bluuebunny/crossref_metadata_2025_split huggingface dataset:
BMI1 promotes osteosarcoma proliferation and metastasis by repressing the transcription of SIK1
Authors: Wang Qiang , Wu Yinghui , Lin Meng , Wang Gaigai , Liu Jinyan , Xie Min , Zheng Bo , Shen Cong , Shen Jun 
Published: March 2022

Abstract
Background
Osteosarcoma (OS) is the most common malignant tumor of bone, and the clinical efficacy of current treatments and associated survival rates need to be further improved by employing novel therapeutic strategies. Although various studies have shown that BMI1 protein is universally upregulated in OS cells and tissues, its specific role and underlying mechanism have not yet been fully explored.

Methods
Expression of BMI1 protein in OS cells was detected by western blot. The effect of BMI1 on proliferation and migration of OS cells (143B and U-2OS cell lines) was investigated in vitro using CCK-8, colony formation and transwell assays, and in vivo using subcutaneous tumorigenesis and lung metastasis assays in xenograft nude mice. Expression of epithelial–mesenchymal transition (EMT)-associated proteins was detected by immunofluorescence imaging. Bioinformatic analysis was performed using ENCODE databases to predict downstream targets of BMI1. SIK1 mRNA expression in osteosarcoma cells was detected by quantitative real-time reverse transcription PCR (qPCR). Chromatin immunoprecipitation-qPCR (ChIP-qPCR) was used to investigate expression of BMI1-associated, RING1B-associated, H2AK119ub-associated and H3K4me3-associated DNA at the putative binding region of BMI1 on the SIK1 promoter in OS cells.

Results
Using both in vitro and in vivo experimental approaches, we found that BMI1 promotes OS cell proliferation and metastasis. The tumor suppressor SIK1 was identified as the direct target gene of BMI1 in OS cells. In vitro experiments demonstrated that SIK1 could inhibit proliferation and migration of OS cells. Inhibition of SIK1 largely rescued the altered phenotypes of BMI1-deficient OS cells. Mechanistically, we demonstrated that BMI1 directly binds to the promoter region of SIK1 in a complex with RING1B to promote monoubiquitination of histone H2A at lysine 119 (H2AK119ub) and inhibit H3K4 trimethylation (H3K4me3), resulting in inhibition of SIK1 transcription. We therefore suggest that BMI1 promotes OS cell proliferation and metastasis by inhibiting SIK1.

Conclusions
Our results reveal a novel molecular mechanism of OS development promoted by BMI1 and provides a new potential target for OS treatment.
How to make healthy early childhood development more likely in marginalized Roma communities: a concept mapping approach
Authors: Chovan Shoshana , Filakovska Bobakova Daniela , Bosakova Lucia , Madarasova Geckova Andrea , Reijneveld Sijmen A. , de Kroon Marlou L. A. 
Published: March 2022

Abstract
Background
This study aims to assess which measures could improve the healthy early childhood development of children from marginalized Roma communities and to identify priority measures.

Methods
Concept mapping approach was used, using mixed methods. In total 54 professionals, including social workers, educators, health care providers, municipality representatives, and project managers participated in our study.

Results
Four distinct clusters of measures targeting living conditions, public resources, healthcare and community interventions, and 27 individual priority measures of highest urgency and feasibility were identified. The cluster ‘Targeting living conditions’, was rated as the most urgent but least feasible, whereas the cluster ‘Targeting health care’, was considered least urgent but most feasible. Among the 27 priority measures, ‘Planning parenthood’ and ‘Scaling up existing projects’ had the highest priority.

Conclusion
Our results reflect the public and political discourse and indicate significant barriers to implementation. Reducing inequalities in early childhood needs to be addressed through coordinated efforts.
Chicago sky blue 6B inhibits α-synuclein aggregation and propagation
Authors: Min Joo-Ok , Strohäker Timo , Jeong Byung-Chul , Zweckstetter Markus , Lee Seung-Jae 
Published: March 2022

AbstractAbnormal deposition of α-synuclein aggregates in Lewy bodies and Lewy neurites is the hallmark lesion in Parkinson’s disease (PD). These aggregates, thought to be the culprit of disease pathogenesis, spread throughout the brain as the disease progresses. Agents that inhibit α-synuclein aggregation and/or spread of aggregates would thus be candidate disease-modifying drugs. Here, we found that Chicago sky blue 6B (CSB) may be such a drug, showing that it inhibits α-synuclein aggregation and cell-to-cell propagation in both in vitro and in vivo models of synucleinopathy. CSB inhibited the fibrillation of α-synuclein in a concentration-dependent manner through direct binding to the N-terminus of α-synuclein. Furthermore, both seeded polymerization and cell-to-cell propagation of α-synuclein were inhibited by CSB treatment. Notably, CSB alleviated behavioral deficits and neuropathological features, such as phospho-α-synuclein and astrogliosis, in A53T α-synuclein transgenic mice. These results indicate that CSB directly binds α-synuclein and inhibits its aggregation, thereby blocking α-synuclein cell-to-cell propagation.
Anti-tumor activity of cetuximab plus avelumab in non-small cell lung cancer patients involves innate immunity activation: findings from the CAVE-Lung trial
Authors: Della Corte Carminia Maria , Fasano Morena , Ciaramella Vincenza , Cimmino Flora , Cardnell Robert , Gay Carl M. , Ramkumar Kavya , Diao Lixia , Di Liello Raimondo , Viscardi Giuseppe , Famiglietti Vincenzo , Ciardiello Davide , Martini Giulia , Napolitano Stefania , Tuccillo Concetta , Troiani Teresa , Martinelli Erika , Wang Jing , Byers Lauren , Morgillo Floriana , Ciardiello Fortunato 
Published: March 2022

Abstract
Background
We recently conducted Cetuximab-AVElumab-Lung (CAVE-Lung), a proof-of-concept, translational and clinical trial, to evaluate the combination of two IgG1 monoclonal antibodies (mAb): avelumab, an anti-PD-L1 drug, and cetuximab, an anti-epidermal growth factor receptor (EGFR) drug, as second- or third-line treatment in non-small cell lung cancer (NSCLC) patients. We have reported clinically relevant anti-tumor activity in 6/16 patients. Clinical benefit was accompanied by Natural Killer (NK) cell-mediated antibody-dependent cell cytotoxicity (ADCC). Among the 6 responding patients, 3 had progressed after initial response to a previous treatment with single agent anti-PD-1, nivolumab or pembrolizumab.

Methods
We report long-term clinical follow-up and additional findings on the anti-tumor activity and on the immune effects of cetuximab plus avelumab treatment for these 3 patients.

Results
As of November 30, 2021, 2/3 patients were alive. One patient was still on treatment from 34 months, while the other two patients had progression free survival (PFS) of 15 and 19 months, respectively. Analysis of serially collected peripheral blood mononuclear cells (PBMC) revealed long-term activation of NK cell-mediated ADCC. Comprehensive genomic profile analysis found somatic mutations and germline rare variants in DNA damage response (DDR) genes. Furthermore, by transcriptomic analysis of The Cancer Genome Atlas (TCGA) dataset we found that DDR mutant NSCLC displayed high STING pathway gene expression. In NSCLC patient-derived three-dimensional in vitro spheroid cultures, cetuximab plus avelumab treatment induced additive cancer cell growth inhibition as compared to single agent treatment. This effect was partially blocked by treatment with an anti-CD16 mAb, suggesting a direct involvement of NK cell activation. Furthermore, cetuximab plus avelumab treatment induced 10-, 20-, and 20-fold increase, respectively, in the gene expression of CCL5 and CXCL10, two STING downstream effector cytokines, and of interferon β, as compared to untreated control samples.

Conclusions
DDR mutations may contribute to DDR-induced STING pathway with sustained innate immunity activation following cetuximab plus avelumab combination in previously treated, PD-1 inhibitor responsive NSCLC patients.
PABPC1-induced stabilization of IFI27 mRNA promotes angiogenesis and malignant progression in esophageal squamous cell carcinoma through exosomal miRNA-21-5p
Authors: Zhang Ying , Chen Chuangzhen , Liu Zhaoyong , Guo Huancheng , Lu Weiqing , Hu Wang , Lin Zhixiong 
Published: March 2022

Abstract
Background
Emerging evidence has demonstrated that RNA-binding protein dysregulation is involved in esophageal squamous cell carcinoma (ESCC) progression. However, the role of poly (A) binding protein cytoplasmic 1 (PABPC1) in ESCC is unclear. We therefore aimed to explore the functions and potential mechanisms of PABPC1 in ESCC progression.

Methods
PABPC1 expression was characterized using immunohistochemistry and qRT-PCR in ESCC tissues and cell lines. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were used to detect histone acetylation in the promoter region of PABPC1. A series of in vitro and in vivo assays were further applied to elucidate the functions and underlying molecular mechanisms of PABPC1 in ESCC angiogenesis and malignant procession.

Results
PABPC1 expression was upregulated in ESCC tissues compared with in normal esophageal epithelial tissues. Elevated PABPC1 expression was correlated with tumor cell differentiation and poor prognosis in patients. Sp1 and p300 cooperated to increase the level of H2K37ac in the PABPC1 promoter. Functionally, PABPC1 overexpression enhanced esophageal squamous cell proliferation and invasion by activating the IFN/IFI27 signaling pathway. PABPC1 interacted with eIF4G to increase the stability of IFI27 mRNA by competing with RNA exosomes in ESCC. Furthermore, PABPC1/IFI27 could increase miR-21-5p expression to enable exosomal delivery of miR-21-5p to human umbilical vein endothelial cells to increase angiogenesis via inhibiting CXCL10.

Conclusion
PABPC1 plays a critical role in ESCC malignant progression by interacting with eIF4G to regulate IFI27 mRNA stability and promote angiogenesis via exosomal miR-21-5p/CXCL10. Taken together, our results suggest that PABPC1 is a promising therapeutic target for ESCC.
Effect of resistance exercise on serum leptin levels in a prospective longitudinal study of women patients with rheumatoid arthritis
Authors: Joo Young Bin , Lee Kyoung Bo , Sul Bomi , Lee Hye-Soon , Lim Seong Hoon , Park Yune-Jung 
Published: March 2022

Abstract
Background
Exercise has an anti-inflammatory effect and reduces fat mass. Leptin has been known to be proinflammatory adipokines mainly produced by adipocytes. However, few studies have investigated the association between exercise and changes in serum leptin levels of patients with RA. This study evaluated the effect of an individualized resistance exercise on inflammatory markers including leptin as well as muscle strength and exercise capacity in patients with rheumatoid arthritis (RA).

Methods
A total of 42 age- and sex-matched participants were assigned to a resistance exercise program (60 min, once a week for 12 weeks, and self-exercise twice a week) or to a control group. Muscle strength, exercise capacities, and inflammatory markers such as cytokines and adipokines were assessed at baseline and at 12 weeks follow-up. Longitudinal changes in muscle strength, exercise capacity, cytokines, and adipokines between groups were tested with repeated measures analysis of variance or using the generalized estimating equation, with adjustment for baseline disease activity score 28-C response protein as a covariate.

Results
A total of 37 of 42 female patients with RA completed this prospective intervention study. Grip strength improved significantly in the exercise group (P < 0.05), while no between-group changes were found. Quadriceps contraction power (P for group-time interaction = 0.035 for the right side and P for group-time interaction = 0.012 for the left side) and 6-minute walking distance (P for group-time interaction = 0.021) were all improved significantly in the exercise group compared with the control group. In addition, serum leptin levels were significantly decreased in the exercise group compared with the control group (P for group-time interaction = 5.22 × 10−5), but not the other cytokines or adipokines. The change in serum leptin levels correlated with the changes in fat mass (Rho = 0.491, P= 0.015) and visceral fat area (Rho = 0.501, P= 0.013).

Conclusion
In addition to muscle strength and exercise capacity, the 12 weeks of individualized resistance exercise reduced serum leptin levels in keeping with body fat mass or visceral fat area, suggesting that serum leptin levels might be a surrogate marker of exercise in RA.
Super-resolving star clusters with sheaves
Authors: Robinson Michael , Capraro Christopher T. 
Published: March 2022

AbstractThis article presents an optimization-based approach for counting and localizing stars within a small cluster, based on photon counts in a focal plane array. The array need not be arranged in any particular way, and relatively small numbers of photons are required to ensure convergence. The stars can be located close to one another, as the location and magnitude errors were found to be low when the separation was larger than 0.2 Rayleigh radii. To ensure generality of our approach, it was constructed as a special case of a general theory built upon topological signal processing using the mathematics of sheaves that is applicable to general source decomposition problems.
Neurosyphilis with a rare magnetic resonance imaging pattern confirmed by metagenomic next-generation sequencing: a case report
Authors: Liu Chang , Zhang Yu , Li Yi , Bu Hui , Liu Ruoxue , Ji Yingxiao , He Junying , Hong Kun 
Published: March 2022

Abstract
Background
Neurosyphilis refers to infection of the central nervous system by Treponema pallidum. The clinical presentation is variable and nonspecific. Neuroimaging findings are complex and that the diagnosis is based on clinical presentation, cerebrospinal fluid (CSF) parameters, and serologic and CSF evidence of syphilis. To date, there is no case report describing Treponema pallidum detected by metagenomic next-generation sequencing (mNGS) in CSF.

Case presentation
In this report, we describe a case of neurosyphilis in a HIV-negative, 29-year-old man, who was admitted to our hospital with an epileptic seizure and progressive cognitive impairment. Brain magnetic resonance imaging (MRI) revealed fluid-attenuated inversion recovery (FLAIR) high signal intensities in bilateral medial and anterior temporal lobes, insula, right pulvinar of the thalami, precuneus, frontal and temporo-occipital lobes. Laboratory examination showed positive results by means of nontreponemal or specific treponemal test in serum and CSF. mNGS of the CSF was also performed to identify Treponema pallidum for the first time.

Conclusions
This case underscores the importance of considering neurosyphilis as a potential cause of mesiotemporal abnormality. In addition, the rapid improvement and wide usability of mNGS technology will bring new breakthroughs in the clinical diagnosis of neurosyphilis.
Contemporary research trends in response robotics
Authors: Dadvar Mehdi , Habibian Soheil 
Published: March 2022

AbstractThe multidisciplinary nature of response robotics has brought about a diversified research community with extended expertise. Motivated by the recent accelerated rate of publications in the field, this paper analyzes the research trends, statistics, and implications of the literature from bibliometric standpoints. The aim is to study the global progress of response robotics research and identify the contemporary trends. To that end, we investigated the collaboration mapping together with the citation network to formally recognize impactful and contributing authors, publications, sources, institutions, funding agencies, and countries. We found how natural and human-made disasters contributed to forming productive regional research communities, while there are communities that only view response robotics as an application of their research. Furthermore, through an extensive discussion on the bibliometric results, we elucidated the philosophy behind research priority shifts in response robotics and presented our deliberations on future research directions.
Ectopic gallbladder with congenital biliary dilatation: a pediatric case report
Authors: Omata Kanako , Yoshida Mariko , Suzuki Kan , Kawashima Hiroshi , Fujishiro Jun 
Published: March 2022

Abstract
Background
An ectopic gallbladder is a rare anomaly and can result in the misinterpretation of imaging findings and clinical confusion. Knowledge of such anomalies facilitates accurate diagnoses and prompt management. We report a pediatric case of an ectopic gallbladder concomitant with congenital biliary dilatation (CBD).

Case presentation
A 9-year-old girl was referred to our hospital for elevated liver enzyme levels. Following physical examination and a review of medical imaging findings, she was diagnosed with Todani type IV-A CBD. We could not visualize the gallbladder by abdominal ultrasonography, CT, and MRI scans; therefore, we suspected gallbladder agenesis. A laparoscopic excision of the extrahepatic bile duct was performed to treat the CBD. Neither a gallbladder nor a cystic duct were revealed on the liver undersurface. Therefore, gallbladder agenesis was considered as a diagnosis based on preoperative imaging and intraoperative findings. However, during dissection of the hepatic hilum, a cyst-like structure was found on the ventral side of the common hepatic duct, slightly to the right, and a small additional duct that originated from the cystic structure was found. Upon incision, a small amount of bile was drained from the small duct. Thus, the cystic structure was diagnosed as an ectopic gallbladder with hypoplasia. Following the removal of the ectopic gallbladder, the extrahepatic bile duct was excised. Subsequently, laparoscopic Roux-en-Y hepaticojejunostomy was performed without any complications. Postoperative histopathological evaluations of the resected specimen revealed Rokitansky–Aschoff sinuses in the resected cystic lesion. The pathological investigations confirmed the diagnosis of an ectopic gallbladder. Following an uneventful postoperative course, the patient was discharged on day nine.

Conclusions
To our knowledge, this is the first pediatric case report describing an ectopic gallbladder concomitant with CBD. If the gallbladder cannot be detected in a preoperative imaging examination, it is important to consider the possibility of an ectopic gallbladder.
Health-related quality of life (HRQoL) from HIV patients’ perspective: comparison of patient-reported outcome (PRO) measures among people living with hiv (PLWH) and other chronic clinical conditions
Authors: Seguiti C. , Salvo P. F. , Di Stasio E. , Lamonica S. , Fedele A. L. , Manfrida S. , Ciccarelli N. , Corvari B. , De Luca C. , Tartaglione L. , Pitocco D. , Cauda R. , Cingolani A. 
Published: March 2022

Abstract
Background
People living with HIV (PLWH) are generally known to suffer from a lower quality of life compared to the one of general population, but still very few is known about the self-perception of quality of life when comparing HIV to non-communicable diseases. We performed a comprehensive assessment of patient’s reported outcomes measures (PROMs) among PLWH and patients affected by other chronic conditions (OC) such as diabetes mellitus type 1, rheumatoid arthritis, breast cancer in hormonal therapy, in order to investigate differences in PROMs outcomes between PLWH and other pathologies.

Methods
A cross-sectional observational study was performed by using questionnaires investigating health-related quality of life (Medical Outcomes Study Short Form 36-item Health Survey), work productivity (WPI), and global health status (EQ-5D-3L). They were administered to patients affected by chronic diseases consecutively observed at a single University Hospital during a 10 months period, with comparable disease related aspects. Logistic regression analysis was used to analyze the association between disease group (HIV vs OC) and PROMs.

Results
230 patients were enrolled (89 PLWH, 143 OC). Mean age: 49 years (SD 10), mean time of disease 12 years (10), 96% were Caucasian, 35% assumed polypharmacy, 42% of male were PLWH versus 16% OC (p < 0.001), 19% PLWH versus 6% OC had clinical complications (p < 0.001). HIV infection was independently associated to a better health-related quality of life in several domains compared with the other conditions, except in mental health, whereas a worst health-related quality of life in most domains was reported by older patients and those experiencing polypharmacy.

Conclusions
In this cohort of patients with chronic conditions followed within the same health setting, PLWH showed better self-reported health outcomes compared to other chronic conditions with comparable characteristics of chronicity. The potential detrimental role of older age and polypharmacy in most outcomes suggests the need of longitudinal assessment of PROMs in clinical practice.
Predictors of severity and mortality in COVID-19 patients
Authors: Assal Hebatallah Hany , Abdel-hamid Hoda M. , Magdy Sally , Salah Maged , Ali Asmaa , Elkaffas Rasha Helmy , Sabry Irene Mohamed 
Published: March 2022

Abstract
Background
Due to limited capacity, health care systems worldwide have been put in challenging situations since the emergence of COVID-19. To prioritize patients who need hospital admission, a better understanding of the clinical predictors of disease severity is required. In the current study, we investigated the predictors of mortality and severity of illness in COVID-19 from a single center in Cairo, Egypt.

Methods
This retrospective cohort study included 175 patients hospitalized with COVID-19 pneumonia and had positive real-time polymerase chain reaction (RT-PCR) results for SARS-CoV-2 from 1 May 2020 to 1 December 2020. Severe COVID-19 was defined as requiring high-flow oxygen (flow rate of more than 8 L/min or use of high flow oxygen cannula), noninvasive ventilation, or invasive mechanical ventilation at any time point during the hospitalization. We used univariate and multivariate regression analyses to examine the differences in patient demographics and clinical and laboratory data collected during the first 24 h of hospitalization related to severe disease or death in all 175 patients.

Results
Sixty-seven (38.3%) of the study subjects had a severe or critical disease. Elevated d-dimer, leukocytosis, and elevated CRP were found to be independent predictors of severe disease. In-hospital mortality occurred in 34 (19.4%) of the cases. Elevated TLC, urea, the use of invasive mechanical ventilation, and the presence of respiratory bacterial co-infection were found to be independently associated with mortality.

Conclusion
Clinical and laboratory data of COVID-19 patients at their hospital admission may aid clinicians in the early identification and triage of high-risk patients.
Antibiotics and Agricultural Change: Purifying Milk and Protecting Health in the Postwar Era
Authors: SMITH-HOWARD KENDRA 
Published: March 2022

Abstract
New ways of understanding milk purity accompanied the introduction of veterinary antibiotics to the dairy farm. Antibiotics—once viewed as substances that could rid milk of bacterial hazards—became understood as food adulterants when residues of the drugs were detected in milk. Although consumers’ concerns about food purity became critical in the postwar era, only in the late 1950s and early 1960s did public health officials and consumers take interest in the potential human health effects of antibiotic residues. Veterinarians and milk processors, not consumers, led the effort to curb indiscriminate use of antibiotics in the 1940s and 1950s. Paying close attention to the context in which farmers chose to use antibiotics and monitored drug residues, this article seeks to explain why farm people adopted veterinary drugs and how they adapted to new regulatory structures and shifting ideas about milk purity.