bluuebunny/crossref_metadata_2025 huggingface dataset:
Silencing SHMT2 inhibits the progression of tongue squamous cell carcinoma through cell cycle regulation
Authors: Liao Yan , Wang Fang , Zhang Yadong , Cai Hongshi , Song Fan , Hou Jinsong
Published: April 2021

Background

Serine hydroxymethyltransferase 2 (SHMT2) is a vital metabolic enzyme in one carbon metabolism catalyzing the conversion of serine to glycine, which has been reported to play a crucial role in the progression of tumors. However, its function in tongue squamous cell carcinoma (TSCC) remains unclear.

Methods

SHMT2 expression was analyzed using samples in online databases, and was assessed through immunohistochemistry staining of collected clinical specimens. The correlation between SHMT2 expression and the cell cycle was predicted through bioinformatic analysis, including weighted gene co-expression network analysis (WGCNA) and gene set enrichment analysis (GSEA). After transfection with siRNA, CCK8 assay, Edu staining, flow cytometry, trans-well assay, and wound healing experiments were performed to verify the functional role of SHMT2 in vitro. A stable cell line with SHMT2 silencing was established to detect the oncogenic function of SHMT2 in vivo.

Results

The expression of SHMT2 was up-regulated in TSCC tissues and cell lines compared with normal groups, and highly expressed SHMT2 significantly indicated a poorer clinical outcome for TSCC patients. Bioinformatic analysis found that high expression of SHMT2 was closely related with biologic process including cell cycle and cell cycle G1/S transition. Down regulating of SHMT2 significantly suppressed the proliferation, invasive and migrative ability of TSCC cells, and induced the prolongation of the G1 phase of the cell cycle in vitro. Furthermore, western blot showed that cell cycle-related regulators such as cyclin-dependent kinase 4 (CDK4) and cyclinD1 expression levels were decreased, while the expression levels of the cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1 were increased after SHMT2 knockdown. Silencing SHMT2 in the HN6 cell line using short hairpin RNA also impeded tumor growth in vivo.

Conclusions

Overexpression of SHMT2 in TSCC indicated low survival rates, and was associated with aggressive behaviors of TSCC. It was also found to be involved in cell cycle regulation of TSCC cells. SHMT2 may serve as a novel prognostic indicator of TSCC.
Shock and awe or incentive-compatible harm reduction? Graphic health warnings on tobacco packages
Authors: Irvine Ian , Nguyen Hai V.
Published: April 2021

Background

Graphic Health Warnings (GHWs) on cigarette packages were first introduced in Canada in 2001 and will become mandatory in the US as of January 2022. While previous studies have evaluated the impacts of GHWs, the data used in these studies have several shortcomings. The objective of this paper was to investigate the likely impact of such warnings in the US based upon the experience of Canada using hitherto unexplored monthly cigarette sales data, and to explore if alternative approaches involving risk-reduced products might be more successful in reducing smoking.

Methods

We used quasi-experimental segmented regression and difference-in-differences analyses. Data on monthly sales (i.e., shipments) of cigarettes from Canadian manufacturers to Canadian retailers during 1995–2005 were obtained from Statistics Canada.

Results

We found that GHWs did not have a significant impact on the sales of cigarettes in Canada. We propose an alternative type of graphical health messaging that actively combines information on how to quit with the legally required messaging. The novelty of the proposal is that it is incentive compatible for the supply side of the market and if adopted in several states, the measure could be tested by using a suitable treatment–control design.

Conclusions

Our findings imply that we should not expect any notable decline in sales or consumption as a result of implementation of GHWs in the US. The main impact of GHWs will be to add to the anti-smoking culture that has grown steadily over several decades, and this may impact smoking in the longer term.
The differences in health-related quality of life between younger and older adults and its associated factors in patients with type 2 diabetes mellitus in Indonesia
Authors: Sari Yunita , Isworo Atyanti , Upoyo Arif Setyo , Taufik Agis , Setiyani Rahmi , Swasti Keksi Girindra , Haryanto Haryanto , Yusuf Saldy , Nasruddin Nasruddin , Kamaluddin Ridlwan
Published: April 2021

Background

It is well known that diabetes mellitus (DM) affects health-related quality of life (HRQOL) in both younger (aged 18–64 years) and older adults (aged ≥ 65 years). However, to date, no study has compared HRQOL and its predictors between younger and older adults with DM in Indonesia. Such a comparison is important because the results can guide nurses and clinicians to establish evidence-based educational programs that are specific and suitable for patients. Therefore, the aim of this study was to investigate the difference in HRQOL and its predictors in younger and older adults with DM in Indonesia.

Methods

A cross-sectional study was conducted on 641 patients with type 2 diabetes mellitus (T2DM) who were recruited via simple random sampling from 16 primary health centers in Banyumas Regency, Indonesia. A self-administered questionnaire containing the Summary of Diabetes Self-Care Activities, the DDS17 Bahasa Indonesia, the Beck Depression Inventory II, the Self-Efficacy for Diabetes Scale, the Family APGAR, and the 36-item Short-Form Health Survey was used to measure diabetes self-management (DSM), diabetes distress (DD), depression, self-efficacy, family support, and HRQOL, respectively. Independent t-tests were used to compare the physical component summary (PCS) and mental component summary (MCS) scores between younger and older adults with T2DM. Hierarchical multiple regression analyses were used to examine the factors associated with HRQOL in both groups.

Results

PCS scores were significantly different between the two groups. Older adults reported lower PCS scores than younger adults. No differences between the two groups were observed in the MCS scores. The hierarchical multiple regression analysis showed that level of education, employment status, number of diabetes-related complications, DSM, DD, depression, and self-efficacy were significant predictors of HRQOL in younger adults, while income, depression, DD, and self-efficacy were significant predictors of HRQOL in older adults. DD was the strongest predictor of HRQOL in younger adults, and depression was the strongest predictor in older adults.

Conclusion

Older adult patients had lower PCS scores than younger adult patients. This study is the first to show that the predictors of HRQOL differ between younger and older adults with T2DM. It provides insights for nurses and clinicians in Indonesia to establish evidence-based, age-specific educational programs.
Effect of robotic-assisted gait training on objective biomechanical measures of gait in persons post-stroke: a systematic review and meta-analysis
Authors: Nedergård Heidi , Arumugam Ashokan , Sandlund Marlene , Bråndal Anna , Häger Charlotte K.
Published: April 2021

Background

Robotic-Assisted Gait Training (RAGT) may enable high-intensive and task-specific gait training post-stroke. The effect of RAGT on gait movement patterns has however not been comprehensively reviewed. The purpose of this review was to summarize the evidence for potentially superior effects of RAGT on biomechanical measures of gait post-stroke when compared with non-robotic gait training alone.

Methods

Nine databases were searched using database-specific search terms from their inception until January 2021. We included randomized controlled trials investigating the effects of RAGT (e.g., using exoskeletons or end-effectors) on spatiotemporal, kinematic and kinetic parameters among adults suffering from any stage of stroke. Screening, data extraction and judgement of risk of bias (using the Cochrane Risk of bias 2 tool) were performed by 2–3 independent reviewers. The Grading of Recommendations Assessment Development and Evaluation (GRADE) criteria were used to evaluate the certainty of evidence for the biomechanical gait measures of interest.

Results

Thirteen studies including a total of 412 individuals (mean age: 52–69 years; 264 males) met eligibility criteria and were included. RAGT was employed either as monotherapy or in combination with other therapies in a subacute or chronic phase post-stroke. The included studies showed a high risk of bias (n = 6), some concerns (n = 6) or a low risk of bias (n = 1). Meta-analyses using a random-effects model for gait speed, cadence, step length (non-affected side) and spatial asymmetry revealed no significant differences between the RAGT and comparator groups, while stride length (mean difference [MD] 2.86 cm), step length (affected side; MD 2.67 cm) and temporal asymmetry calculated in ratio-values (MD 0.09) improved slightly more in the RAGT groups. There were serious weaknesses with almost all GRADE domains (risk of bias, consistency, directness, or precision of the findings) for the included outcome measures (spatiotemporal and kinematic gait parameters). Kinetic parameters were not reported at all.

Conclusion

There were few relevant studies and the review synthesis revealed a very low certainty in current evidence for employing RAGT to improve gait biomechanics post-stroke. Further high-quality, robust clinical trials on RAGT that complement clinical data with biomechanical data are thus warranted to disentangle the potential effects of such interventions on gait biomechanics post-stroke.
RETRACTED ARTICLE: Calcium-dependent cytosolic phospholipase A2 activation is implicated in neuroinflammation and oxidative stress associated with ApoE4
Authors: Wang Shaowei , Li Boyang , Solomon Victoria , Fonteh Alfred , Rapoport Stanley I. , Bennett David A. , Arvanitakis Zoe , Chui Helena C. , Miller Carol , Sullivan Patrick M. , Wang Hoau-Yan , Yassine Hussein N.
Published: April 2021

Background

Apolipoprotein E4 (APOE4) is associated with a greater response to neuroinflammation and the risk of developing late-onset Alzheimer’s disease (AD), but the mechanisms for this association are not clear. The activation of calcium-dependent cytosolic phospholipase A2 (cPLA2) is involved in inflammatory signaling and is elevated within the plaques of AD brains. The relation between APOE4 genotype and cPLA2 activity is not known.

Methods

Mouse primary astrocytes, mouse and human brain samples differing by APOE genotypes were collected for measuring cPLA2 expression, phosphorylation, and activity in relation to measures of inflammation and oxidative stress.

Results

Greater cPLA2 phosphorylation, cPLA2 activity and leukotriene B4 (LTB4) levels were identified in ApoE4 compared to ApoE3 in primary astrocytes, brains of ApoE-targeted replacement (ApoE-TR) mice, and in human brain homogenates from the inferior frontal cortex of patients with AD carrying APOE3/E4 compared to APOE3/E3. Greater cPLA2 phosphorylation was also observed in human postmortem frontal cortical synaptosomes and primary astrocytes after treatment with recombinant ApoE4 ex vivo. In ApoE4 astrocytes, the greater levels of LTB4, reactive oxygen species (ROS), and inducible nitric oxide synthase (iNOS) were reduced after cPLA2 inhibition.

Conclusions

Our findings implicate greater activation of cPLA2 signaling system with APOE4, which could represent a potential drug target for mitigating the increased neuroinflammation with APOE4 and AD.
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

Background

Oxidative 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.

Methods

We 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.

Results

Here, 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.

Conclusions

NFKBIA 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

Background

Training 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.

Method

A 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.

Results

Four 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.

Conclusion

The 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

Background

Currently, 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.

Methods

Using 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.

Results

Multiple 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.

Conclusions

This 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

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

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

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

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

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

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

Breast 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

The 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

5G 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.
5G connected and automated driving: use cases, technologies and trials in cross-border environments
Authors: Hetzer Dirk , Muehleisen Maciej , Kousaridas Apostolos , Barmpounakis Sokratis , Wendt Stefan , Eckert Kurt , Schimpe Andreas , Löfhede Johan , Alonso-Zarate Jesus
Published: April 2021

Cooperative, connected and automated mobility (CCAM) across Europe requires harmonized solutions to support cross-border seamless operation. The possibility of providing CCAM services across European countries has an enormous innovative business potential. However, the seamless provision of connectivity and the uninterrupted delivery of real-time services pose technical challenges which 5G technologies aim to solve.
The situation is particularly challenging given the multi-country, multi-operator, multi-telco-vendor, multi-car-manufacturer and cross-network-generation scenario of any cross-border scenario. Motivated by this, the 5GCroCo project, with a total budget of 17 million Euro and partially funded by the European Commission, aims at validating 5G technologies in the Metz-Merzig-Luxembourg cross-border 5G corridor considering the borders between France, Germany and Luxembourg. The activities of 5GCroCo are organized around three use cases: (1) Tele-operated Driving, (2) high-definition map generation and distribution for automated vehicles and (3) Anticipated Cooperative Collision Avoidance (ACCA). The results of the project help contribute to a true European transnational CCAM. This paper describes the overall objectives of the project, motivated by the discussed challenges of cross-border operation, the use cases along with their requirements, the technical 5G features that will be validated and provides a description of the planned trials within 5GCroCo together with some initial results.
The REPRISE project: protocol for an evaluation of REProducibility and Replicability In Syntheses of Evidence
Authors: Page Matthew J. , Moher David , Fidler Fiona M. , Higgins Julian P. T. , Brennan Sue E. , Haddaway Neal R. , Hamilton Daniel G. , Kanukula Raju , Karunananthan Sathya , Maxwell Lara J. , McDonald Steve , Nakagawa Shinichi , Nunan David , Tugwell Peter , Welch Vivian A. , McKenzie Joanne E.
Published: April 2021

Background

Investigations of transparency, reproducibility and replicability in science have been directed largely at individual studies. It is just as critical to explore these issues in syntheses of studies, such as systematic reviews, given their influence on decision-making and future research. We aim to explore various aspects relating to the transparency, reproducibility and replicability of several components of systematic reviews with meta-analysis of the effects of health, social, behavioural and educational interventions.

Methods

The REPRISE (REProducibility and Replicability In Syntheses of Evidence) project consists of four studies. We will evaluate the completeness of reporting and sharing of review data, analytic code and other materials in a random sample of 300 systematic reviews of interventions published in 2020 (Study 1). We will survey authors of systematic reviews to explore their views on sharing review data, analytic code and other materials and their understanding of and opinions about replication of systematic reviews (Study 2). We will then evaluate the extent of variation in results when we (a) independently reproduce meta-analyses using the same computational steps and analytic code (if available) as used in the original review (Study 3), and (b) crowdsource teams of systematic reviewers to independently replicate a subset of methods (searches for studies, selection of studies for inclusion, collection of outcome data, and synthesis of results) in a sample of the original reviews; 30 reviews will be replicated by 1 team each and 2 reviews will be replicated by 15 teams (Study 4).

Discussion

The REPRISE project takes a systematic approach to determine how reliable systematic reviews of interventions are. We anticipate that results of the REPRISE project will inform strategies to improve the conduct and reporting of future systematic reviews.
Advanced consistency management of highly-distributed transactional database in a hybrid cloud environment using novel R-TBC/RTA approach
Authors: Dizdarevic Jasmina , Avdagic Zikrija , Orucevic Fahrudin , Omanovic Samir
Published: April 2021

This paper examines possibilities for improving the existing strategies of consistency management for highly-distributed transactional database in a hybrid cloud environment. With a detailed analysis of the existing consistency models for distributed database and standard strategies including Classic, Quorum and Tree Based Consistency (TBC), it is concluded that an improved advanced model of so-called visible adaptive consistency needs to be applied in a highly-distributed cloud environment, as necessary and sufficient degree of synchronization of all replicas. Along with the proposed model, research and development of an advanced novel strategy for consistency management Rose TBC (R-TBC) approach has been conducted, by improving standard TBC approach. Regarding implementation, a specific agglomerative Rose Tree Algorithm (RTA) has been developed, based on Bayesian hierarchical clustering and Graph Partitioning Algorithm - Multidimensional Data Clustering (GPA-MDC) intelligent partitioning of transactional Cloud Database Management System (CDBMS). The final result is constructed R-TBC model that changes in accordance with dynamic changes of entire heterogeneous CDBMS environment.
Bacteriophage cocktail supplementation improves growth performance, gut microbiome and production traits in broiler chickens
Authors: Upadhaya Santi Devi , Ahn Je Min , Cho Jae Hyoung , Kim Jin Young , Kang Dae Kyung , Kim Sung Woo , Kim Hyeun Bum , Kim In Ho
Published: April 2021

Background

Effective antibiotic alternatives are urgently needed in the poultry industry to control disease outbreaks. Phage therapy mainly utilizes lytic phages to kill their respective bacterial hosts and can be an attractive solution to combating the emergence of antibiotic resistance in livestock.

Methods

Five hundred and four, one-day-old broilers (Ross 308) were allotted to 1 of 4 treatment groups in a completely randomized design. Treatments consisted of CON (basal diet), PC (CON + 0.025% Avilamax®), BP 0.05 (CON + 0.05% bacteriophage), and BP 0.10 (CON + 0.10% bacteriophage).

Results

A significant linear effect on body weight gain (BWG) was observed during days 1–7, days 22–35, and cumulatively in bacteriophage (BP) supplemented groups. The BWG tended to be higher (P = 0.08) and the feed intake (FI) was increased (P = 0.017) in the PC group over CON group. A greater (P = 0.016) BWG and trends in increased FI (P = 0.06) were observed in the experiment in birds fed PC than CON diet. At the genus level, the relative abundance ofLactobacilluswas decreased in PC (65.28%), while it was similar in BP 0.05 and BP 0.10 (90.65%, 86.72%) compared to CON (90.19%). At the species level, the relative abundance ofLactobacillus salivaruswas higher in BP 0.05 (40.15%) and BP 0.10 (38.58%) compared to the CON (20.04%) and PC (18.05%). A linear reduction in the weight of bursa of Fabricius (P = 0.022) and spleen (P = 0.052) was observed in birds fed graded level of BP and an increase(P = 0.059) in the weight of gizzard was observed in birds fed PC over BP diets. Linear and quadratic responses were observed in redness of breast muscle color in birds fed graded level of BP.

Conclusions

The inclusion of the 0.05% and 0.1% BP cocktail linearly improved broiler weight during the first 7 days, 22–35 days and cumulatively, whereas 0.05% BP addition was sufficient for supporting immune organs, bursa and spleen as well as enhancing gut microbiome, indicating the efficacy of 0.05% BP as a substitute antibiotic growth promoter in broiler diets.
Sightings trends and behaviour of manta rays in Fernando de Noronha Archipelago, Brazil
Authors: Bucair Nayara , Venables Stephanie K. , Balboni Ana Paula , Marshall Andrea D.
Published: April 2021

Despite substantial progress in mobulid research over the past decade, knowledge gaps in manta ray ecology and behaviour remain, particularly in the South Atlantic Ocean. Opportunistic photographic and video records of manta rays collected between 2002 and 2019 at Fernando de Noronha Archipelago (FNA) in northeast Brazil provide evidence to support the year-round use of the region by manta rays (believed to beMobulacf.birostris). From a total of 130 sighting records, manta rays exhibited feeding behaviour in 36.9% (n = 48) of sightings, indicating that the shallow waters surrounding the archipelago are used as feeding grounds. Approximately half of the records (53.8%) corresponded to identified individuals that were re-sighted repeatedly, using the area in different seasons and for several years. Of the compiled records, 69.2% of sightings were of small individuals (≤3 m disc width). All identified males had undeveloped claspers and females had no visible mating scars, suggesting a juvenile population. Despite being limited to a small local sample, here we present the first report of manta rays atFNAand provide preliminary evidence of feeding behaviour by juvenile manta rays in Brazil. This information contributes to our understanding of the regional distribution and habitat use of manta rays in Brazilian waters.
Patients at high risk of suicide before and during a COVID-19 lockdown: ecological momentary assessment study
Authors: Cobo Aurora , Porras-Segovia Alejandro , Pérez-Rodríguez María Mercedes , Artés-Rodríguez Antonio , Barrigón Maria Luisa , Courtet Philippe , Baca-García Enrique
Published: April 2021

The coronavirus disease 2019 (COVID-19) outbreak may have affected the mental health of patients at high risk of suicide. In this study we explored the wish to die and other suicide risk factors using smartphone-based ecological momentary assessment (EMA) in patients with a history of suicidal thoughts and behaviour. Contrary to our expectations we found a decrease in the wish to die during lockdown. This is consistent with previous studies showing that suicide rates decrease during periods of social emergency. Smartphone-based EMA can allow us to remotely assess patients and overcome the physical barriers imposed by lockdown.
Advancements in Microfluidic Systems for the Study of Female Reproductive Biology
Authors: Bodke Vedant V , Burdette Joanna E
Published: April 2021

The female reproductive tract is a highly complex physiological system that consists of the ovaries, fallopian tubes, uterus, cervix, and vagina. An enhanced understanding of the molecular, cellular, and genetic mechanisms of the tract will allow for the development of more effective assisted reproductive technologies, therapeutics, and screening strategies for female specific disorders. Traditional 2-dimensional and 3-dimensional static culture systems may not always reflect the cellular and physical contexts or physicochemical microenvironment necessary to understand the dynamic exchange that is crucial for the functioning of the reproductive system. Microfluidic systems present a unique opportunity to study the female reproductive tract, as these systems recapitulate the multicellular architecture, contacts between different tissues, and microenvironmental cues that largely influence cell structure, function, behavior, and growth. This review discusses examples, challenges, and benefits of using microfluidic systems to model ovaries, fallopian tubes, endometrium, and placenta. Additionally, this review also briefly discusses the use of these systems in studying the effects of endocrine disrupting chemicals and diseases such as ovarian cancer, preeclampsia, and polycystic ovarian syndrome.
Bone-marrow of the Guinea-pig as a Mesodermal Inductor in Implantation Experiments with Embryos of Triturus
Authors: Toivonen Sulo
Published: April 2021

Marrow from the thigh-bone of the guinea-pig, treated in 70 per cent, alcohol, has been used as the inductor material in implantation experiments with gastrulae of Triturus. The inductor has induced mesodermal structures such as limb rudiments, notochords, pronephric tubules, and mesenchyme, and, in addition to these, proctodaea with anal openings. These last are regarded as secondary induction products of the induced mesoderm. The only suggestion of neural induction consisted of darkly staining cells, which may perhaps be regarded as neural. The results show that the mesoderm-inducing agent is independent of the agents inducing neural structures, and the ‘spinal’ agent earlier postulated can thus be further divided into components inducing mesoderm and inducing neural structures. The question as to what is the specific action, independent of the mesoderminducing agent, of the neural-inducing component in the previously established ‘spinal’ inductor, is discussed.
Tip regeneration and positional information in the slug ofDictyostelium discoideum
Authors: Lokeshwar Balakrishna L. , Nanjundiah Vidyanand
Published: April 2021

We show in this paper that in the case of the slug of the cellular slime mould Dictyostelium discoideum the time which it takes for a new tip to regenerate at a given level can be used as a measure of positional information at that level. Our basic experiment consists of amputating slugs at various distances from the existing tip and thereby inducing the regeneration of a fresh tip; the time needed for regeneration is estimated by two independent methods. An identical operation, when performed in the anterior portion of a previously cut slug, tells us how this position-dependent regeneration time adjusts to a sudden change in the size of the slug. The reasons which lead us to conclude that tip regeneration times are in one-to-one correspondence with positional information are as follows, (i) Depending on their positions, the cells in a slug take different times to regenerate a new tip following amputation; (ii) regeneration times are scaled in relation to the total length of the slug and increase monotonically with the length cut off; and (iii) as judged by the regeneration time, cells can assess and remember their positions relative to the length of the slug. Our results highlight the importance of two rate processes. One might think of the slower process as being related to the setting up of a system of positional information in the slug, and the faster process as being a reflection of the kinetics of the positional value changing locally till it reaches the level appropriate to a tip.