bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute tonsillitis and its complications: an overview
Authors: Bartlett A , Bola S , Williams R
Published: February 2021

Acute tonsillitis may be defined as inflammation of the tonsils, predominantly due to infection. It is part of the spectrum of pharyngitis, which ranges from localised tonsillar infection to generalised infection of the pharynx and commonly affects young healthy adults. Simple sore throats secondary to viral or bacterial pharyngitis are very common and generally do not require hospital admission or antimicrobial treatment. Supportive management in the form of analgesia and adequate hydration is often sufficient. However, there is potential for life-threatening complications to develop, highlighting the need for basic knowledge in the management of these conditions.

This article aims to provide an overview of acute tonsillitis and its complications, including peritonsillar and parapharyngeal abscess formation. Specific attention will be given to the pathogenesis, diagnosis, investigation and management of each condition, in particular advising on emergency pre-shore treatment and indications for referral to an Ear, Nose and Throat Department. We will also summarise important guidelines and evidence from the literature to support these management decisions.
‘The Drug of War’ – a historical review of the use of Ketamine in military conflicts
Authors: Mercer S J
Published: February 2021

Anaesthesia for surgery during armed conflict was traditionally based on simple and reliable techniques. These often required a minimum of equipment and drugs while ensuring rapid and safe patient recovery. Ketamine, which first became available in Britain in the 1970s, was thought to offer certain favorable characteristics for use as a military anaesthetic agent. This article discusses the use of ketamine in many of the major armed conflicts that have occurred since its introduction. It also catalogues the methods used by anaesthetists at the time and their opinions of the drug’s success.
Case Study - Leprosy
Authors: Wood A M , Wood C M , Bakker-Dyos J
Published: February 2021

We present the case of a 26 year old Indian base worker who attended the Role 2 enhanced hospital in Iraq with a case of leprosy. The patient presented four times over a 12 month period with non-specific pain in the right hand and forearm combined with a large lesion of dry skin and reduced sensation in the forearm. A clinical diagnosis of leprosy was made, which was subsequently confirmed as paucibacillary leprosy by skin smears sent to the UK. It was not possible to treat the patient locally and a recommendation made to the patient’s employer that the patient return to India to commence treatment.
Significant Neurological Presentations in Commando Trained Personnel: Case Studies and Consideration of Differential Diagnosis
Authors: Williams RJ , Howes RJ , Chabda S , Chalder A
Published: February 2021

A 27-year-old Royal Marine presented to his sickbay following two episodes of sudden onset visual disturbance. A subsequent MRI Scan demonstrated ischaemic changes in the territory of his right posterior cerebral artery. Transthoracic echocardiography was normal but a bubble contrast study was strongly positive indicating the presence of a relatively large patent foramen ovale (PFO). He underwent endovascular closure of his patent foramen ovale and was subsequently upgraded back to full duties.

A 35-year-old Army Sergeant presented with sudden onset collapse, right sided weakness, dysarthria and confusion. He was airlifted to a Host Nation hospital and following a normal CT head underwent thrombolysis in the Emergency Department. This was unsuccessful but a CT guided embolectomy led to complete resolution of symptoms. Subsequent transthoracic echo revealed a PFO. He underwent endovascular closure and has since been returned to full duties.

The incidence of PFO is common affecting 27% of the population but the incidence of ischaemic stroke in young adults (aged 15-45 years old) is rare. This maybe linked to the size of the PFOs in symptomatic individuals.1

These case reports emphasise the requirement for further investigation of individuals presenting with collapse and persisting neurology. Differential diagnosis and initial management for primary care and pre-hospital clinicians is also reviewed.
The Birmingham Military Trauma Registrar. A Personal View
Authors: Hollingsworthx A C
Published: February 2021

The military registrar is responsible for the co-ordination of care of returning battlefield casualties at Role 4 Royal Centre for Defence Medicine (RCDM). Traditionally two military specialty registrars (StR) providing a 24-hour a day service 365 days a year have shared this responsibility.

For Military StR3 General Surgical trainees this is now a recognized training post providing military trainees the opportunity of gaining exposure to battlefield casualties at an early stage in their specialty training.

This is a personal account of my time as the military registrar and the training opportunities to be gained for this model of military medical training.

Whilst the post is busy and the on call rota demanding the opportunities for surgical trainees are excellent and the requirements of the Intercollegiate Surgical Curriculum Programme (ISCP) can be met ensuring seamless progression to StR 4 training. This is a highly desirable post for junior military registrars.
The management of acute appendicitis
Authors: Brogden T G , Streets C G
Published: February 2021

Appendicitis is the most common general surgical condition and peaks in incidence at the age of those serving in the military. Diagnosis can be extremely difficult with very vague signs and symptoms. This review aims to highlight management considerations that should be taken into account when faced with appendicitis in a military setting, including in the pre-hospital and pre-shore environment. Current controversies surrounding appendicitis management, and the effect these might have on the management of the military patient, are debated.
An audit of the cost effectiveness of protocol-driven versus surgeon-directed pre-operative assessment of NHS patients referred to a General Surgeon
Authors: Woolley S D , Walsh L , Lambert A W
Published: February 2021

Aims

Pre-operative assessment (POA) is now commonplace and follows established protocols. This audit compares the costeffectiveness
of surgeon-directed (SD) POA compared to the standard practice of protocol-driven (PD) POA.

Methods

One hundred and fifty-six NHS patients who were referred to a single surgeon during 2009 were allocated to one of three groups. Group 1: SDPOA required no investigations, whereas the PDPOA would have mandated only Methycillin-Resistant Staphylococcus aureus (MRSA) screening and urinalysis; Group 2: SDPOA required no pre-operative investigations, whereas the PDPOA would have required investigations to be performed; Group 3: SDPOA recommended selective investigations, PDPOA required additional tests. For each group the investigations requested and performed, their cost and whether the results affected patient care were recorded. There is no individual PDPOA group, but the cost of the extra tests was calculated where the PDPOA protocols were followed and therefore the cost differed between the SDPOA and PDPOA.

Results

The total cost for all investigations for the 156 patients was £43,985. A potential cost saving of £9,694 (group 2) and £8,898 (group 3) was demonstrated. The total potential saving identified for all 3 groups was £18,592, which was 42% of the total cost of all the investigations. Patient care was not affected by these additional investigations.

Conclusions

There were no observed peri-operative complications during the study, implying that the additional pre-operative investigations were clinically unnecessary and identifying an additional cost saving of £18,592.
New Joiners Routine (NJR) – A novel screening tool in military primary care
Authors: McMenamin D , Rainey O , Evans G
Published: February 2021

Introduction– This paper describes and audits a novel method of health care screening in a military setting and questions the validity of the current PULHHEEMS system. The system involves screening patients at entry into an establishment with the aim of making them fit for task.

Methods– A retrospective DMICP case note review was conducted over 3 months following the introduction of the New Joiners Routine (NJR), to assess the level of positive screening findings, and the number of medical interventions that resulted from this screening. Key Performance Indicators (KPIs) were also assessed during the time frame of the audit.

Results – 131/194 (67.5%) had an unmet health need/ positive screening finding. This led to 66 medical interventions in 54 (25.7%) patients. KPIs during this period were markedly improved.

Discussion – Although not conclusive, this audit strongly suggests an improvement in culture in making personnel fit for task, and reflects the medical evidence of moving away from asymptomatic periodic health screening to targeted health screening.
Injuries and medical issues on the Zambezi “Great River”
Authors: Hammond T , Hammond AM
Published: February 2021

We report the injuries and medical issues incurred during a rowing expedition conducted along the Zambezi River in May 2011. All injuries and illnesses requiring medical intervention were recorded during a 30-day expedition. There were 22 rowers and 8 support staff sustaining 32 injuries, an injury incidence of 36 per 1000 days. We discuss the medical issues regarding conducting an expedition along the Zambezi and the medical preparation and education required to successfully support wilderness expeditions.
The management of upper respiratory tract infections
Authors: Rennie R , Rennie B
Published: February 2021

Upper respiratory tract infections (URTIs), generally termed colds, sore throats and coughs, are common presentations in primary care. This article discusses the clinical picture, management, significant differential diagnosis, and specifically, when antibiotics may be required for an URTI.
A generalization of the Einstein–Maxwell equations
Authors: Cotton Fredrick W.
Published: February 2021

The proposed modifications of the Einstein–Maxwell equations include: (1) the addition of a scalar term to the electromagnetic side of the equation rather than to the gravitational side, (2) the introduction of a four-dimensional, nonlinear electromagnetic constitutive tensor, (3) the addition of curvature terms arising from the non-metric components of a general symmetric connection and (4) the addition of a non-isotropic pressure tensor. The scalar term is defined by the condition that a spherically symmetric particle be force-free and mathematically well behaved everywhere. The constitutive tensor introduces two structure fields: One contributes to the mass and the other contributes to the angular momentum. The additional curvature terms couple both to particle solutions and to localized electromagnetic and gravitational wave solutions. The pressure term is needed for the most general spherically symmetric, static metric. It results in a distinction between the Schwarzschild mass and the inertial mass.
New methods in spectral theory of N-body Schrödinger operators
Authors: Adachi T. , Itakura K. , Ito K. , Skibsted E.
Published: February 2021

We develop a new scheme of proofs for spectral theory of the [Formula: see text]-body Schrödinger operators, reproducing and extending a series of sharp results under minimum conditions. Our main results include Rellich’s theorem, limiting absorption principle bounds, microlocal resolvent bounds, Hölder continuity of the resolvent and a microlocal Sommerfeld uniqueness result. We present a new proof of Rellich’s theorem which is unified with exponential decay estimates studied previously only for [Formula: see text]-eigenfunctions. Each pair-potential is a sum of a long-range term with first-order derivatives, a short-range term without derivatives and a singular term of operator- or form-bounded type, and the setup includes hard-core interaction. Our proofs consist of a systematic use of commutators with ‘zeroth order’ operators. In particular, they do not rely on Mourre’s differential inequality technique.
Coordinating Vulnerable Supply Chains with Option Contracts
Authors: Liu Zhongyi , Hua Shengya , Wang Guanying
Published: February 2021

We investigate vulnerable supply chain coordination with an option contract in the presence of supply chain disruption risk caused by external and internal disturbances. The supply chain consists of a single risk-neutral supplier and a risk-averse retailer. We characterize the retailer’s order quantity decision under the Conditional Value-at-Risk (CVaR) criterion and the supplier’s production decision. The results show that facing disruption risk and risk-aversion, both the retailer and the supplier would be more prudent to order and produce less than the risk-neutral scenario, inducing damage to the supply chain performance. The number of options purchased is decreasing in disruption risk and the risk-aversion of the retailer. The supplier will increase production as the disruption risk decreases or the shortage penalty increases. When the supplier does not know the risk-aversion of the retailer, the former will produce more and bear a higher overstock risk. We also investigate conditions that facilitate vulnerable supply chain coordination and find that the existence of risk-aversion and disruption risk restrict the option price and exercise price to lower price levels. Finally, we compare the option contract with wholesale price contract from the supplier’s and retailer’s perspectives through a numerical study.
Hamiltonian dynamics of gonihedric string theory
Authors: Molgado Alberto , Rojas Efraín
Published: February 2021

We develop in a consistent manner the Ostrogradski–Hamilton framework for gonihedric string theory. The local action describing this model, being invariant under reparametrizations, depends on the modulus of the mean extrinsic curvature of the worldsheet swept out by the string, and thus we are confronted with a genuine second-order in derivatives field theory. In our geometric approach, we consider the embedding functions as the field variables and, even though the highly nonlinear dependence of the action on these variables, we are able to complete the classical analysis of the emerging constraints for which, after implementing a Dirac bracket, we are able to identify both the gauge transformations and the proper physical degrees of freedom of the model. The Ostrogradski–Hamilton framework is thus considerable robust as one may recover in a straightforward and consistent manner some existing results reported in the literature. Further, in consequence of our geometrical treatment, we are able to unambiguously recover as a by-product the Hamiltonian approach for a particular relativistic point-particle limit associated with the gonihedric string action, that is, a model linearly depending on the first Frenet–Serret curvature.
A Spatial Source Location Privacy-aware Duty Cycle for Internet of Things Sensor Networks
Authors: Bradbury Matthew , Jhumka Arshad , Maple Carsten
Published: February 2021

Source Location Privacy (SLP) is an important property for monitoring assets in privacy-critical sensor network and Internet of Things applications. Many SLP-aware routing techniques exist, with most striking a tradeoff between SLP and other key metrics such as energy (due to battery power). Typically, the number of messages sent has been used as a proxy for the energy consumed. Existing work (for SLP against a local attacker) does not consider the impact of sleeping via duty cycling to reduce the energy cost of an SLP-aware routing protocol. Therefore, two main challenges exist: (i) how to achieve a low duty cycle without loss of control messages that configure the SLP protocol and (ii) how to achieve high SLP without requiring a long time spent awake. In this article, we present a novel formalisation of a duty cycling protocol as a transformation process. Using derived transformation rules, we present the
first
duty cycling protocol for an SLP-aware routing protocol for a
local eavesdropping attacker
. Simulation results on grids demonstrate a duty cycle of 10%, while only increasing the capture ratio of the source by 3 percentage points, and testbed experiments on FlockLab demonstrate an 80% reduction in the average current draw.
Pains and Gains of Peer-Reviewing in Software Engineering (4)
Authors: Soldani Jacopo
Published: February 2021

The "Pains and Gains of Peer-Reviewing in Software Engineering" column of SEN aims at fostering a constructive and stimulating discussion on peer-reviewing in software engineering venues. This fourth editorial introduces a new contribution to the column, which reports on the recently released ACM SIGSOFT Empirical Standards for evaluating specific kinds of studies.
Prolonged β2-adrenergic agonist treatment improves glucose homeostasis in diet-induced obese UCP1−/− mice
Authors: van Beek Sten M.M , Kalinovich Anastasia , Schaart Gert , Bengtsson Tore , Hoeks Joris
Published: February 2021

Improvements in whole body glucose homeostasis of rodents upon prolonged β2-adrenergic agonist supplementation could potentially be attributed to UCP1-mediated BAT thermogenesis. Indeed, we show that acute injection with the β2-AR agonist clenbuterol induces BAT activation in mice. However, we also demonstrate that prolonged clenbuterol supplementation robustly improves whole body glucose and insulin tolerance in a similar way in both DIO WT and UCP1−/− mice, indicating that β2-AR agonist supplementation improves whole body glucose homeostasis independent of UCP1-mediated BAT thermogenesis.
High-throughput LC-MS method to investigate postprandial lipemia: considerations for future precision nutrition research
Authors: Mucinski Justine M. , Vena Jennifer E. , Ramos-Roman Maria A. , Lassman Michael E. , Szuszkiewicz-Garcia Magdalene , McLaren David G. , Previs Stephen F. , Shankar Sudha S. , Parks Elizabeth J.
Published: February 2021

A novel method to test human intestinal lipid handling using stable isotope labeling is presented and, for the first time, plasma appearance and lipid turnover were quantified in 12 healthy men following meals with varying amounts of fat. The method can be applied to studies in precision nutrition characterizing individual response to support basic science research or drug development. This report discusses key questions for consideration in precision nutrition that were highlighted by the data.
DPP4 inhibition mitigates ANG II-mediated kidney immune activation and injury in male mice
Authors: Nistala Ravi , Meuth Alex I. , Smith Cassandra , An Jianzhong , Habibi Javad , Hayden M. R. , Johnson Megan , Aroor Annayya , Whaley-Connell Adam , Sowers James R. , McKarns Susan C. , Bender Shawn B.
Published: February 2021

This work highlights the role of dipeptidyl peptidase-4 (DPP4) in promoting ANG II-mediated kidney inflammation and injury. Specifically, ANG II infusion in mice led to increases in blood pressure and kidney DPP4 activity, which then led to activation of CD8+ T cells, Ly6C− macrophages, and neutrophils and suppression of anti-inflammatory T helper 2 lymphocytes and regulatory T cells. Collectively, this led to kidney injury, characterized by mesangial expansion, mitochondrial damage, and albuminuria, which were mitigated by DPP4 inhibition independent of blood pressure reduction.
Integration of metabolomics and transcriptomics reveals convergent pathways driving radiation-induced salivary gland dysfunction
Authors: Meeks Lauren , De Oliveira Pessoa Diogo , Martinez Jessica A. , Limesand Kirsten H. , Padi Megha
Published: February 2021

Radiation therapy for head and neck cancer causes damage to the surrounding salivary glands, resulting in salivary gland hypofunction and xerostomia. Current treatments do not provide lasting restoration of salivary gland function following radiation; therefore, a new mechanistic understanding of the radiation-induced damage response is necessary for identifying therapeutic targets. The purpose of the present study was to investigate the metabolic phenotype of radiation-induced damage in parotid salivary glands by integrating transcriptomic and metabolomic data. Integrated data were then analyzed to identify significant gene-metabolite interactions. Mice received a single 5 Gy dose of targeted head and neck radiation. Parotid tissue samples were collected 5 days following treatment for RNA sequencing and metabolomics analysis. Altered metabolites and transcripts significantly converged on a specific region in the metabolic reaction network. Both integrative pathway enrichment using rank-based statistics and network analysis highlighted significantly coordinated changes in glutathione metabolism, energy metabolism (TCA cycle and thermogenesis), peroxisomal lipid metabolism, and bile acid production with radiation. Integrated changes observed in energy metabolism suggest that radiation induces a mitochondrial dysfunction phenotype. These findings validated previous pathways involved in the radiation-damage response, such as altered energy metabolism, and identified robust signatures in salivary glands, such as reduced glutathione metabolism, that may be driving salivary gland dysfunction.
Personality Characteristics and Oral Health-Related Quality of Life in an Iranian Adult Population
Authors: Hasheminejad Naimeh , Hajizamani Hamidreza , Tayebeh Malek Mohammadi , Thomson William Murray
Published: February 2021

Self-rated oral health and oral health-related quality of life is known to be influenced by various personality characteristics. The aim of this study was to understand how personality characteristics affect oral health-related quality of life ratings in an Iranian adult population. The study included 443 adult participants recruited from a public dental clinic in Kerman, southeast of Iran. The Oral Health Impact Profile-14 questionnaire was used to assess oral health-related quality of life. Personality traits were determined using the 20-item Positive Affectivity Negative Affectivity Scale. Locker’s single-item global self-rating of oral health was used to obtain information on self-rated oral health. Pearson correlation and negative binomial regression were used for data analysis. A higher negative affectivity score was associated with worse oral heath related quality of life, and a higher positive affectivity score was associated with better rating of oral health-related quality of life. On average, individuals who described their oral health as worse scored higher on Oral Health Impact Profile-14. Negative affectivity and positive affectivity influence individuals’ perceptions of their oral health and quality of life. If possible, investigations of oral health-related quality of life measures should also include a brief personality assessment.
Identification of a Novel Metastasis-Related miRNAs-Based Signature for Predicting the Prognosis of Hepatocellular Carcinoma
Authors: Chen Yuan , Wang Guifu , Xu Hao , Wang Hao , Bai Dousheng
Published: February 2021

Hepatocellular carcinoma (HCC) is one of the most common internal malignancies worldwide and is associated with a poor prognosis. Abnormal expression of miRNAs is believed to play a role in the recurrent metastasis of HCC. However, limited studies on the role of miRNAs in HCC metastasis have been carried out. Therefore, this study is aimed at exploring the potential value of metastasis-related miRNAs (MRMs) in HCC. We retrieved MRMs were from the Human Cancer Metastasis Database. Differential miRNAs were identified for tumor samples of HCC patients and normal samples based on the TCGA database. Further, univariate and multivariate Cox regression analyses were used to screen MRMs known to be independent prognostic factors in HCC. These MRMs were then used to build a prognostic signature. All patients were classified into high-risk and low-risk groups based on the median of the signature scores. Moreover, GO and KEGG pathway enrichment analyses were performed to predict the function of these MRMs. Finally, a nomogram was constructed to predict the OS of patients at 1, 2, and 3 years. In our study, a total of seven prognostic MRMs (miR-140-3p, miR-9-5p, miR-942-5p, miR-324-3p, miR-29c-5p, miR-551a, and miR-149-5p) were identified and used for constructing the prognostic signature based on the training cohort. Patients in the low-risk HCC group showed better overall survival (OS) than those in the high-risk group. The results were validated using the validation cohort. In summary, the findings of this study provide evidence that MRMs-based prognostic signature is an independent biomarker in the prognosis of HCC patients.
The Impact of Urban Rail Transit on Industrial Agglomeration Based on the Intermediary Effects of Factor Agglomeration
Authors: Li Zhonghui , Xia Tongshui , Xia Zhiqing , Wang Xinjun
Published: February 2021

Urban rail transit is an important form of infrastructure for a city or even a country. This paper uses location entropy to measure the industrial agglomeration level of cities at the prefecture level or above in China from 2006 to 2018 and empirically tests the mechanisms of urban rail transit construction, factor agglomeration, and industrial agglomeration. The empirical results show the following: (1) the construction of urban rail transit infrastructure has a significant positive effect on the agglomeration of the labor force, capital, and technological innovation; (2) urban rail transit construction effectively induces agglomeration in the urban manufacturing industry and consumer service industry; and (3) the impact of urban rail transit construction on agglomeration in the urban manufacturing industry and consumer services industry is primarily due to the intermediary effects of factor agglomeration. The results show that gradually improving the urban rail transit network, strengthening the construction of comprehensive rail transit hubs, and optimizing capital allocation within urban rail transit allow for the full utilization of urban rail transit construction in promoting industrial agglomeration.
Willingness to Pay for Hexanal Technology among Banana Farmers in Meru County, Kenya
Authors: Kahwai Jane N. , Mburu John I. , Oulu Martin O. , Hutchinson Margaret J.
Published: February 2021

From the perspective of food categories, fresh produce are the leading sources of food loss and waste globally. Their highly perishable nature shortens their shelf-lives leading to high postharvest losses if not properly handled. Currently, these losses are estimated at sixty-six percent based on total weight. Reduction of these losses will ensure constant supply of food along the supply chain as well as economic empowerment of the rural poor. Hexanal which is a naturally occurring compound has been developed as an intervention to prolong shelf-life of delicate tropical fruits such as bananas while also maintaining their quality. However, empirical evidence is still required on the usefulness of hexanal to farmers. It is envisaged that such evidence would inform scaling up of the technology in Kenya. This study assessed willingness to pay for hexanal and the factors influencing WTP amounts among banana farmers in Meru County, Kenya. Primary data was collected from 130 respondents who were grouped into aware and not aware of Hexanal. Results indicate that farmers who are aware of hexanal had a higher mean WTP Ksh 466.47 (US $4.66) compared to those not aware Ksh 331.86 (US $3.32). Factors such as age and income influenced the WTP amounts between subsamples. The major key policy implication of the study is the importance of stakeholders investing in the dissemination of information on hexanal among farmers to enhance uptake.
Synthesis and Characterization of Magnetic Fe3O4/Zeolite NaA Nanocomposite for the Adsorption Removal of Methylene Blue Potential in Wastewater Treatment
Authors: Tran Ngoc Bich Thi , Duong Ngoc Bich , Le Ngoc Long
Published: February 2021

In this research, the magnetic Fe3O4/zeolite NaA nanocomposite (Fe3O4/ZA), Fe3O4 nanoparticles, and zeolite NaA have been synthesized by facile hydrothermal methods for adsorption removal of methylene blue from aqueous solution. The as-synthesized Fe3O4/ZA nanocomposite was characterized by X-ray diffraction (XRD), MicroRaman analysis, Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), energy-dispersive X-ray (EDX) spectroscopy, X-ray fluorescence (XRF), N2 adsorption isotherms (BET), and UV-VIS analysis. The results show that with a small weight loading of Fe3O4, the ∼3.3% Fe3O4/ZA sample exhibits a high adsorption capacity (∼40.36 mg·g−1) and removal efficiency (∼96.8%) compared to that of the zeolite NaA (∼32.99 mg·g−1 and 79.11%, respectively). Interestingly, the removal efficiency and the adsorption capacity increase rapidly with the increase of adsorption time (10–60 minutes) and Fe3O4 loading (∼3.3–9.3% wt.) in the Fe3O4/ZA composition. The adsorption mechanism of MB molecules of the Fe3O4/ZA can be addressed at the combination of the interaction between active sites on the surfaces and edges of the invert spinel ferrite Fe3O4 nanoparticles and zeolite NaA with MB molecules. Our approach provides a simple, efficient, and scalable synthesis process that render practical applications of the magnetic Fe3O4/ZA nanocomposite as a lower-cost adsorbent for wastewater treatment.
Experimental Study on Immersion Effects of Pressure Water on the Tensile Characteristics of Sandstone Samples
Authors: Yin Dawei , Chen Shaojie , Chen Bing , Liu Rui , Li Faxin
Published: February 2021

In this study, Brazilian splitting tests were conducted on sandstone samples subjected to drying and immersing at water pressures of 0, 1, and 3 MPa (immersion duration of 120 h). Investigation of the immersion effects of pressure water on the tensile characteristics of the samples revealed that their tensile strengths decreased with the immersion water pressure. Relative to a sandstone sample subjected to drying alone, immersing at water pressures of 0, 1, and 3 MPa reduced the tensile strength by 12.96%, 19.03%, and 30.16%, respectively. Although the immersed samples experienced splitting failure indicative of obvious brittle failure characteristics, decreases in the postpeak stress reduction rate with immersion water pressure revealed that the intensity of brittle failure weakened with pressure. Based on the obtained data, the deformation evolution process of the sandstone samples could be divided into five stages: deformation adjustment, formation of local deformation zones, local deformation zone propagation, failure surface formation, and sample failure. The water pressure aggravated the physicochemical reactions between water and the hydrophilic minerals in the sandstone, promoting argillisation, dissolution, and loss of hydrophilic minerals and interparticle cementitious materials. As a result of these immersion micromechanisms, the deterioration of the sandstone samples increased with the immersion water pressure, with the average porosities of the fracture surfaces at 0, 1, and 3 MPa increasing by 142.86%, 368.37%, and 593.88%, respectively, relative to the dried sample. As a result of these morphological changes, the sandstone samples subjected to water pressure immersion failed at small axial stresses with low levels of applied mechanical energy.
Experimental Study on the Effects of Stress‐Induced Damage on the Microstructure and Mechanical Properties of Soft Rock
Authors: Wang Hao , Wang Yong-Yan , Yu Zhuo-Qun , Li Jian-Guang
Published: February 2021

After rocks are damaged under stress loading, the changes of their microstructural and mechanical properties are major factors that affect construction safety in geotechnical engineering projects. Studying the microstructures and mechanical behaviors of stress‐damaged rocks can help better guide construction and reduce construction risks for geotechnical engineering projects. In this study, a sandstone was first artificially predamaged and then subsequently subjected to scanning electron microscopy (SEM) analysis, computed tomography (CT) scanning, and uniaxial compression testing. Afterwards, the rock microstructures were three‐dimensionally (3D) reconstructed, and the pores were classified and characterized based on their diameters. Moreover, the microstructural and mechanical parameters of the rock were subjected to significance analysis. The results showed that as the stress‐induced damage (σi) increased, the uniaxial compressive strength (σc) of the soft rock decreased by 13.7–31.8%; as σi increased from 11.2 to 19.6 MPa, the elastic modulus (E) of the soft rock increased by up to 28.8%; and as σi increased beyond 19.6 MPa, there was a significant (22.3%) decrease in E. Stress‐induced damage significantly affected the spatial distribution of the pores’ structure of the soft rock. Changes in the spatial structure of the pores led to the formation of cracks. The microstructural parameters of the stress‐damaged soft rock were correlated with its mechanical parameters.
Testis‐Specific Thioredoxins TXNDC2, TXNDC3, and TXNDC6 Are Expressed in Both Testicular and Systemic DLBCL and Correlate with Clinical Disease Presentation
Authors: Chan Mikko C. , Savela Janette , Ollikainen Riina K. , Teppo Hanna-Riikka , Miinalainen Ilkka , Pirinen Risto , Kari Esa J. M. , Kuitunen Hanne , Turpeenniemi-Hujanen Taina , Kuittinen Outi , Kuusisto Milla E. L.
Published: February 2021

DLBCL is the most common type of non‐Hodgkin lymphoma with a substantial group of patients suffering a poor prognosis. Therefore more specific markers are required for better understanding of disease biology and treatment. This study demonstrates that testis‐specific antioxidant enzymes TXNDC2, TXNDC3, and TXNDC6 alongside oxidative stress marker 8‐OHdG are expressed in both testicular and systemic DLBCL, and their presence or absence has correlations with clinical risk factors such as the number of extranodal effusion, the appearance of B‐symptoms, and treatment response. Biopsy samples were collected from 28 systemic and 21 testicular male DLBCL patients. The samples were histostained with TXNDC2, TXNDC3, TXNDC6, and 8‐OHdG, then graded by a hematopathologist blinded to clinical data. Immunoelectron microscopy was used as a second method to confirm the reliability of the acquired immunohistochemistry data. The absence of nuclear TXNDC2 expression in testicular DLBCL cells correlated with worse primary treatment response, cytoplasmic TXNDC3 expression in testicular and systemic DLBCL associated with lower frequency of B‐symptoms, and TXNDC6 expression in cytoplasm in systemic DLBCL had a clinical significance with higher LD levels suggesting a role in the biological nature of these lymphomas. Overall, TXNDC3 cytoplasmic expression is correlated with a more positive outcome in both testicular and systemic DLBCL, while TXNDC6 cytoplasmic expression is associated with a negative outcome in systemic DLBCL.
A Method for Determining the Mechanical Parameters of Solution Pore and Crevice Limestone Based on Porosity
Authors: Hu Zheng , Wen Tao , Zheng Kexun , Wang Yankun
Published: February 2021

Limestone stratum has great anisotropy, which is distributed from large karst caves, pipelines, and faults to small solution pores, and crevices. In this paper, uniaxial compression tests of solution pore and crevice limestones from Mamaya I hydropower station and Ronglai hydropower station are conducted, and the porosity of these limestones is measured. The results show that there is a good power function relationship between compressive strength and the porosity of the solution pore and crevice limestone. Based on the Hoek–Brown criterion, the method for determining mechanical parameters of the solution pore and crevice limestones is proposed, taking the porosity of the rock into consideration. Then, the relationships between the rock mass parameters mb, s, and a and the porosity n are deduced. Based on the proposed method, the variation laws of the mechanical parameters of the limestones, including uniaxial compressive strength (UCS), tensile strength, deformation modulus, shear strength parameters are analyzed. The proposed method simplifies the complexity of mechanical parameters selection by quantifying GSI, avoids the subjectivity and uncertainty, and has good reliability and suitability in the pore and crevice limestone stratum, which has a certain guiding significance for the construction of similar sites.
Axial Loading Behaviour of Self‐Compacting Concrete‐Filled Thin‐Walled Steel Tubular Stub Columns
Authors: Wang Yunyang , Xiao Lei , Jiang Chu , Jia Yandong , Yang Guang , Li Meng , Tang Xiangliang , Chen Duo
Published: February 2021

This paper presents an experimental investigation on the mechanical behaviour of self‐compacting concrete‐filled thin‐walled steel tubular (SCCFTST) stub columns loaded in axial compression to failure. Four specimens were tested to study the effect of diameter to wall thickness (D/t) ratios on the ultimate load, failure modes, and ductility of the columns. Confinement of the steel tube to concrete was also addressed. The failure modes, load versus displacement curves, and load versus strain curves were examined in detail. The experimental results showed that the ultimate state is reached when severe local buckling and rupture occurred on the steel tubes, and the concrete near the rupture has been crushed. The columns with larger D/t ratios appeared more local buckling, and its location is more close to the end of the columns. The SCCFTST stub columns with smaller D/t ratios show higher ultimate load and better ductility, and the steel tubes can exert higher confinement to the concrete.
Knockdown of MALAT1 Inhibits the Progression of Chronic Periodontitis via Targeting miR‐769‐5p/HIF3A Axis
Authors: Chen Qinchao , Cao Meng , Ge Hanyi
Published: February 2021

Purpose. Chronic periodontitis (CP) is a long‐lasting inflammatory disease that seriously affects oral health. This study is aimed at investigating the regulatory mechanism of metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) in CP. Methods. Primary human periodontal ligament cells (PDLCs) were treated with P. gingivalis lipopolysaccharide (LPS) to establish a CP model. Quantitative real‐time PCR (qRT‐PCR) was used to measure the expression of MALAT1 and miR‐769‐5p in gingival tissues of patients with CP and LPS‐treated PDLCs. Cell viability was detected by 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) assay. Enzyme‐linked immunosorbent assay (ELISA) was used to measure the levels of inflammatory cytokines. The protein levels of caspase‐3, Bax, Bcl‐2, and hypoxia‐inducible factor (HIF) 3A were determined by western blot assay. Dual‐luciferase reporter (DLR) assay was applied to validate the target relationships between miR‐769‐5p and MALAT1/HIF3A. Results. The expression of MALAT1 and HIF3A was enhanced, and the expression of miR‐769‐5p was reduced in gingival tissues of patients with CP and LPS‐treated PDLCs. MALAT1 knockdown promoted cell viability and inhibited inflammation and cell apoptosis in LPS‐treated PDLCs. MALAT1 targeted miR‐769‐5p and negatively regulated miR‐769‐5p expression. miR‐769‐5p overexpression promoted cell viability and inhibited inflammation and cell apoptosis in LPS‐treated PDLCs. Besides, miR‐769‐5p targeted HIF3A and negatively modulated HIF3A expression. Both miR‐769‐5p inhibition and HIF3A overexpression reversed the inhibitory effects of MALAT1 silencing on LPS‐induced PDLC injury in vitro. Conclusion. MALAT1 knockdown attenuated LPS‐induced PDLC injury via regulating the miR‐769‐5p/HIF3A axis, which may supply a new target for CP treatment.
Optimized Doxorubicin Chemotherapy for Diffuse Large B-cell Lymphoma Exploits Nanocarrier Delivery to Transferrin Receptors
Authors: Arumov Artavazd , Liyanage Piumi Y. , Trabolsi Asaad , Roberts Evan R. , Li Lingxiao , Ferreira Braulio C.L.B. , Gao Zhen , Ban Yuguang , Newsam Austin D. , Taggart Melissa W. , Vega Francisco , Bilbao Daniel , Leblanc Roger M. , Schatz Jonathan H.
Published: February 2021

New treatments are needed to address persistent unmet clinical needs for diffuse large B-cell lymphoma (DLBCL). Overexpression of transferrin receptor 1 (TFR1) is common across cancer and permits cell-surface targeting of specific therapies in preclinical and clinical studies of various solid tumors. Here, we developed novel nanocarrier delivery of chemotherapy via TFR1-mediated endocytosis, assessing this target for the first time in DLBCL. Analysis of published datasets showed novel association of increased TFR1 expression with high-risk DLBCL cases. Carbon–nitride dots (CND) are emerging nanoparticles with excellent in vivo stability and distribution and are adaptable to covalent conjugation with multiple substrates. In vitro, linking doxorubicin (Dox) and transferrin (TF) to CND (CND–Dox–TF, CDT) was 10–100 times more potent than Dox against DLBCL cell lines. Gain- and loss-of-function studies and fluorescent confocal microscopy confirmed dependence of these effects on TFR1-mediated endocytosis. In contrast with previous therapeutics directly linking Dox and TF, cytotoxicity of CDT resulted from nuclear entry by Dox, promoting double-stranded DNA breaks and apoptosis. CDT proved safe to administer in vivo, and when incorporated into standard frontline chemoimmunotherapy in place of Dox, it improved overall survival by controlling patient-derived xenograft tumors with greatly reduced host toxicities. Nanocarrier-mediated Dox delivery to cell-surface TFR1, therefore, warrants optimization as a potential new therapeutic option in DLBCL.

Significance:

Targeted nanoparticle delivery of doxorubicin chemotherapy via the TRF1 receptor presents a new opportunity against high-risk DLBCL tumors using potency and precision.
Induction of ADAM10 by Radiation Therapy Drives Fibrosis, Resistance, and Epithelial-to-Mesenchyal Transition in Pancreatic Cancer
Authors: Mueller Adam C. , Piper Miles , Goodspeed Andrew , Bhuvane Shiv , Williams Jason S. , Bhatia Shilpa , Phan Andy V. , Van Court Benjamin , Zolman Kathryn L. , Peña Brisa , Oweida Ayman J. , Zakem Sara , Meguid Cheryl , Knitz Michael W. , Darragh Laurel , Bickett Thomas E. , Gadwa Jacob , Mestroni Luisa , Taylor Matthew R.G. , Jordan Kimberly R. , Dempsey Peter , Lucia M. Scott , McCarter Martin D. , Chiaro Marco Del , Messersmith Wells A. , Schulick Richard D. , Goodman Karyn A. , Gough Michael J. , Greene Casey S. , Costello James C. , Neto Antonio Galveo , Lagares David , Hansen Kirk C. , Van Bokhoven Adrie , Karam Sana D.
Published: February 2021

Stromal fibrosis activates prosurvival and proepithelial-to-mesenchymal transition (EMT) pathways in pancreatic ductal adenocarcinoma (PDAC). In patient tumors treated with neoadjuvant stereotactic body radiation therapy (SBRT), we found upregulation of fibrosis, extracellular matrix (ECM), and EMT gene signatures, which can drive therapeutic resistance and tumor invasion. Molecular, functional, and translational analysis identified two cell-surface proteins, a disintegrin and metalloprotease 10 (ADAM10) and ephrinB2, as drivers of fibrosis and tumor progression after radiation therapy (RT). RT resulted in increased ADAM10 expression in tumor cells, leading to cleavage of ephrinB2, which was also detected in plasma. Pharmacologic or genetic targeting of ADAM10 decreased RT-induced fibrosis and tissue tension, tumor cell migration, and invasion, sensitizing orthotopic tumors to radiation killing and prolonging mouse survival. Inhibition of ADAM10 and genetic ablation of ephrinB2 in fibroblasts reduced the metastatic potential of tumor cells after RT. Stimulation of tumor cells with ephrinB2 FC protein reversed the reduction in tumor cell invasion with ADAM10 ablation. These findings represent a model of PDAC adaptation that explains resistance and metastasis after RT and identifies a targetable pathway to enhance RT efficacy.

Significance:

Targeting a previously unidentified adaptive resistance mechanism to radiation therapy in PDAC tumors in combination with radiation therapy could increase survival of the 40% of PDAC patients with locally advanced disease.

See related commentary by Garcia Garcia et al., p. 3158
Evolving Status of Clinical Immunotherapy with Oncolytic Adenovirus
Authors: Farrera-Sal Martí , Moya-Borrego Laura , Bazan-Peregrino Miriam , Alemany Ramon
Published: February 2021

Cancer immunotherapy targeting immune checkpoint inhibitors shows efficacy in several human cancers, but “cold tumors” that lack immune cells are typically unresponsive. Among the potential therapeutic approaches that could “heat” or promote lymphocyte infiltration of cold tumors, oncolytic viruses have attracted interest for their lytic and immunogenic mechanisms of action. In this article, we review the use of oncolytic adenoviruses in cancer immunotherapy, with a particular focus on preclinical and clinical data of oncolytic adenovirus-triggered immune responses against tumor antigens. We also discuss parameters to consider in clinical trial design and the combination of oncolytic adenoviruses with conventional treatments or other immunotherapies.
Abstract IA005: DNA damaging agents in endometrial cancer
Authors: Westin Shannon Neville
Published: February 2021

The time for “one size fits all” treatment is over in endometrial cancer. Endometrial cancer has a number of potential targetable molecular aberrations, including those that predict response to DNA damaging agents such as PARP inhibitors. This talk will explore the preclinical and clinical data to support DNA damaging agents, alone and in combination, in the treatment of endometrial cancer. Biomarkers for response will be critically reviewed.

Citation Format: Shannon Neville Westin. DNA damaging agents in endometrial cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr IA005.
Abstract IA006: Endocrine therapy and ER/PR combinations
Authors: MacKay Helen J.
Published: February 2021

Endocrine therapy is the “original” targeted therapy in endometrial cancer (EC). Despite over 60 years experience with this treatment modality we have yet to answer some key questions including which women derive benefit and how do we identify them? Despite a high proportion of ECs being ER and/or PR positive, endocrine therapy is only associated with modest benefit. Greater understanding of ER and PR biology may help identify patient populations who will derive benefit and assist in optimizing this approach. Favourable toxicity profiles and multiple pathway interactions suggest the potential for combining endocrine and other targeted agents. We discuss the preliminary data and hypothesize on potential strategies to accelerate the pace of development in this area.

Citation Format: Helen J. MacKay. Endocrine therapy and ER/PR combinations [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr IA006.