bluuebunny/crossref_metadata_2025_split huggingface dataset:
IκBα targeting promotes oxidative stress-dependent cell death
Authors: Carrà Giovanna , Ermondi Giuseppe , Riganti Chiara , Righi Luisella , Caron Giulia , Menga Alessio , Capelletto Enrica , Maffeo Beatrice , Lingua Marcello Francesco , Fusella Federica , Volante Marco , Taulli Riccardo , Guerrasio Angelo , Novello Silvia , Brancaccio Mara , Piazza Rocco , Morotti Alessandro 
Published: April 2021

AbstractBackgroundOxidative stress is a hallmark of many cancers. The increment in reactive oxygen species (ROS), resulting from an increased mitochondrial respiration, is the major cause of oxidative stress. Cell fate is known to be intricately linked to the amount of ROS produced. The direct generation of ROS is also one of the mechanisms exploited by common anticancer therapies, such as chemotherapy.MethodsWe assessed the role of NFKBIA with various approaches, including in silico analyses, RNA-silencing and xenotransplantation. Western blot analyses, immunohistochemistry and RT-qPCR were used to detect the expression of specific proteins and genes. Immunoprecipitation and pull-down experiments were used to evaluate protein-protein interactions.ResultsHere, by using an in silico approach, following the identification of NFKBIA (the gene encoding IκBα) amplification in various cancers, we described an inverse correlation between IκBα, oxidative metabolism, and ROS production in lung cancer. Furthermore, we showed that novel IκBα targeting compounds combined with cisplatin treatment promote an increase in ROS beyond the tolerated threshold, thus causing death by oxytosis.ConclusionsNFKBIA amplification and IκBα overexpression identify a unique cancer subtype associated with specific expression profile and metabolic signatures. Through p65-NFKB regulation, IκBα overexpression favors metabolic rewiring of cancer cells and distinct susceptibility to cisplatin. Lastly, we have developed a novel approach to disrupt IκBα/p65 interaction, restoring p65-mediated apoptotic responses to cisplatin due to mitochondria deregulation and ROS-production.
Podiatry as a career in the UK ‐ what attracts Generation Z? A qualitative exploration with university and college students
Authors: Whitham D. , Whitham S. , Trowell M. , Otter S. 
Published: April 2021

AbstractBackgroundTraining for a career in podiatry is reported to provide graduates with excellent employability, alongside professional autonomy and suitable renumeration. Yet, there has been an ongoing decline in the number of those applying to study the subject. There is limited literature associated with this topic and we sought to explore the factors that attract ‘generation Z’ (those born 1995–2010) to a potential career in podiatry.MethodA qualitative design framework underpinned by phenomenological principles used four focus groups over a two‐year period to generate data from participants at University and in Further Education. Focus group conversations were led by external facilitator, recorded, independently transcribed verbatim and anonymised prior to thematic analysis. This was followed by external, independent verification of themes.ResultsFour main themes were determined from the analysis i) a lack of awareness of podiatry; ii) podiatry: accessible course, accessible career; iii) career status; iv) breadth/opportunity of the scope of practice. Both positive and negative experiences were reported and highlighted key gaps in how the attractiveness of a career in podiatry is portrayed.ConclusionThe chronic lack of awareness of podiatry as a career clearly needs to be addressed, ideally with more positive role modelling in mainstream and popular media. The career status offered together with the breadth of, and opportunity associated with, the scope of practice should continue to be celebrated.
Human breast microbiome correlates with prognostic features and immunological signatures in breast cancer
Authors: Tzeng Alice , Sangwan Naseer , Jia Margaret , Liu Chin-Chih , Keslar Karen S. , Downs-Kelly Erinn , Fairchild Robert L. , Al-Hilli Zahraa , Grobmyer Stephen R. , Eng Charis 
Published: April 2021

AbstractBackgroundCurrently, over half of breast cancer cases are unrelated to known risk factors, highlighting the importance of discovering other cancer-promoting factors. Since crosstalk between gut microbes and host immunity contributes to many diseases, we hypothesized that similar interactions could occur between the recently described breast microbiome and local immune responses to influence breast cancer pathogenesis.MethodsUsing 16S rRNA gene sequencing, we characterized the microbiome of human breast tissue in a total of 221 patients with breast cancer, 18 individuals predisposed to breast cancer, and 69 controls. We performed bioinformatic analyses using a DADA2-based pipeline and applied linear models with White’stor Kruskal–WallisH-tests with Benjamini–Hochberg multiple testing correction to identify taxonomic groups associated with prognostic clinicopathologic features. We then used network analysis based on Spearman coefficients to correlate specific bacterial taxa with immunological data from NanoString gene expression and 65-plex cytokine assays.ResultsMultiple bacterial genera exhibited significant differences in relative abundance when stratifying by breast tissue type (tumor, tumor adjacent normal, high-risk, healthy control), cancer stage, grade, histologic subtype, receptor status, lymphovascular invasion, or node-positive status, even after adjusting for confounding variables. Microbiome–immune networks within the breast tended to be bacteria-centric, with sparse structure in tumors and more interconnected structure in benign tissues. Notably,Anaerococcus,Caulobacter, andStreptococcus, which were major bacterial hubs in benign tissue networks, were absent from cancer-associated tissue networks. In addition,PropionibacteriumandStaphylococcus, which were depleted in tumors, showed negative associations with oncogenic immune features;StreptococcusandPropionibacteriumalso correlated positively with T-cell activation-related genes.ConclusionsThis study, the largest to date comparing healthy versus cancer-associated breast microbiomes using fresh-frozen surgical specimens and immune correlates, provides insight into microbial profiles that correspond with prognostic clinicopathologic features in breast cancer. It additionally presents evidence for local microbial–immune interplay in breast cancer that merits further investigation and has preventative, diagnostic, and therapeutic potential.
Toll-like receptor 2 induced senescence in intervertebral disc cells of patients with back pain can be attenuated by o-vanillin
Authors: Mannarino Matthew , Cherif Hosni , Li Li , Sheng Kai , Rabau Oded , Jarzem Peter , Weber Michael H. , Ouellet Jean A. , Haglund Lisbet 
Published: April 2021

Abstract
Background
There is an increased level of senescent cells and toll-like teceptor-1, -2, -4, and -6 (TLR) expression in degenerating intervertebral discs (IVDs) from back pain patients. However, it is currently not known if the increase in expression of TLRs is related to the senescent cells or if it is a more general increase on all cells. It is also not known if TLR activation in IVD cells will induce cell senescence.

Methods
Cells from non-degenerate human IVD were obtained from spine donors and cells from degenerate IVDs came from patients undergoing surgery for low back pain. Gene expression of TLR-1,2,4,6, senescence and senescence-associated secretory phenotype (SASP) markers was evaluated by RT-qPCR in isolated cells. Matrix synthesis was verified with safranin-O staining and Dimethyl-Methylene Blue Assay (DMMB) confirmed proteoglycan content. Protein expression of p16INK4a, SASP factors, and TLR-2 was evaluated by immunocytochemistry (ICC) and/or by enzyme-linked immunosorbent assay (ELISA).

Results
An increase in senescent cells was found following 48-h induction with a TLR-2/6 agonist in cells from both non-degenerate and degenerating human IVDs. Higher levels of SASP factors, TLR-2 gene expression, and protein expression were found following 48-h induction with TLR-2/6 agonist. Treatment with o-vanillin reduced the number of senescent cells, and increased matrix synthesis in IVD cells from back pain patients. Treatment with o-vanillin after induction with TLR-2/6 agonist reduced gene and protein expression of SASP factors and TLR-2. Co-localized staining of p16INK4a and TLR-2 demonstrated that senescent cells have a high TLR-2 expression.

Conclusions
Taken together our data demonstrate that activation of TLR-2/6 induce senescence and increase TLR-2 and SASP expression in cells from non-degenerate IVDs of organ donors without degeneration and back pain and in cells from degenerating human IVD of patients with disc degeneration and back pain. The senescent cells showed high TLR-2 expression suggesting a link between TLR activation and cell senescence in human IVD cells. The reduction in senescence, SASP, and TLR-2 expression suggest o-vanillin as a potential disease-modifying drug for patients with disc degeneration and back pain.
Cytomegalovirus‐associated esophagitis on early esophageal cancer in immunocompetent host: a case report
Authors: Murakami Daisuke , Harada Hideaki , Yamato Masayuki , Amano Yuji 
Published: April 2021

Abstract
Background
Cytomegalovirus (CMV)-associated gastrointestinal diseases usually occur in immunocompromised patients; however, few cases has also been described in healthy hosts despite still unclear pathological mechanisms. CMV esophagitis causes various lesions, such as erythematous mucosa, erosions, and ulcers, although such inflammatory changes can appear in superficial esophageal cancers or in surrounding areas. CMV-associated esophagitis has been also reported in cancer patients, but typically in those with advanced and/or terminal stage cancers secondary to chemoradiotherapy-induced immunosuppression or the physiologic demands of the malignancy itself. To our best knowledge, we firstly report on an immunocompetent patient subject to endoscopic submucosal dissection (ESD) for early esophageal cancer complicated with CMV infection.

Case presentation
A 77-year-old man underwent esophagogastroduodenoscopy (EGD) at a local clinic. EGD revealed a lugol-unstained reddish lesion with whitish exudates in the middle-distal esophagus. Histological evaluation of lesion biopsy revealed atypical squamous epithelium with CMV-positive granulation tissue and aggregates of macrophages, prompting referral for further examination and treatment. Magnifying endoscopy with narrow-band imaging showed an erosive lesion with white moss in a well-demarcated brownish area with irregular mesh-like microvessels. ESD was performed for diagnosis and treatment. Histopathological examination of the resected specimen revealed superficial, moderately differentiated squamous cell carcinoma (SCC) with multiple lymphatic infiltration, and few CMV-positive cells were found in the erosive part of the SCC. Interestingly, he had no underlying conditions to predispose to CMV infection and no risk factors for esophageal cancer, other than gender and age. He received neither steroids for stricture prevention nor antiviral agents post-EGD and 4-month follow-up was negative for esophagitis.

Conclusions
This is the first report of a case of CMV esophagitis superimposed on early esophageal cancer in an immunocompetent host and might provide valuable information for possible adverse effects of steroid administration during ESD procedures, despite their common use for prevention of post-ESD stricture.
Association of small intestinal bacterial overgrowth with Parkinson’s disease: a systematic review and meta-analysis
Authors: Li Xiaoqing , Feng Xin , Jiang Zhongxiang , Jiang Zheng 
Published: April 2021

Abstract
Objective
Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease after Alzheimer's disease (AD) worldwide. The prevalence of small intestinal bacterial overgrowth (SIBO) in PD patients is high. We conducted this comprehensive systematic review and meta-analysis to determine the association between SIBO and PD.

Methods
A comprehensive literature search of the PubMed, Cochrane Library and EMBASE databases was performed to identify studies correlating SIBO with PD. Studies were screened, and relevant data were extracted and analysed. We calculated the pooled prevalence of SIBO in all individuals with PD and compared the prevalence of SIBO between the two groups to calculate an odds ratio (OR) and 95% confidence interval (CI). Egger’s test was performed to assess publication bias.

Results
Eleven studies with 973 participants met the inclusion criteria. The pooled prevalence of SIBO in patients with PD was 46% (95% CI 36–56). A random-effects model was applied given the heterogeneity (I2 = 83%) detected among the studies. Egger’s test indicated no publication bias (p = 0.0657). Subgroup analyses showed that the prevalence of SIBO was greater in studies including patients diagnosed using the lactulose hydrogen breath test (LBT) (51%, 95% CI 37–65) than in those including patients diagnosed using the glucose hydrogen breath test (GBT) (35%, 95% CI 20–50), and the prevalence of SIBO in PD was highest (55%, 95% CI 38–72) in patients diagnosed by the LBT and GBT. The prevalence of SIBO was 52% (95% CI 40–64) among patients from Western countries and 33% (95% CI 22–43) among patients from Eastern countries. The pooled OR of SIBO in PD patients compared with healthy controls was 5.22 (95% CI 3.33–8.19, p < 0.00001). We did not identify an obvious predictor of SIBO in PD patients.

Conclusion
In conclusion, our meta-analysis found a strong association between SIBO and PD with approximately half of PD patients testing positive for SIBO. These relationships significantly differed based on diagnostic test and geographic area.
COVID-19 pandemic and families' utilization of well-child clinics and pediatric practices attendance in Germany
Authors: Vogel Mandy , Beger Christoph , Gausche Ruth , Jurkutat Anne , Pfaeffle Roland , Körner Antje , Meigen Christof , Poulain Tanja , Kiess Wieland 
Published: April 2021

Abstract
Objective
The COVID-19 pandemic and the measures implemented to stop the pandemic had a broad impact on our daily lives. Besides work and social life, health care is affected on many levels. In particular, there is concern that attendance in health care programs will drop or hospital admissions will be delayed due to COVID-19-related anxieties, especially in children. Therefore, we compared the number of weekly visits to 78 German pediatric institutions between 2019 and 2020.

Results
We found no significant differences during the first 10 weeks of the year. However, and importantly, from April, the weekly number of visits was more than 35% lower in 2020 than in 2019 (p = 0.005). In conclusion, the COVID-19 pandemic seems to relate to families´ utilization of outpatient well-child clinics and pediatric practice attendance in Germany.
Core Alzheimer’s disease cerebrospinal fluid biomarker assays are not affected by aspiration or gravity drip extraction methods
Authors: Doecke James D. , Francois Cindy , Fowler Christopher J. , Stoops Erik , Bourgeat Pierrick , Rainey-Smith Stephanie R. , Li Qiao-Xin , Masters Colin L. , Martins Ralph N. , Villemagne Victor L. , Collins Steven J. , Vanderstichele Hugo Marcel 
Published: April 2021

Abstract
Background
CSF biomarkers are well-established for routine clinical use, yet a paucity of comparative assessment exists regarding CSF extraction methods during lumbar puncture. Here, we compare in detail biomarker profiles in CSF extracted using either gravity drip or aspiration.

Methods
Biomarkers for β-amyloidopathy (Aβ1–42, Aβ1–40), tauopathy (total tau), or synapse pathology (BACE1, Neurogranin Trunc-p75, α-synuclein) were assessed between gravity or aspiration extraction methods in a sub-population of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study (cognitively normal, N = 36; mild cognitive impairment, N = 8; Alzheimer’s disease, N = 6).

Results
High biomarker concordance between extraction methods was seen (concordance correlation > 0.85). Passing Bablock regression defined low beta coefficients indicating high scalability.

Conclusions
Levels of these commonly assessed CSF biomarkers are not influenced by extraction method. Results of this study should be incorporated into new consensus guidelines for CSF collection, storage, and analysis of biomarkers.
Complete androgen insensitivity syndrome in a 13-year-old Lebanese child, reared as female, with bilateral inguinal hernia: a case report
Authors: Farah Stephanie , El Masri Dana , Hirbli Kamal 
Published: April 2021

Abstract
Background
Androgen insensitivity syndrome is a rare X-linked disorder of sex development, caused by mutations in the androgen receptor. In this case, a 13-year-old child, reared as female, presenting for primary amenorrhea, was diagnosed with complete androgen insensitivity syndrome.

Case presentation
A 13-year-old Caucasian child, reared as female, presents with primary amenorrhea. Physical examination revealed female appearance and a short vagina with blind-ended pouch. Laboratory examination showed high levels of testosterone and anti-Müllerian hormone; uterus and ovaries were absent. Karyotype confirmed a 46,XY pattern. Deoxyribonucleic acid analysis of the androgen receptor gene revealed a homozygous mutation p.R856C in exon 7. Gender was assigned as female, and she was started on hormonal therapy and underwent gonadectomy.

Conclusion
Androgen insensitivity syndrome comprises a large spectrum of presentations. High index of suspicion is needed. Investigation of girls with bilateral inguinal hernia is critical.
Signaling pathways governing breast cancer stem cells behavior
Authors: Song Kai , Farzaneh Maryam 
Published: April 2021

AbstractBreast cancer is the second common cancer and the leading cause of malignancy among females overall. Breast cancer stem cells (BCSCs) are a small population of breast cancer cells that play a critical role in the metastasis of breast cancer to other organs in the body. BCSCs have both self-renewal and differentiation capacities, which are thought to contribute to the aggressiveness of metastatic lesions. Therefore, targeting BCSCs can be a suitable approach for the treatment and metastasis of breast cancer. Growing evidence has indicated that the Wnt, NFκB, Notch, BMP2, STAT3, and hedgehog (Hh) signaling pathways govern epithelial-to-mesenchymal transition (EMT) activation, growth, and tumorigenesis of BCSCs in the primary regions. miRNAs as the central regulatory molecules also play critical roles in BCSC self-renewal, metastasis, and drug resistance. Hence, targeting these pathways might be a novel therapeutic approach for breast cancer diagnosis and therapy. This review discusses known signaling mechanisms involved in the stimulation or prevention of BCSC self-renewal, metastasis, and tumorigenesis.
Stability of BSE infectivity towards heat treatment even after proteolytic removal of prion protein
Authors: Langeveld Jan P. M. , Balkema-Buschmann Anne , Becher Dieter , Thomzig Achim , Nonno Romolo , Andréoletti Olivier , Davidse Aart , Di Bari Michele A. , Pirisinu Laura , Agrimi Umberto , Groschup Martin H. , Beekes Michael , Shih Jason 
Published: April 2021

AbstractThe unconventional infectious agents of transmissible spongiform encephalopathies (TSEs) are prions. Their infectivity co-appears with PrPSc, aberrant depositions of the host’s cellular prion protein (PrPC). Successive heat treatment in the presence of detergent and proteolysis by a keratinase from Bacillus licheniformis PWD-1 was shown before to destroy PrPSc from bovine TSE (BSE) and sheep scrapie diseased brain, however data regarding expected reduction of infectivity were still lacking. Therefore, transgenic Tgbov XV mice which are highly BSE susceptible were used to quantify infectivity before and after the bovine brain treatment procedure. Also four immunochemical analyses were applied to compare the levels of PrPSc. After heating at 115 °C with or without subsequent proteolysis, the original BSE infectivity of 106.2–6.4 ID50 g−1 was reduced to a remaining infectivity of 104.6–5.7 ID50 g−1 while strain characteristics were unaltered, even after precipitation with methanol. Surprisingly, PrPSc depletion was 5–800 times higher than the loss of infectivity. Similar treatment was applied on other prion strains, which were CWD1 in bank voles, 263 K scrapie in hamsters and sheep PG127 scrapie in tg338 ovinized mice. In these strains however, infectivity was already destroyed by heat only. These findings show the unusual heat resistance of BSE and support a role for an additional factor in prion formation as suggested elsewhere when producing prions from PrPC. Leftover material in the remaining PrPSc depleted BSE preparation offers a unique substrate for searching additional elements for prion infectivity and improving our concept about the nature of prions.
Evaluation of LiDAR data processing at the mobile network edge for connected vehicles
Authors: Ojanperä Tiia , Mäkelä Jukka , Majanen Mikko , Mämmelä Olli , Martikainen Ossi , Väisänen Jani 
Published: April 2021

Abstract5G mobile network technology together with edge computing will create new opportunities for developing novel road safety services in order to better support connected and automated driving in challenging situations. This paper studies the feasibility and benefits of localized mobile network edge applications for supporting vehicles in diverse conditions. We study a particular scenario, where vehicle sensor data processing, required by road safety services, is installed into the mobile network edge in order to extend the electronic horizon of the sensors carried by other vehicles. Specifically, we focus on a LiDAR data-based obstacle warning case where vehicles receive obstacle warnings from the mobile network edge. The proposed solution is based on a generic system architecture. In this paper, we first evaluate different connectivity and computing options associated with such a system using ns-3 simulations. Then, we introduce a proof-of-concept implementation of the LiDAR-based obstacle warning scenario together with first results from an experimental evaluation, conducted both in a real vehicle testbed environment and in a laboratory setting. As a result, we obtain first insights on the feasibility of the overall solution and further enhancements needed.