bluuebunny/crossref_metadata_2025 huggingface dataset:
Distribution of the reef manta rayMobula alfrediand the oceanic manta rayMobula birostrisin the Philippines: a collaborative effort for conservation
Authors: Rambahiniarison Joshua , Agustines Ariana , Alexopoulos Konstantinos , Araujo Gonzalo , Armstrong Asia O. , Arnold Shannon , Barruga Aldrin , Cañete Titus , Conales Segundo , Delijero Kymry , Enolva Nonie P. , Flam Anna L. , Keane Eliya , Labaja Jessica , Legaspi Christine G. , Murie Calum , Murray Ryan , Oliver Simon P. , Pierce Simon J. , Ponzo Alessandro , Rohner Christoph A. , Schifferer Rosanna , Snow Sally , Spakowski Martina , Stevens Guy M. W. , Tilgel Timur , Wong Jessica N. C. , Yaptinchay Arnel Andrew , Barr Yotam
Published: December 2022

Little is known about manta ray population size, structure and connectivity in the Philippines. In collaboration with dive operators, non‐governmental organizations and authorities, sightings of manta rays were collated into a single national database. Using in‐water photographs and videos gathered through citizen science and dedicated research efforts, this study compiled sightings between 2004 and 2020, showing 22 separate sites throughout the archipelago with manta rays present. A total of 392 individual reef manta rays (Mobula alfredi) and 107 oceanic manta rays (Mobula birostris) were identified from the collected footage. Four specific sites in the provinces of Masbate and Palawan together hosted 89% of all identified individuals and accounted for 95% of sightings, highlighting these areas are key aggregation sites. This study also reports the movements ofM. birostriswithin the Philippines, based on photo‐identification of three individuals moving 150 km between Cebu and Masbate. Despite the growing number of recreational divers in Daanbantayan and San Jacinto, an 80% decline inM. birostrissightings was observed at these sites. To ensure effective future conservation, it is recommended that efforts focus on the identification and protection of manta ray hotspots and migratory corridors, the creation of a sustainable tourism framework and, most important, the implementation of mitigation strategies to reduce fisheries interactions.
What does gender equality need? Revisiting the formal and informal in feminist legal politics
Authors: COOPER DAVINA
Published: December 2022

This article explores the political conflict over reforming how sex and gender categories are used in British law, focusing on the speculative legal proposal to ‘decertify’ sex and gender. Three interconnected arguments are advanced. First, diverging views on decertification are both about and seek to marshal competing perspectives on the value and risks of formalization and its undoing. Second, understanding these views, and decertification more generally, benefits from an account of the formal and informal as interconnected movements of (un)settling, (un)acknowledgement, system (un)intelligibility, and (non‐)deference which remains irreducible to the presence or absence of state and law. Third, while formalization can pin down responsibilities and entitlements, it can also fix unequal and exclusionary status relationships. Focusing on positive action in the final part of the article, I consider how movements of formalization and informalization interrelate and the choices available, in conditions of decertification, if positive action is to counter gender inequality.
Resuscitating the resuscitation: A single‐centre experience on extracorporeal cardiopulmonary resuscitation
Authors: Ozturk Zeynelabidin , Kesici Selman , Ertugrul İlker , Aydin Ahmet , Yilmaz Mustafa , Bayrakci Benan
Published: December 2022

Aim

Extracorporeal cardiopulmonary resuscitation (ECPR) is the rapid deployment of venoarterial extracorporeal membrane oxygenation (ECMO) during active cardiopulmonary resuscitation or in patients with intermittent return of spontaneous circulation. This study aimed to describe the demographic characteristics and outcomes of patients undergoing ECPR to identify survival‐associated factors.

Methods

The study was conducted in an extracorporeal life support centre of a tertiary hospital in Turkey and included all patients who underwent ECPR for in‐hospital cardiac arrest between April 2013 and June 2021. Complications included bleeding, neurological injury, renal failure, hepatic failure, limb ischemia and bloodstream infections. The primary outcomes were survival of ECMO and survival to discharge. Neurological outcomes were assessed using the Pediatric Cerebral Performance Category Scale for children and the Category of Cerebral Performance Scale for adults.

Results

The study included 26 patients (24 paediatric, 2 adults), 22 (85%) of them had cardiac pathology. Bleeding was the most common complication. Twelve (46%) patients survived ECMO, 9 (35%) survived to discharge. Sex, age, primary diagnosis, cardiac arrest rhythm and ECMO duration were not significantly associated with the primary outcomes. Bleeding, neurological injury and renal failure were associated with poorer survival to discharge. The neurological outcomes of all survivors to discharge were good.

Conclusions

ECPR is not commonly accessible. Sharing the experience of the few treating centres to date is crucial to accumulating sufficient knowledge about its efficiency and raising clinician awareness. This limited single‐centre experience demonstrated the utility of ECPR.
High‐resolution sequencing of nine elite upland cotton cultivars uncovers genic variations and breeding improvement targets
Authors: Wang Nian , Li Yuanxue , Shen Chao , Yang Yang , Wang Hongya , Yao Tian , Zhang Xianlong , Lindsey Keith , Lin Zhongxu
Published: December 2022

Structural variations (SVs) are critical factors affecting genome evolution and important traits. However, identification results and functional analyses of SVs in upland cotton are rare. Here, based on the genetic relationships, breeding history and cumulative planting area of upland cotton in China, nine predominant cultivars from the past 60 years (1950s–2010s) were selected for long read sequencing to uncover genic variations and breeding improvement targets for this crop. Based on the ZM24 reference genome, 0.88–1.47 × 104 SVs per cultivar were identified, and an SV set was constructed. SVs affected the expression of a large number of genes during fiber elongation, and a transposable element insertion resulted in the glandless phenotype in upland cotton. Six widespread inversions were identified based on nine draft genomes and high‐throughput chromosome conformation capture data. Multiple haplotype blocks that were always associated with aggregated SVs were demonstrated to play a pivotal role in the agronomic traits of upland cotton and drove its adaptation to the northern planting region. Exotic introgression was the source of these haplotype blocks and increased the genetic diversity of upland cotton. Our results enrich the genome resources of upland cotton, and the identified SVs will promote genetic and breeding research in cotton.
Highly recurrent BRAF p.V595E mutation in canine papillary oral squamous cell carcinoma
Authors: Peralta Santiago , Webb Suzin M. , Katt William P. , Grenier Jennifer K. , Duhamel Gerald E.
Published: December 2022

Oral squamous cell carcinoma (OSCC) is the most common oral epithelial malignancy in dogs. It exhibits locally aggressive biological behaviour with the potential to metastasize, and a reported 1‐year survival rate of 0% when left untreated. Expression studies suggest that aberrant MAPK signalling plays a key role in canine OSCC tumorigenesis, which is consistent with BRAF and HRAS MAPK‐activating mutations reported in some tumours. Several morphological subtypes of canine OSCC have been described, with papillary, conventional, and basaloid as the most common patterns. We hypothesized that mutational differences may underlie these phenotypic variations. In this study, targeted Sanger sequencing and restriction fragment length polymorphism assays demonstrate that up to 85.7% of canine papillary OSCC (n = 14) harbour a BRAF p.V595E mutation. Assessment of neoplastic epithelial cell proliferation using Ki67 immunolabelling (n = 10) confirmed a relatively high proliferation activity, consistent with their known aggressive clinical behaviour. These findings underscore a consistent genetic feature of canine papillary OSCC and provide a basis for the development of novel diagnostic and targeted therapeutic approaches that can improve the quality of veterinary care.
Retrospective evaluation of the use of small‐bore wire‐guided catheters for the management of peritoneal effusion in cats and dogs
Authors: Crosby Jilli , Humm Karen , Cook Simon D.
Published: December 2022

Objective

To describe the use of small‐bore wire‐guided catheters in the management of peritoneal effusion in cats and dogs and to detail any associated adverse events.

Design

Retrospective study.

Setting

University teaching hospital

Animals

Forty‐five client‐owned animals that had peritoneal catheters placed for management of peritoneal effusion between July 2010 and June 2021.

Interventions

None.

Measurements and Main Results

Forty‐five cases were included (25 dogs and 20 cats). Twenty‐eight animals had the catheter placed to aid management of a uroabdomen, 8 of which recovered without surgical management, 11 had the catheter placed to allow autotransfusion of hemoabdomen, 3 had peritonitis, and 3 had ascites secondary to cardiac disease. Twenty‐seven cases (15 dogs and 12 cats) received sedation (n = 24) or local anesthesia alone (n = 3) to facilitate catheter placement, and 6 cases had the catheter placed while under general anesthesia. Median length of catheter persistence was 24 hours (range: 2–144 h). The most common adverse events reported were impaired drainage (n = 7) and leakage at the insertion site (n = 4).

Conclusions

Peritoneal catheters can be inserted percutaneously for management of peritoneal effusion. Indications include stabilization and conservative management of uroabdomen, and autotransfusion. They can often be placed with minimal or no sedation and adverse events appear infrequent in occurrence.
Advantages of the retroperitoneal retrocolic space as the transplant site for encapsulated xenogeneic islets
Authors: Geng Zhen , Zhang Qi , Li Ting , Huang Ting , Wang Hailian , Zhou Qiao , Deng Shaoping , Zhao Yanshuang , Li Yanjiao , Cheng Chunming , Gonelle‐Gispert Carmen , Buhler Leo H. , Wang Yi
Published: December 2022

Objective

Islet allotransplantation has demonstrated improved clinical outcomes using the hepatic portal vein as the standard infusion method. However, the current implantation site is not ideal due to the short‐term thrombotic and long‐term immune destruction. Meanwhile, the shortage of human organ donors further limits its application. To find a new strategy, we tested a new polymer combination for islet encapsulation and transplantation. Meanwhile, we explored a new site for xenogeneic islet transplantation in mice.

Method

We synthesized a hydrogel combining alginate plus poly‐ethylene‐imine (Alg/PEI) for the encapsulation of rat, neonatal porcine, and human islets. Transplantation was performed into the retroperitoneal retro‐colic space of diabetic mice. Control mice received free islets under the kidney capsule or encapsulated islets into the peritoneum. The biochemical indexes were measured, and the transplanted islets were harvested for immunohistochemical staining of insulin and glucagon.

Results

Mice receiving encapsulated rat, porcine and human islets transplanted into the retroperitoneal space maintained normoglycemia for a median of 275, 145.5, and 146 days, respectively. In contrast, encapsulated xenogeneic islets transplanted into the peritoneum, maintained function for a median of 61, 95.5, and 82 days, respectively. Meanwhile, xenogeneic islets transplanted free into the kidney capsule lost their function within 3 days after transplantation. Immunohistochemical staining of encapsulated rat, porcine and human islets, retrieved from the retroperitoneal space, allowed to distinguish morphological normal insulin expressing β‐ and glucagon expressing α‐cells at 70, 60, and 100 days post‐transplant, respectively.

Conclusion

Transplantation of Alg/PEI encapsulated xenogeneic islets into the retroperitoneal space provides a valuable new implantation strategy for the treatment of type 1 diabetes.
Effects of intrarenal angiotensin 1–7 infusion on renal haemodynamic and excretory function in anaesthetised two‐kidney one‐clip and deoxycorticosterone acetate‐salt hypertensive rats
Authors: Barry Elaine F. , Abdulla Mohammed H. , O'Neill Julie , AlMarabeh Sara , Beshara Julie , Parna‐Gile Erin , Johns Edward J.
Published: December 2022

This study investigated the action of angiotensin 1–7 (Ang (1–7)) on renal haemodynamic and excretory function in the two‐kidney one‐clip (2K1C) and deoxycorticosterone acetate (DOCA)‐salt rat models of hypertension, in which the endogenous renin–angiotensin system (RAS) activity was likely to be raised or lowered, respectively. Rats were anaesthetised and prepared for the measurement of mean arterial pressure and kidney function during renal interstitial infusion of Ang (1–7) or saline. Kidney tissue concentrations of angiotensin II (Ang II) and Ang (1–7) were determined. Intrarenal infusion of Ang (1–7) into the clipped kidney of 2K1C rats increased urine flow (UV), absolute (UNaV) and fractional sodium (FENa) excretions by 110%, 214% and 147%, respectively. Renal Ang II concentrations of the clipped kidney were increased with no major changes in Ang (1–7) concentration. By contrast, Ang (1–7) infusion decreased UV, UNaV, and FENa by 27%, 24% and 21%, respectively in the non‐clipped kidney in which tissue Ang (1–7) concentrations were increased, but renal Ang II concentrations were unchanged compared to sham animals. Ang (1–7) infusion in DOCA‐salt rats had minimal effects on glomerular filtration rate but significantly decreased UV, UNaV and FENa by ∼30%. Renal Ang (1–7) concentrations were higher and Ang II concentrations were lower in DOCA‐salt rats compared to sham rats. These findings demonstrate that the intrarenal infusion of exogenous Ang (1–7) elicits different renal excretory responses the magnitude of which is dependent on the balance between the endogenous renal Ang II–AT1 receptor axis and Ang (1–7)–Mas receptor axis.
Time to Preference: Early Preference Uptake under the EU-Canada Comprehensive Economic and Trade Agreement and the EU-Korea Free Trade Agreement
Authors: Nilsson Lars
Published: December 2022

This study examines the uptake of trade preferences under the EU-Canada Comprehensive Economic and Trade Agreement and the EU-Korea Free Trade Agreement during their respective first 21 months of application. The research analyzes the impact of time on the preference utilization rate of EU imports from Canada and Korea and EU exports to the two countries. The findings shed light on how EU member states perform vis-à-vis each trade partner and whether certain product groups appear more successful than others in terms of using trade preferences. The study further analyzes the potential effects of learning how to use preferences over time. Finally, the study argues that firm-pair transaction level data is necessary for discerning more conclusive answers regarding why trade preferences are (not) used.
The results point to that lack of knowledge and awareness is the most plausible reason to a low use of trade preferences in the early days of an agreement. To increase preference utilization rates in the beginning as well as later during agreement implementation, continuous information campaigns appear to be essential, not least since importing and exporting firms change over time.
The Effect of Bilateral Labor Agreements on Trade
Authors: Maximova Anna , Paraschiv Mihai
Published: December 2022

The period following the end of World War II is marked by increased international cooperation aimed, among other things, at promoting economic integration. As part of these efforts, national governments adopted policies to remove/reduce barriers to the exchange of goods and services as well as the movement of capital and labor. Although the impact of international trade and investment treaties on trade has been extensively documented, little to no attention has been paid to the potential impact of bilateral labor agreements (BLAs) on commerce flows. This study uses a novel dataset of BLAs within a gravity framework and finds that, over 5 years following signature, BLAs have a positive and significant effect on aggregate exports and exports of differentiated goods (i.e., chemicals and miscellaneous manufactured goods).
What set Siberia ablaze?
Authors: Schaepman-Strub Gabriela , Kim Jin-Soo
Published: December 2022

Shifting air currents and early snowmelt drove extreme Arctic fires from 2019 to 2021
Clonal Spread of Carbapenem-Resistant Klebsiella pneumoniae Sequence Type 11 in Chinese Pediatric Patients
Authors: Liu Xiong , Wang Kaiying , Chen Jiali , Lyu Jingwen , Li Jinhui , Chen Qichao , Lin Yanfeng , Tian Benshun , Song Hongbin , Li Peng , Gu Bing
Published: December 2022

We report a nosocomial outbreak among pediatric patients caused by clonal dissemination ofblaKPC-2-carrying ST11K. pneumoniae. Strains of various sequence types coexist in the complex hospital environment; the quick emergence and spread of ST11 strains were mainly due to the plasmid-mediated acquisition of resistance genes. The spread of hospital infection was highly associated with several specific wards, suggesting the importance of genomic surveillance on wards at high risk of infection.
Severe myalgic encephalomyelitis/chronic fatigue syndrome in children and young people: a British Paediatric Surveillance Unit study
Authors: Royston Alexander Peter , Rai Manmita , Brigden Amberly , Burge Sarah , Segal Terry Y , Crawley Esther M
Published: December 2022

Objectives

Primary objective: to determine the point prevalence and incidence rate of severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in children aged 5–16 years over 13 months. Secondary objectives: to describe the demographic features, symptoms, impact on activities of daily living, school attendance and time to diagnosis.

Design

Prospective surveillance study conducted by the British Paediatric Surveillance Unit. Paediatricians was asked if they had assessed a child with severe ME/CFS (screening definition for prevalence and incidence: children (5–16 years) diagnosed with ME/CFS so severe that they are unable to attend school for more than 1 hour a week during the last 6 weeks of the school term).

Participants

Patients 5–16 years of age, seen by paediatricians and two large ME/CFS specialist services across the UK and Ireland.

Outcome measures

Paediatrician-completed questionnaires describing demographics, symptoms, function and treatment, (applying National Institute for Health and Care Excellence (NICE)-recommended criteria to assess severity of ME/CFS). Diagnosis of severe, probable severe or possible severe ME/CFS was made only with evidence of NICE-recommended screening blood tests.

Results

285 cases were reported, of which of which 33 were severe, 4 probable severe and 55 possible severe. Estimated prevalence was 3.2 per million children (95% CI 2.2 to 4.5). Including possible/probable severe ME/CFS gave 8.9 per million children (95% CI 7.2 to 11). The incidence rate was 0.90 per million children-years (95% CI 0.43 to 1.65) (1.97 per million children-years (95% CI 1.24 to 2.99)). Median age was 13 years and 58% of cases were female. Median time to diagnosis was 0.47 years.

Conclusions

Although the incidence of children presenting with severe ME/CFS is low, all were very disabled. In addition, the majority receive little or no education. Paediatricians need to consider how to provide rehabilitation and education for these disabled young people.
Clinicopathological and genetic analyses of pulmonary enteric adenocarcinoma
Authors: Okada Fumi , Takeda Maiko , Fujii Tomomi , Uchiyama Tomoko , Sasaki Shoh , Matsuoka Minami , Nitta Yuji , Terada Chiyoko , Maebo Katsuya , Morita Kohei , Ishida Eiwa , Sawabata Noriyoshi , Ohbayashi Chiho
Published: December 2022

Aims

Pulmonary enteric adenocarcinoma (PEAC) is a rare variant of pulmonary adenocarcinoma. Due to its rarity, few pathological and molecular studies have been performed on PEAC. We herein conducted clinicopathological, immunohistochemical and molecular analyses of PEAC with a focus on its differentiation from invasive mucinous adenocarcinoma (IMA).

Methods

We examined the clinicopathological features of 16 cases of PEAC and performed a genetic analysis using next-generation sequencing (NGS). The results obtained were compared with those for IMA.

Results

The average age of patients with PEAC (seven men and nine women) was 72.9 years. A comparison of clinical data on PEAC and IMA revealed no significant differences in age, sex or smoking history. Fifteen PEAC cases had dirty necrosis. Immunohistochemically, the positive rates for each antibody in PEAC were as follows: CK7, 88% (14/16); CK20, 81% (13/16); CDX2, 88% (14/16); p53, 69% (11/16); MUC1, 100% (16/16); MUC2, 19% (3/16); MUC5AC, 69% (11/16); MUC6, 19% (3/16). The positive rates for these antibodies in IMA were 100%, 87%, 0%, 7%, 93%, 0%, 100% and 80%, respectively.EGFRmutations, theMETexon 14 skipping mutation,BRAFmutations, theALKfusion gene andROS-1fusion gene were not detected in any cases of PEAC or IMA. Among PEAC cases, NGS identifiedKRASmutations in seven (44%, 7/16) andTP53mutations in nine (56%, 9/16). Among IMA cases, the most commonly mutated gene wasKRAS(90%).

Conclusions

The rates of dirty necrosis, immunopositivity for CDX2 andTP53mutations were significantly higher, while that ofKRASmutations was significantly lower in PEAC cases than in IMA cases.
Sex-specific correlates of valvular and arterial calcification burden in patients with moderate aortic stenosis
Authors: Deslandes Marianne , Paquin Amélie , Guzzetti Ezequiel , Beaudoin Jonathan , Barriault Alexandra , Salaun Erwan , Clavel Marie-Annick
Published: December 2022

Introduction

There are significant sex differences in the prevalence and severity of cardiac calcifying processes. Women harbour more severe mitral annular calcification (MAC), while men exhibit worse aortic valve (AVC) and coronary artery (CAC) calcification. To better understand these differences, we investigated the correlates of cardiac calcification according to sex.

Methods

We conducted a cross-sectional study of 406 patients with ≥mild aortic stenosis (AS) defined by an aortic valve area ≤1.5 cm2, a peak aortic jet velocity >2.0 m/s, or a mean transvalvular gradient >15 mm Hg. Doppler-echocardiography and non-contrast multidetector CT were performed concomitantly to assess AS and cardiac calcifications.

Results

Mean age was 71±11 years and 33% were women. The AS haemodynamics were not significantly different between sexes (all p>0.50), with a mean indexed aortic valve area of 0.59±0.21 cm2/m2, peak aortic jet velocity of 2.78 (2.37–3.68) m/s, and mean gradient of 17.9 (12.8–31.3) mm Hg for the whole cohort. Compared with men, women harboured lower AVC (480 (222–1191) vs 1003 (484–2329) Agatston unit, AU; p<0.0001) and CAC (366 (50–914) vs 618 (167–1357) AU; p=0.007), but more severe MAC (60 (1–887) vs 48 (0–351) AU; p=0.08) and ascending aorta calcification (227 (43–863) vs 142 (7–493) AU; p=0.03). After comprehensive adjustment, sex remained an independent predictor of each cardiac calcification subtype (all p<0.02) except for the ascending aorta (p=0.32). In multivariable analysis, certain variables, like age or bicuspid aortic valve, were associated with the calcification scores in both sexes. Sex-specific predictors of calcification burden were absence of angiotensin receptor blockers (β=−0.26; p=0.007) and renal impairment (β=0.26; p=0.003) for AVC, and bisphosphonates (β=0.20; p=0.05) for CAC in women; coronary artery disease (β=0.25; p=0.001) for AVC, and angiotensin receptor blockers (β=0.19; p=0.02) and calcium/vitamin D (β=0.15; p=0.02) for MAC in men.

Conclusion

In AS, factors associated with cardiac valvular and arterial calcification differ between sexes, suggesting an important contributory role of sex in the pathophysiology of these calcifying processes.
Performance of a convolutional autoencoder designed to remove electronic noise from p-type point contact germanium detector signals
Authors: Anderson Mark R. , Basu Vasundhara , Martin Ryan D. , Reed Charlotte Z. , Rowe Noah J. , Shafiee Mehdi , Ye Tianai
Published: December 2022

We present a convolutional autoencoder to denoise pulses from a p-type point contact high-purity germanium detector similar to those used in several rare event searches. While we focus on training procedures that rely on detailed detector physics simulations, we also present implementations requiring only noisy detector pulses to train the model. We validate our autoencoder on both simulated data and calibration data from an $$^{241}$$

241

Am source, the latter of which is used to show that the denoised pulses are statistically compatible with data pulses. We demonstrate that our denoising method is able to preserve the underlying shapes of the pulses well, offering improvement over traditional denoising methods. We also show that the shaping time used to calculate energy with a trapezoidal filter can be significantly reduced while maintaining a comparable energy resolution. Under certain circumstances, our denoising method can improve the overall energy resolution. The methods we developed to remove electronic noise are straightforward to extend to other detector technologies. Furthermore, the latent representation from the encoder is also of use in quantifying shape-based characteristics of the signals. Our work has great potential to be used in particle physics experiments and beyond.
Novel Critical Gate-Based Circuit Path-Level NBTI-Aware Aging Circuit Degradation Prediction
Authors: Xu Hui , Zhu Rui , Sun Xia , Fang Xianjin , Qi Pan , Liang Huaguo , Huang Zhengfeng
Published: December 2022

With the rapid development of semiconductor technology, chip integration is getting beyond imagination. Aging has become one of the main threats to circuit reliability. In order to develop aging degradation prediction, it is critical to evaluate aging to avoid circuit failures. At present, the research on aging prediction is mainly focused at the transistor and gate levels: at transistor level, the precision is high, but the speed is low; whereas, the gate-level accuracy is not high, but the speed is very fast. In this paper, a path-level aging prediction framework based on the novel critical gate is proposed. The 10-year Negative Bias Temperature Instability (NBTI) aging delay of the critical subcircuit extracted by the novel critical gate is obtained, and the aging delay trend is learnt by using a linear regression model. Then the critical path aging delay can be obtained quickly based on the framework developed by machine learning using the linear regression model. The experimental results of ISCAS’85 and ISCAS’89 benchmark circuits based on 45-nm PTM show that the proposed framework is superior to the existing methods.
Design and Analysis of a Buck–Boost DC–DC Converter with Delta-Sigma Modulator Controller
Authors: Hekmati Hamed , Nasri Abbas , Toofan Siroos
Published: December 2022

This paper presents a low-ripple and high-efficiency buck–boost DC–DC converter with delta-sigma modulator controller that converts 1.8 V to 1.2 V and 3.3 V. A current and voltage closed-loop controller has been designed to achieve better performance simultaneously such as lower settling-time, steady-state error and over shoot and under shoot. The converter is started in the current controller mode initially, when the output voltage approaches the desired value, the power stage is controlled with the voltage controller mode. PI compensator and a third-order delta-sigma modulator are utilized in the voltage mode. Also, the closed-loop stability of the designed converter has been analyzed with Lyapunov method using converter nonlinear model. This work has been simulated in MATLAB-SIMULINK environment. The performance results show that the maximum efficiency of the closed-loop DC–DC converter is 90% at 5[Formula: see text]MHz switching frequency, and the output voltage ripple is 0.5% and 0.6% for the buck and boost modes, respectively. Also, the simulation results demonstrate the closed-loop stability of the converter in the presence of 10% load variation.
A two-dimensional stochastic fractional non-local diffusion lattice model with delays
Authors: Wang Yejuan , Wang Yu , Han Xiaoying , Kloeden Peter E.
Published: December 2022

The well-posedness, regularity and general stability of solutions to a two-dimensional stochastic non-local delay diffusion lattice system with a time Caputo fractional operator of order [Formula: see text] are investigated in [Formula: see text] spaces for [Formula: see text]. First, the global existence and uniqueness of solutions are established by using a temporally weighted norm, the Burkholder–Davis–Gundy inequality and the Banach fixed point theorem. Then the continuous dependence of solutions on initial values is established in the sense of [Formula: see text]th moment. In particular, the [Formula: see text]th moment Hölder regularities in time and [Formula: see text]th moment general stability, including polynomial and logarithmic stability of solutions, are obtained.
APPLICATIONS OF THE EXTENSION INNOVATION METHOD IN TREATMENT REGIMENS GENERATION WITH DEEP LEARNING
Authors: YE GUANGZAI , YE XUEYING , GUO JIANLAN , GAO SHUANG , LI BIN
Published: December 2022

Traditional treatment research lays much emphasis on therapeutic effects of a single drug or combination drugs, failing to explore appropriate treatment regimens that can be formed based on the state of an illness, medical history, financial capacity, and adverse drug reactions. For this reason, the extension innovation method is introduced to implement doctors’ thinking process in formulating treatment regimens in deep learning. First, an extension model is established for diseases according to the basic-element theory and the extension set theory based on the magnetic resonance image classification result under deep learning. Subsequently, extension analysis is made to analyze pathogenesis and corresponding treatment procedures; and multiple feasible treatment regimens are generated through extension transformation. At last, priority-degree evaluation is carried out to quantitatively assess the proposed treatment regimens and select a better regime from them. Here, ankylosing spondylitis (AS) is taken for example to validate the feasibility of applying the extension innovation method in treatment regime generation. Main contributions of this research are that both the extension model and the priority-degree evaluation method are introduced in treatment regime generation. In this way, after the deep learning method was used to automatically extract and classify medical image data features and determine the disease activity stage of ankylosing spondylitis, a formal and quantitative effective method can be provided for establishing the framework model of diseases and evaluating corresponding therapeutic regimens, then a foundation can be laid for arithmetic research on intelligent treatment regime generation via computer simulation of human thinking.
Serum Fat-Soluble Vitamin Levels of 6,082 Minors in Zhuzhou City
Authors: Tang Qiong , Ye Xiao-Min , Yang Yi-Can , Zhang Shi-Bin , Yan Li-Juan , Gong Dai , Zou Li , Wen Xiang-Lan
Published: December 2022

Objective. To explore the nutritional status of serum fat-soluble vitamins such as vitamin A, 25-hydroxyvitamin D, and vitamin E of minors in the Zhuzhou area to provide a scientific basis for clinical guidance to supplement fat-soluble vitamins reasonably. Method. A total of 6,082 minors who underwent physical examination from January 2017 to February 2019 in the Children’s Health Department of Zhuzhou Hospital affiliated with XiangYa School of Medicine of Central South University were selected as the subjects to measure the levels of serum fat-soluble vitamins A, D, and E. Results. (1) Their average levels of serum vitamin A, 25-hydroxyvitamin D, and vitamin E were (0.34 ± 0.08) mg/mL, (34.65 ± 10.24) ng/mL, and (10.11 ± 2.65) mg/mL, respectively. (2) Serum vitamin E showed a gender difference (

P
<
0.001

). (3) The average levels of serum 25-hydroxyvitamin D and vitamin E in infancy, early childhood, preschool age, school age, and adolescence decreased gradually (

P
<
0.05

). In contrast, the average level of serum vitamin A ranged between 0.32 mg/mL and 0.37 mg/mL. (4) The age was negatively correlated with serum 25-hydroxyvitamin D (r = −0.517,

P
<
0.001

) and weakly negatively correlated with vitamin E (r = −0.366,

P
<
0.001

), but weakly positively correlated with vitamin A (r = 0.269,

P
<
0.001

). Conclusion. Minors from infancy to adolescence in Zhuzhou should strengthen their supplementation of fat-soluble vitamins.
Abstract A012: Using clinical characteristics and molecular markers to predict the risk of subsequent ipsilateral breast events after excision of DCIS
Authors: Colditz Graham A. , Liu Ying , Strand Siri H. , King Lorraine , Marks Jeff , Maley Carlo , West Robert B. , Hwang E. Shelley
Published: December 2022

Purpose: To examine incremental values of estrogen receptor (ER) status, body mass index (BMI), menopausal status, and a multi-gene classifier over commonly used clinical factors (i.e. age, tumor grade, comedonecrosis, surgical margins, and treatment) in predicting risk of ipsilateral recurrence (IR) within five years after DCIS diagnosis. Methods: A derivation cohort consisted of participants in the discovery cohort, a retrospective multicenter cohort study in women undergoing surgical resection for DCIS between 01/01/1998 and 02/29/2016. The validation cohort provided cases meeting the same eligibility criteria as the discovery cohort. This analysis includes 313 participants with RNA-seq data who either developed IR 1-5 years after initial DCIS diagnosis or were free from subsequent breast events at least five years. Cox proportional hazards regression was used to estimate hazard ratios (HRs) of IR in 216 TBCRC participants (76 with IR). We developed the clinical score using clinical predictors (aforementioned clinical factors and ER) and their regression coefficients from the model with the maximum predictive accuracy (e.g. c-index) and the minimum number of predictors, and the summary score integrating the clinical score and multi-gene classifier. Predictive performance of clinical and summary scores was validated in 97 RAHBT patients (20 with IR). Results: In the discovery cohort, ER negativity, but not BMI or menopausal status, was independently associated with a higher IR risk (HR=2.06, 95% CI 1.18-3.58), and adding ER to the clinical factors-based model increased predictive accuracy (c-index 0.68 to 0.70). The clinical score-adjusted HR was 14.96 (95% CI 8.64-25.91) for multi-gene classifier. Summary scores were better in predicting IR risk than clinical scores (c-index 0.82 vs. 0.70). Compared with their low-risk counterparts, the HR was 4.79 (95% CI 2.55-8.98) in the clinical score-defined high-risk group and 29.02 (95% CI 14.23-59.15) in the summary score-defined high-risk group. In the validation cohort, model performance was improved using summary scores as compared to clinical scores (c-index 0.74 vs. 0.58). Conclusion: Combination of clinical factors and multigene classifier provided more accurate risk estimates of IR within five years after excision of DCIS than clinical factors alone.

Citation Format: Graham A. Colditz, Ying Liu, Siri H. Strand, Lorraine King, Jeff Marks, Carlo Maley, Robert B. West, E. Shelley Hwang. Using clinical characteristics and molecular markers to predict the risk of subsequent ipsilateral breast events after excision of DCIS [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr A012.
Abstract B002: A facilitating role for semaphorin-7a in regulating cell invasion and matrix remodeling for DCIS progression
Authors: Dahms Petra
Published: December 2022

Approximately 25% of newly diagnosed breast cancer cases are non-invasive or pre-invasive breast cancers known as ductal carcinoma in situ (DCIS). DCIS can progress to invasive ductal carcinoma (IDC), conferring a more dangerous prognosis; however, there is a gap in knowledge regarding what ultimately causes this transition. Understanding epithelial invasion in the mammary gland will provide insight on how DCIS ultimately progresses to IDC. Our lab has found that DCIS transforms to IDC under the “wound-healing” pressure of postpartum tissue remodeling – termed postpartum mammary gland involution. This invasive transformation is dependent, in part, on collagen-induced cyclooxygenase (COX2) expression. We identified that a membrane-bound signaling molecule, semaphorin-7a (SEMA7A), promotes both collagen deposition and COX-2 expression and therefore DCIS progression. SEMA7A is also naturally upregulated in mammary epithelial cells during postpartum involution and in DCIS relative to normal epithelium. We have identified that inhibition or silencing of SEMA7A can inhibit DCIS invasion. While this demonstrates that SEMA7A expression is sufficient to promote innate capacity for tumor cell invasiveness, we have yet to investigate how SEMA7A interacts with the tumor microenvironment (TME) to promote stromal changes known to advance this transition, such as collagen remodeling or immune cell recruitment. We have demonstrated a potential role for DCIS-associated macrophages in facilitating this transition. Additionally, we have found that SEMA7A polarizes macrophages to an M2-like state, and this promotes remodeling of the lymphatic vasculature as well as tumor cell entry into lymphatic vessels. Furthermore, we have shown that SEMA7A promotes expression of matrix remodeling enzymes that can, in turn, promote shedding of SEMA7A into the TME where it can affect other cell types. We are utilizing intravital imaging to visualize tumor/lymphatic/macrophage interactions as well as second harmonic imaging to visualize SEMA7A-dependent changes in the collagen structure surrounding DCIS lesions. Our results suggest that SEMA7A mediates DCIS invasion through both intrinsic and extrinsic mechanisms, which could facilitate progression to metastasis. By understanding how SEMA7A regulates DCIS progression we can begin to introduce potential targets for preventative therapies for development of invasive disease – including targeting SEMA7A itself. Since SEMA7A is low in most adult tissues it is expected that such a therapeutic would be less toxic for patients than the current prescribed therapies.

Citation Format: Petra Dahms. A facilitating role for semaphorin-7a in regulating cell invasion and matrix remodeling for DCIS progression [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr B002.
Abstract B010: Dynamics of fibril collagen remodeling in early DCIS invasions: integrating in silico modeling and tumor histology
Authors: Rejniak Katarzyna A. , Poonja Sharan , Mathur Shreya , Damaghi Mehdi , Bui Marilyn
Published: December 2022

Progression from a ductal carcinoma in situ (DCIS) to an invasive ductal carcinoma (IDC) involves changes in the surrounding extracellular matrix (ECM) fibril patterns before and during the development of ductal microinvasions, i.e., small cohorts of tumor cells that breach the duct and migrate through the stroma. We used a combination of mathematical modeling (with the hybrid agent-based model silicoDCIS) and advanced image analysis techniques applied to histological and fluorescent images in order to identify the rules of cell-ECM interactions that guide the emergence of various alignment patterns of the ECM fibrils. This includes the three tumor associated collagen signatures (TACS) previously observed in laboratory experiments. This integrated approach provides an in silico tool for testing biomechanical hypotheses of tumor cell-tumor matrix interactions. These findings can be compared to the patient histology samples and may help to define criteria for identification of DCIS to IDC transition and future development of new diagnostic methods.

Citation Format: Katarzyna A. Rejniak, Sharan Poonja, Shreya Mathur, Mehdi Damaghi, Marilyn Bui. Dynamics of fibril collagen remodeling in early DCIS invasions: integrating in silico modeling and tumor histology [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr B010.
Abstract B012: Exosome microRNAs are progressively altered and contribute to invasive progression of ductal carcinoma in situ
Authors: Hannafon Bethany , Dogra Samrita , Elayapillai Sugantha Priya , Lausen James , Bruns Matthew , Behbod Fariba , Gin Amy , Xu Chao , Zhang Roy , Ding Wei-Qun
Published: December 2022

Ductal carcinoma in situ (DCIS) is a benign breast condition that increases the risk of invasive breast cancer (IBC). Clinically, not all DCIS will progress to IBC and the major drivers of progression are not well understood. The role of small extracellular vesicles, also known as exosomes, is well described in advanced cancers, however, little is known about their role in the invasive progression of in situ breast disease. In this study, we sought to evaluate the role of exosomes and their RNA contents in the progression of DCIS, using the MCF10 isogenic series, in vitro assays and the mouse intraductal model of breast cancer progression. We observed a significant increase of exosome loading of microRNAs (miRNAs) between normal and benign states that increased with each stage. We demonstrate that pro-invasive programs were attenuated when overall exosome and miRNA secretion was inhibited by Rab27A and Dicer knockdown, respectively. Comparisons of exosome miRNA expression changes revealed the greatest differential expression between in situ and invasive cells, with miR-205 being the most significantly different, suggesting a mechanistic role for exosome miRNAs in invasive progression. Modulation of miR-205 levels affected epithelial to mesenchymal transition and the invasive programs in vitro. Progression of DCIS in vivo resulted in increased levels of specific circulating exosome miRNAs, while inhibition of exosome secretion (Rab27A knockdown) attenuated invasive progression and reduced circulating levels of exosome miRNAs. These observations suggest that exosome miRNAs are differentially loaded and expressed, and promote the invasive progression of DCIS and that circulating exosome miRNAs are a potential source of biomarkers of the DCIS to invasive transition.

Citation Format: Bethany Hannafon, Samrita Dogra, Sugantha Priya Elayapillai, James Lausen, Matthew Bruns, Fariba Behbod, Amy Gin, Chao Xu, Roy Zhang, Wei-Qun Ding. Exosome microRNAs are progressively altered and contribute to invasive progression of ductal carcinoma in situ [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr B012.
Abstract B014: Improving prediction of second events after DCIS using whole breast mammogram images
Authors: Jiang Shu (Joy) , Colditz Graham A.
Published: December 2022

Purpose: We aim to improve prediction of subsequent events after DCIS. Current models show relatively poor performance predicting subsequent events and often are limited to ipsilateral events. National population-based SEER data including over160,000 cases of DCIS and followed an average of 90 months indicate that second events (including risk of invasive breast cancer – IBC) are equality likely in the ipsilateral and contralateral breast. Thus, additional information on risk may be obtained by more complete modeling of risk estimating recurrence. Mammographic images have been largely ignored despite evidence that even breast density improves prediction of breast cancer in the general population. Furthermore, we have shown whole breast mammogram images (WBI) included in Cox models significantly improves prediction of breast cancer risk over using mammographic breast density alone and breast cancer risk factors. Population: We retrieved digital mammograms for women diagnosed with DCIS at Washington University School of Medicine from 2008 onwards and followed for subsequent diagnosis of pathology confirmed breast lesions. Using more than 100 cases and controls matched on year of mammogram and age we fit Cox models to evaluate risk of ipsilateral invasive breast cancer. To compare and accommodate laterality of subsequent breast lesions, we fit competing risk models using baseline covariates that are available on the women-level as well as WBI that are side-specific. Results: Preliminary analysis shows WBI predicts subsequent invasive breast cancer. Further, we will demonstrate appropriate models adjusting for competing risk gives unbiased estimates of invasive breast cancer. Conclusion: WBI and competing risk analysis improves our understanding of associations for side of occurrence of subsequent breast lesions after an initial diagnosis of DCIS.

Citation Format: Shu (Joy) Jiang, Graham A. Colditz. Improving prediction of second events after DCIS using whole breast mammogram images [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr B014.