bluuebunny/crossref_metadata_2025_split huggingface dataset:
NLRP3 inflammasome-mediated cytokine production and pyroptosis cell death in breast cancer
Authors: Faria Sara Socorro , Costantini Susan , de Lima Vladmir Cláudio Cordeiro , de Andrade Victor Pianna , Rialland Mickaël , Cedric Rebe , Budillon Alfredo , Magalhães Kelly Grace 
Published: April 2021

AbstractBreast cancer is the most diagnosed malignancy in women. Increasing evidence has highlighted the importance of chronic inflammation at the local and/or systemic level in breast cancer pathobiology, influencing its progression, metastatic potential and therapeutic outcome by altering the tumor immune microenvironment. These processes are mediated by a variety of cytokines, chemokines and growth factors that exert their biological functions either locally or distantly. Inflammasomes are protein signaling complexes that form in response to damage- and pathogen-associated molecular patterns (DAMPS and PAMPS), triggering the release of pro-inflammatory cytokines. The dysregulation of inflammasome activation can lead to the development of inflammatory diseases, neurodegeneration, and cancer. A crucial signaling pathway leading to acute and chronic inflammation occurs through the activation of NLRP3 inflammasome followed by caspase 1-dependent release of IL-1β and IL-18 pro-inflammatory cytokines, as well as, by gasdermin D-mediated pyroptotic cell death. In this review we focus on the role of NLRP3 inflammasome and its components in breast cancer signaling, highlighting that a more detailed understanding of the clinical relevance of these pathways could significantly contribute to the development of novel therapeutic strategies for breast cancer.
Gene coexpression network approach to develop an immune prognostic model for pancreatic adenocarcinoma
Authors: Gu Xiaoqiang , Zhang Qiqi , Wu Xueying , Fan Yue , Qian Jianxin 
Published: April 2021

Abstract
Background
Pancreatic adenocarcinoma (PAAD) is a nonimmunogenic tumor, and very little is known about the relationship between the host immune response and patient survival. We aimed to develop an immune prognostic model (IPM) and analyze its relevance to the tumor immune profiles of patients with PAAD.

Methods
We investigated differentially expressed genes between tumor and normal tissues in the TCGA PAAD cohort. Immune-related genes were screened from highly variably expressed genes with weighted gene correlation network analysis (WGCNA) to construct an IPM. Then, the influence of IPM on the PAAD immune profile was comprehensively analyzed.

Results
A total of 4902 genes highly variably expressed among primary tumors were used to construct a weighted gene coexpression network. One hundred seventy-five hub genes in the immune-related module were used for machine learning. Then, we established an IPM with four core genes (FCGR2B, IL10RA, and HLA-DRA) to evaluate the prognosis. The risk score predicted by IPM was an independent prognostic factor and had a high predictive value for the prognosis of patients with PAAD. Moreover, we found that the patients in the low-risk group had higher cytolytic activity and lower innate anti-PD-1 resistance (IPRES) signatures than patients in the high-risk group.

Conclusions
Unlike the traditional methods that use immune-related genes listed in public databases to screen prognostic genes, we constructed an IPM through WGCNA to predict the prognosis of PAAD patients. In addition, an IPM prediction of low risk indicated enhanced immune activity and a decreased anti-PD-1 therapeutic response.
High-salt diet downregulates TREM2 expression and blunts efferocytosis of macrophages after acute ischemic stroke
Authors: Hu Mengyan , Lin Yinyao , Men Xuejiao , Wang Shisi , Sun Xiaobo , Zhu Qiang , Lu Danli , Liu Sanxin , Zhang Bingjun , Cai Wei , Lu Zhengqi 
Published: April 2021

Abstract
Background
A high-salt diet (HSD) is one of the major risk factors for acute ischemic stroke (AIS). As a potential mechanism, surplus salt intake primes macrophages towards a proinflammatory phenotype. In this study, whether HSD could blunt the efferocytic capability of macrophages after ischemic stroke, thus exacerbating post-stroke neural inflammation, was investigated.

Methods
Wild-type male C57BL/6 mice were fed with fodder containing 8% sodium chloride for 4 weeks and subjected to transient middle cerebral occlusion (tMCAO). Disease severity, macrophage polarization as well as efferocytic capability were evaluated. Bone marrow-derived macrophages were cultured in vitro, and the impact of high salinity on their efferocytic activity, as well as their expression of phagocytic molecules, were analyzed. The relationships among sodium concentration, macrophage phenotype, and disease severity in AIS patients were explored.

Results
HSD-fed mice displayed increased infarct volume and aggravated neurological deficiency. Mice fed with HSD suffered exacerbated neural inflammation as shown by higher inflammatory mediator expression and immune cell infiltration levels. Infiltrated macrophages within stroke lesions in HSD-fed mice exhibited a shift towards proinflammatory phenotype and impaired efferocytic capability. As assessed with a PCR array, the expression of triggering receptor expressed on myeloid cells 2 (TREM2), a receptor relevant to phagocytosis, was downregulated in high-salt-treated bone marrow-derived macrophages. Enhancement of TREM2 signaling restored the efferocytic capacity and cellular inflammation resolution of macrophages in a high salinity environment in vitro and in vivo. A high concentration of urine sodium in AIS patients was found to be correlated with lower TREM2 expression and detrimental stroke outcomes.

Conclusions
HSD inhibited the efferocytic capacity of macrophages by downregulating TREM2 expression, thus impeding inflammation resolution after ischemic stroke. Enhancing TREM2 signaling in monocytes/macrophages could be a promising therapeutic strategy to enhance efferocytosis and promote post-stroke inflammation resolution.
Alcohol marketing versus public health: David and Goliath?
Authors: Madden Mary , McCambridge Jim 
Published: April 2021

AbstractBackgroundAlcohol harms are rising globally, and alcohol policies, where they exist, are weak or under-developed. Limited progress has been made since the formulation of the World Health Organisation (WHO) Global Strategy in 2010. WHO is seeking to accelerate progress in implementing international efforts to reduce the harmful use of alcohol. The threat to global health posed by tobacco is well understood by policy communities and populations globally; by contrast alcohol is much less so, despite available evidence.The competition for epistemic authorityGlobal alcohol corporations have sought to become trusted sources of advice for policy makers and consumers, while continuing to grow their markets. Evidence-informed public health messaging faces formidable competition from transnational corporations as the worlds of corporate and political communications, social and mainstream media become increasingly linked, presenting new opportunities for corporate actors to shape global health governance. Alcohol messaging that uses means of persuasion tied to industry agendas does not tell a clear story about commercial determinants of health, and does not contribute to health improvement. On the contrary, the basic tenets of an evidence-informed population-based approach are denied and the policy measures supported by high quality evidence are being opposed, because they are inimical to commercial interests. A David and Goliath metaphor for this state of affairs, which seems to fit at first glance, may unwittingly reinforce the status quo.ConclusionPublic opinion on alcohol and policy issues varies across time and place and can be influenced by dedicated public health interventions. Alcohol marketing dominates people’s thinking about alcohol because we currently allow this to happen. Greater ambition is needed in developing countermarketing and other interventions to promote evidence-informed ideas with the public. Alcohol policies need to be further developed, and implemented more widely, in order to arrest the growing burden of alcohol harms across the world.
Decision-making process for introduction of maternal vaccines in Kenya, 2017–2018
Authors: Otieno Nancy A. , Malik Fauzia A. , Nganga Stacy W. , Wairimu Winnie N. , Ouma Dominic O. , Bigogo Godfrey M. , Chaves Sandra S. , Verani Jennifer R. , Widdowson Marc-Alain , Wilson Andrew D. , Bergenfeld Irina , Gonzalez-Casanova Ines , Omer Saad B. 
Published: April 2021

Abstract
Background
Maternal immunization is a key strategy for reducing morbidity and mortality associated with infectious diseases in mothers and their newborns. Recent developments in the science and safety of maternal vaccinations have made possible development of new maternal vaccines ready for introduction in low- and middle-income countries. Decisions at the policy level remain the entry point for maternal immunization programs. We describe the policy and decision-making process in Kenya for the introduction of new vaccines, with particular emphasis on maternal vaccines, and identify opportunities to improve vaccine policy formulation and implementation process.

Methods
We conducted 29 formal interviews with government officials and policy makers, including high-level officials at the Kenya National Immunization Technical Advisory Group, and Ministry of Health officials at national and county levels. All interviews were recorded and transcribed. We analyzed the qualitative data using NVivo 11.0 software.

Results
All key informants understood the vaccine policy formulation and implementation processes, although national officials appeared more informed compared to county officials. County officials reported feeling left out of policy development. The recent health system decentralization had both positive and negative impacts on the policy process; however, the negative impacts outweighed the positive impacts. Other factors outside vaccine policy environment such as rumours, sociocultural practices, and anti-vaccine campaigns influenced the policy development and implementation process.

Conclusions
Public policy development process is complex and multifaceted by its nature. As Kenya prepares for introduction of other maternal vaccines, it is important that the identified policy gaps and challenges are addressed.
Resolvin D1 reduces cancer growth stimulating a protective neutrophil-dependent recruitment of anti-tumor monocytes
Authors: Mattoscio Domenico , Isopi Elisa , Lamolinara Alessia , Patruno Sara , Medda Alessandro , De Cecco Federica , Chiocca Susanna , Iezzi Manuela , Romano Mario , Recchiuti Antonio 
Published: April 2021

Abstract
Background
Innovative therapies to target tumor-associated neutrophils (PMN) are of clinical interest, since these cells are centrally involved in cancer inflammation and tumor progression. Resolvin D1 (RvD1) is a lipid autacoid that promotes resolution of inflammation by regulating the activity of distinct immune and non-immune cells. Here, using human papilloma virus (HPV) tumorigenesis as a model, we investigated whether RvD1 modulates PMN to reduce tumor progression.

Methods
Growth-curve assays with multiple cell lines and in vivo grafting of two distinct HPV-positive cells in syngeneic mice were used to determine if RvD1 reduced cancer growth. To investigate if and how RvD1 modulates PMN activities, RNA sequencing and multiplex cytokine ELISA of human PMN in co-culture with HPV-positive cells, coupled with pharmacological depletion of PMN in vivo, were performed. The mouse intratumoral immune cell composition was evaluated through FACS analysis. Growth-curve assays and in vivo pharmacological depletion were used to evaluate anti-tumor activities of human and mouse monocytes, respectively. Bioinformatic analysis of The Cancer Genome Atlas (TCGA) database was exploited to validate experimental findings in patients.

Results
RvD1 decreased in vitro and in vivo proliferation of human and mouse HPV-positive cancer cells through stimulation of PMN anti-tumor activities. In addition, RvD1 stimulated a PMN-dependent recruitment of classical monocytes as key determinant to reduce tumor growth in vivo. In human in vitro systems, exposure of PMN to RvD1 increased the production of the monocyte chemoattractant protein-1 (MCP-1), and enhanced transmigration of classical monocytes, with potent anti-tumor actions, toward HPV-positive cancer cells. Consistently, mining of immune cells infiltration levels in cervical cancer patients from the TCGA database evidenced an enhanced immune reaction and better clinical outcomes in patients with higher intratumoral monocytes as compared to patients with higher PMN infiltration.

Conclusions
RvD1 reduces cancer growth by activating PMN anti-cancer activities and encouraging a protective PMN-dependent recruitment of anti-tumor monocytes. These findings demonstrate efficacy of RvD1 as an innovative therapeutic able to stimulate PMN reprogramming to an anti-cancer phenotype that restrains tumor growth.
Longitudinal assessment of IFN-I activity and immune profile in critically ill COVID-19 patients with acute respiratory distress syndrome
Authors:   the RICO study group, Venet Fabienne , Cour Martin , Rimmelé Thomas , Viel Sebastien , Yonis Hodane , Coudereau Remy , Amaz Camille , Abraham Paul , Monard Céline , Casalegno Jean-Sebastien , Brengel-Pesce Karen , Lukaszewicz Anne-Claire , Argaud Laurent , Monneret Guillaume 
Published: April 2021

AbstractBackgroundSince the onset of the pandemic, only few studies focused on longitudinal immune monitoring in critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS) whereas their hospital stay may last for several weeks. Consequently, the question of whether immune parameters may drive or associate with delayed unfavorable outcome in these critically ill patients remains unsolved.MethodsWe present a dynamic description of immuno-inflammatory derangements in 64 critically ill COVID-19 patients including plasma IFNα2 levels and IFN-stimulated genes (ISG) score measurements.ResultsARDS patients presented with persistently decreased lymphocyte count and mHLA-DR expression and increased cytokine levels. Type-I IFN response was initially induced with elevation of IFNα2 levels and ISG score followed by a rapid decrease over time. Survivors and non-survivors presented with apparent common immune responses over the first 3 weeks after ICU admission mixing gradual return to normal values of cellular markers and progressive decrease of cytokines levels including IFNα2. Only plasma TNF-α presented with a slow increase over time and higher values in non-survivors compared with survivors. This paralleled with an extremely high occurrence of secondary infections in COVID-19 patients with ARDS.ConclusionsOccurrence of ARDS in response to SARS-CoV2 infection appears to be strongly associated with the intensity of immune alterations upon ICU admission of COVID-19 patients. In these critically ill patients, immune profile presents with similarities with the delayed step of immunosuppression described in bacterial sepsis.
Computational methods for chromosome-scale haplotype reconstruction
Authors: Garg Shilpa 
Published: April 2021

AbstractHigh-quality chromosome-scale haplotype sequences of diploid genomes, polyploid genomes, and metagenomes provide important insights into genetic variation associated with disease and biodiversity. However, whole-genome short read sequencing does not yield haplotype information spanning whole chromosomes directly. Computational assembly of shorter haplotype fragments is required for haplotype reconstruction, which can be challenging owing to limited fragment lengths and high haplotype and repeat variability across genomes. Recent advancements in long-read and chromosome-scale sequencing technologies, alongside computational innovations, are improving the reconstruction of haplotypes at the level of whole chromosomes. Here, we review recent and discuss methodological progress and perspectives in these areas.
Impact of early detection and vaccination strategy in COVID-19 eradication program in Jakarta, Indonesia
Authors: Aldila Dipo , Samiadji Brenda M. , Simorangkir Gracia M. , Khosnaw Sarbaz H. A. , Shahzad Muhammad 
Published: April 2021

AbstractObjectiveSeveral essential factors have played a crucial role in the spreading mechanism of COVID-19 (Coronavirus disease 2019) in the human population. These factors include undetected cases, asymptomatic cases, and several non-pharmaceutical interventions. Because of the rapid spread of COVID-19 worldwide, understanding the significance of these factors is crucial in determining whether COVID-19 will be eradicated or persist in the population. Hence, in this study, we establish a new mathematical model to predict the spread of COVID-19 considering mentioned factors.ResultsInfection detection and vaccination have the potential to eradicate COVID-19 from Jakarta. From the sensitivity analysis, we find that rapid testing is crucial in reducing the basic reproduction number when COVID-19 is endemic in the population rather than contact trace. Furthermore, our results indicate that a vaccination strategy has the potential to relax social distancing rules, while maintaining the basic reproduction number at the minimum possible, and also eradicate COVID-19 from the population with a higher vaccination rate. In conclusion, our model proposed a mathematical model that can be used by Jakarta’s government to relax social distancing policy by relying on future COVID-19 vaccine potential.
The power of three-dimensional printing technology in functional restoration of rare maxillomandibular deformity due to genetic disorder: a case report
Authors: Oren Daniel , Dror Amiel A. , Bramnik Tania , Sela Eyal , Granot Igal , Srouji Samer 
Published: April 2021

Abstract
Background
Thalassemia is an inherited autosomal recessive blood disorder causing abnormal formation of hemoglobin, known as a syndrome of anemia with microcytic erythrocytes. It is the most common genetic disorder worldwide, with a high prevalence among individuals of Mediterranean descent. The state of homozygosity of the beta-globin mutated gene is known as beta-thalassemia major, and these patients require regular blood transfusions and iron chelation therapy for survival. The rapid loss of red blood cells among affected individuals activates compensatory mechanisms of excessive medullary and extramedullary hematopoiesis, leading to severe skeletal bone deformity.

Case presentation
We present the case of a 39-year-old Bedouin male, diagnosed with beta-thalassemia major at infancy, with diagnosed homozygosity for the intervening sequence 2-1 (guanine > adenine) mutation. Since early infancy, he started receiving blood transfusions with a gradual increase in treatment frequency through adulthood due to the severe clinical progression of the disease. He was referred to the oral and maxillofacial surgery department at Galilee Medical Center to evaluate his facial deformity in the upper jaw and treat his severe periodontal disease. The patient presented maxillary overgrowth, and severe dental deformity resulted in progressive disfigurement and difficulty chewing, swallowing, and speaking. To address the challenge of surgical treatment, we utilized the advantage of three-dimensional planning and printing technology to simulate the optimal result. Resection of maxillary bone overgrowth and insertion of custom-made subperiosteal implants were followed by rehabilitation of both jaws to the patients' satisfaction at 3-year follow-up.

Conclusions
The ongoing implementation of state-of-the-art technologies such as virtual reality and three-dimensional printing has become a prominent component in surgical toolsets. Comprehensive case simulation and accurate planning before surgery will improve surgical results and patient satisfaction. This approach is highly advocated when approaching a case of rare maxillofacial deformity associated with either genetic or orphan diseases.
Hidradenoma papilliferum of the hymen: a case report
Authors: Birge Ozer , Bakır Mehmet Sait , Karadag Ceyda , Eldarova Zivar , Simsek Tayup 
Published: April 2021

Abstract
Background
Hidradenoma papilliferum is a rare benign neoplasm arising from apocrine glands. It occurs commonly on the anogenital region of middle-aged women. It usually presents as a slow growing, solitary asymptomatic, skin colored or red nodule less than 1 cm in diameter.

Case presentation
The case is a 38-year-old, white woman who presented with a painful nodule occurring within a month in the himenal region of the posterior vaginal introitus. The nodule was excisied and the histology revealed a hidradenoma papilliferum. The diagnosis and treatment of hidradenoma papilliferum is possible with surgical removal and histopathological evaluation of nodules.

Conclusion
When an adult woman presents with a noduler lesion in the anogenital area, sexually transmitted diseases and other benign and malignant vulvar lesions, as well as malignant transformation is very rare but,should be kept in mind; however because it has been reported and long-term clinical follow-up is suggested
Extracellular vesicles derived from umbilical cord mesenchymal stromal cells alleviate pulmonary fibrosis by means of transforming growth factor-β signaling inhibition
Authors: Shi Liyan , Ren Jing , Li Jiping , Wang Dongxu , Wang Yusu , Qin Tao , Li Xiuying , Zhang Guokun , Li Chunyi , Wang Yimin 
Published: April 2021

Abstract
Background
Pulmonary fibrosis (PF), the end point of interstitial lung diseases, is characterized by myofibroblast over differentiation and excessive extracellular matrix accumulation, leading to progressive organ dysfunction and usually a terminal outcome. Studies have shown that umbilical cord-derived mesenchymal stromal cells (uMSCs) could alleviate PF; however, the underlying mechanism remains to be elucidated.

Methods
The therapeutic effects of uMSC-derived extracellular vesicles (uMSC-EVs) on PF were evaluated using bleomycin (BLM)-induced mouse models. Then, the role and mechanism of uMSC-EVs in inhibiting myofibroblast differentiation were investigated in vivo and in vitro.

Results
Treatment with uMSC-EVs alleviated the PF and enhanced the proliferation of alveolar epithelial cells in BLM-induced mice, thus improved the life quality, including the survival rate, body weight, fibrosis degree, and myofibroblast over differentiation of lung tissue. Moreover, these effects of uMSC-EVs on PF are likely achieved by inhibiting the transforming growth factor-β (TGF-β) signaling pathway, evidenced by decreased expression levels of TGF-β2 and TGF-βR2. Using mimics of uMSC-EV-specific miRNAs, we found that miR-21 and miR-23, which are highly enriched in uMSC-EVs, played a critical role in inhibiting TGF-β2 and TGF-βR2, respectively.

Conclusion
The effects of uMSCs on PF alleviation are likely achieved via EVs, which reveals a new role of uMSC-EV-derived miRNAs, opening a novel strategy for PF treatment in the clinical setting.