displaying a constitutive immune response or treated with stress-priming agrochemicals. We selected molecular markers from our transcriptomic analysis and identified PEI as the main cause of this adverse reaction. We show that PEI-SWNT response is concentration-dependent and, when persistent over time, leads to cell death. We probed a panel of PEI variant-functionalized SWNTs across two plant species and identified biocompatible SWNT surface functionalizations.

Conclusions
While SWNTs themselves are well tolerated by plants, SWNTs surface-functionalized with positively charged polymers become toxic and produce cell death. We use molecular markers to identify more biocompatible SWNT formulations. Our results highlight the importance of nanoparticle surface chemistry on their biocompatibility and will facilitate the use of functionalized nanomaterials for agricultural improvement.

Graphical Abstract
A cascade targeting strategy based on modified bacterial vesicles for enhancing cancer immunotherapy
Authors: Zhai Yuewen , Ma Yuying , Pang Bo , Zhang Jinnan , Li Ying , Rui Yalan , Xu Tian , Zhao Yu , Qian Zhiyu , Gu Yueqing , Li Siwen 
Published: December 2021

AbstractBackgroundAs an efficient tumor immunotherapy, PD-1 antibody has been gradually used in clinical tumor treatment, but the low response rate and excessive immune response limit its extensive application.ResultsHerein, a therapeutic regime for the reinvigoration and activation of the tumor immune microenvironment is introduced to improve the anti-tumor effect of the PD-1 antibody. To comprehensively improve the effect of the immunotherapy and reduce excessive immune response, a biomimetic cascade targeting nanosystem, siRNA@PLOV, which was fused by photothermal sensitive liposomes (PTSLs) and attenuatedSalmonellaouter membrane vesicles (OMVs), was administered in the tumor therapy for targeting of tumor tissues and T cells within tumor respectively. The fused PLOVs which not only retained the biological character of the OMVs, but also enhanced the drug loading ability. The results demonstrated that the immunogenicity of OMVs and photothermal effects can obviously increase the infiltration of T cells and the silencing of CD38 can effectively improve the T cell cytotoxicity, especially combining with PD-1 antibody.ConclusionsInteresting, this study revealed that anti-PD-1 administration on the 5th day after siRNA@PLOV treatment had the best performance in killing tumors compared with other groups. In addition, this new therapeutic regime also presents a novel strategy for inducing “vaccine effects”, conclusively highlighting its potential in preventing tumor recurrence and improving prognosis.Graphical Abstract
A redox-responsive dihydroartemisinin dimeric nanoprodrug for enhanced antitumor activity
Authors: Li Yawei , Pei Qing , Cui Baiji , Zhang Hongmei , Han Liu , Li Wenqing , Zhu Wenhe , Feng Xianmin , Xie Zhigang 
Published: December 2021

AbstractRedox-responsive drug delivery system emerges as a hopeful platform for tumor treatment. Dihydroartemisinin (DHA) has been investigated as an innovative tumor therapeutic agent. Herein, a DHA dimeric prodrug bridged with disulfide bond as linker (DHA2-SS) has been designed and synthesized. The prepared prodrugs could self-assemble into nanoparticles (SS NPs) with high DHA content (> 90%) and robust stability. These SS NPs display sensitive redox responsive capability and can release DHA under the tumor heterogeneity microenvironment. SS NPs possess preferable antitumor therapeutic activity in contrast with free DHA. Moreover, the possible anti-cancer mechanism of SS NPs was investigated through RNA-seq analysis, bioinformatics and molecular biological method. SS NPs could induce apoptosis via mitochondrial apoptosis pathway, as well as glycolysis inhibition associate with the regulation of PI3K/AKT/HIF-1α signal path, which may offer an underlying therapeutic target for liver cancer. Our study highlights the potential of using redox responsive prodrug nanoparticles to treat cancer, meanwhile provides insights into the anti-cancer mechanism of DHA prodrug.Graphical Abstract
Sternocleidomastoid flap for pedicled reconstruction in head & neck surgery- revisiting the anatomy and technique
Authors: Srivastava Apurva , Kumar Tarun , Pandey Shashi Kant , Shukla Ram Chandra , Pai Esha , Pandey Manoj 
Published: December 2021

AbstractBackgroundPrevious studies on sternocleidomastoid flaps, have defined the importance of preserving sternocleidomastoid (SCM) branch of superior thyroid artery (STA). This theory drew criticism, as this muscle is known to be a type II muscle, i.e., the muscle has one dominant pedicle (branches from the occipital artery at the superior pole) and smaller vascular pedicles entering the belly of muscle (branches from STA and thyrocervical trunk) at the middle and lower pole respectively. It was unlikely for the SCM branch of STA to supply the upper and lower thirds of the muscle. We undertook a cadaveric angiographic study to investigate distribution of STA supply to SCM muscle.MethodsIt is a cross-sectional descriptive study on 10 cadaveric SCM muscles along with ipsilateral STA which were evaluated with angiography using diatrizoate (urograffin) dye. Radiographic films were interpreted looking at the opacification of the muscle. Results were analyzed using frequency distribution and percentage.ResultsOut of ten specimens, near complete opacification was observed in eight SCM muscle specimens. While one showed poor uptake in the lower third of the muscle, the other showed poor uptake in the upper third segment of muscle.ConclusionBased on the above findings we suggest to further investigate sternocleidomastoid muscle as a type III flap, as the STA branch also supplies the whole muscle along with previously described pedicle from occipital artery. However, this needs to be further corroborated intra-operatively using scanning laser doppler. This also explains better survival rates of superior thyroid artery based sternomastoid flaps.
Effectiveness of a large-scale, sustained and comprehensive community health worker program in improving population health: the experience of an urban health district in South Africa
Authors: Thomas L. S. , Buch E. , Pillay Y. , Jordaan J. 
Published: December 2021

Abstract
Introduction
South Africa is an upper middle-income country with wide wealth inequality. It faces a quadruple burden of disease and poor health outcomes, with access to appropriate and adequate health care a challenge for millions of South Africans. The introduction of large-scale, comprehensive community health worker (CHW) programs in the country, within the context of implementing universal health coverage, was anticipated to improve population health outcomes. However, there is inadequate local (or global) evidence on whether such programs are effective, especially in urban settings.

Methods
This study is part of a multi-method, quasi-experimental intervention study measuring effectiveness of a large-scale CHW program in a health district in an urban province of South Africa, where CHWs now support approximately one million people in 280,000 households. Using interviewer administered questionnaires, a 2019 cross-sectional survey of 417 vulnerable households with long-term CHW support (intervention households) are compared to 417 households with no CHW support (control households). Households were selected from similar vulnerable areas from all sub-levels of the Ekurhuleni health district.

Results
The 417 intervention and control households each had good health knowledge. Compared to controls, intervention households with long-term comprehensive CHW support were more likely to access early care, get diagnosed for a chronic condition, be put on treatment and be well controlled on chronic treatment. They were also more likely to receive a social grant, and have a birth certificate or identity document. The differences were statistically significant for social support, health seeking behavior, and health outcomes for maternal, child health and chronic care.

Conclusion
A large-scale and sustained comprehensive CHW program in an urban setting improved access to social support, chronic and minor acute health services at household and population level through better health-seeking behavior and adherence to treatment. Direct evidence from households illustrated that such community health worker programs are therefore effective and should be part of health systems in low- and middle-income countries.
Health workforce strategies in response to major health events: a rapid scoping review with lessons learned for the response to the COVID-19 pandemic
Authors: Coates Alison , Fuad Asli-Oubah , Hodgson Amanda , Bourgeault Ivy Lynn 
Published: December 2021

Abstract
Background
The early weeks of the COVID-19 pandemic brought multiple concurrent threats—high patient volume and acuity and, simultaneously, increased risk to health workers. Healthcare managers and decision-makers needed to identify strategies to mitigate these adverse conditions. This paper reports on the health workforce strategies implemented in relation to past large-scale emergencies (including natural disasters, extreme weather events, and infectious disease outbreaks).

Methods
We conducted a rapid scoping review of health workforce responses to natural disasters, extreme weather events, and infectious disease outbreaks reported in the literature between January 2000 and April 2020. The 3582 individual results were screened to include articles which described surge responses to past emergencies for which an evaluative component was included in the report. A total of 37 articles were included in our analysis.

Results
The reviewed literature describes challenges related to increased demand for health services and a simultaneous decrease in the availability of the workforce. Many articles also described impacts on infrastructure that hindered emergency response. These challenges aligned well with those faced during the early days of the COVID-19 pandemic. In the published literature, the workforce strategies that were described aimed either to increase the numbers of health workers in a given area, to increase the flexibility of the health workforce to meet needs in new ways, or to support and sustain health workers in practice. Workforce responses addressed all types and cadres of health workers and were executed in a wide range of settings. We additionally report on the barriers and facilitators of workforce strategies reported in the literature reviewed. The strategies that were reported in the literature aligned closely with our COVID-specific conceptual framework of workforce capacity levers, suggesting that our framework may have heuristic value across many types of health disasters.

Conclusions
This research highlights a key deficiency with the existing literature on workforce responses to emergencies: most papers lack substantive evaluation of the strategies implemented. Future research on health workforce capacity interventions should include robust evaluation of impact and effectiveness.
Engaging citizens in the development of a health system performance assessment framework: a case study in Ireland
Authors: Brito Fernandes Óscar , Barbazza Erica , Ivanković Damir , Jansen Tessa , Klazinga Niek S. , Kringos Dionne S. 
Published: December 2021

Abstract
Background
The launch in 2017 of the Irish 10-year reform programme Sláintecare represents a key commitment in the future of the health system. An important component of the programme was the development of a health system performance assessment (HSPA) framework. In 2019, the Department of Health of Ireland (DoH) and Health Service Executive (HSE) commissioned the technical support of researchers to develop an outcome-oriented HSPA framework which should reflect the shared priorities of multiple stakeholders, including citizens. This study describes the method applied in the Irish context and reflects on the added value of using a citizen panel in the development of an HSPA framework.

Methods
A panel of 15 citizens was convened, recruited by a third-party company using a sampling strategy to achieve a balanced mix representing the Irish society. Panellists received lay-language preparatory materials before the meeting. Panellists used a three-colour scheme to signal the importance of performance measures. An exit questionnaire was administered to understand how participants experienced being part of the panel. The citizen panel was the first in a series of three panels towards the development of the HSPA framework, followed by panels including representatives of the DoH and HSE, and representatives from professional associations and special interest groups.

Results
The citizen panel generated 249 health performance measures ranging across 13 domains. Top-ranking domains to the citizen panel (people-centredness, coordination of care, and coverage) were less prioritized by the other panels; domains less prioritized by the citizen panel, such as accessibility, responsiveness, efficiency, and effectiveness, were of higher priority in the other panels. Citizen panellists shared a similar understanding of what a citizen panel involves and described their experience at the panel as enjoyable, interesting, and informative.

Conclusions
The priorities of the citizen panel were accounted for during all phases of developing the HSPA framework. This was possible by adopting an inclusive development process and by engaging citizens early on. Citizen engagement in HSPA development is essential for realizing citizen-driven healthcare system performance and generating trust and ownership in performance intelligence. Future research could expand the use of citizen panels to assess, monitor, and report on the performance of healthcare systems.
Dynamic transcriptome analysis reveals signatures of paradoxical effect of vemurafenib on human dermal fibroblasts
Authors: Corrales Eyleen , Levit-Zerdoun Ella , Metzger Patrick , Kowar Silke , Ku Manching , Brummer Tilman , Boerries Melanie 
Published: December 2021

Abstract
Background
Vemurafenib (PLX4032) is one of the most frequently used treatments for late-stage melanoma patients with the BRAFV600E mutation; however, acquired resistance to the drug poses as a major challenge. It remains to be determined whether off-target effects of vemurafenib on normal stroma components could reshape the tumor microenvironment in a way that contributes to cancer progression and drug resistance.

Methods
By using temporally-resolved RNA- and ATAC-seq, we studied the early molecular changes induced by vemurafenib in human dermal fibroblast (HDF), a main stromal component in melanoma and other tumors with high prevalence of BRAFV600 mutations.

Results
Transcriptomics analyses revealed a stepwise up-regulation of proliferation signatures, together with a down-regulation of autophagy and proteolytic processes. The gene expression changes in HDF strongly correlated in an inverse way with those in BRAFV600E mutant malignant melanoma (MaMel) cell lines, consistent with the observation of a paradoxical effect of vemurafenib, leading to hyperphosphorylation of MEK1/2 and ERK1/2. The transcriptional changes in HDF were not strongly determined by alterations in chromatin accessibility; rather, an already permissive chromatin landscape seemed to facilitate the early accessibility to MAPK/ERK-regulated transcription factor binding sites. Combinatorial treatment with the MEK inhibitor trametinib did not preclude the paradoxical activation of MAPK/ERK signaling in HDF. When administered together, vemurafenib partially compensated for the reduction of cell viability and proliferation induced by trametinib. These paradoxical changes were restrained by using the third generation BRAF inhibitor PLX8394, a so-called paradox breaker compound. However, the advantageous effects on HDF during combination therapies were also lost.

Conclusions
Vemurafenib induces paradoxical changes in HDF, enabled by a permissive chromatin landscape. These changes might provide an advantage during combination therapies, by compensating for the toxicity induced in stromal cells by less specific MAPK/ERK inhibitors. Our results highlight the relevance of evaluating the effects of the drugs on non-transformed stromal components, carefully considering the implications of their administration either as mono- or combination therapies.
Interleukin-1 receptor antagonist inhibits metastatic potential by down-regulating CXCL12/CXCR4 signaling axis in colorectal cancer
Authors: Ma Jiachi , Liang Wanqing , Qiang Yaosheng , Li Lei , Du Jun , Pan Chengwu , Chen Bangling , Zhang Chensong , Chen Yuzhong , Wang Qingkang 
Published: December 2021

Abstract
Background
The aim of this study was to investigate the co-operative role of CXCR4/CXCL12 axis and IL-1Ra in metastatic processes mechanism by interactions between colorectal cancer cells and stromal cells in their microenvironment.

Methods
Expression of IL-1α, interleukin-1 receptor type I (IL-1 RI), CXCL12 and CXCR4 mRNA and proteins were determined by RT-PCR and Western blot. The effect of secreted level of CXCL12 by IL-1Ra on fibroblasts was measured by ELISA. CXCL12 regulate metastatic potential of colorectal cancer was evaluated by proliferation, invasion and angiogenesis assays, respectively, in which invasion and angiogenesis assays used an in vitro system consisting of co-cultured colorectal cells and stromal cells.

Results
IL-1α was expressed in high liver metastatic colorectal cancer cell lines (HT-29 and WiDr). The colorectal cancer cell-derived IL-1α and rIL-1α significantly promoted CXCL12 expression by fibroblasts, and this enhancing effect can be significantly inhibited by IL-1Ra (P < 0.01). CXCL12 not only enhanced the migration and proliferation of human umbilical vein endothelial cells, but also significantly enhanced angiogenesis (P < 0.01). Furthermore, the high liver-metastatic colorectal cancer cell line (HT-29), which secretes IL-1α, significantly enhanced angiogenesis compared to the low liver-metastatic cell line (CaCo-2), which does not produce IL-1α (P < 0.01). On the contrary, IL-1Ra can significantly inhibit migration, proliferation and angiogenesis (P < 0.01).

Conclusion
Autocrine IL-1α and paracrine CXCL12 co-enhances the metastatic potential of colorectal cancer cells; IL-1Ra can inhibit the metastatic potential of colorectal cancer cells via decrease IL-1α/CXCR4/CXCL12 signaling pathways.

Graphical Abstract
SIRT5 functions as a tumor suppressor in renal cell carcinoma by reversing the Warburg effect
Authors: Yihan Liu , Xiaojing Wang , Ao Liu , Chuanjie Zhang , Haofei Wang , Yan Shen , Hongchao He 
Published: December 2021

Abstract
Background
The aim of this study was to investigate the biological functions and underlying mechanisms of SIRT5 in clear cell renal cell carcinoma (ccRCC).

Methods
SIRT5 expression data in The Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC) were selected, and the correlations between SIRT5 expression and various clinicopathological parameters were analysed. SIRT5 expression in ccRCC tissues was examined using immunohistochemistry. Stable cell lines with SIRT5 knockdown were established. In vitro and in vivo experiments were conducted to investigate the functional roles of SIRT5 in the cellular biology of ccRCC, including cell viability assays, wound healing assays, soft agar colony formation assays, Transwell invasion assays, qRT–PCR, and Western blotting. In addition, microarrays, rescue experiments and Western blotting were used to investigate the molecular mechanisms underlying SIRT5 functions.

Results
SIRT5 expression was downregulated in ccRCC compared with normal tissues, which correlated with a poor prognosis of ccRCC. SIRT5 knockdown significantly increased cell proliferation, migration and invasion in vitro. In vivo experiments revealed that SIRT5 knockdown promoted ccRCC tumorigenesis and metastasis. Mechanistically, SIRT5 deglycosylated PDHA1 at K351 and increased PDC activity, thereby altering the metabolic crosstalk with the TCA cycle and inhibiting the Warburg effect. SIRT5 overexpression was related to low succinylation of PDHA1.

Conclusions
Downregulated SIRT5 expression in ccRCC accelerated the Warburg effect through PDHA1 hypersuccinylation and induced tumorigenesis and progression, indicating that SIRT5 may become a potential target for ccRCC therapy.