bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex steroid hormones and risk of breast cancer: a two-sample Mendelian randomization study
Authors: Nounu Aayah , Kar Siddhartha P. , Relton Caroline L. , Richmond Rebecca C.
Published: October 2022

Background

Breast cancer (BC) has the highest cancer incidence and mortality in women worldwide. Observational epidemiological studies suggest a positive association between testosterone, estradiol, dehydroepiandrosterone sulphate (DHEAS) and other sex steroid hormones with postmenopausal BC. We used a two-sample Mendelian randomization analysis to investigate this association.

Methods

Genetic instruments for nine sex steroid hormones and sex hormone-binding globulin (SHBG) were obtained from genome-wide association studies (GWAS) of UK Biobank (total testosterone (TT) N: 230,454, bioavailable testosterone (BT) N: 188,507 and SHBG N: 189,473), The United Kingdom Household Longitudinal Study (DHEAS N: 9722), the LIFE-Adult and LIFE-Heart cohorts (estradiol N: 2607, androstenedione N: 711, aldosterone N: 685, progesterone N: 1259 and 17-hydroxyprogesterone N: 711) and the CORtisol NETwork (CORNET) consortium (cortisol N: 25,314). Outcome GWAS summary statistics were obtained from the Breast Cancer Association Consortium (BCAC) for overall BC risk (N: 122,977 cases and 105,974 controls) and subtype-specific analyses.

Results

We found that a standard deviation (SD) increase in TT, BT and estradiol increased the risk of overall BC (OR 1.14, 95% CI 1.09–1.21, OR 1.19, 95% CI 1.07–1.33 and OR 1.03, 95% CI 1.01–1.06, respectively) and ER + BC (OR 1.19, 95% CI 1.12–1.27, OR 1.25, 95% CI 1.11–1.40 and OR 1.06, 95% CI 1.03–1.09, respectively). An SD increase in DHEAS also increased ER + BC risk (OR 1.09, 95% CI 1.03–1.16). Subtype-specific analyses showed similar associations with ER+ expressing subtypes: luminal A-like BC, luminal B-like BC and luminal B/HER2-negative-like BC.

Conclusions

TT, BT, DHEAS and estradiol increase the risk of ER+ type BCs similar to observational studies. Understanding the role of sex steroid hormones in BC risk, particularly subtype-specific risks, highlights the potential importance of attempts to modify and/or monitor hormone levels in order to prevent BC.
Zoledronic Acid for prevention of bone and muscle loss after BAriatric Surgery (ZABAS)-a study protocol for a randomized controlled trial
Authors: Gam Søren , Gram Bibi , Juhl Claus Bogh , Hermann Anne Pernille , Hansen Stinus Gadegaard
Published: October 2022

Background

Bariatric surgery has adverse effects on the muscular-skeletal system with loss of bone mass and muscle mass and an increase in the risk of fracture. Zoledronic acid is widely used in osteoporosis and prevents bone loss and fracture. Bisphosphonates may also have positive effects on skeletal muscle. The aim of this study is to investigate the effects of zoledronic acid for the prevention of bone and muscle loss after bariatric surgery. 

Methods/design

This is a randomized double-blind placebo-controlled study. Sixty women and men with obesity aged 35 years or older will complete baseline assessments before randomization to either zoledronic acid (5 mg in 100 ml isotonic saline) or placebo (100 ml isotonic saline only) 3 weeks before surgery with Roux-en-Y-gastric bypass (RYGB) or sleeve gastrectomy (SG). Follow-up assessments are performed 12 and 24 months after surgery. The primary outcome is changes in lumbar spine volumetric bone mineral density (vBMD) assessed by quantitative computed tomography (QCT). Secondary bone outcomes are changes in proximal femur vBMD assessed by QCT. Changes in cortical and trabecular bone microarchitecture and estimated bone strength will be assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT). Cortical material bone strength at the mid-tibia diaphysis will be assessed using microindentation and fasting blood samples will be obtained to assess biochemical markers of bone turnover and calcium metabolism. 

Secondary muscle outcomes include whole body lean mass assessed using dual-energy X-ray absorptiometry. Dynamometers will be used to assess handgrip, shoulder, ankle, and knee muscle strength. Short Physical Performance Battery, 7.6-m walking tests, 2-min walking test, and a stair climb test will be assessed as biomarkers of physical function. Self-reported physical activity level is assessed using International Physical Activity Questionnaire (IPAQ).

Discussion

Results from this study will be instrumental for the evidence-based care of patients undergoing bariatric surgery.

Trial registration

ClinicalTrials.gov NCT04742010. Registered on 5 February 2021.
Developing principles for sharing information about potential trial intervention benefits and harms with patients: report of a modified Delphi survey
Authors: Svobodova Martina , Jacob Nina , Hood Kerry , Gillies Katie , Hale Rachel , Bostock Jennifer , Bower Peter , Edwards Adrian , Farthing Penelope , Rawlinson Sarah , Treweek Shaun , Howick Jeremy
Published: October 2022

Background

The way information about potential harms of trial intervention is shared within participant information leaflets (PILs) varies widely and can cause subjective ‘nocebo’ harms. This study aimed to develop principles to improve the composition of information about potential trial intervention benefits and harms within PILs so that variability and avoidable harms are reduced.

Methods

We conducted a two-round modified online Delphi survey, followed by a consensus meeting. For the first round of the survey, 27 statements were developed based on previous research and relevant guidance from the UK, the USA and the World Health Organization. Participants included members from each of the following stakeholder groups: patient and public representatives, research ethics committee members, industry representatives, medico-legal experts, psychologists and trial managers. Each participant was asked to rate their degree of agreement or disagreement with each statement on a 9-point Likert scale. In the second round, participants were invited to reappraise their ratings after reviewing the results of the first round. Finally, two members from each stakeholder group participated in a meeting to confirm those statements for which there was agreement.

Results

Two hundred and fifty participants completed round 1, and 201 participants completed round 2. In round 1, consensus was reached for 16 statements. In round 2, consensus was reached for an additional three statements. The consensus meeting confirmed the survey results and consolidated the statements. This process resulted in seven principles: (1) all potential harms of a given intervention should be listed, (2) all potential harms should be separated into serious and less serious, (3) it must be made explicit that not all potential harms are known, (4) all potential benefits should be listed, (5) all potential benefits and harms need to be compared with what would happen if the participant did not take part in the trial, (6) suitable visual representations should be added where appropriate and (7) information regarding potential benefits and harms should not be presented apart by one or more pages.

Conclusions

Our modified Delphi process successfully generated seven principles that can and should be used to guide how information is conveyed to patients in information leaflets regarding potential trial benefits and harms.
A multinational, phase 2, randomised, adaptive protocol to evaluate immunogenicity and reactogenicity of different COVID-19 vaccines in adults ≥75 already vaccinated against SARS-CoV-2 (EU-COVAT-1-AGED): a trial conducted within the VACCELERATE network
Authors: Neuhann Julia M. , Stemler Jannik , Carcas Antonio , Frías-Iniesta Jesús , Bethe Ullrich , Heringer Sarah , Tischmann Lea , Zarrouk Marouan , Cüppers Arnd , König Franz , Posch Martin , Cornely Oliver A.
Published: October 2022

Background

In the ongoing COVID-19 pandemic, advanced age is a risk factor for a severe clinical course of SARS-CoV-2 infection. Thus, older people may benefit in particular from booster doses with potent vaccines and research should focus on optimal vaccination schedules. In addition to each individual’s medical history, immunosenescence warrants further research in this population. This study investigates vaccine-induced immune response over 1 year.

Methods/design

EU-COVAT-1-AGED is a randomised controlled, adaptive, multicentre phase II protocol evaluating different booster strategies in individuals aged ≥75 years (n=600) already vaccinated against SARS-CoV-2. The initial protocol foresaw a 3rd vaccination (1st booster) as study intervention. The present modified Part B of this trial foresees testing of mRNA-1273 (Spikevax®) vs. BNT162b2 (Comirnaty®) as 4th vaccination dose (2nd booster) for comparative assessment of their immunogenicity and safety against SARS-CoV-2 wild-type and variants. The primary endpoint of the trial is to assess the rate of 2-fold antibody titre increase 14 days after vaccination measured by quantitative enzyme-linked immunosorbent assay (Anti-RBD-ELISA) against wild-type virus. Secondary endpoints include the changes in neutralising antibody titres (Virus Neutralisation Assay) against wild-type as well as against Variants of Concern (VOC) at 14 days and up to 12 months. T cell response measured by qPCR will be performed in subgroups at 14 days as exploratory endpoint. Biobanking samples are being collected for neutralising antibody titres against potential future VOC. Furthermore, potential correlates between humoral immune response, T cell response and neutralising capacity will be assessed.

The primary endpoint analysis will be triggered as soon as for all patients the primary endpoint (14 days after the 4th vaccination dose) has been observed.

Discussion

The EU-COVAT-1-AGED trial Part B compares immunogenicity and safety of mRNA-1273 (Spikevax®) and BNT162b2 (Comirnaty®) as 4th SARS-CoV-2 vaccine dose in adults ≥75 years of age. The findings of this trial have the potential to optimise the COVID-19 vaccination strategy for this at-risk population.

Trial registration

ClinicalTrials.govNCT05160766. Registered on 16 December 2021.

Protocol version: V06_0: 27 July 2022
Sequencing Mycobacteria and Algorithm-determined Resistant Tuberculosis Treatment (SMARTT): a study protocol for a phase IV pragmatic randomized controlled patient management strategy trial
Authors: Van Rie Annelies , De Vos Elise , Costa Emilyn , Verboven Lennert , Ndebele Felex , Heupink Tim H. , Abrams Steven ,   SMARTT team, Maraba Noriah , Makkan Heeran , Beattie Trevor , Sibeko Zandile Rachel , Bohlela S’thabiso , Segwaba Pulane , Ogunbayo Emmanuel Ayodeji , Mhlambi Nomadlozi , Wells Felicia , Rigouts Leen , Maartens Gary , Conradie Francesca , Black John , Potgieter Sam , Fanampe Boitumelo , Van der Spoel Van Dyk Anneke , Charalambous Salome , Churchyard Gavin , Warren Rob
Published: October 2022

Background

Rifampicin-resistant tuberculosis (RR-TB) remains an important global health problem. Ideally, the complete drug-resistance profile guides individualized treatment for all RR-TB patients, but this is only practised in high-income countries. Implementation of whole genome sequencing (WGS) technologies into routine care in low and middle-income countries has not become a reality due to the expected implementation challenges, including translating WGS results into individualized treatment regimen composition.

Methods

This trial is a pragmatic, single-blinded, randomized controlled medical device trial of a WGS-guided automated treatment recommendation strategy for individualized treatment of RR-TB. Subjects are 18 years or older and diagnosed with pulmonary RR-TB in four of the five health districts of the Free State province in South Africa. Participants are randomized in a 1:1 ratio to either the intervention (a WGS-guided automated treatment recommendation strategy for individualized treatment of RR-TB) or control (RR-TB treatment according to the national South African guidelines). The primary effectiveness outcome is the bacteriological response to treatment measured as the rate of change in time to liquid culture positivity during the first 6 months of treatment. Secondary effectiveness outcomes include cure rate, relapse rate (recurrence of RR-TB disease) and TB free survival rate in the first 12 months following RR-TB treatment completion. Additional secondary outcomes of interest include safety, the feasibility of province-wide implementation of the strategy into routine care, and health economic assessment from a patient and health systems perspective.

Discussion

This trial will provide important real-life evidence regarding the feasibility, safety, cost, and effectiveness of a WGS-guided automated treatment recommendation strategy for individualized treatment of RR-TB. Given the pragmatic nature, the trial will assist policymakers in the decision-making regarding the integration of next-generation sequencing technologies into routine RR-TB care in high TB burden settings.

Trial registration

ClinicalTrials.gov NCT05017324. Registered on August 23, 2021.
Eligibility screening older research participants using remote cognitive assessment—experiences and reflections from a primary care randomised controlled trial
Authors: Brundle Caroline , Heaven Anne , Clegg Andrew
Published: October 2022

Background

The COVID-19 pandemic forced many research teams to adjust the way they conduct studies, including moving to remote delivery of some or all of their recruitment and data collection processes. The Montreal Cognitive Assessment (MoCA) is widely used in research and is available in multiple formats for different groups and assessment settings. Here, we reflect on our experiences of administering the MoCA Blind/Telephone as part of the initial telephone eligibility check for participation in a randomised controlled trial with community-dwelling older people with frailty.

Main body

In response to COVID-19, a number of changes were made to the trial’s screening and recruitment procedures, to minimise the amount of time the researchers would spend in the participants’ homes when recruitment began in May 2021. One of the changes was for the researchers to conduct a cognitive assessment for eligibility during an initial telephone call, rather than during the subsequent home visit for consent and baseline data collection. We found that in comparison with conducting the assessment in-person, telephone administration caused uncertainty for the researchers about whether participants were struggling to answer questions due to cognition or hearing impairment. Some participants experienced practical difficulties when combining holding a telephone and completing one of the assessment items. It was hard for the researchers to judge the emotional impact that undertaking the assessment was having on the older people on the telephone, without visual warning signs of fatigue or mood. We discuss the potential impact of these issues on trial recruitment and participant engagement, and the feasibility of videoconferencing as an alternative method of conducting the MoCA.

Conclusion

The MoCA is a useful tool when cognitive impairment is part of screening and data collection and it is helpful to have the option to use the test remotely. However, as we have found, telephone testing is not always straightforward. Researchers should weigh up the pros and cons for each individual study, especially those involving older adults. If choosing remote methods, consider the practicality of using videoconferencing and think about the possible impact of telephone assessment on the relationship with the (potential) research participants.

Trial registration

Personalised care planning for older people with frailty ISRCTN16123291 28/08/2020.
MetaRNN: differentiating rare pathogenic and rare benign missense SNVs and InDels using deep learning
Authors: Li Chang , Zhi Degui , Wang Kai , Liu Xiaoming
Published: October 2022

Multiple computational approaches have been developed to improve our understanding of genetic variants. However, their ability to identify rare pathogenic variants from rare benign ones is still lacking. Using context annotations and deep learning methods, we present pathogenicity prediction models, MetaRNN and MetaRNN-indel, to help identify and prioritize rare nonsynonymous single nucleotide variants (nsSNVs) and non-frameshift insertion/deletions (nfINDELs). We use independent test sets to demonstrate that these new models outperform state-of-the-art competitors and achieve a more interpretable score distribution. Importantly, prediction scores from both models are comparable, enabling easy adoption of integrated genotype-phenotype association analysis methods. All pre-computed nsSNV scores are available athttp://www.liulab.science/MetaRNN. The stand-alone program is also available athttps://github.com/Chang-Li2019/MetaRNN.
Mobile group I introns at nuclear rDNA position L2066 harbor sense and antisense homing endonuclease genes intervened by spliceosomal introns
Authors: Lian Kjersti , Furulund Betty M. N. , Tveita Anders A. , Haugen Peik , Johansen Steinar D.
Published: October 2022

Background

Mobile group I introns encode homing endonucleases that confer intron mobility initiated by a double-strand break in the intron-lacking allele at the site of insertion. Nuclear ribosomal DNA of some fungi and protists contain mobile group I introns harboring His-Cys homing endonuclease genes (HEGs). An intriguing question is how protein-coding genes embedded in nuclear ribosomal DNA become expressed. To address this gap of knowledge we analyzed nuclear L2066 group I introns from myxomycetes and ascomycetes.

Results

A total of 34 introns were investigated, including two identified mobile-type introns in myxomycetes with HEGs oriented in sense or antisense directions. Intriguingly, both HEGs are interrupted by spliceosomal introns. The intron in Didymium squamulosum, which harbors an antisense oriented HEG, was investigated in more detail. The group I intron RNA self-splices in vitro, thus generating ligated exons and full-length intron circles. The intron HEG is expressed in vivo in Didymium cells, which involves removal of a 47-nt spliceosomal intron (I-47) and 3′ polyadenylation of the mRNA. The D. squamulosum HEG (lacking the I-47 intron) was over-expressed in E. coli, and the corresponding protein was purified and shown to confer endonuclease activity. The homing endonuclease was shown to cleave an intron-lacking DNA and to produce a pentanucleotide 3′ overhang at the intron insertion site.

Conclusions

The L2066 family of nuclear group I introns all belong to the group IE subclass. The D. squamulosum L2066 intron contains major hallmarks of a true mobile group I intron by encoding a His-Cys homing endonuclease that generates a double-strand break at the DNA insertion site. We propose a potential model to explain how an antisense HEG becomes expressed from a nuclear ribosomal DNA locus.
New mechanism for mesenchymal stem cell microvesicle to restore lung permeability: intracellular S1P signaling pathway independent of S1P receptor-1
Authors: Ye Lifang , Song Jieqiong , Zheng Yijun , Zhong Ming , Liu Jun , Zhu Duming , Hu Shuling
Published: October 2022

Background

Microvesicles (MVs) derived from human bone marrow mesenchymal stem cell (MSC) were demonstrated to restore lung protein permeability and attenuate acute lung injury. In our previous study, we found that MSC MV increased sphingosine-1-phosphate (S1P) kinase1 mRNA levels in injured human lung microvascular endothelial cells (HLMVEC) significantly. However, the role of S1P signaling in MSC MV to restore lung protein permeability is unknown.

Methods

In this study, we hypothesized that MSC MV might restore lung permeability in part through increasing intracellular S1P signaling pathway in injured HLMVEC independent of S1P receptors. We used the transwell co-culture system to study the effect of MSC MV on protein permeability of Lipopolysaccharide (LPS) damaged HLMVEC.

Results

Our results showed that LPS significantly increased the permeability of HLMVEC to FITC-dextran (70 kDa) within 24 h. MSC MV restores this permeability and, to a large extent, prevents the cytoskeleton protein F-actin from recombining into “actin stress fibers,” and restores the positions of tight junctions and adhesion junctions in the damaged HLMVEC. This therapeutic effect of MSC MV was related to the increase in the S1P level in injured HLMVEC and was not eliminated when adding the antagonist of S1P receptor, suggesting that MSC MV to restore lung permeability was independent of S1P receptors on HLMVEC. Laser confocal further observed that Ca2+ mobilization and Rac1 activation in LPS injured HLMVEC were increased in parallel with the increase in intracellular S1P level after MSC MV treatment.

Conclusions

In short, MSC MV partially restored protein permeability across HLMVEC through the intracellular S1P signaling pathway independent of S1P receptor-1.
Inhibition of sphingolipid metabolism in osteosarcoma protects against CD151-mediated tumorigenicity
Authors: Wang Hongsheng , Jin Xinmeng , Zhang Yangfeng , Wang Zhuoying , Zhang Tao , Xu Jing , Shen Jiakang , Zan Pengfei , Sun Mengxiong , Wang Chongren , Hua Yingqi , Ma Xiaojun , Sun Wei
Published: October 2022

Osteosarcoma is the most common primary bone tumor, with a poor prognosis owing to the lack of efficient molecular-based targeted therapies. Previous studies have suggested an association between CD151 and distinct consequences in osteosarcoma tumorigenicity. However, the potential of CD151 as a therapeutic target has not yet been sufficiently explored. Here, we performed integrated transcriptomic and metabolomic analyses of osteosarcoma and identified sphingolipid metabolism as the top CD151-regulated pathway. CD151 regulates sphingolipid metabolism primarily through SPTCL1, the first rate-limiting enzyme in sphingolipid biosynthesis. Mechanistically, depletion of CD151 enhanced c-myc polyubiquitination and subsequent degradation. c-myc is vital for the transcriptional activation of SPTLC1. Functionally, sphingolipid synthesis and the SPTLC1 inhibitor, myriocin, significantly suppressed the clonogenic growth of CD151-overexpression cells. Importantly, myriocin selectively restrained CD151-high expression tumor growth in preclinical patient-derived xenograft models. Collectively, these data establish that CD151 is a key mediator of sphingolipid metabolism and provide a new approach to developing novel CD151-based targeted therapies for osteosarcoma.
Epidemiological and etiological characteristics of mild hand, foot and mouth disease in children under 7 years old, Nanjing, China, 2010–2019
Authors: Wang Junjun , Ding Songning , Xie Weijia , Wang Taiwu , Qin Ying , Zheng Jiandong , Yang Xiaokun , Zhao Hongting , Peng Zhibin , Ma Tao
Published: October 2022

Background

Mild hand, foot and mouth disease (HFMD) cases make up a relatively high proportion of HFMD while have often been overlooked. This study aimed to investigate the epidemiological and etiological characteristics of mild HFMD in Nanjing.

Methods

Data on mild HFMD cases, during 2010–2019 in Nanjing, were collected from the China Information System for Disease Control and Prevention. This study mainly focused on mild cases aged < 7 years. Descriptive analysis was used to summarize epidemiological and etiological characteristics of mild cases. Flexible spatial scan statistic was used to detect spatial clusters of mild cases.

Results

A total of 175,339 mild cases aged < 7 years were reported, accounting for 94.4% of all mild cases. There was a higher average annual incidence of mild HFMD in children aged < 7 years (4,428 cases/100,000) compared with children aged ≥ 7 years (14 cases/100,000, P < 0.001), and especially children aged 1-year-old (7,908 cases/100,000). Mild cases showed semi-annual peaks of activity, including a major peak (April to July) and a minor peak (September to November). The average annual incidence was higher in males (5,040 cases/100,000) than females (3,755 cases/100,000). Based on the cumulative reported cases, the most likely cluster was detected, including Yuhuatai District, Jiangning District, Jiangbei new Area, and Pukou District. The annual distribution of enterovirus serotypes showed a significant difference. During 2010–2016, Enterovirus 71 (EV71), Coxsackievirus A16 (Cox A16), and other non-EV71/Cox A16 EVs, accounted for 29.1%, 34.6%, 36.3% of all the enterovirus test positive cases, respectively. Moreover, during 2017–2019, Cox A6, Cox A16, EV71, and other non-EV71/Cox A16/Cox A6 EVs, accounted for 47.3%, 32.5%, 10.7%, 9.5%, respectively.

Conclusions

Children under 7 years old are at higher risk of mild HFMD. Regions with high risk are mainly concentrated in the areas surrounding central urban areas. Cox A16 and Cox A6 became the dominant serotypes and they alternated or were co-epidemic. Our findings could provide valuable information for improving the regional surveillance, prevention and control strategies of HFMD.
HaNDL syndrome: a reversible cerebral vasoconstriction triggered by an infection? A case report and a case-based review
Authors: Fiamingo Giuseppe , Canavero Isabella , Gastaldi Matteo , Coloberti Elisa , Buongarzone Gabriele , Ghiotto Natascia , Bacila Ana , Costa Alfredo , Ravaglia Sabrina
Published: October 2022

Background

The syndrome of transient Headache and Neurological Deficits with cerebrospinal fluid (CSF) Lymphocytosis (HaNDL) is classified among secondary headaches attributed to “non-infectious, inflammatory intracranial disease”. Despite its classification among secondary headaches, the current definition of HaNDL does not contemplate a causal agent. Thus, the aetiology, as well as the pathogenesis of both the headache and the transient focal deficits, remains unknown.

Case presentation

We describe a 29-year-old healthy male developing episodes of thunderclap headaches associated with recurrence of hemiparesis/hemi-paraesthesia; CSF showed lymphocytosis 200/mm3 and increased albumin; brain MRI revealed widespread leptomeningeal enhancement and a non-enhancing, circular diffusion restriction in the splenium of corpus callosum. Screening for neurotropic pathogens detected Epstein-Barr (EBV) DNA in serum and CSF, interpreted as a primary EBV infection once the seroconversion of EBV nuclear antigen (EBNA) IgM to IgG was proven on follow-up. Transcranial Doppler detected, during headache, increased flow velocity in middle cerebral arteries, possibly indicating vasospasm. Oral nimodipine was administered, with prompt clinical recovery, resolution of CSF/MRI abnormalities, and normalization of flow velocities in middle cerebral arteries.

Case-based review

Although the definition of HaNDL does not contemplate a viral trigger or abnormal brain imaging, we found other literature cases of HaNDL associated with direct or indirect signs of CNS infection.

Conclusions

At least in a proportion of patients, a viral aetiology may have a role in HaNDL. Whatever the aetiology, we suggest that the pathogenic mechanism may rely on the (viral or other) agent ultimately triggering cerebral vasoconstriction, which would explain both focal symptoms and headache. Calcium channel blockers might be a therapeutic option.
Tumor microenvironment and immunotherapy of oral cancer
Authors: Liu Chang , Wang Min , Zhang Haiyang , Li Chunyan , Zhang Tianshou , Liu Hong , Zhu Song , Chen Jie
Published: October 2022

Oral cancer is one of the most common malignant tumors of the head and neck, not only affects the appearance, but also affects eating and even endangers life. The clinical treatments of oral cancer mainly include surgery, radiotherapy, and chemotherapy. However, unsatisfactory therapeutic effect and toxic side effects are still the main problems in clinical treatment. Tumor microenvironment (TME) is not only closely related to the occurrence, growth, and metastasis of tumor but also works in the diagnosis, prevention, and treatment of tumor and prognosis. Future studies should continue to investigate the relationship of TME and oral cancer therapy. This purpose of this review was to analyze the characteristics of oral cancer microenvironment, summarize the traditional oral cancer therapy and immunotherapy strategies, and finally prospect the development prospects of oral cancer immunotherapy. Immunotherapy targeting tumor microenvironment is expected to provide a new strategy for clinical treatment of oral cancer.
Ink-lithographic fabrication of silver-nanocrystal-based multiaxial strain gauge sensors through the coffee-ring effect for voice recognition applications
Authors: Ahn Junhyuk , Choi Hyung Jin , Bang Junsung , Son Gayeon , Oh Soong Ju
Published: October 2022

Human voice recognition techniques have remarkable potential for clinical applications because information from acoustic signals can reflect human body conditions. This paper reports the fabrication of Ag nanocrystal (NC)-based multiaxial wearable strain gauge sensors by ink-lithography for voice recognition systems. Benefiting from the one-step-device-fabrication strategy of ink-lithography, which can yield Ag NC patterns with specific dimensions and endow physical properties, the Ag NC-based multiaxial strain sensors can be fabricated on an ultrathin substrate (~ 6 μm). Additionally, the coffee-ring effect can be induced onto the Ag NC patterns to realize high sensitivity and angle dependence (gauge factors $${G}_{0^\circ }$$

G

0
∘

 = 11.7 ± 1.2 and $${G}_{90^\circ }$$

G

90
∘

 = 105.5 ± 20.1); moreover, the voice onset time for voice recognition can be detected by the sensors. These features assist in distinguishing between voiced and voiceless plosive contrasts via measurements of contact-based voice onset time differences and can act as a cornerstone for further advancements in wearable sensors as well as voice recognition and analysis.

Graphical Abstract
Small nuclei identification with a hemispherical brain PET
Authors: Takahashi Miwako , Akamatsu Go , Iwao Yuma , Tashima Hideaki , Yoshida Eiji , Yamaya Taiga
Published: October 2022

Background

To confirm the performance of the first hemispherical positron emission tomography (PET) for the brain (Vrain) that we developed to visualise the small nuclei in the deep brain area, we compared 18F-fluorodeoxyglucose (FDG) brain images with whole-body PET images.

Methods

Ten healthy male volunteers (aged 22–45 years) underwent a representative clinical whole-body PET, followed by Vrain each for 10 min. These two scans were initiated 30 min and 45 min after FDG injection (4.1 ± 0.5 MBq/kg), respectively. First, we visually identified the small nuclei and then compared their standardised uptake values (SUVs) with the participants’ age. Next, the SUVs of each brain region, which were determined by applying a volume-of-interest template for anatomically normalised PET images, were compared between the brain images with the Vrain and those with the whole-body PET images.

Results

Small nuclei, such as the inferior colliculus, red nucleus, and substantia nigra, were more clearly visualised in Vrain than in whole-body PET. The anterior nucleus and dorsomedial nucleus in the thalamus and raphe nucleus in the brainstem were identified in Vrain but not in whole-body PET. The SUVs of the inferior colliculus and dentate gyrus in the cerebellum positively correlated with age (Spearman’s correlation coefficient r = 0.811, p = 0.004; r = 0.738, p = 0.015, respectively). The SUVs of Vrain were slightly higher in the mesial temporal and medial parietal lobes than those in whole-body PET.

Conclusions

This was the first time that the raphe nuclei, anterior nuclei, and dorsomedial nuclei were successfully visualised using the first hemispherical brain PET.

Trial registration 

Japan Registry of Clinical Trials, jRCTs032210086, Registered 13 May 2021, https://jrct.niph.go.jp/latest-detail/jRCTs032210086.
Modulation of bioactive calcium phosphate micro/nanoparticle size and shape during in situ synthesis of photo-crosslinkable gelatin methacryloyl based nanocomposite hydrogels for 3D bioprinting and tissue engineering
Authors: Bhattacharyya Amitava , Janarthanan Gopinathan , Kim Taeyang , Taheri Shiva , Shin Jisun , Kim Jihyeon , Bae Hyun Cheol , Han Hyuk-Soo , Noh Insup
Published: October 2022

Background

The gelatin-methacryloyl (GelMA) polymer suffers shape fidelity and structural stability issues during 3D bioprinting for bone tissue engineering while homogeneous mixing of reinforcing nanoparticles is always under debate.

Method

In this study, amorphous calcium phosphates micro/nanoparticles (CNP) incorporated GelMA is synthesized by developing specific sites for gelatin structure-based nucleation and stabilization in a one-pot processing. The process ensures homogenous distribution of CNPs while different concentrations of gelatin control their growth and morphologies. After micro/nanoparticles synthesis in the gelatin matrix, methacrylation is carried out to prepare homogeneously distributed CNP-reinforced gelatin methacryloyl (CNP GelMA) polymer. After synthesis of CNP and CNP GelMA gel, the properties of photo-crosslinked 3D bioprinting scaffolds were compared with those of the conventionally fabricated ones.

Results

The shape (spindle to spherical) and size (1.753 μm to 296 nm) of the micro/nanoparticles in the GelMA matrix are modulated by adjusting the gelatin concentrations during the synthesis. UV cross-linked CNP GelMA (using Irgacure 2955) has significantly improved mechanical (three times compressive strength), 3D printability (160 layers, 2 cm self-standing 3D printed height) and biological properties (cell supportiveness with osteogenic differentiation). The photo-crosslinking becomes faster due to better methacrylation, facilitating continuous 3D bioprinting or printing.

Conclusion

For 3D bioprinting using GelMA like photo cross-linkable polymers, where structural stability and homogeneous control of nanoparticles are major concerns, CNP GelMA is beneficial for even bone tissue regeneration within short period.

Graphical Abstract
Deworming among preschool age children in sub-Saharan Africa: pooled prevalence and multi-level analysis
Authors: Belay Daniel Gashaneh , Kibret Anteneh Ayelign , Diress Mengistie , Gela Yibeltal Yismaw , Sinamaw Deresse , Simegn Wudneh , Andualem Amare Agmas , Seid Abdulwase Mohammed , Bitew Desalegn Anmut , Seid Mohammed Abdu , Eshetu Habitu Birhan , Jemere Tsega Degu , Shiferaw Yalelet Fentaw , Shibabaw Yadelew Yimer , Chilot Dagmawi
Published: October 2022

Background

Sub-Saharan Africa (SSA) preschool age children are more vulnerable to soil-transmitted helminths (STH) which caused millions of morbidity because of low socioeconomic status and lack of clean water and sanitation. Despite this problem, there is minimal evidence on the prevalence and factors associated with deworming medication utilization among preschool age children (pre-SAC) in SSA regions. Hence this study aimed to assess the prevalence and determinants of deworming among preschool age children in SSA.

Methods

Demographic and Health Survey (DHS) data were used for this study with a total weighted 192,652 children aged 24–59 months. Taking deworming medication in the 6 months preceding the interview was our outcome of interest. A multi-level binary logistic regression model was fitted. Adjusted odds ratio (AOR) with 95% confidence interval (CI) was taken to identify significant variables.

Results

The prevalence of deworming medication utilization among preschool age children in SSA was 45.03% (95% CI 44.46%, 45.60%), ranging from 41.82% in Malawi to 50.5% in Lesotho. It was 44.91% (95% CI 44.32%, 45.51%) among countries having endemic STH infection and 46.01% (95% CI 43.64%, 48.38%) for none endemic countries. Factors such as; secondary and above women education [AOR = 2.18; 95% CI 2.10, 2.26], occupation [AOR = 1.31; 95% CI 1.27, 1.34], having ≥ 11 family members [AOR = 0.68; 95% CI 0.64, 0.70], household media exposure [AOR = 1.16; 95% CI 1.13, 1.19] and richer wealth status [AOR = 1.23; 95% CI 1.16, 1.27], vitamin A supplementation [AOR = 6.18; 95% CI 6.02, 6.33] and living rural residence [AOR = 0.94; 95% CI 0.92, 0.98] have significantly associated with deworming among preschool age children.

Conclusions

Utilization of deworming medication among pre-SAC children in sub-Saharan Africa is below half. Factors, such as the education status of women, family size, household media exposure, wealth status, diarrhea, vitamin A supplementation, and residence were significant variables. To increase the utilization of deworming medication for pre-SAC, WHO should work as an integrated approach with other stakeholders, by strengthening women’s education, and media exposure. Maternal employment should be promoted and prior attention should be given to rural children.
A participatory student workshop on climate change and sustainability: a comparative case study
Authors: Larose Carole , Blaisot Christine , Burke Eleanor
Published: October 2022

Climate change is an environmental and existential issue of great urgency, especially for today’s youth. Until recently, the French national school curriculum had not given students much opportunity to learn about climate change (CC), its causes and repercussions, and mitigating measures to reach sustainable climate conditions. This article describes a six-week participatory, experiential workshop that brought together two groups of French students (one age 10 and the other age 16) to learn and teach each other about CC. Older students learned about the Conference of the Parties, COP21 Paris agreement and the IPCC climate findings and recommendations. Together the two groups developed greater understanding about CC, and proposed concrete environmental actions that they could undertake at home and in their local district to reduce greenhouse gas (GHG) emissions. We examine four products of their collaboration:

slide presentations that they created jointly,

students’ written reflections on learning about sustainability and CC,

the group’s list of proposed personal and family actions to decrease their carbon footprint, and

notes from a meeting with local governmental officials.

We draw inferences from these sources, and extract two recurrent themes in the students’ learning. These themes highlight a mismatch between youth’s sense of urgency to respond to the climate emergency and the older generation’s sluggish pace of addressing it. This article is a qualitative case study of a successful attempt to raise students’ awareness of sustainability and climatic issues, and to involve them in thinking collaboratively with others about the tasks ahead to address the problem of climate change from a local perspective.
One Health security lessons from a year-long webinar series on international COVID-19 response
Authors: Kennedy Caroline R. M. , de Bruin Yuri Bruinen , Lequarré Anne-Sophie , Ackerman Rebecca T. , Luster Jill , Tsang Tiffany M. , McInturff Kari D. , Carter Cassandra P. , Pilch Richard
Published: October 2022

Following the principles outlined by the Global Outbreak Alert and Response Network, the Federal Bureau of Investigation’s International Biosecurity and Prevention Forum, the European Commission’s Joint Research Centre, and the Middlebury Institute of International Studies’ James Martin Center for Nonproliferation Studies cohosted a webinar series from April 2020 to January 2021 on COVID-19 management across Africa, Europe, and North America. We provide here an overview of the webinar series and discuss how lessons learned during the COVID-19 pandemic and debated during the webinars can be used to bridge One Health with biological threat-driven health security. This report can be used to inform recommendations for future One Health security approaches to strengthen global capacity and multidisciplinary cooperation.
The impact of perceived customer discrimination on negative word-of-mouth: the mediating role of customer embarrassment
Authors: Ahmed Farhan , Liang DaPeng , Abdullah Muhammad Ibrahim , Sarfraz Muddassar , Saeed Zeeshan
Published: October 2022

Disadvantaged or minority customers are always vulnerable to discriminatory treatment by service employees. Discrimination against minority customers has become a frequent headline in the news. The main objective of this research is to construct a model that explains the relationship between perceived customer discrimination, negative word-of-mouth, and customer embarrassment. The paper proposes a direct relationship between perceived customer discrimination and switching intentions and an indirect relationship via customer embarrassment. Furthermore, discriminatory service experiences are classified into three categories to add transparency to customers’ discriminatory experiences. This research also investigates the mediating role played by customer embarrassment. We collected data from minority customers to prove the proposed hypotheses' statistical significance. A survey was designed to collect data from respondents using self-administrative questionnaires. The data collection process was rigorous and yielded 252 useful questionnaires. Direct and indirect hypotheses testing was carried out by using Analysis of Moment Structures software. The research findings reveal that perceived customer discrimination significantly influences customer embarrassment. Furthermore, all perceived customer discrimination, i.e., overt, subtle, and service-level, significantly impact customer embarrassment. It is also found that customer embarrassment statistically impacts negative word-of-mouth. Additionally, the mediating role of customer embarrassment is also successfully substantiated. The paper includes implications for theory and practice, limitations of research, and future research options.
BDAODV: A Security Routing Protocol to detect the Black hole Attacks in Mobile Ad Hoc Networks
Authors:   Faculty of Information Technology, Huy Le Duc ,   Ha Noi University of Business and Technology, Viet Nam, Ha Truong Thi Thu , Tam Nguyen Van
Published: October 2022

One of the challenges of Mobile Ad Hoc Networks (MANET) is black hole attack. This is a form of destructive attack, causing very heavy damage to network performance once successfully implemented. By replying to the route with HC=1 and the largest SN, the malicious node fools the source node into thinking that it has the best and freshest cost-effective route to the destination node. As a result, all the data packets get caught in the malicious node and go missing without being able to reach the destination node. Most of the previous research was based on the characterization of black hole attacks or simple check mechanisms to detect cyberattacks. This leads to limitations that need to be overcome such as: Error rate in malicious node detection algorithm, routing waste, data routing efficiency in normal network scenario. This paper proposes a black hole attack detection algorithm (BDA) based on statistical theory. BDA collects information in real time so it can detect and prevent black hole attacks as they begin to act. The proposed solution uses a balance threshold value, calculated based on statistical theory, as the threshold for detecting black hole attack. A node that replies to the route with an SN value greater than the threshold is identified as a malicious node and isolated immediately upon attack. The article also proposes a black hole attack detection routing protocol (BDAODV) by improving the AODV protocol using BDA solution. The performance of the BDAODV protocol is evaluated and compared with related solutions on a network model with random mobile nodes. The simulation results have shown that the proposed protocol has very good performance in the network scenario under black hole attack with different number of malicious nodes.
Minimizing the PAPR for FBMC/OQAM Signals Using Enhanced-PTS with Low Complexity Search
Authors:   Department of Electrical Engineering, Pan African University, P.O. BOX 62000 Nairobi, Kenya, Ango Mahaman Noura Issaka , Mwangi Elijah , Idrissa Moctar Mossi
Published: October 2022

The filter bank multicarrier with offset quadrature amplitude modulation (FBMC/OQAM) scheme has recently become a focus of interest for many scholars and researchers. Despite its impressive advantages over Orthogonal Frequency Division Multiplexing (OFDM), the FBMC/OQAM system exhibits high Peak-to-Average Power Ratio (PAPR) which could plague its performance if it is not properly managed. In this paper, we proposed a PAPR reduction scheme that improves the Partial Transmit Sequence (PTS) to an enhanced PTS (EPTS), then employs a low complexity search to determine the optimal combination of phase factors. In the enhanced PTS, the FBMC/OQAM data blocks are partitioned into sub-blocks by taking into account their overlapping arrangement, then a segmentation operation is performed to the overall overlapping partitioned data blocks in order to form several segments of sub-blocks. After that, the segments are optimized consecutively by applying a phase factor search approach. Referred to as enhanced PTS with iterative flipping (EPTS-IF), the proposed scheme optimizes consecutively the segments of sub-blocks by employing Iterative Flipping approach. The PAPR reduction performance and the computational complexity of the proposed scheme have been evaluated through computer simulations and theoretical analysis which revealed a significant PAPR reduction gain of approximately 30.48%, and at a low computational cost.
Null-Steering Beamformers for Suppressing Unknown Direction Interferences in Sidelobes
Authors:   Hanoi University of Industry, Hanoi, 100000, Vietnam, Tong Luyen V. , Kha Kha M. , Nguyen Cuong V. , Nguyen Trung L. , Truong Giang B. V.
Published: October 2022

This paper proposes an efficient null-steering beamformer for adaptive pattern synthesis of uniform linear arrays based on binary bat algorithm (BBA) and the amplitude-only control of array excitation weights. The proposed beamformer is able to suppress unknown direction interferences in the sidelobes while simultaneously maintaining the main lobe and suppressing the sidelobes. The performance of the proposal has been investigated via a couple of scenarios including operation speed and adaptive null-steering ability with or without the effect of mutual coupling in half-wave dipole uniform linear arrays (DULA). The simulation results have proved that the proposed beamformer is a promising approach for adaptive pattern synthesis in the case of interference suppression. In addition, this proposal outperforms those using binary particle swarm optimization (BPSO) on the operation speed and null-steering efficiency.
Performance Analysis of FS-FBMC/OQAM System Using Turbo and LDPC Codes
Authors:   Department of Electronics and Communication Engineering, Jamia Millia Islamia, New Delhi, 110025, India, Mobin Anam , Ahmad Anwar
Published: October 2022

Filter Bank Multicarrier (FBMC) with offset QAM (OQAM) is a possible waveform candidate for 5G and future wireless systems and standards. FBMC is realized using either polyphase network (PPN)-FFT or Frequency Spread (FS)-FBMC. In this paper, channel coding schemes such as turbo codes and low-density parity check (LDPC) codes were investigated in terms of their peak-to-average power ratio (PAPR) and bit-error-rate (BER) reduction performances for FS-FBMC/OQAM and Orthogonal Frequency Division Multiplexing (OFDM) systems in additive white Gaussian noise (AWGN) channel. Simulation results show that turbo coded and LDPC coded FS-FBMC/OQAM systems performed better than turbo coded and LDPC coded OFDM systems in terms of BER performance. Also, LDPC coded FS-FBMC/OQAM system because of its adequate BER performance, reasonable PAPR performance, and reduced computational complexity was found to be an appropriate choice among other systems for 5G and future wireless networks. It was also found that incorporating channel coding resulted in a very large coding gain with only a minor rise in the system's PAPR value.