bluuebunny/crossref_metadata_2025 huggingface dataset:
Nairobi Early Childcare in Slums (NECS) Study Protocol: a mixed-methods exploration of paid early childcare in Mukuru slum, Nairobi
Authors: Hughes Robert C , Kitsao-Wekulo Patricia , Bhopal Sunil , Kimani-Murage Elizabeth W , Hill Zelee , Kirkwood Betty R
Published: December 2020

Introduction

The early years are critical. Early nurturing care can lay the foundation for human capital accumulation with lifelong benefits. Conversely, early adversity undermines brain development, learning and future earning.

Slums are among the most challenging places to spend those early years and are difficult places to care for a child. Shifting family and work structures mean that paid, largely informal, childcare seems to be becoming the ‘new normal’ for many preschool children growing up in rapidly urbanising Africa. However, little is known about the quality of this childcare.

Aims

To build a rigorous understanding what childcare strategies are used and why in a typical Nairobi slum, with a particular focus on provision and quality of paid childcare. Through this, to inform evaluation of quality and design and implementation of interventions with the potential to reach some of the most vulnerable children at the most critical time in the life course.

Methods and analysis

Mixed methods will be employed. Qualitative research (in-depth interviews and focus group discussions) with parents/carers will explore need for and decision-making about childcare. A household survey (of 480 households) will estimate the use of different childcare strategies by parents/carers and associated parent/carer characteristics. Subsequently, childcare providers will be mapped and surveyed to document and assess quality of current paid childcare. Semistructured observations will augment self-reported quality with observable characteristics/practices. Finally, in-depth interviews and focus group discussions with childcare providers will explore their behaviours and motivations. Qualitative data will be analysed through thematic analysis and triangulation across methods. Quantitative and spatial data will be analysed through epidemiological methods (random effects regression modelling and spatial statistics).

Ethics and dissemination

Ethical approval has been granted in the UK and Kenya. Findings will be disseminated through journal publications, community and government stakeholder workshops, policy briefs and social media content.
Neurocognitive performance and mental health of retired female football players compared to non-contact sport athletes
Authors: Prien Annika , Feddermann-Demont Nina , Verhagen Evert , Twisk Jos , Junge Astrid
Published: December 2020

Background

Adverse long-term effects of playing football due to repetitive head impact exposure on neurocognition and mental health are controversial. To date, no studies have evaluated such effects in women.

Aims

To (1) compare neurocognitive performance, cognitive symptoms and mental health in retired elite female football players (FB) with retired elite female non-contact sport athletes (CON), and to (2) assess whether findings are related to history of concussion and/or heading exposure in FB.

Methods

Neurocognitive performance, mental health and cognitive symptoms were assessed using computerised tests (CNS-vital signs), paper pen tests (Category fluency, Trail-Making Test, Digit Span, Paced Auditory Serial Addition Test), questionnaires (Hospital Anxiety and Depression Scale, SF-36v2 Health Survey) and a symptom checklist. Heading exposure and concussion history were self-reported in an online survey and in a clinical interview, respectively. Linear regression was used to analyse the effect of football, concussion and heading exposure on outcomes adjusted for confounders.

Results

FB (n=66) performed similar to CON (n=45) on neurocognitive tests, except for significantly lower scores on verbal memory (mean difference (MD)=−7.038, 95% CI −12.98 to –0.08, p=0.038) and verbal fluency tests (MD=−7.534, 95% CI –13.75 to –0.46, p=0.016). Among FB weaker verbal fluency performance was significantly associated with ≥2 concussions (MD=−10.36, 95% CI –18.48 to –2.83, p=0.017), and weaker verbal memory performance with frequent heading (MD=−9.166, 95% CI –17.59 to –0.123, p=0.041). The depression score differed significantly between study populations, and was significantly associated with frequent heading but not with history of concussion in FB.

Conclusion

Further studies should investigate the clinical relevance of our findings and whether the observed associations point to a causal link between repetitive head impacts and verbal memory/fluency or mental health.
Clinical Significance of Chitotriosidase in Outpatients with Advanced Heart Failure
Authors: Cetin Sanlialp Sara , Nar Gokay , Senol Hande
Published: December 2020

The previous studies have shown that plasma chitotriosidase (CHIT) levels increase in many diseases with inflammation. However, there are no reported studies investigating the relationship between CHIT and chronic heart failure (CHF) which is an inflammatory process. Therefore, we aimed to investigate the role of CHIT in diagnosis and severity of CHF in this study. 36 patients (50% male, mean age 63.17±10.18 years) with left ventricular ejection fraction <40% and 27 controls (44% male, mean age 61.33±8.73 years) were included in this study. Patients with CHF were divided into two groups as ischemic heart failure (IHF) and non-ischemic heart failure (NIHF) according to the underlying etiology. Plasma CHIT and N-terminal pro brain natriuretic peptide (NT-proBNP) levels were measured by ELISA method. Plasma CHIT and NT-proBNP levels were higher in patients with CHF than in controls (CHIT 931.25±461.39 ng/mL, 232.79±61.28 ng/mL, p<0.001; NT-proBNP, 595.31±428.11 pg/mL vs 78.13±30.47 pg/L; p<0.001). Also, the levels of these parameters increased in IHF compared with NIHF (CHIT, 1139.28±495.22 ng/mL, 671.22±237.21 ng/mL, p=0.002; NT-proBNP, 792.87±461.26 pg/mL vs 348.36±202.61 pg/mL, p=0.001) and there was a strong correlation between NT-proBNP and CHIT (r=0.969, p<0.001). According to this study findings, plasma CHIT level increases in CHF and its increased levels are correlated with NT-proBNP which is used diagnosis and prognosis of HF.
Restarting and timing of oral anticoagulation after traumatic intracranial hemorrhage: a review and summary of ongoing and planned prospective randomized clinical trials
Authors: King Ben , Milling Truman , Gajewski Byron , Costantini Todd W , Wick Jo , Price Michelle A , Mudaranthakam Dinesh , Stein Deborah M , Connolly Stuart , Valadka Alex , Warach Steven
Published: December 2020

Anticoagulant-associated traumatic intracranial hemorrhage (tICrH) is a devastating injury with high morbidity and mortality. For survivors, treating clinicians face the dilemma of restarting oral anticoagulation with scarce evidence to guide them. Thromboembolic risk is high from the bleeding event, patients’ high baseline risks, that is, the pre-existing indication for anticoagulation, and the risk of immobility after the bleeding episode. This must be balanced with potentially devastating hematoma expansion or new hemorrhagic lesions. Retrospective evidence and expert opinion support restarting oral anticoagulants in most patients with tICrH, but timing is uncertain. Researchers have failed to make clear distinctions between tICrH and spontaneous intracranial hemorrhage (sICrH), which have differing natural histories. While both appear to benefit from restarting, sICrH has a higher rebleeding risk and similar or lower thrombotic risk. Clinical equipoise on restarting is also divergent. In sICrH, equipoise is centered on whether to restart. In tICrH, it is centered on when. Several prospective randomized clinical trials are ongoing or about to start to examine the risk–benefit of restarting. Most of them are restricted to patients with sICrH, with antiplatelet control groups. Most are also restricted to direct oral anticoagulants (DOACs), as they are associated with a lower overall risk of ICrH. There is some overlap with tICrH via subdural hematoma, and one trial is specific to restart timing with DOACs in only traumatic cases. This is a narrative review of the current evidence for restarting anticoagulation and restart timing after tICrH along with a summary of the ongoing and planned clinical trials.
Multifocal haematogenous osteomyelitis and septic physitis in a dog
Authors: Blondel Margaux , Gros Lucile , Lucas Marie‐Noelle , Delverdier Maxence , Palierne Sophie
Published: December 2020

A 10‐month‐old male cane corso was evaluated for a four‐day history of lethargy and anorexia associated with right thoracic limb lameness. Physical examination, diagnostic imaging and cytological findings were suggestive of a pyothorax and a right antebrachium subperiosteal abscess, which were managed by surgical drainage of the abscess and placement of thoracostomy tubes. Following adapted antibiotic therapy and appropriate analgesia, the dog clinically improved. However, 10 days after admission, the patient became hyperthermic and presented a warm, generalised soft tissue swelling affecting both hindlimbs and painful metaphyseal regions. Radiographic findings were suggestive of multifocal haematogenous osteomyelitis and septic physitis. Blood culture came back positive with a multiresistant bacterium. Given the poor prognosis, the dog was euthanased. Postmortem examination confirmed the presence of severe multicentric osteomyelitis, physitis and arthritis, associated with infective endocarditis and chronic bacterial exudative pleuritis.
Alpheus richpalmeri, a new species of snapping shrimp from the tropical eastern Atlantic (Malacostraca: Decapoda: Alpheidae)
Authors: Anker Arthur
Published: December 2020

A new snapping shrimp, Alpheus richpalmeri sp. nov., is described based on three specimens collected in the muddy–rocky intertidal of São Tomé Island, Gulf of Guinea, tropical eastern Atlantic. The new species belongs to the Alpheus brevirostris (Olivier, 1811) species group, sharing a series of morphological features and a similar colour pattern with two Atlantic species of the group, e.g., Alpheus roblesi Bracken-Grissom and Felder, 2014 and Alpheus ulalae Bracken-Grissom and Felder, 2014, as well as with the Indo-West Pacific Alpheus platyunguiculatus (Banner, 1953). The new species may have been previously reported from the tropical eastern Atlantic by A. Crosnier and J. Forest (1966. Ann. Inst. Oceanogr. Monaco, 44: 199–314) under the name Alpheus floridanus floridanus Kingsley, 1878, which is clearly different from the lectotype of Alpheus floridanus Kingsley, 1878 upon which H.D. Bracken-Grissom and D.L. Felder (2014. Zootaxa, 3895(4): 451–491) based their redescription of this species. The form previously known as Alpheus floridanus var. africana Balss, 1916, or Alpheus floridanus africanus, is elevated to full species rank as Alpheus africanus stat. nov., based on morphological differences and geographical separation from A. floridanus.
3-Sequent achromatic sum of graphs
Authors: Dominic Charles , Devassia Jobish Vallikavungal
Published: December 2020

Three vertices [Formula: see text] in a graph [Formula: see text] are said to be [Formula: see text]-sequent if [Formula: see text] and [Formula: see text] are adjacent edges in [Formula: see text]. A 3-sequent coloring (3s coloring) is a function [Formula: see text] such that if [Formula: see text] and [Formula: see text] are 3-sequent vertices, then either [Formula: see text] or [Formula: see text] (or both). The [Formula: see text]-sequent achromatic number of a graph [Formula: see text], denoted [Formula: see text], equals the maximum number of colors that can be used in a coloring of the vertices’ of [Formula: see text] such that if [Formula: see text] and [Formula: see text] are any two sequent edges in [Formula: see text], then either [Formula: see text] or [Formula: see text] is colored the same as [Formula: see text]. The [Formula: see text]-sequent achromatic sum of a graph [Formula: see text], denoted [Formula: see text], is the greatest sum of colors among all proper 3s-coloring that requires [Formula: see text] colors. This research initiates the study of [Formula: see text]-sequent achromatic sum and finds the exact values of this parameter for some known graphs. Furthermore, we calculate the [Formula: see text] of corona product, Cartesian product of the graphs and some important results have been proved and a comparative study is carried out.
Effect of Using Rice Husk Char as an Additive on Phosphate Recovery from Swine Wastewater by Magnesium Metal Corrosion
Authors: Wang Fang , Zou Xiaoyu , Wei Jiapu , Liu Yuxuan , Lv Hang , Wu Xu
Published: December 2020

The recovery of phosphate from swine wastewater is highly significant in order to alleviate eutrophication in aquatic ecosystems, and the increasing scarcity in phosphorus resources. This study reports on a strategy to recover phosphate from swine wastewater using rice husk char as an additive via magnesium metal corrosion. The results demonstrated high levels of recovery efficiency at relatively low cost. When the mass ratio of rice husk char to magnesium was 2:1, the pH of this solution increased to 9.75, and the phosphate recovery efficiency from real swine wastewater reached 96.80% at a Reynolds number of 13931 without aeration. Evaluation of economic feasibility revealed that the proposed method was $0.79 kg−1 of PO4-P. Approximately 57.98% of the cost may be saved compared with the use of magnesium metal pellets coupled with graphite pellets.
Protective effects of pulmonary surfactant on decompression sickness in rats
Authors: Yu Xuhua , Xu Jiajun , Liu Wenwu , Zhang Ze , He Chunyang , Xu Weigang
Published: December 2020

This is the first study exploring the effects of aerosol surfactant on DCS prevention and it was proven to be an efficient and simple method. The role of surfactant in facilitating off-gassing was thought to be the critical mechanism in bubble degrading and subsequent DCS prevention.
Preventive measures for the critical postexercise period in sickle cell trait and disease
Authors: Messonnier Laurent A. , Bartolucci Pablo , d’Humières Thomas , Dalmais Etienne , Lacour Jean-René , Freund Hubert , Galactéros Frédéric , Féasson Léonard
Published: December 2020

The immediate postexercise/physical activity period is critical for sickle cell trait (SCT) carriers and disease (SCD) patients. Exercise-related blood acidosis is known to trigger the cascade of HbS deoxygenation and polymerization, leading to red blood cell sickling and subsequent complications. Unfortunately, two facts worsen exercise-related blood acidosis during the initial postexercise period: First, blood lactate and H+ concentrations continue to increase for several minutes after exercise completion, exacerbating blood acidosis. Second, blood lactate concentration remains elevated and pH altered for 20–45 min during inactivity after intense exercise, keeping acid/base balance disturbed for a long period after exercise. Therefore, the risk of complications (including vasoocclusive crises and even sudden death) persists and even worsens several minutes after intense exercise completion in SCT carriers or SCD patients. Light physical activity following intense exercise (namely, active recovery) may, by accelerating lactate removal and acid/base balance restoration, reduce the risk of complications. Scientific evidence suggests that light exercise at or below the first lactate threshold is an appropriate strategy.
Developmental origins of metabolic diseases
Authors: Hoffman Daniel J. , Powell Theresa L. , Barrett Emily S. , Hardy Daniel B.
Published: December 2020

Almost 2 billion adults in the world are overweight, and more than half of them are classified as obese, while nearly one-third of children globally experience poor growth and development. Given the vast amount of knowledge that has been gleaned from decades of research on growth and development, a number of questions remain as to why the world is now in the midst of a global epidemic of obesity accompanied by the “double burden of malnutrition,” where overweight coexists with underweight and micronutrient deficiencies. This challenge to the human condition can be attributed to nutritional and environmental exposures during pregnancy that may program a fetus to have a higher risk of chronic diseases in adulthood. To explore this concept, frequently called the developmental origins of health and disease (DOHaD), this review considers a host of factors and physiological mechanisms that drive a fetus or child toward a higher risk of obesity, fatty liver disease, hypertension, and/or type 2 diabetes (T2D). To that end, this review explores the epidemiology of DOHaD with discussions focused on adaptations to human energetics, placental development, dysmetabolism, and key environmental exposures that act to promote chronic diseases in adulthood. These areas are complementary and additive in understanding how providing the best conditions for optimal growth can create the best possible conditions for lifelong health. Moreover, understanding both physiological as well as epigenetic and molecular mechanisms for DOHaD is vital to most fully address the global issues of obesity and other chronic diseases.
Differences in Clinical Features and Laboratory Results between Adults and Children with SARS‐CoV‐2 Infection
Authors: Li Xiaoli , Rong Yan , Zhang Peiyan , Wang Junli , Qie Liping , Rong Lei , Xu Jian
Published: December 2020

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection in children accounts for a small proportion of all infections and is usually mild or asymptomatic. There are few studies on the clinical characteristics of SARS‐CoV‐2 infection in children, and the causes of the low prevalence in children remain unclear. Herein, we compared the epidemiological and clinical characteristics of SARS‐CoV‐2 infection between adults and children. Fifty‐two patients with Coronavirus Disease 2019 (COVID‐19) were retrospectively analyzed, including 38 adults and 14 children. Their clinical information such as epidemiological exposure history, laboratory indicators, chest computed tomography (CT) performance, and number of SARS‐CoV‐2 positive days were analyzed and compared. In children, 5 (35.71%) had mild COVID‐19 and 9 (64.29%) had common type, while, in adults, 9 (23.68%) cases were mild, and 29 (76.32%) were common COVID‐19. Among them, family clustering infection accounted for 50% (7/14) of child cases and 23.68% (9/36) of adult cases. Epidemiological exposure history, clinical classification, clinical symptoms, chest CT manifestations, and number of SARS‐CoV‐2‐positive days were not significantly different between children and adults. However, the percentage of neutrophils in adults was significantly higher than that in children (P < 0.05). The percentage and absolute value of lymphocytes, platelet counts, aspartate aminotransferase, and aspartate aminotransferase/alanine aminotransferase in adults were lower than those in children (P < 0.05). Conclusively, children infected with SARS‐CoV‐2 show the characteristics of family clustering, and the proportion of mild and asymptomatic infections is higher. For families with a history of epidemiological exposure, routine SARS‐CoV‐2 nucleic acid testing and chest CT examination should be performed in asymptomatic children to determine whether they are infected. Unlike adults, although the reduction of lymphocytes and platelets in children is not common, it is necessary to be alert to the increased risk of liver damage in children.
Multiplication Operators on Orlicz Generalized Difference (sss)
Authors: Bakery Awad A. , Mohamed OM Kalthum S. K.
Published: December 2020

In this article, we inspect the sufficient conditions on the Orlicz generalized difference sequence space to be premodular Banach (sss). We look at some topological and geometrical structures of the multiplication operators described on Orlicz generalized difference prequasi normed (sss).
Comparison of Two Preparation Methods for Platelet-Rich Plasma Eye Drops for Release of Growth Factors and De-Epithelization Rabbit Model
Authors: Kobayashi Tatsuhiko , Suzuki Takashi , Saito Tomohiko , Itokawa Takashi , Hori Yuichi
Published: December 2020

Purpose. To compare two platelet-rich plasma (PRP) preparation methods (double spin (D-PRP) and TriCell PRP (T-PRP)) for eye drops, concentration yields of platelets and other cells, release of growth factors, and efficacy of the de-epithelization rabbit model. Methods. PRP was extracted by D-PRP and T-PRP from 30 ml blood from healthy adults. After extraction, platelets and leukocytes were counted. D-PRP and T-PRP were preserved during A: 1 h storage at room temperature, B: 1 h storage at −20°C, C: 24 h storage at 4°C, and D: 24 h storage at −20°C. Platelet-derived growth factor (PDGF) was measured. Freezing/thawing PRP eye drops and control were instilled in the de-epithelization rabbit model four times per day for 5 days. Histology was compared between eyes treated with control, D-PRP, and T-PRP. Results. 14 ml of D-PRP and 4 ml of T-PRP were extracted from 30 ml whole blood samples. D-PRP and T-PRP had 41.36 ± 8.43 × 104 and 67.02 ± 13.55 × 104 platelets and 0.41 ± 0.24 × 103/ml and 10.09 ± 4.29 × 103/ml leucocytes, respectively. In the four storage methods, PDGF concentrations in T-PRP were higher than those in D-PRP eye drops. Freezing/thawing D-PRP and T-PRP increased PDGF concentrations. Histology showed corneal epithelium thickness in T-PRP-treated eyes after healing (38.41 ± 9.10 μm) was significantly higher than that in control-treated (27.77 ± 4.76 μm) and D-PRP-treated eyes (18.32 ± 3.14 μm) (

P

 < 0.05). There was no corneal damage with inflammation in corneal stroma and epithelium of all tested groups. Electron microscopy revealed strong adhesion between cell junctions in T-PRP-treated eyes. Conclusions. Freezing/thawing of PRP extracted with the T-PRP kit may result in high platelet and leukocyte concentration and produce high PDGF concentration. PRP eye drops including leucocytes could increase thickness of corneal epithelium without corneal inflammation.
Transient Dexmedetomidine Bolus-Induced Excessive Urination Intraoperatively in a 68-Year-Old Male
Authors: McGuire Joseph A. , Niazi Summer A. , Sizemore Daniel C.
Published: December 2020

Excessive urination can be a perioperative challenge for providers due to the possibility of secondary hypernatremia. Dexmedetomidine has previously been reported by several groups to induce a polyuric-like syndrome; however, the exact mechanism in humans remains unclear. In this report, we discuss a case of intraoperative, transient dexmedetomidine bolus-induced excessive urination and suggest a potential mechanism by which this may occur in a subset of the population.
Equivalent Permeability Distribution for Fractured Porous Rocks: The Influence of Fracture Network Properties
Authors: Chen Tao
Published: December 2020

Equivalent fracture models are widely used for simulations of groundwater exploitation, geothermal reservoir production, and solute transport in groundwater systems. Equivalent permeability has a great impact on such processes. In this study, equivalent permeability distributions are investigated based on a state-of-the-art numerical upscaling method (i.e., the multiple boundary method) for fractured porous rocks. An ensemble of discrete fracture models is created based on power law length distributions. The equivalent permeability is upscaled from discrete fracture models based on the multiple boundary method. The results show that the statistical distributions of equivalent permeability tensor components are highly related to fracture geometry and differ from each other. For the histograms of the equivalent permeability, the shapes of

k

x
x

and

k

y
y

change from a power law-like distribution to a lognormal-like distribution when the fracture length and the number of fractures increase. For the off-diagonal component

k

x
y

, it is a normal-like distribution and its range expands when the fracture length and the number of fractures increase. The mean of diagonal equivalent permeability tensor components increases linearly with the fracture density. The analysis helps in generating stochastic equivalent permeability models in fractured porous rocks and reduces uncertainties when applying equivalent fracture models.
Study on Delay Optimization of Fog Computing Edge Nodes Based on the CPSO-LB Algorithm
Authors: Wu J. Y. , Xin R. , Zhao J. B. , Zheng T. , Jiang D. , Zhang P. F.
Published: December 2020

With the development of modern science and technology as well as the steady advancement of urbanization, intelligent networks have emerged and are replacing traditional networks with the identity of next-generation networks. And information security is one of the most important research directions in the intelligent network construction. In order to resist the threat of privacy leakage during the data transmission of intelligent terminal, an original four-layer fog computing system which is suitable for intelligent network data collection, transmission, and processing structure is established in the paper. With the help of the Paillier algorithm for encryption and fine-grained aggregation, the fine-grained aggregated data as coefficients are embed in the cloud node, and Horner’s rule is conformed for unary polynomials, which further aggregates to reduce the amount of transmitted data, so that communication overhead is reduced as well. Meanwhile, the resolvability of Horner’s rules allows EPSI to finally obtain the subregional information plain text, and it is summed up to obtain cloud-level information data. Therefore, the comparative analysis of simulation experiments with other algorithms proves that the rational optimization of the research content in this paper plays a higher security role.
An Unusual Case of Ventricular Tachycardia in a Young Patient Associated with Cannabis Use
Authors: Sampat Parth J. , Riaz Sana , Bisen Maneesh , Carhart Robert
Published: December 2020

Marijuana has become the most widely used illicit drug in the United States. Approximately 43.5 million Americans aged 12 or above have reported the use of marijuana in the last year. The use of cannabinoids and its relationship with cardiac effects are not well known. Many types of arrhythmias have been noted with the use of cannabis products with atrial fibrillation being the most common arrhythmia associated with the use of cannabis. We present a case of a 36-year-old male who presented with pounding chest pain, dyspnea, and diaphoresis following marijuana use. He was found to be in ventricular tachycardia which responded to amiodarone. Workup done was negative for any structural disease, and cardiac catheterization was negative for coronary artery disease. He was ultimately discharged on metoprolol. In this report, we focus on how marijuana can be associated with many arrhythmias including ventricular tachycardia with focus on mechanisms by which it can occur. We believe a detailed social history with screening for cannabis use can identify more cases of arrhythmias that can be potentially associated with marijuana use.
Effects of Acupuncture on Explosive Force Production by the Healthy Female Shoulder Joint
Authors: Wang I-Lin , Chen Yi-Ming , Wang Jun , Hu Rui , Zhang Ke-Ke , Ho Chun-Sheng
Published: December 2020

Background. Acupuncture is often used to treat chronic conditions, such as pain. In recent years, given the importance of the explosive forces generated by shoulder muscles for the completion of motor tasks, studies in which nerves were stimulated through acupuncture to increase the explosive forces were conducted. This study explored the effect of acupuncture on explosive force production by the muscles of the female shoulder joint. Methods. Eighteen healthy women underwent shoulder adduction (Add), abduction (Abd), flexion (Flex), and extension (Ext) tests with an isokinetic measurement system. Acupuncture was used to stimulate the Zhongfu (LU1), Tianfu (LI3), Xiabai (LU4), Binao (LI14), Naohui (SJ13), Jianliao (SJ14), and Xiaoluo (SJ12) points, and electromyography (EMG) signals were recorded before and after acupuncture. Results. After acupuncture, there was a significant difference in the average maximum work, the average maximum power, the average maximum speed, the total work in Add/Abd and Flex/Ext, the EMG signals, and the stiffness of the muscles in Abd and Ext (P < 0.05). There were no significant differences in the average maximum torque in Abd or Flex. Conclusion. Based on the results, there may be a significant correlation between the manipulation of different acupoints by acupuncture and the average maximum torque and stiffness. Acupuncture may stimulate nerves to activate muscles and induce a postactivation potentiation effect that improves explosive force production. Therefore, acupuncture as an auxiliary tool may increase the explosive forces generated by acupoint‐related muscles by stimulating nerves.
The Role of Coal Mechanical Characteristics on Reservoir Permeability Evolution and Its Effects on CO2 Sequestration and Enhanced Coalbed Methane Recovery
Authors: Han Hao , Liang Shun , Liang Yaowu , Fu Xuehai , Kang Junqiang , Yu Liqiang , Tang Chuanjin
Published: December 2020

Elastic modulus is an important parameter affecting the permeability change in the process of coalbed methane (CBM)/enhanced coalbed methane (ECBM) production, which will change with the variable gas content. Much research focuses on the constant value of elastic modulus; however, variable stiffness of coal during CO2 injection has been considered in this work. The coupled thermo-hydro-mechanical (THM) model is established and then validated by primary production data, as well as being applied in the prediction of CO2/N2-ECBM recovery. The results show that the harder coal seam is beneficial to primary production, while the softer coal seam results in greater CO2/N2-ECBM recovery and CO2 sequestration. N2 and CO2 mixture injection could be applied to balance early N2 breakthrough and pronounced matrix swelling induced by CO2 adsorption, and to prolong the process of effective CH4 recovery. Besides, reduction in stiffness of coal seam during CO2 injection would moderate the significant permeability loss induced by matrix swelling. With the increase of the weakening degree of coal seam stiffness, CO2 cumulative storage also shows an increasing trend. Neglecting the weakening effect of CO2 adsorption on coal seam stiffness could underestimate the injection capacity of CO2. Injection of hot CO2 could improve the permeability around injection well and then enhance CO2 cumulative storage and CBM recovery. Furthermore, compared with ECBM production, injection temperature is more favorable for CO2 storage, especially within hard coal seams. Care should be considered that significant permeability change is induced by mechanical characteristics alterations in deep burial coal seams in further study, especially for CO2-ECBM projects.
The Constitutive Model of Rockfill Based on Property‐Dependent Plastic Potential Theory for Geomaterials
Authors: Li Xuefeng , Li Ruijie , Zhang Junhui , Wang Qi
Published: December 2020

To better control the strength and deformation of the roadbed, a constitutive model of rockfill was established based on property‐dependent plastic potential theory for geomaterials. The effect of the particle gradation on the anisotropy was described in the model. According to the effect of the particle grading and crushing on the fractal dimension, the fractal theory and fabric tensor were introduced to establish the yield and failure criteria of the rockfill. By combining the property‐dependent concepts of the materials and the results of the rockfill strength test, a critical state line considering the microstructure, fractal dimension, particle breakage, and stress state of the rockfill was established. The dilatancy equation was derived based on the novel potential theory and the hardening criterion affected by the critical state was established. A constitutive model of the rockfill in the general stress space was established under the framework of the novel potential theory. The 3D strength and its intensity change in the π plane were simulated through the drainage strength test results, which verified the description of the critical state under various stress paths. By simulating the stress‐strain relationship, the validity and rationality of the model were verified.
Construction of Nomograms for Predicting Lung and Bone Metastases in Patients with Intrahepatic Cholangiocarcinoma and Identification of Patients Who Can Benefit from Chemotherapy
Authors: Shi Ning , Zou Yiping , Zhang Yuanpeng , Han Hongwei , Chen Zhihong , Ruan Shiye , Jin Liang , Ma Zuyi , Chen Zhenrong , Lou Qi , Jin Haosheng
Published: December 2020

Objective. The purpose of our study is to build nomograms for predicting the possibility of lung metastasis (LM) and bone metastasis (BM) in patients with intrahepatic cholangiocarcinoma (ICC). Methods. 1527 patients diagnosed with ICC between 2010 and 2016 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Univariable and multivariable logistic regression analyses were used to recognize the predictors of LM and BM, respectively. Then two nomograms were established. We applied the C-index, calibration plot, receiver-operating characteristic (ROC) curve, and decision curve analysis (DCA) to evaluate the novel nomograms. The maximum values of the Youden indexes from the ROC curves were utilized to select the cutoff points of the nomograms. The Kaplan–Meier survival curves were used to evaluate the effect of chemotherapy in different groups. The bootstrap resampling method was chosen for internal validation. Results. Five predictors for LM and three predictors for BM were identified, and two nomograms were constructed. The nomograms had high values of C-indexes, reaching 0.821 (95% CI 0.772–0.871) for LM and 0.759 (95% CI 0.700–0.818) for BM. C-indexes of 0.814 for LM and 0.749 for BM were also observed in internal validation. The calibration plots, ROC curves, and DCAs exhibited favorable performances for predicting LM and BM. The cutoff points of total points in nomograms were 108 for LM and 144 for BM, which could distinguish between high-risk and low-risk groups for LM and BM. Chemotherapy is suggested to undergo for patients in high-risk groups. Conclusions. The nomograms could assess the possibility of LM and BM in ICC patients and determine the optimal treatment.
The Stability Analysis of Roadway near Faults under Complex High Stress
Authors: Zhang Biao , Zhou Huaqiang , Chang Qingliang , Zhao Xu , Sun Yuantian
Published: December 2020

Based on geological conditions of 3318 working face haulage roadway in Xuchang Coal Mine, as well as the space‐time relationship with surrounding gob, theoretical analysis and numerical simulation were used to study the influence of fault structure on the original rock stress of 3318 working face transport roadway. Considering the composite action of the leading supporting pressure of 3318 working face and the structure and the lateral supporting pressure of gob, the stress distribution and deformation law of roadway under the complex and high‐stress condition are studied. The results show that, under the superposition of lateral abutment pressure of goaf and abutment pressure of adjacent working face and fault structure, the peak stress of roadway roof and floor moves to the surface of roadway surrounding rock, and its distribution law changes from obvious symmetry to asymmetry; surrounding rock on both sides of roadway forms asymmetric circular concentrated stress area; roof and floor and two sides of roadway show asymmetric characteristics. This reveals the stability characteristics of roadway surrounding rock under the action of multiple perturbation stresses.
Cytogenomic Abnormalities in 19 Cases of Salivary Gland Tumors of Parotid Gland Origin
Authors: Zerjav Marie , DiAdamo Autumn , Grommisch Brittany , Katherine Amato , Chai Hongyan , Peng Gang , Li Peining
Published: December 2020

Salivary gland tumors (SGTs) of parotid origin are a group of diverse neoplasms which are difficult to classify due to their rarity and similar morphologic patterns. Chromosome analysis can detect clonal abnormalities, and array comparative genomic hybridization (aCGH) analysis can define copy number alterations (CNAs) from tumor specimens. Of the 19 cases of various types of SGTs submitted for cytogenomic analyses, an abnormal clone was detected in nine cases (47%), and CNAs were detected in 14 cases (74%). Recurrent rearrangements involving the PLAG1 gene at 8q12, recurrent CNAs including deletions of 6q, 9p (CDKN2A), and 17p (TP53), loss of Y chromosome, and gain of chromosome 7 were defined from these cases. Combined karyotyping and aCGH analyses could improve diagnostic yield. Future study for more precisive correlation of SGT classification with cytogenomic abnormalities will facilitate better diagnosis and treatment.
A Randomized Phase IIb Study of Low-dose Tamoxifen in Chest-irradiated Cancer Survivors at Risk for Breast Cancer
Authors: Bhatia Smita , Palomares Melanie R. , Hageman Lindsey , Chen Yanjun , Landier Wendy , Smith Kandice , Umphrey Heidi , Reich Caroline A. , Zamora Kathryn W. , Armenian Saro H. , Bevers Therese B. , Blaes Anne , Henderson Tara , Hodgson David , Hudson Melissa M. , Korde Larissa A. , Melin Susan A. , Merajver Sofia D. , Overholser Linda , Pruthi Sandhya , Wong F. Lennie , Garber Judy E.
Published: December 2020

Purpose:

Low-dose tamoxifen reduces breast cancer risk, but remains untested in chest-irradiated cancer survivors—a population with breast cancer risk comparable with BRCA mutation carriers. We hypothesized that low-dose tamoxifen would be safe and efficacious in reducing radiation-related breast cancer risk.

Patients and Methods:

We conducted an investigator-initiated, randomized, phase IIb, double-blinded, placebo-controlled trial (FDA IND107367) between 2010 and 2016 at 15 U.S. sites. Eligibility included ≥12 Gy of chest radiation by age 40 years and age at enrollment ≥25 years. Patients were randomized 1:1 to low-dose tamoxifen (5 mg/day) or identical placebo tablets for 2 years. The primary endpoint was mammographic dense area at baseline, 1 and 2 years. IGF-1 plays a role in breast carcinogenesis; circulating IGF-1 and IGF-BP3 levels at baseline, 1 and 2 years served as secondary endpoints.

Results:

Seventy-two participants (low-dose tamoxifen: n = 34, placebo: n = 38) enrolled at a median age of 43.8 years (35–49) were evaluable. They had received chest radiation at a median dose of 30.3 Gy. Compared with the placebo arm, the low-dose tamoxifen arm participants had significantly lower mammographic dense area (P = 0.02) and IGF1 levels (P < 0.0001), and higher IGFBP-3 levels (P = 0.02). There was no difference in toxicity biomarkers (serum bone-specific alkaline phosphatase, lipids, and antithrombin III; urine N-telopeptide cross-links) between the treatment arms. We did not identify any grade 3–4 adverse events related to low-dose tamoxifen.

Conclusions:

In this randomized trial in chest-irradiated cancer survivors, we find that low-dose tamoxifen is effective in reducing established biomarkers of breast cancer risk and could serve as a risk-reduction strategy.
An Anti–CD22-seco-CBI-Dimer Antibody–Drug Conjugate (ADC) for the Treatment of Non-Hodgkin Lymphoma That Provides a Longer Duration of Response than Auristatin-Based ADCs in Preclinical Models
Authors: Yu Shang-Fan , Lee Donna W. , Zheng Bing , del Rosario Geoffrey , Leipold Douglas , Booler Helen , Zhong Fiona , Carrasco-Triguero Montserrat , Hong Kyu , Yan Peter , Rowntree Rebecca K. , Schutten Melissa M. , Pillow Thomas , Sadowsky Jack D. , Dragovich Peter S. , Polson Andrew G.
Published: December 2020

We are interested in developing a second generation of antibody–drug conjugates (ADCs) for the treatment of non-Hodgkin lymphoma (NHL) that could provide a longer duration of response and be more effective in indolent NHL than the microtubule-inhibiting ADCs pinatuzumab vedotin [anti–CD22-vc-monomethyl auristatin E (MMAE)] and polatuzumab vedotin (anti–CD79b-vc-MMAE). Pinatuzumab vedotin (anti–CD22-vc-MMAE) and polatuzumab vedotin (anti–CD79b-vc-MMAE) are ADCs that contain the microtubule inhibitor MMAE. Clinical trial data suggest that these ADCs have promising efficacy for the treatment of NHL; however, some patients do not respond or become resistant to the ADCs. We tested an anti-CD22 ADC with a seco-CBI-dimer payload, thio-Hu anti–CD22-(LC:K149C)-SN36248, and compared it with pinatuzumab vedotin for its efficacy and duration of response in xenograft models and its ability to deplete normal B cells in cynomolgus monkeys. We found that anti–CD22-(LC:K149C)-SN36248 was effective in xenograft models resistant to pinatuzumab vedotin, gave a longer duration of response, had a different mechanism of resistance, and was able to deplete normal B cells better than pinatuzumab vedotin. These studies provide evidence that anti–CD22-(LC:K149C)-SN36248 has the potential for longer duration of response and more efficacy in indolent NHL than MMAE ADCs and may provide the opportunity to improve outcomes for patients with NHL.
Abstract IA20: Lymph protects metastasizing melanoma cells from ferroptosis
Authors: Morrison Sean J.
Published: December 2020

Cancer cells, including melanoma, often metastasize regionally through lymphatics before metastasizing systemically through the blood; however, the reason for this is unclear. We discovered that melanoma cells in lymph experience less oxidative stress and form more metastases than melanoma cells in blood. Immunocompromised mice with patient-derived melanomas and immunocompetent mice with mouse melanomas had more melanoma cells per microliter of tumor-draining lymph than tumor-draining blood. Cells metastasizing through blood, but not lymph, became dependent on the ferroptosis inhibitor GPX4. Cells pre-treated with chemical ferroptosis inhibitors formed more metastases than untreated cells after intravenous, but not intralymphatic, injection. We observed multiple differences between lymph fluid and blood plasma that may contribute to decreased oxidative stress and ferroptosis in lymph, including higher levels of glutathione and oleic acid, and less free iron, in lymph. Oleic acid protected melanoma cells from ferroptosis in an Acsl3-dependent manner and increased their capacity to form metastatic tumors. Melanoma cells from lymph nodes were more resistant to ferroptosis and formed more metastases after intravenous injection than melanoma cells from subcutaneous tumors. Exposure to the lymphatic environment thus protects melanoma cells from ferroptosis and increases their ability to survive during subsequent metastasis through the blood.

Citation Format: Sean J. Morrison. Lymph protects metastasizing melanoma cells from ferroptosis [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr IA20.
Abstract PO-001: xCT expression alters the epigenome and induces genomic instability
Authors: Hill Dalton , Rahman Jamshedur , Kluwe Christien , Massion Pierre P.
Published: December 2020

Metabolic reprogramming, remodeling of the epigenetic landscape, and genomic instability are three processes that drive tumorigenesis. While each has been investigated individually, there is a growing interest in the interplay between each process during early cancer development. High expression of the cystine/glutamate antiporter SLC7A11 (xCT) is frequently seen in lung cancer. Our lab previously demonstrated overexpression of xCT in normal bronchial airway epithelial cells is sufficient to induce metabolic reprogramming. In this study, we investigated the effects of xCT overexpression in normal bronchial airway epithelial cells. We hypothesize that xCT overexpression both induces genomic instability and alters the epigenome in normal bronchial airway epithelial cells through the perturbation of intracellular metabolite levels. Through utilizing an alkaline comet assay, we discovered that xCT overexpression induces DNA damage, increasing the percentage of DNA in the comet tail by 15.1% (P=0.002). Furthermore, we found that xCT overexpression induces alterations to the histone modification landscape, most notably increasing H3K9me3 and H3K9ac by 3.2 and 3.9-fold (P=0.08) respectively. Finally, xCT overexpression shows higher tumorigenic potential through increased colony formation in a soft agar assay. Taken together, xCT overexpression in normal bronchial airway epithelial cells increases tumorigenic potential, induces metabolic reprogramming, causes higher levels of DNA damage, and alters the epigenetic landscape. Future experiments elucidating the links between these processes, including ChIP-seq and whole-genome bisulfite sequencing are currently underway. Establishing causal links between metabolic reprogramming, epigenetic alterations, and genomic instability are imperative in elucidating an effective, potentially multifaceted approach to treating early-stage lung cancer.

Citation Format: Dalton Hill, Jamshedur Rahman, Christien Kluwe, Pierre P. Massion. xCT expression alters the epigenome and induces genomic instability [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PO-001.
Abstract PO-005: Tet2 inactivation enhances the anti-tumor efficiency of tumor-infiltrating lymphocytes (TILs)
Authors: Lee Minjung , Li Jiangfang , Fang Shaohai , Han Wei , Moczygemba Margarita , Zhou Yubin , Li Jia , Sun Deqiang , Huang Yun
Published: December 2020

Inactivation of tumor infiltrating lymphocytes (TILs) is one of the mechanisms mitigating anti-tumor immunity during tumor onset and progression. Epigenetic abnormalities are regarded as a major culprit contributing to the dysfunction of TILs within tumor microenvironments. In this study, we used a murine model of melanoma to discover that Tet2 inactivation significantly enhances the anti-tumor activity of TILs, with the efficacy comparable to immune checkpoint inhibition imposed by anti-PD-L1 treatment. Single-cell RNA-seq analysis further revealed that Tet2-deficient TILs exhibit effector-like features. Transcriptomic and ATAC-seq analysis further demonstrated that Tet2 deletion reshapes the chromatin accessibility and favors the binding of transcription factors geared toward CD8+ T cell activation. In summary, our study establishes that Tet2 constitutes one of the epigenetic barriers contributing to dysfunction of TILs, and that Tet2 inactivation could benefit anti-tumor immunity to boost tumor suppression.

Citation Format: Minjung Lee, Jiangfang Li, Shaohai Fang, Wei Han, Margarita Moczygemba, Yubin Zhou, Jia Li, Deqiang Sun, Yun Huang. Tet2 inactivation enhances the anti-tumor efficiency of tumor-infiltrating lymphocytes (TILs) [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PO-005.