bluuebunny/crossref_metadata_2025 huggingface dataset:
Fear of happiness through the prism of the dual continua model of mental health
Authors: Blasco‐Belled Ana , Rogoza Radosław , Alsinet Carles , Torrelles‐Nadal Cristina
Published: May 2021

Objective

Two studies were conducted to investigate fear of happiness through the lens of the dual continua model of mental health.

Methods

In Study 1, we examined whether depression (indicator of mental illness) and happiness (indicator of mental health) predicted fear of happiness through a Structural Equation Model. In Study 2, we ran a quasi‐experimental design to examine differences in affect (positive and negative), happiness and depression when engaging in either fearless or fearful beliefs of happiness.

Results

Fear of happiness was positively and negatively predicted by depression and happiness, respectively. Fearless individuals reported higher positive affect and happiness, and lower negative affect and depression, than fearful individuals.

Conclusions

Fearing happiness might act as a maladaptive self‐verifying motive to enhance one's perspective of the world. Given the likelihood of modifying maladaptive cognitive patterns, we highlight different psychological interventions that can address the negative impact of fearful beliefs of happiness.
Examining models of psychologists' telepsychology use during the COVID‐19 pandemic: A national cross‐sectional study
Authors: McKee Grace B. , Pierce Bradford S. , Donovan Emily K. , Perrin Paul B.
Published: May 2021

Objective

The aim of this study is to apply the theory of reasoned action (TRA) and technology acceptance model (TAM) to psychologists' telepsychology use during the COVID‐19 pandemic.

Methods

A sample of 2619 US‐licensed psychologists completed a survey assessing telepsychology use and aspects of both models in May 2020.

Results

Cross‐sectional TRA and TAM path models evidenced excellent fit in explaining psychologists' telepsychology use. The TRA indicated that psychologists' attitudes concerning telepsychology and subjective norms were associated with intentions to use telepsychology, which related to percentage of clinical work performed via telepsychology. The TAM showed that perceived usefulness of telepsychology and perceived ease of use were associated with attitudes toward telepsychology. Perceived usefulness was associated with psychologists' intention to use telepsychology, as was perceived ease of use.

Conclusion

Efforts to facilitate telepsychology provision during the pandemic and broadly may benefit from trainings and campaigns to address attitudes toward telepsychology, subjective norms, and perceived ease of use.
Androgen replacement therapy for cancer‐related symptoms in male: result of prospective randomized trial (ARTFORM study)
Authors: Izumi Kouji , Iwamoto Hiroaki , Yaegashi Hiroshi , Nohara Takahiro , Shigehara Kazuyoshi , Kadono Yoshifumi , Nanjo Shigeki , Yamada Tadaaki , Ohtsubo Koshiro , Yano Seiji , Mizokami Atsushi
Published: May 2021

Background

Hypogonadism associated with cancer is reported to cause cachexia and a variety of physical and psychological symptoms. This study aims to evaluate whether androgen replacement therapy can improve cancer‐related symptoms in male advanced cancer patients.

Methods

An investigator‐initiated, prospective, and randomized controlled study was conducted. Patients with low serum testosterone levels (total or free testosterone levels were <2.31 ng/mL or <11.8 pg/mL, respectively) were randomly assigned to the control or testosterone enanthate administration (testosterone group) groups. Testosterone enanthate was injected into the muscle tissue at a dose of 250 mg every 4 weeks (baseline, week 4, and week 8). Differences in quality of life questionnaires and cachexia‐related serum protein levels between groups were assessed.

Results

This study enrolled and randomized 106 and 81 patients, respectively. Moreover, 41 and 40 patients were in the control and testosterone groups, respectively. Although no significant differences in the change of subscales and total scores in Functional Assessment of Anorexia/Cachexia Treatment were noted from the baseline between the two groups, the testosterone group showed a significantly better change in the ‘unhappiness’ item of the Edmonton Symptom Assessment System at week 12 compared with baseline versus the control group (−1.4 and 0.0 points, respectively; mean, P = 0.007). No significant differences exist in the change of serum interleukin‐6 and insulin‐like growth factor‐1 levels at week 12 from the baseline between the control and testosterone groups. Consequently, the testosterone group significantly inhibited the change in serum tumour necrotic factor‐α level at week 12 from the baseline compared with the control group (+0.4 and +0.1 pg/mL, respectively; mean, P = 0.005).

Conclusions

Although testosterone enanthate did not improve most of the items in health‐related quality of life questionnaires, testosterone enanthate induced a significantly better change in the ‘unhappiness’ item at week 12 compared with the control. Testosterone enanthate may be a potential treatment option for male advanced cancer patients.
Prediction of COVID‐19 cases during Tokyo's Olympic and Paralympic Games
Authors: Tokuda Yasuharu , Kuniya Toshikazu
Published: May 2021

Tokyo's Olympic and Paralympic Games set to begin in late July 2021 without spectators from abroad, but vaccine rollout has been slow in Japan compared with other developed countries. In this study, COVID‐19 epidemic curve in Tokyo is developed based on weekly reported data from January 23, 2020, until April 16, 2021. The maximum daily number of infected cases in Tokyo in August 2021 would be 7,991 if the current pace of vaccinations would be used (1/1,000 per day). This daily number is greater than the highest daily cases (2,447) recorded on January 7, 2021. However, if the rollout pace could be doubled (1/500 per day), the peak daily new cases would be 4,470 in August. If it could be quadrupled (1/250 per day), the peak would be noted at 2,128 in July and the highest number in August would be 1,977. If vaccine rollout could not be enhanced, the cancellation might be an acceptable decision, since health is the most precious to local people and our Olympians.
Visualising the urethra for prostate radiotherapy planning
Authors: Richardson Matthew , Skehan Kate , Wilton Lee , Sams Joshua , Samuels Justin , Goodwin Jonathan , Greer Peter , Sridharan Swetha , Martin Jarad
Published: May 2021

Introduction

The prostatic urethra is an organ at risk for prostate radiotherapy with genitourinary toxicities a common side effect. Many external beam radiation therapy protocols call for urethral sparing, and with modulated radiotherapy techniques, the radiation dose distribution can be controlled so that maximum doses do not fall within the prostatic urethral volume. Whilst traditional diagnostic MRI sequences provide excellent delineation of the prostate, uncertainty often remains as to the true path of the urethra within the gland. This study aims to assess if a high‐resolution isotropic 3D T2 MRI series can reduce inter‐observer variability in urethral delineation for radiotherapy planning.

Methods

Five independent observers contoured the prostatic urethra for ten patients on three data sets; a 2 mm axial CT, a diagnostic 3 mm axial T2 TSE MRI and a 0.9 mm isotropic 3D T2 SPACE MRI. The observers were blinded from each other’s contours. A Dice Similarity Coefficient (DSC) score was calculated using the intersection and union of the five observer contours vs an expert reference contour for each data set.

Results

The mean DSC of the observer vs reference contours was 0.47 for CT, 0.62 for T2 TSE and 0.78 for T2 SPACE (P < 0.001).

Conclusions

The introduction of a 0.9 mm isotropic 3D T2 SPACE MRI for treatment planning provides improved urethral visualisation and can lead to a significant reduction in inter‐observer variation in prostatic urethral contouring.
Group A rotavirus prevalence and genotypes among adult outpatients with diarrhea in Beijing, China, 2011–2018
Authors: Tian Yi , Gao Zhiyong , Li Weihong , Liu Baiwei , Chen Yanwei , Jia Lei , Yan Hanqiu , Wang Quanyi
Published: May 2021

Group A rotavirus (RVA) is one of the most common causes of severe diarrhea in children worldwide. However, RVA is also an important pathogen causing adult diarrhea, with higher infection rates in older patients. To provide evidence for rotavirus epidemic control and to inform vaccine development, we analyzed the molecular epidemiology of RVA among adult outpatients with diarrhea in Beijing from 2011 to 2018. Stool specimens were collected monthly from 14 districts. RVA was detected using enzyme‐linked immunosorbent assay and real‐time reverse‐transcription polymerase chain reaction (RT‐PCR). Genotyping of rotavirus was performed using multiplex semi‐nested RT‐PCR. Phylogenetic analysis was performed using maximum likelihood methods implemented in MEGA software (version 6.06). Logistic regression and chi‐square tests were used to assess differences among age groups, districts, years, and genotype distributions. The prevalence of rotavirus was 10.16% (1310 of 12,893) among adult outpatients with diarrhea from 2011 to 2018 in Beijing. The highest prevalence (13.74%, 600 of 4367) was observed among those aged 41 to 65 years. November, December, and January had the highest positive detection rates. In 2011, G3P[8] and G9P[8] were the dominant genotypes. Starting from 2012, G9P[8] became the dominant genotype. Most G9 strains belonged to the G9‐VI clade. Most P[8] strains belonged to the P[8]‐III clade. RVA is a major cause of adult diarrhea in Beijing. Continuous molecular surveillance is needed, and transmission of rotavirus between children and adults should be investigated further.
Treatment strategy and endpoint of catheter ablation for bi‐atrial tachycardia after substrate modification ablation in a low voltage zone of the left atrial anterior wall: Long‐term results
Authors: Arai Tomoyuki , Hojo Rintaro , Tokioka Sayuri , Kitamura Takeshi , Fukamizu Seiji
Published: May 2021

Background

The termination of bi‐atrial tachycardia (BiAT) via the ablation of the Bachmann's bundle (BB) and mitral isthmus (MI) has been previously reported; however, the strategy and long‐term results of catheter ablation for BiAT remain unclear.

Methods

The data of nine patients with BiAT who underwent low voltage zone (LVZ) ablation of the left atrial anterior wall (LAAW) after pulmonary vein isolation were reviewed. Patients with a P wave duration <100 ms during sinus rhythm underwent MI ablation and those with a P wave duration >100 ms underwent BB ablation.

Results

MI ablation was performed in three patients and six patients underwent BB ablation. The difference in the P wave duration before and after ablation was significantly different between the ablation sites (MI group: 5.0 ms difference; BB group; 38.5 ms difference; P = .024). The P wave duration was prolonged by >20 ms and was 120 ms or more after ablation in 5/6 patients who underwent BB ablation. The total recurrence rate was 11.0% (mean: 26.9 months).

Conclusion

The recurrence of BiAT after MI or BB ablation is low. When BB ablation was performed, the P wave duration was prolonged by >20 ms and was at least 120 ms after the ablation, which may be an endpoint that can be used to measure the success of the ablation.
Ambulatory ECG monitoring for syncope and collapse in United States, Europe, and Japan: The patients’ viewpoint
Authors: Altinsoy Meltem , Sutton Richard , Kohno Ritsuko , Sakaguchi Scott , Mears Robin K. , Benditt David G.
Published: May 2021

Background

Practice guidelines provide clinicians direction for the selection of ambulatory ECG (AECG) monitors in the evaluation of syncope/collapse. However, whether patients’ understand differences among AECG systems is unknown.

Methods and Results

A survey was conducted of USA (n = 99), United Kingdom (UK)/Germany (D) (n = 75) and Japan (n = 40) syncope/collapse patients who underwent diagnostic AECG monitoring. Responses were quantitated using a Likert‐like 7‐point scale (mean ± SD) or percent of patients indicating a Top 2 box (T2B) for a particular AECG attribute. Patient ages and diagnosed etiologies of syncope/collapse were similar across geographies. Patients were queried on AECG attributes including the ability to detect arrhythmic/cardiac causes of collapse, instructions received, ease of use, and cost. Patient perception of the diagnostic capabilities and ease of use did not differ significantly among the AECG technologies; however, USA patients had a more favorable overall view of ICM/ILRs (T2B: 42.4%) than did UK/D (T2B: 28%) or Japan (T2B: 17.5%) patients. Similarly, US patient rankings for education received regarding device choice and operation tended to be higher than UK/D or Japan patients; nevertheless, at their best, the Likert scores were low (approximately 4.7‐6.0) suggesting need for education improvement. Finally, both US and UK/D patients were similarly concerned with ICM costs (T2B, 31% vs 20% for Japan).

Conclusions

Patients across several geographies have a similar but imperfect understanding of AECG technologies. Given more detailed education the patient is likely to be a more effective partner with the clinician in establishing a potential symptom‐arrhythmia correlation.
Mass spectrometry‐based strategies for single‐cell metabolomics
Authors: Hu Rui , Li Ying , Yang Yunhuang , Liu Maili
Published: May 2021

Single cell analysis has drawn increasing interest from the research community due to its capability to interrogate cellular heterogeneity, allowing refined tissue classification and facilitating novel biomarker discovery. With the advancement of relevant instruments and techniques, it is now possible to perform multiple omics including genomics, transcriptomics, metabolomics or even proteomics at single cell level. In comparison with other omics studies, single‐cell metabolomics (SCM) represents a significant challenge since it involves many types of dynamically changing compounds with a wide range of concentrations. In addition, metabolites cannot be amplified. Although difficult, considerable progress has been made over the past decade in mass spectrometry (MS)‐based SCM in terms of processing technologies and biochemical applications. In this review, we will summarize recent progress in the development of promising MS platforms, sample preparation methods and SCM analysis of various cell types (including plant cell, cancer cell, neuron, embryo cell, and yeast cell). Current limitations and future research directions in the field of SCM will also be discussed.
A framework of linear canonical transform on pseudo‐differential operators and its application
Authors: Kumar Manish , Pradhan Tusharakanta
Published: May 2021

The primary aim of this paper is to define a class of pseudo‐differential operators (PDOs) involving linear canonical transform (LCT) associated with the symbol b(x, y). An integral representation of PDOs
is given. Boundedness of the composition of operators
and
are derived. Further, new integral operators
are defined, and their boundedness properties are also investigated. The secondary aim is to find some applications of LCT to solve the boundary value problems of generalized partial differential equations and obtain their solution in closed form. Furthermore, particular cases of these differential equations are discussed, and demonstration of these equations' solutions are shown graphically.
Optimized 64‐channel array configurations for accelerated simultaneous multislice acquisitions in 3T cardiac MRI
Authors: Etzel Robin , Mekkaoui Choukri , Ivshina Ekaterina S. , Reese Timothy G. , Sosnovik David E. , Hansen Sam‐Luca J. D. , Ghotra Anpreet , Kutscha Nicolas , Chemlali Chaimaa , Wald Lawrence L. , Mahnken Andreas H. , Keil Boris
Published: May 2021

Purpose

Three 64‐channel cardiac coils with different detector array configurations were designed and constructed to evaluate acceleration capabilities in simultaneous multislice (SMS) imaging for 3T cardiac MRI.

Methods

Three 64‐channel coil array configurations obtained from a simulation‐guided design approach were constructed and systematically evaluated regarding their encoding capabilities for accelerated SMS cardiac acquisitions at 3T. Array configuration AUni‐sized consists of uniformly distributed equally sized loops in an overlapped arrangement, BGapped uses a gapped array design with symmetrically distributed equally sized loops, and CDense has non‐uniform loop density and size, where smaller elements were centered over the heart and larger elements were placed surrounding the target region. To isolate the anatomic variation from differences in the coil configurations, all three array coils were built with identical semi‐adjustable housing segments. The arrays’ performance was compared using bench‐level measurements and imaging performance tests, including signal‐to‐noise ratio (SNR) maps, array element noise correlation, and SMS acceleration capabilities. Additionally, all cardiac array coils were evaluated on a healthy volunteer.

Results

The array configuration CDense with the non‐uniformly distributed loop density showed the best overall cardiac imaging performance in both SNR and SMS encoding power, when compared to the other constructed arrays. The diffusion weighted cardiac acquisitions on a healthy volunteer support the favorable accelerated SNR performance of this array configuration.

Conclusion

Our results indicate that optimized highly parallel cardiac arrays, such as the 64‐channel coil with a non‐uniform loop size and density improve highly accelerated SMS cardiac MRI in comparison to symmetrically distributed loop array designs.
Contemporary Challenges of Nursing CPD: Time to change the model to meet citizens’ needs
Authors: Jackson Carolyn , Manley Kim
Published: May 2021

The purpose of this paper is to present the evidence shared with a citizen Consensus panel detailing key issues associated with how nursing CPD can best influence the quality of health and social care experienced by citizens and communities. It presents a summary of contemporary theory, research and evidence of the effectiveness of nursing CPD and outlines four key challenges: (i) how to strengthen the focus on patient experience as the starting point for CPD; (ii) the lack of evidence of CPD effectiveness and accountability in its transfer to practice; (iii) evaluation of CPD effectiveness; and (iv) involving citizens in targeting CPD where it is most needed. It briefly describes the methods used to facilitate public consultation through a citizen Consensus panel as part of a collaborative project with the RCN Strategic Research Alliance in 2020 and outlines 7 themes identified as important by the public for future development. The main challenge for nursing is capitalizing on the workplace as a learning resource that can integrate learning with development, improvement, knowledge translation, inquiry and innovation. This requires skilled facilitators, particularly at meso‐ levels, and systems leaders with the full skillset to develop system‐wide cultures of learning that enable everyone to flourish and create good places to work. The paper concludes that the development of CPD process measures would indicate how CPD investment contributes to person‐centred, safe and effective care and system transformation and enable commissioners and education providers to optimize CPD’s full potential.
Obesity and Cancer Risk in White and Black Adults: A Prospective Cohort Study
Authors: Brown Justin C. , Yang Shengping , Mire Emily F. , Wu Xiaocheng , Miele Lucio , Ochoa Augusto , Zabaleta Jovanny , Katzmarzyk Peter T.
Published: May 2021

Objective

Anthropometric measures of obesity, including BMI and waist circumference (WC), do not quantify excess adiposity and metabolic abnormalities consistently across racial populations. This study tested the hypothesis that participant race modifies the association of anthropometric measures of obesity and cancer risk.

Methods

This prospective cohort (The Pennington Center Longitudinal Study) included 18,296 adults, 6,405 (35.0%) male sex and 6,273 (34.3%) Black race. The primary exposures were BMI (weight in kilograms/height in meters squared) and WC (centimeters). The primary end point was the time from study enrollment to diagnosis of histologically confirmed invasive cancer.

Results

During a median follow‐up of 14.0 years (interquartile range: 9.8‐19.0 years), invasive cancer occurred in 1,350 participants. Among men, race modified the association of BMI (Pinteraction = 0.02) and WC (Pinteraction = 0.01) with cancer incidence; compared with a BMI of 22 kg/m2, a BMI of 35 kg/m2 in White men was associated with a hazard ratio of 1.83 (95% CI: 1.58‐2.12), whereas in Black men, the hazard ratio was 0.89 (95% CI: 0.72‐1.11). Among women, race did not modify the association of BMI (Pinteraction = 0.41) or WC (Pinteraction = 0.36) with cancer incidence.

Conclusions

In this diverse cohort of adults, participant race and sex modified the prognostic associations of anthropometric measures of obesity and cancer risk.
Characterisation of dysplastic liver nodules using low‐pass DNA sequencing and detection of chromosome arm‐level abnormalities in blood‐derived cell‐free DNA
Authors: Fateen Waleed , Johnson Philip J , Wood Henry M , Zhang Han , He Shan , El‐Meteini Mahmoud , Wyatt Judy I , Aithal Guruprasad P , Quirke Philip
Published: May 2021

High‐grade dysplasia carries significant risk of transformation to hepatocellular carcinoma (HCC). Despite this, at the current standard of care, all non‐malignant hepatic nodules including high‐grade dysplastic nodules are managed similarly. This is partly related to difficulties in distinguishing high‐risk pathology in the liver. We aimed to identify chromosome arm‐level somatic copy number alterations (SCNAs) that characterise the transition of liver nodules along the cirrhosis–dysplasia–carcinoma axis. We validated our findings on an independent cohort using blood‐derived cell‐free DNA. A repository of non‐cancer DNA sequences obtained from patients with HCC (n = 389) was analysed to generate cut‐off thresholds aiming to minimise false‐positive SCNAs. Tissue samples representing stages from the multistep process of hepatocarcinogenesis (n = 184) were subjected to low‐pass whole genome sequencing. Chromosome arm‐level SCNAs were identified in liver cirrhosis, dysplastic nodules, and HCC to assess their discriminative capacity. Samples positive for 1q+ or 8q+ arm‐level duplications were likely to be either HCC or high‐grade dysplastic nodules as opposed to low‐grade dysplastic nodules or cirrhotic tissue with an odds ratio (OR) of 35.5 (95% CI 11.5–110) and 16 (95% CI 6.4–40.2), respectively (p < 0.0001). In an independent cohort of patients recruited from Nottingham, UK, at least two out of four alterations (1q+, 4q−, 8p−, and 8q+) were detectable in blood‐derived cell‐free DNA of patients with HCC (n = 22) but none of the control patients with liver cirrhosis (n = 9). Arm‐level SCNAs on 1q+ or 8q+ are associated with high‐risk liver pathology. These can be detected using low‐pass sequencing of cell‐free DNA isolated from blood, which may be a future early cancer screening tool for patients with liver cirrhosis. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Impact of COVID‐19 on adolescent and emerging adult brain tumor survivors and their parents
Authors: Fisher Allison P. , Patronick Jamie , Gerhardt Cynthia A. , Radonovich Krestin , Salloum Ralph , Wade Shari L.
Published: May 2021

Background

The COVID‐19 pandemic has prompted unprecedented challenges, contributing to greater difficulties among families of children with special health care needs, such as pediatric brain tumor survivors. We examined the impact of the pandemic on psychosocial functioning of adolescent and emerging adult survivors and their parents. We hypothesized that COVID‐19 disruptions and survivor social connectedness would be associated with survivor‐reported posttraumatic stress and family outcomes, including family functioning, parenting, and parent mental health.

Procedure

Fifty‐five families (44 survivors, 48 parents) were recruited via phone and email to participate in the study. Survivors were ages 13–25 (M = 19.62, SD = 3.47) and at least 5 years post diagnosis. Parents completed the COVID‐19 Exposure and Family Impact Survey (CEFIS), and survivors completed the Environmental influences on Child Health Outcomes (ECHO) COVID‐19 child self‐report form, which assessed pandemic impacts on their psychosocial functioning.

Results

Parents reported a mean of 7.52 (SD = 2.83) disruptions to their families’ lives. The pandemic negatively affected survivors’ life satisfaction (Mdiff = 0.46, t(44) = 3.96, p < .001), with 92% reporting reduced social connectedness (n = 39). Total disruptions due to COVID‐19 and survivor social connectedness predicted survivor‐reported posttraumatic stress, above and beyond survivors’ pre‐pandemic psychosocial risk. Most parents reported positive changes in their parenting (n = 31, 67.4%) and family cohesion (n = 30, 66.7%). However, they also reported worsened mood (n = 28, 62.3%) and increased anxiety (n = 31, 71.1%).

Conclusions

Parents and survivors reported positive and negative impacts of COVID‐19, which had downstream consequences on survivor psychosocial functioning. Follow‐up care should consider potential adverse effects on social connectedness and stress symptoms.
Mapping the interaction between eukaryotic initiation factor 4A (eIF4A) and the inhibitor hippuristanol using carbene footprinting and mass spectrometry
Authors: Lloyd James R. , Hogan Amy , Paschalis Vasileios , Bellamy‐Carter Jeddidiah , Bottley Andrew , Seymour Graham B. , Hayes Christopher J. , Oldham Neil J.
Published: May 2021

Protein‐ligand interactions are central to protein activity and cell functionality. Improved knowledge of these relationships greatly benefits our understanding of key biological processes and aids in rational drug design towards the treatment of clinically relevant diseases. Carbene footprinting is a recently developed mass spectrometry‐based chemical labelling technique that provides valuable information relating to protein‐ligand interactions, such as the mapping of binding sites and associated conformational change. Here, we show the application of carbene footprinting to the interaction between eIF4A helicase and a natural product inhibitor, hippuristanol, found in the coral Isis hippuris. Upon addition of hippuristanol we identified reduced carbene labelling (masking) in regions of eIF4A previously implicated in ligand binding. Additionally, we detected hippuristanol‐associated increased carbene labelling (unmasking) around the flexible hinge region of eIF4A, indicating ligand‐induced conformational change. This work represents further development of the carbene footprinting technique and demonstrates its potential in characterising medicinally relevant protein‐ligand interactions.
Dose intra‐subject escalation to an event (DIETE): A new method for phase 1 dose‐finding utilizing systematic intra‐subject dose escalation with application to T‐cell engagers
Authors: Xu Chenjia , Zhuo Bin , Rasmussen Hans Erik
Published: May 2021

T‐cell engagers are a class of oncology drugs which engage T‐cells to initiate immune response against malignant cells. T‐cell engagers have features that are unlike prior classes of oncology drugs (e.g., chemotherapies or targeted therapies), because (1) starting dose level often must be conservative due to immune‐related side effects such as cytokine release syndrome (CRS); (2) dose level can usually be safely titrated higher as a result of subject's immune system adaptation after first exposure to lower dose; and (3) due to preventive management of CRS, these safety events rarely worsen to become dose limiting toxicities (DLTs). It is generally believed that for T‐cell engagers the dose intensity of the starting dose and the peak dose intensity both correlate with improved efficacy. Existing dose finding methodologies are not designed to efficiently identify both the initial starting dose and peak dose intensity in a single trial. In this study, we propose a new trial design, dose intra‐subject escalation to an event (DIETE) design, that can (1) estimate the maximum tolerated initial dose level (MTD1); and (2) incorporate systematic intra‐subject dose‐escalation to estimate the maximum tolerated dose level subsequent to adaptation induced by the initial dose level (MTD2) with a survival analysis approach. We compare our framework to similar methodologies and evaluate their key operating characteristics.
A Dual Functionality of Ternary Metal‐Oxide Nanoflakes for High‐Performance of Micro Supercapacitor and Electrochemical Sensing of Dyes in Water
Authors: Marimuthu Munuswamy , Ganesan Shanmugam , Yesuraj Johnbosco
Published: May 2021

The energy density limit of the metal oxide system increases by altering the bi‐metallic system to ternary metal oxide systems. Here we report, the synthesized ternary metal oxide system for distinct dual applications (Micro supercapacitor and Dye‐sensing activity). The nanoflake‐shaped materials [MNC‐A (Ni 1.0 Co 0.9 and Mg 0.4) O 0.6 and MNC‐B (Ni 1.0 Co 0.5 Mg 0.5) O1.0] were synthesized by the hydrothermal method followed by an annealing process. The synthesized tri‐metal‐oxide were analyzed using various physicochemical and electrochemical analyses to examine their material and electrochemical properties respectively. The obtained nanoflake‐like structure can render rich active reaction sites and rapid ion diffusion pathways. When examined as an asymmetric supercapacitor electrode material, it delivers outstanding specific capacitance of 198 Ag−1 at 0.3 Fg−1. Furthermore, the asymmetric supercapacitor provides a high‐energy density of 70.7 W h kg−1 at 0.36 kW kg−1 and a high‐power density of 4.5 kW kg−1 at 11.0 W h kg−1 respectively. Particularly, it maintains the high cyclic stability and retained 99.8 % initial specific capacitance after 50,000 charge/discharge cycles at the current density of 2 A g−1. Interestingly, the three interconnected systems deliver enough power to brighten a 3 V LED for up to 2 minutes. Also, the active material used as an electrode for the detection of low‐level dissolved dyes in water (ppm).
A Review of Recent Advances in the Inhibition of Sweet Corrosion
Authors: Xhanari Klodian , Wang Yefei , Yang Zhen , Finšgar Matjaž
Published: May 2021

This review paper discusses the research work published in the last decade on the use of organic compounds and natural products as corrosion inhibitors for steel in CO2 and CO2/H2S coexisting environments. The carbon and mild steel samples tested are mostly immersed in CO2‐saturated NaCl/brine solutions or simulated oilfield waters. The influence of temperature, immersion time, CO2 partial pressure, pre‐corrosion, flow rate/rotation speed, and the synergistic effect of other compounds on the corrosion inhibition effectiveness of organic compounds and natural products is presented. Primarily, weight loss and electrochemical techniques were used to evaluate the corrosion inhibition effectiveness of these compounds.
Islands and complexity of eternal black hole and radiation subsystems for a doubly holographic model
Authors: Bhattacharya Aranya , Bhattacharyya Arpan , Nandy Pratik , Patra Ayan K.
Published: May 2021

Abstract

We study the entanglement islands and subsystem volume complexity corresponding to the left/ right entanglement of a conformal defect in d-dimensions in Randall-Sundrum (RS) braneworld model with subcritical tension brane. The left and right modes of the defect mimic the eternal black hole and radiation system respectively. Hence the entanglement entropy between the two follows an eternal black hole Page curve which is unitarity compatible. We compute the volumes corresponding to the left and right branes with preferred Ryu-Takanayagi (RT) surfaces at different times, which provide a probe of the subregion complexity of the black hole and the radiation states respectively. An interesting jump in volume is found at Page time, where the entanglement curve is saturated due to the inclusion of the island surfaces. We explain various possibilities of this phase transition in complexity at Page time and argue how these results match with a covariant proposal qualitatively.
Fibre-base duality of 5d KK theories
Authors: Braun Andreas P. , Chen Jin , Haghighat Babak , Sperling Marcus , Yang Shuhang
Published: May 2021

Abstract

We study circle compactifications of 6d superconformal field theories giving rise to 5d rank 1 and rank 2 Kaluza-Klein theories. We realise the resulting theories as M-theory compactifications on local Calabi-Yau 3-folds and match the prepotentials from geometry and field theory. One novelty in our approach is that we include explicit dependence on bare gauge couplings and mass parameters in the description which in turn leads to an accurate parametrisation of the prepotential including all parameters of the field theory. We find that the resulting geometries admit “fibre-base” duality which relates their six-dimensional origin with the purely five-dimensional quantum field theory interpretation. The fibre-base duality is realised simply by swapping base and fibre curves of compact surfaces in the local Calabi-Yau which can be viewed as the total space of the anti-canonical bundle over such surfaces. Our results show that such swappings precisely occur for surfaces with a zero self-intersection of the base curve and result in an exchange of the 6d and 5d pictures.
A Note on the Majority Dynamics in Inhomogeneous Random Graphs
Authors: Shang Yilun
Published: May 2021

In this note, we study discrete time majority dynamics over an inhomogeneous random graph G obtained by including each edge e in the complete graph $$K_n$$

K
n

independently with probability $$p_n(e)$$

p
n

(
e
)

. Each vertex is independently assigned an initial state $$+1$$

+
1

(with probability $$p_+$$

p
+

) or $$-1$$

-
1

(with probability $$1-p_+$$

1
-

p
+

), updated at each time step following the majority of its neighbors’ states. Under some regularity and density conditions of the edge probability sequence, if $$p_+$$

p
+

is smaller than a threshold, then G will display a unanimous state $$-1$$

-
1

asymptotically almost surely, meaning that the probability of reaching consensus tends to one as $$n\rightarrow \infty $$

n
→
∞

. The consensus reaching process has a clear difference in terms of the initial state assignment probability: In a dense random graph $$p_+$$

p
+

can be near a half, while in a sparse random graph $$p_+$$

p
+

has to be vanishing. The size of a dynamic monopoly in G is also discussed.
Under- and over-investment in education: the role of locked-in fertility
Authors: Nakagawa Masao , Oura Asuka , Sugimoto Yoshiaki
Published: May 2021

This research argues that, in the presence of idiosyncratic ability shocks after childbirth, irreversible fertility decisions distort the resource allocation between the quantity and quality of children. In underdeveloped environments, where family size is locked into large levels, education investment places a heavy financial burden on households, which deprives some competent children of learning opportunities. In contrast, in more developed environments, family size is locked into smaller levels, which facilitates education investment even for some children with low aptitude. A redistributive policy to mitigate the distortion is proposed for each stage.
Detecting multiple generalized change-points by isolating single ones
Authors: Anastasiou Andreas , Fryzlewicz Piotr
Published: May 2021

We introduce a new approach, called Isolate-Detect (ID), for the consistent estimation of the number and location of multiple generalized change-points in noisy data sequences. Examples of signal changes that ID can deal with are changes in the mean of a piecewise-constant signal and changes, continuous or not, in the linear trend. The number of change-points can increase with the sample size. Our method is based on an isolation technique, which prevents the consideration of intervals that contain more than one change-point. This isolation enhances ID’s accuracy as it allows for detection in the presence of frequent changes of possibly small magnitudes. In ID, model selection is carried out via thresholding, or an information criterion, or SDLL, or a hybrid involving the former two. The hybrid model selection leads to a general method with very good practical performance and minimal parameter choice. In the scenarios tested, ID is at least as accurate as the state-of-the-art methods; most of the times it outperforms them. ID is implemented in the R packages IDetect and breakfast, available from CRAN.
CYP2D6 phenotype explains reported yohimbine concentrations in four severe acute intoxications
Authors: Mueller-Schoell Anna , Michelet Robin , Weinelt Ferdinand , Kloft Charlotte , Mikus Gerd
Published: May 2021

The indole alkaloid yohimbine is an alpha-2 receptor antagonist used for its sympathomimetic effects. Several cases of yohimbine intoxication have been reported and the most recent one involved four individuals taking a yohimbine-containing drug powder. All individuals developed severe intoxication symptoms and were admitted to the hospital. Even though all individuals were assumed to have taken the same dose of the drug powder, toxicology analyses revealed yohimbine blood concentrations of 249–5631 ng/mL, amounting to a 22-fold difference. The reason for this high variability remained to be elucidated. We used recently reported knowledge on the metabolism of yohimbine together with state-of-the art nonlinear mixed-effects modelling and simulation and show that a patient’s cytochrome P450 2D6 (CYP2D6) phenotype can explain the large differences observed in the measured concentration after intake of the same yohimbine dose. Our findings can be used both for the identification of safe doses in therapeutic use of yohimbine and for an explanation of individual cases of overdosing.
Generic pointed quartic curves in $${\mathbb {R}}{\mathbb {P}}^{2}$$ and uninodal dessins
Authors: Jaramillo Puentes Andrés
Published: May 2021

In this article we obtain a rigid isotopy classification of generic pointed quartic curves (A, p) in $${\mathbb {R}}{\mathbb {P}}^{2}$$

R

P

2

by studying the combinatorial properties of dessins. The dessins are real versions, proposed by Orevkov (Ann Fac Sci Toulouse 12(4):517–531, 2003), of Grothendieck’s dessins d’enfants. This classification contains 20 classes determined by the number of ovals of A, the parity of the oval containing the marked point p, the number of ovals that the tangent line $$T_p A$$

T
p

A

intersects, the nature of connected components of $$A\setminus T_p A$$

A
\

T
p

A

adjacent to p, and in the maximal case, on the convexity of the position of the connected components of $$A\setminus T_p A$$

A
\

T
p

A

. We study the combinatorial properties and decompositions of dessins corresponding to real uninodal trigonal curves in real ruled surfaces. Uninodal dessins in any surface with non-empty boundary can be decomposed in blocks corresponding to cubic dessins in the disk $${\mathbf {D}}^2$$

D

2

, which produces a classification of these dessins. The classification of dessins under consideration leads to a rigid isotopy classification of generic pointed quartic curves in $${\mathbb {R}}{\mathbb {P}}^{2}$$

R

P

2

. This classification was first obtained in Rieken (Geometr Ded 185(1):171–203, 2016) based on the relation between quartic curves and del Pezzo surfaces.
Finite automata with undirected state graphs
Authors: Kutrib Martin , Malcher Andreas , Schneider Christian
Published: May 2021

We investigate finite automata whose state graphs are undirected. This means that for any transition from state p to q consuming some letter a from the input there exists a symmetric transition from state q to p consuming a letter a as well. So, the corresponding language families are subregular, and in particular in the deterministic case, subreversible. In detail, we study the operational descriptional complexity of deterministic and nondeterministic undirected finite automata. To this end, the different types of automata on alphabets with few letters are characterized. Then, the operational state complexity of the Boolean operations as well as the operations concatenation and iteration is investigated, where tight upper and lower bounds are derived for unary as well as arbitrary alphabets under the condition that the corresponding language classes are closed under the operation considered.
Conditioning treatment with CD27 Ab enhances expansion and antitumor activity of adoptively transferred T cells in mice
Authors: Wasiuk Anna , Weidlick Jeff , Sisson Crystal , Widger Jenifer , Crocker Andrea , Vitale Laura , Marsh Henry C. , Keler Tibor , He Li-Zhen
Published: May 2021

Cyclophosphamide plus fludarabine (C/F) are currently used to improve the expansion and effectiveness of adoptive cell therapy (ACT). However, these chemotherapeutics cause pan-leukopenia and adverse events, suggesting that safer and more effective conditioning treatments are needed to improve ACT outcomes. Previously, we reported that varlilumab, a CD27-targeting antibody, mediatesTreg-preferential T cell depletion, CD8-T cell dominant costimulation, and systemic immune activation in hCD27 transgenic mice and cancer patients. We reasoned that the activities induced by varlilumab may provide an effective conditioning regimen for ACT. Varlilumab pretreatment of hCD27+/+mCD27− /−mice resulted in prominent proliferation of transferred T cells isolated from wild-type mice. These studies uncovered a critical role for CD27 signaling for the expansion of transferred T cells, as transfer of T cells from CD27 deficient mice or treatment with a CD70 blocking antibody greatly reduced their proliferation. In this model, varlilumab depletes endogenous hCD27+/+T cells and blocks their subsequent access to CD70, allowing for more CD70 costimulation available to the mCD27+/+transferred T cells. CD27-targeted depletion led to a greater expansion of transferred T cells compared to C/F conditioning and resulted in longer median survival and more cures than C/F conditioning in the E.G7 tumor model receiving OT-I cell therapy. We propose that translation of this work could be achieved through engineering of T cells for ACT to abrogate varlilumab binding but preserve CD70 ligation. Thus, varlilumab could be an option to chemotherapy as a conditioning regimen for ACT.
PTCH1 mutation promotes antitumor immunity and the response to immune checkpoint inhibitors in colorectal cancer patients
Authors: Wang Yanni , Chen Huan , Jiao Xi , Wu Lihong , Yang Ying , Zhang Jiao , Wu Lijia , Liu Chang , Zhuo Na , Li Shuang , Gong Jifang , Li Jian , Zhang Xiaotian , Wang Xicheng , Peng Zhi , Qi Changsong , Wang Zhenghang , Li Jie , Li Yan , Lu Zhihao , Zhang Henghui , Shen Lin
Published: May 2021

Immunotherapy has emerged as an effective therapeutic strategy for various cancers, including colorectal cancer (CRC), but only a subset of MSI-H patients can benefit from such therapy. Patched1 (PTCH1) is a frequently altered gene in CRCs and its mutations contribute to unregulated Hedgehog (Hh) signaling. In the study, we evaluated the association of PTCH1 mutations with CRC immunity based on our single-center cohort and multiple cancer genomic datasets. Among 21 enrolled patients, six (28.6%) harbored a PTCH1 mutation based on WES analyses. In CRC patients, the PTCH1 mutation subgroup experienced a higher durable clinical benefit rate than the PTCH1 wild-type subgroup (100% vs. 40%, P = 0.017). In addition, patients with the PTCH1 mutation experienced greater progression-free survival (PFS, P = 0.037; HR, 0.208) and overall survival (OS, P = 0.045; HR, 0.185). A validation cohort from the MSKCC also confirmed the correlation between PTCH1 mutation and better prognosis (P = 0.022; HR, 0.290). Mechanically, diverse antitumor immune signatures were more highly enriched in PTCH1-mutated tumors than in PTCH1 wild-type tumors. Furthermore, PTCH1-mutated tumors had higher proportions of CD8 + T cells, activated NK cells, and M1 type macrophage infiltration, as well as elevated gene signatures of several steps in the cancer-immunity cycle. Notably, the PTCH1 mutation was correlated with tumor mutational burden (TMB), loss of heterozygosity score, and copy number variation burden. Our results show that the mutation of PTCH1 is a potential biomarker for predicting the response of CRC patients to immunotherapy.
Favorable Outcomes of Neoadjuvant Chemotherapy and Limited Para‐Aortic Lymph Node Dissection for Advanced Gastric Cancer with Para‐aortic Lymph Node Metastasis
Authors: Ri Motonari , Ohashi Manabu , Eto Kojiro , Ishizuka Naoki , Atsumi Shinichiro , Makuuchi Rie , Ida Satoshi , Kumagai Koshi , Sano Takeshi , Nunobe Souya
Published: May 2021

Background

Although para‐aortic lymph node (PALN) metastasis from gastric cancer is a non‐curative lesion, gastrectomy with complete PALN dissection (PAND) following neoadjuvant chemotherapy (NAC) is a tentative standard treatment in Japan, based on the results of a small‐scale phase II clinical trial. However, whether complete PAND (C‐PAND) is always necessary for such diseases is open to debate.

Methods

Patients who received NAC followed by R0 gastrectomy for gastric cancer with clinical PALN metastasis at the Cancer Institute Hospital in Tokyo from 2005 to 2017 were reviewed in the present study. We assessed surgical findings and long‐term outcomes.

Results

In total, 44 patients receiving gastrectomy with C‐PAND (n = 22) or limited PAND (L‐PAND; n = 22) were included. Operation time was significantly longer in the C‐PAND than in the L‐PAND groups (363 min vs. 271 min, P = 0.037). There was no difference between the two groups in the ypStage classification and pattern of recurrence. The 5‐year overall survival (OS) and relapse‐free survival (RFS) curves were higher in the L‐PAND group than the C‐PAND group, without reaching a significant difference. The 5‐year OS (42.9% vs. 75.7%, p = 0.017) and RFS (14.3% vs. 48.6%, p = 0.002) were significantly worse in the group of three or more, than in the group of less than three pathological PALN metastasis, whereas increasing numbers of harvested PALN were not associated with improved survival.

Conclusions

Curative gastrectomy with L‐PAND following NAC for gastric cancer involving PALN may be an alternative treatment to C‐PAND.