bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of diverse cicer milkvetch (Astragalus cicer L.) germplasm for agro-morphological traits under a stockpiling system
Authors: MacTaggart D.R. , Biligetu B. , Lardner H.A.
Published: March 2023

Cicer milkvetch ( Astragalus cicer L.) is a non-bloating perennial forage legume suitable for stockpiled grazing in the fall because of its rapid regrowth and high nutritive value. Genetically diverse germplasm are needed for the development of improved cicer milkvetch cultivars that can provide consistent production across variable climatic conditions. The objective of this research was to assess the diversity and relationship of 27 cicer milkvetch populations to inform the selection of populations for future cultivars that have superior agro-morphological traits during summer and fall growth. A completely randomized field trial was established in 2019 near Clavet, Saskatchewan. In 2020 and 2021, forage dry matter yield (DMY), maximum stem length, leaf number per stem, rhizome spread, and stem density were recorded on 27 populations of cicer milkvetch in late June at a first harvest and mid-October at a stockpile harvest. All five traits were different ( p < 0.05) among the populations at both harvests except for leaf number per stem in late June. Principal component analysis identified that the first three principal components described 89% of the variation in agro-morphological traits at the first and stockpile harvests. Of the agro-morphological traits, maximum stem length had the greatest correlation with forage DMY at the first harvest ( r = 0.69) and stockpile harvest ( r = 0.6). Our research demonstrates that there is a high morphological diversity among cicer milkvetch populations, and plant introductions, PI 362266, PI 576963, PI 440143, and PI 362254 could be used as novel genetic resources for the development of climate-resilient cultivars.
USING REDUNDANCY ANALYSIS TO EXPLAIN INTENTIONS TO PARTICIPATE IN INCUBATORS: A GENDER PERSPECTIVE
Authors: BURTON KRISTIN , ZAKARIA RIMI , WANG YEFENG
Published: March 2023

A key support mechanism for early-stage entrepreneurs is business incubator programs, which provide tailored assistance and a conducive work environment for new business development. However, incubators are not created equal in terms of their effectiveness and reach. Extant research on business incubation is also largely gender-neutral. In addition, a scholarly gap exists when it comes to our understanding of the cognitive, behavioral and socio-cultural barriers to incubation and entrepreneurship. This research contributes to filling this gap by designing a pre-experiential behavioral intention model rooted in social psychology theories to explain the entrepreneur’s intention to participate in incubation programs. A multidimensional construct of perception and its underlying dimensions (e.g., usefulness, ease of use and self-efficacy) is developed and tested. Studying 344 early-stage entrepreneurs, it is found that perceived utility and ease of use relate to the decision to join an incubation program. Furthermore, when female entrepreneurs are not convinced whether incubation programs are beneficial considering their use and access, they are less likely to join incubation. Our empirical results highlight the need for adopting behavioral interventions and inclusionary best practices to expand the effect of business incubation programs.
DOES RELIGIOSITY MATTER FOR NEW VENTURE CREATION AMONG GEN Y AND GEN Z IN INDONESIA?
Authors: SUTIKNO BAYU , HAMDI MUHAMMAD , INDARTI NURUL , MANIK HARDO FIRMANA GIVEN GRACE , LUKITO-BUDI ANDY SUSILO , ANGGADWITA GRISNA
Published: March 2023

This study provides empirical evidence of the role of religiosity in new venture creation and its additional moderating roles in individual entrepreneurial orientation and knowledge-sharing attitudes. It uses the lens of social cognitive and social capital theories by incorporating the generational cohort theory to explore Gen Y and Gen Z. This is a hypothetico-deductive study that employs a semi-structured survey of 84 Gen Y and 154 Gen Z respondents from Indonesia. The findings revealed that the effect of religiosity on venture creation was significantly negative for the Gen Y, and the two moderators played a significant role in the relationship between religiosity and venture creation only for the Gen Y. The findings of this study provide the new empirical discourse that even though the Gen Y and the Gen Z are considered digital natives, they have different religious views and behaviors notably when it comes to the decision to set up a new business. This study provides and opens new avenues for future research on this topic and highlights the urgency to explore the religious behavior of earlier generations towards venture creation.
Peer-to-Peer (P2P) Lending Risk Management: Assessing Credit Risk on Social Lending Platforms Using Textual Factors
Authors: Siering Michael
Published: March 2023

Peer-to-peer (P2P) lending platforms offer Internet users the possibility to borrow money from peers without the intervention of traditional financial institutions. Due to the anonymity on such social lending platforms, determining the creditworthiness of borrowers is of high importance. Beyond the disclosure of traditional financial variables that enable risk assessment, peer-to-peer lending platforms offer the opportunity to reveal additional information on the loan purpose. We investigate whether this self-disclosed information is used to show reliability and to outline creditworthiness of platform participants. We analyze more than 70,000 loans funded at a leading social lending platform. We show that linguistic and content-based factors help to explain a loan's probability of default and that content-based factors are more important than linguistic variables. Surprisingly, not every information provided by borrowers underlines creditworthiness. Instead, certain aspects rather indicate a higher probability of default. Our study provides important insights on information disclosure in the context of peer-to-peer lending, shows how to increase performance in credit scoring and is highly relevant for the stakeholders on social lending platforms.
DuCape: Dual Quaternion and Capsule Network–Based Temporal Knowledge Graph Embedding
Authors: Zhang Sensen , Liang Xun , Tang Hui , Zheng Xiangping , X. Zhang Alex , Ma Yuefeng
Published: March 2023

Recently, with the development of temporal knowledge graph technology, more and more Temporal Knowledge Graph Embedded (TKGE) models have been developed. The effectiveness of TKGE largely depends on the ability to model intrinsic relation patterns and capture specific information about entities and relations. However, existing approaches can capture only some of them with insufficient modeling capacity, and none has a “deep” architecture for modeling the entries in a quadruple at the same dimension. In this article, we propose a more powerful KGE framework named
DuCape
, which combines a dual quaternion and capsule network in modeling for the first time to make up for the defects of existing TKGE models. In dual quaternion vector space, the head entity learns a
k
-dimensional rigid transformation parametrized by relation and time, falling near its corresponding tail entity. Further, we employ the embeddings of entities, relations, and time trained from dual quaternion vector space as the input to capsule networks. Experimental results on several basic datasets show that the DuCape model constructed in this article is superior to existing state-of-the-art models.
Changes in Microstructure of Ni–Co Dispersed Samaria-Doped Ceria Hydrogen Electrodes for the Improved Durability via Reversible Cycling Operation of Solid Oxide Cells
Authors: Da’as Eman Husni , Nishino Hanako , Uchida Hiroyuki
Published: March 2023

We have quantitatively analyzed changes in the microstructure of double-layer hydrogen electrodes for solid oxide cells (SOCs), which consist of porous samaria-doped ceria (SDC) with highly dispersed Ni−Co nanoparticles as the catalyst layer (CL) and a thin current collecting layer of Ni‒YSZ cermet, whose durability we recently found to undergo a remarkable improvement via reversible cycling operation between steam electrolysis and fuel cell-modes. It was demonstrated by focused ion beam-scanning electron microscopy (FIB-SEM) that the Ni content in the CL was nearly fully maintained by the cycling operation, compared with a significant decrease in Ni after the electrolysis single-mode operation. The lower parts of many Ni‒Co particles were observed to be anchored tightly on the SDC support after the cycling operation, probably due to a strong interaction between Ni‒Co and SDC. Such a stabilization of the microstructure is proposed to contribute to the improved durability.
MK2 nonenzymatically promotes nuclear translocation of caspase-3 and resultant apoptosis
Authors: Del Rosario Othello , Suresh Karthik , Kallem Medha , Singh Gayatri , Shah Anika , Zheng Linda , Yun Xin , Philip Nicolas M. , Putcha Nirupama , McClure Marni B. , Jiang Haiyang , D’Alessio Franco , Srivastava Meera , Bera Alakesh , Shimoda Larissa A. , Merchant Michael , Rane Madhavi J. , Machamer Carolyn E. , Mock Jason , Hagan Robert , Koch Abigail L. , Punjabi Naresh M. , Kolb Todd M. , Damarla Mahendra
Published: March 2023

We have previously identified mitogen-activated protein kinase-activated protein kinase 2 (MK2) is required for caspase-3 nuclear translocation in the execution of apoptosis; however, little is known of the underlying mechanisms. Therefore, we sought to determine the role of kinase and nonkinase functions of MK2 in promoting nuclear translocation of caspase-3. We identified two non-small cell lung cancer cell lines for use in these experiments based on low MK2 expression. Wild-type, enzymatic and cellular localization mutant MK2 constructs were expressed using adenoviral infection. Cell death was evaluated by flow cytometry. In addition, cell lysates were harvested for protein analyses. Phosphorylation of caspase-3 was determined using two-dimensional gel electrophoresis followed by immunoblotting and in vitro kinase assay. Association between MK2 and caspase-3 was evaluated using proximity-based biotin ligation assays and co-immunoprecipitation. Overexpression of MK2 resulted in nuclear translocation of caspase-3 and caspase-3-mediated apoptosis. MK2 directly phosphorylates caspase-3; however, phosphorylation status of caspase-3 or MK2-dependent phosphorylation of caspase-3 did not alter caspase-3 activity. The enzymatic function of MK2 was dispensable in nuclear translocation of caspase-3. MK2 and caspase-3 associated together and a nonenzymatic function of MK2, chaperoned nuclear trafficking, is required for caspase-3-mediated apoptosis. Taken together, our results demonstrate a nonenzymatic role for MK2 in the nuclear translocation of caspase-3. Furthermore, MK2 may function as a molecular switch in regulating the transition between the cytosolic and nuclear functions of caspase-3.
Mosaic Loss of Y Chromosome in White Blood Cells: Its Impact on Men’s Health
Authors: Sano Soichi , Thel Mark C. , Walsh Kenneth
Published: March 2023

We present a brief introduction of loss of Y chromosome (LOY) in blood and describe the known risk factors for this condition. We then overview the associations between LOY and age-related disease traits. Finally, we discuss murine models and the potential mechanisms by which LOY contributes to disease.
Women’s Satisfaction with Abortion Care and Associated Factors in Public Health Facilities of Mojo Town, East Ethiopia
Authors: Oda Tola , Sento Midekso , Negera Atoma
Published: March 2023

Background. Client satisfaction is an important and commonly used indicator for measuring the quality of health care as it affects clinical outcomes, patient retention, and medical malpractice claims. To limit unintended pregnancies and avoid repeated abortions promoting abortion care services is crucial. In Ethiopia, problems related to abortion were neglected, and access to quality abortion care was very limited. Similarly, information related to abortion care service, particularly clients’ satisfaction, and associated factors are limited in the study area that the study will be going to fill. Methods. A facility-based cross-sectional study design was employed on 255 women who came for abortion service in public health facilities of Mojo town and were included consecutively. The data was coded and entered into Epi info version 7 software and exported to SPSS version 20 for analysis. Bivariable and multivariable logistic regression models were applied to identify the associated factors. Model fitness and multicollinearity were checked by using the Hosmer-Lemeshow goodness of fit test and the variance inflation factor (VIF). Adjusted odds ratios and their 95% confidence were reported. Results. A total of 255 study subjects were included in this study with a 100% response rate. The study depicted that 56.5% (95% CI: 51.3, 61.7 of the clients were satisfied with abortion care service. Having college and above educational level (AOR: 0.27; 95% CI: (0.14, 0.95), employee occupation (AOR: 1.86; 95% CI: (1.41, 2.93), medical abortion as a type of uterine evacuation (AOR: 3.93; 95% CI: (1.75, 8.83), and natural method of family planning users (AOR: 0.36; 95% CI: (0.08, 0.60) were factors associated with women’s satisfaction. Conclusion. The overall satisfaction towards abortion care was considerably lower. Waiting time, cleanness of rooms, lack of laboratory service, and availability of service providers are mentioned factors for client dissatisfaction.
Stochastic Optimal Selection and Analysis of Allowable Photovoltaic Penetration Level for Grid-Connected Systems Using a Hybrid NSGAII-MOPSO and Monte Carlo Method
Authors: Abubakar Ali , Borkor Reindorf Nartey , Amoako-Yirenkyi Peter
Published: March 2023

Generally, the main focus of the grid-linked photovoltaic systems is to scale up the photovoltaic penetration level to ensure full electricity consumption coverage. However, due to the stochasticity and nondispatchable nature of its generation, significant adverse impacts such as power overloading, voltage, harmonics, current, and frequency instabilities on the utility grid arise. These impacts vary in severity as a function of the degree of penetration level of the photovoltaic system. Thus, the design problem involves optimizing the two conflicting objectives in the presence of uncertainty without violating the grid’s operational limitations. Nevertheless, existing studies avoid the technical impact and scalarize the conflicting stochastic objectives into a single stochastic objective to lessen the degree of complexity of the problem. This study proposes a stochastic multiobjective methodology to decide on the optimum allowable photovoltaic penetration level for an electricity grid system at an optimum cost without violating the system’s operational constraints. Five cutting-edge multiobjective optimization algorithms were implemented and compared using hypervolume metric, execution time, and nonparametric statistical analysis to obtain a quality solution. The results indicated that a Hybrid NSGAII-MOPSO had better convergence, diversity, and execution time capacity to handle the complex problem. The analysis of the obtained optimal solution shows that a practical design methodology could accurately decide the maximum allowable photovoltaic penetration level to match up the energy demand of any grid-linked system at a minimum cost without collapsing the grid’s operational limitations even under fluctuating weather conditions. Comparatively, the stochastic approach enables the development of a more sustainable and affordable grid-connected system.
Correlation between CT Score and KL-6: A Severity Assessing in Juvenile Dermatomyositis Associated Interstitial Lung Disease
Authors: Wang Chi , Hou Jun , Lai Jianming , Tao Ran , Yang Yang , Hao Wenhan , Yuan Xinyu , Yan Yuchun
Published: March 2023

Background. There is no radiological measurement to estimate the severity of pediatrics juvenile dermatomyositis (JDM) with interstitial lung disease (ILD). We validated the effectiveness of CT scoring assessment in JDM patients with ILD. Aim. To establish a CT scoring system and calculate CT scores in JDM patients with ILD and to determine its reliability and the correlation with Krebs von den Lungen-6 (KL-6). Methods. The study totally enrolled 46 JDM-ILD patients and 16 JDM without ILD (non-ILD, NILD) patients. The chest CT images (7.0 ± 3.6 years; 32 male and 30 female) were all analyzed. CT scores of six lung zones were retrospectively calculated, included image pattern score and distribution range score. Image pattern score was defined as follows: increased broncho-vascular bundle (1 point); ground glass opacity (GGO) (2 points); consolidation (3 points); GGO with bronchiectasis (4 points); consolidation with bronchiectasis (5 points); and honeycomb lung (6 points). Distribution range score was defined as no infiltrate (0 point); <30% (1 point); 30%–60% (2 points); and ≥60% (3 points). Two pediatric radiologists reviewed all CT images independently. The ROC curve was established, and the optimal cutoff score for severity discrimination was set. Results. The agreement between two observers was excellent, and the ICC was 0.930 (95% CI 0.882–0.959,

p
<
0.01

). CT score and KL-6 level had a positive linear correlation (r = 0.784,

p
<
0.01

). However, the correlation between CT scores of different lung zone and KL-6 level was different. The KL-6 cut off level suggested for JDM with ILD was 209.0 U/ml, with 73.9% sensitivity and 87.5% specificity, and the area under curve was (AUC) 0.864 (

p
<
0.01

). Conclusion. The CT scoring system we established, as a semiquantitative method, can effectively evaluate ILD in JDM-PM patients and provide reliable evidence for treatment.
Improvement of

q

2

Resolution in Semileptonic Decays Based on Machine Learning
Authors: Ge Panting , Huang Xiaotao , Saur Miroslav , Sun Liang
Published: March 2023

The neutrino closure method is often used to obtain kinematics of semileptonic decays with one unreconstructed particle in hadron collider experiments. The kinematics of decays can be deducted by a twofold ambiguity with a quadratic equation. To resolve the twofold ambiguity, a novel method based on machine learning (ML) is proposed. We study the effect of different sets of features and regressors on the improvement of reconstructed invariant mass squared of

ℓ
ν

system (

q

2

). The result shows that the best performance is obtained by using the flight vector as the features and the multilayer perceptron (MLP) model as the regressor. Compared with the random choice, the MLP model improves the resolution of reconstructed

q

2

by ~40%. Furthermore, the possibility of using this method on various semileptonic decays is shown.
Unsupervised Domain Adaptation with Differentially Private Gradient Projection
Authors: Zheng Maobo , Zhang Xiaojian , Ma Xuebin
Published: March 2023

Domain adaptation is a viable solution for deep learning with small data. However, domain adaptation models trained on data with sensitive information may be a violation of personal privacy. In this article, we proposed a solution for unsupervised domain adaptation, called DP‐CUDA, which is based on differentially private gradient projection and contradistinguisher. Compared with the traditional domain adaptation process, DP‐CUDA involves searching for domain‐invariant features between the source domain and target domain first and then transferring knowledge. Specifically, the model is trained in the source domain by supervised learning from labeled data. During the training of the target model, feature learning is used to solve the classification task in an end‐to‐end manner using unlabeled data directly, and the differentially private noise is injected into the gradient. We conducted extensive experiments on a variety of benchmark datasets, including MNIST, USPS, SVHN, VisDA‐2017, Office‐31, and Amazon Review, to demonstrate our proposed method’s utility and privacy‐preserving properties.
The Relationship between Motor Symptoms, Signs, and Parkinsonism with Facial Emotion Recognition Deficits in Individuals with 22q11.2 Deletion Syndrome at High Genetic Risk for Psychosis
Authors: Accinni Tommaso , Fanella Martina , Frascarelli Marianna , Buzzanca Antonino , Kotzalidis Georgios D. , Putotto Carolina , Marino Bruno , Panzera Alessia , Moschillo Antonella , Pasquini Massimo , Biondi Massimo , Di Bonaventura Carlo , Di Fabio Fabio
Published: March 2023

Background. The 22q11.2 Deletion Syndrome (22q11.2DS) is a genetic condition at high risk of developing both psychosis and motor disorders. Social Cognition (SC) deficits have been associated not only with schizophrenia but also with Parkinson’s disease (PD). The present study assessed SC deficits in 22q11.2DS and investigated the interaction between motor symptoms and deficits in Facial Emotion Expressions (FEE) recognition and in Theory of Mind (ToM) tasks in people with 22q11.2DS. Methods. We recruited 38 individuals with 22q11.2DS without psychosis (

N
=
38

, DEL) and 18 with 22q11.2DS and psychosis (

N
=
18

, DEL_SCZ). The Positive And Negative Syndrome Scale (PANSS), Ekman’s 60 Faces Test (EK-60F), the Awareness of Social Inference Test (TASIT EmRec), and the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale part III (UPDRS III) were administered. Correlations were sought between UPDRS III and both TASIT EmRec and EK-60F scores. Analyses were conducted separately for each psychopathological subgroup. Results. Higher UPDRS III (

p
=
0.04

) and lower EK-60F (

p
=
0.025

) scores were observed in the DEL_SCZ group. We found inverse correlations between UPDRS III and both TASIT EmRec (

r
=
−
0.289

,

p
=
0.031

) and EK-60F (

r
=
−
0.387

,

p
=
0.006

) scores in the whole sample. Correlations were no longer significant in the DEL_SCZ group (UPDRS III-TASIT EmRec

p
=
0.629

; UPDRS III-EK60F

p
=
0.933

) whilst being stronger in the DEL group (TASIT EmRec,

r
=
−
0.560

,

p
<
0.001

; EK60F,

r
=
−
0.542

,

p
<
0.001

). Analyses were adjusted for CPZ Eq and IQ. Conclusions. A modulation between FEE recognition deficits and motor symptoms and signs was observed in the 22q11.2DS group, likely affecting patients’ quality of life.
Year-Round Experimental Analysis of the Productivity of Vapour-Based Multistage Solar Still: A Developmental Study
Authors: Mkhize Mfanafuthi Mthandeni , Msomi Velaphi
Published: March 2023

The standalone vapour-based multistage solar still with stacked stages (MSS-SS) belongs to a pool of widely studied small-scale water desalination devices through solar thermal energy. This work contributes to the body of knowledge by presenting a system with new configurations. There is a need to develop small-scale systems to be reliable devices for freshwater provision, as brackish water is available for processing. The experimental study was conducted in a field under actual weather conditions, with the data logged and analysed to study the systems’ behaviour under varying meteorological conditions. A maximum distillate yield of 7790 ml, corresponded to a maximum daily average solar radiation at high range. There was a 21.8% decrease to 6090 ml at moderate daily average range and a further decline of 80.5% to 1190 ml in the low daily average range, representing a significant drop in the distillate yield caused by the insufficient heat collection at low range. The high, moderate, and low ranges corresponded to summer, spring and autumn, and winter, respectively. The lower values of the moderate range were the most optimum operationally. The impulsive modes were ideal for high rates of the heat inputs, while the continuous were for low rates. The assumption of a continuous mode and a further increase in the rate of thermal energy input caused thermal damage necessitating the augmentation of the thermal energy storage (TES) device due to a larger collector-to-basin area (CBA) ratio. The distillate yield trends from the stages were dynamic and were the inverse of the stage temperature, which was dictated by the mode and rate of the thermal energy input. These trends were such that stage 5 > 3 > 2 > 1 > 4 at moderate to high ranges and changed a low range. The summer season enhanced the cumulative saline water (SW) preheating and heat recovery to 66.8°C. The economic analysis found that at its most productive level, the cost of producing water per litre (CPL) from the vapour-based MSS-SS was R 4.05. The small-scale water purification systems are helpful, especially in remote areas.
Potential Targets and Mechanisms of Jiedu Quyu Ziyin Decoction for Treating SLE-GIOP: Based on Network Pharmacology and Molecular Docking
Authors: Li Jie , Chang Run-yu , Chen Lin-feng , Qian Su-hai , Wang Rong-yun , Lan Ji-le , Huang Lin , Ding Xing-hong
Published: March 2023

Background. Systemic lupus erythematosus (SLE) is characterized by poor regulation of the immune response leading to chronic inflammation and multiple organ dysfunction. Glucocorticoid (GC) is currently one of the main treatments. However, a high dose or prolonged use of GC may result in glucocorticoid-induced osteoporosis (GIOP). Jiedu Quyu Ziyin decoction (JP) is effective in treating SLE and previous clinical studies have proved that JP can prevent and treat SLE steroid osteoporosis (SLE-GIOP). We aim to examine JPs main mechanism on SLE-GIOP through network pharmacology and molecular docking. Methods. TCMSP and TCMID databases were used to screen potential active compounds and targets of JP. The SLE-GIOP targets are collected from GeneCards, OMIM, PharmGkb, TTD, and DrugBank databases. R software was used to obtain the cross-targets of JP and SLE-GIOP and to perform GO and KEGG enrichment analysis. Cytoscape software was used to make the Chinese Medicines-Active Ingredient-Intersection Targets network diagram. STRING database construct protein–protein interaction network and obtain the core targets. Auto Dock Tools and Pymol software were used for docking. Results. Fifty eight targets overlapped between JP and SLE-GIOP were suggested as potential targets of JP in the treatment of SLE-GIOP. Network topology analysis identified five core targets. GO enrichment analysis was obtained 1,968 items, and the top 10 biological process, closeness centrality, and molecular function were displayed. A total of 154 signaling pathways were obtained by KEGG enrichment analysis, and the top 30 signaling pathways were displayed. JP was well bound by MAPK1, TP53, and MYC according to the molecular docking results. Conclusion. We investigated the potential targets and signaling pathways of JP against SLE-GIOP in this study. It shows that JP is most likely to achieve the purpose of treating SLE-GIOP by promoting the proliferation and differentiation of osteoblasts. A solid theoretical foundation will be provided for the future study of clinical and experimental topics.
Narrow Alveolar Ridge Management with Modified Ridge Splitting Technique: A Report of 3 Cases
Authors: Kim Heon-Young , Park Jung-Hyun , Kim Jin-Woo , Kim Sun-Jong
Published: March 2023

Purpose. In this study, we report the usefulness of implant placement with modified ridge splitting technique from three cases of patients with narrow alveolar ridge. Materials and Methods. Three patients were those who visited the Department of Oral and Maxillofacial Surgery of Ewha Medical Center for consultation regarding implant placement. Through clinical and radiographic evaluation, narrowed alveolar ridge after tooth loss was confirmed in all three patients. For them, it was necessary to use the modified ridge split technique with bone augmentation for the implant to be well placed with enough bone width. Results. In all cases, sufficient bone width was confirmed for implant placement, and bone volume was well maintained after prosthetic restoration without any complications. Initial width of alveolar bone was 4.9 mm on average and was well maintained at an average of 7.6  mm at 1-year follow-up after implant installation. Conclusion. Although the number of subjects in this case report was small and was done by only one surgeon, we suggest that modified ridge splitting technique might be a useful surgical method to enhance narrow edentulous alveolar ridges and enable successful implant placement with shorter healing period compared with single guided bone regeneration.
Somatic Mosaic Chromosomal Alterations and Death of Cardiovascular Disease Causes among Cancer Survivors
Authors: Sun Maxine , Cyr Marie-Christyne , Sandoval Johanna , Lemieux Perreault Louis-Philippe , Busque Lambert , Tardif Jean-Claude , Dubé Marie-Pierre
Published: March 2023

Background:

Cancer survivors are at an increased risk of cardiovascular disease (CVD) compared with the general population. We sought to evaluate the impact of mosaic chromosomal alterations (mCA) on death of CVD causes, coronary artery disease (CAD) causes, and of any cause in patients with a cancer diagnosis.

Methods:

The study was a prospective cohort analysis of 48,919 UK Biobank participants with a cancer diagnosis. mCAs were characterized using DNA genotyping array intensity data and long-range chromosomal phase inference. Multivariable Cox regression models were used to ascertain the associations of mCAs. Exploratory endpoints included various incident cardiovascular phenotypes.

Results:

Overall, 10,070 individuals (20.6%) carried ≥ 1 mCA clone. In adjusted analyses, mCA was associated with an increased risk of death of CAD causes [HR, 1.37; 95% confidence interval (CI), 1.09–1.71; P = 0.006]. In sub-analyses, we found that carriers of mCAs diagnosed with kidney cancer had an increased risk of death of CVD causes (HR, 2.03; 95% CI, 1.11–3.72; P = 0.022) and CAD causes (HR, 3.57; 95% CI, 1.44–8.84; P = 0.006). Women diagnosed with breast cancer who carried a mCA also had a higher risk of death of CAD causes (HR, 2.46; 95% CI, 1.23–4.92; P = 0.011).

Conclusions:

Among cancer survivors, carriers of any mCA are at an increased risk of CAD death compared with noncarriers. Mechanistic studies should be considered to better ascertain the biological mechanisms underneath the observed associations between mCAs and cardiovascular events for specific cancer types.

Impact:

There may be clinical relevance in considering mCAs in patients diagnosed with cancer and undergoing treatment.
Supplementary Table S5 from A Multipronged Unbiased Strategy Guides the Development of an Anti-EGFR/EPHA2–Bispecific Antibody for Combination Cancer Therapy
Authors: El Zawily Amr , Vizeacoumar Frederick S. , Dahiya Renuka , Banerjee Sara L. , Bhanumathy Kalpana K. , Elhasasna Hussain , Hanover Glinton , Sharpe Jessica C. , Sanchez Malkon G. , Greidanus Paul , Stacey R. Greg , Moon Kyung-Mee , Alexandrov Ilya , Himanen Juha P. , Nikolov Dimitar B. , Fonge Humphrey , White Aaron P. , Foster Leonard J. , Wang Bingcheng , Toosi Behzad M. , Bisson Nicolas , Mirzabekov Tajib A. , Vizeacoumar Franco J. , Freywald Andrew
Published: March 2023

Table S5: GO analysis of the shRNA screen in αEPHA2-Cond cells.
Supplementary Table S2 from A Multipronged Unbiased Strategy Guides the Development of an Anti-EGFR/EPHA2–Bispecific Antibody for Combination Cancer Therapy
Authors: El Zawily Amr , Vizeacoumar Frederick S. , Dahiya Renuka , Banerjee Sara L. , Bhanumathy Kalpana K. , Elhasasna Hussain , Hanover Glinton , Sharpe Jessica C. , Sanchez Malkon G. , Greidanus Paul , Stacey R. Greg , Moon Kyung-Mee , Alexandrov Ilya , Himanen Juha P. , Nikolov Dimitar B. , Fonge Humphrey , White Aaron P. , Foster Leonard J. , Wang Bingcheng , Toosi Behzad M. , Bisson Nicolas , Mirzabekov Tajib A. , Vizeacoumar Franco J. , Freywald Andrew
Published: March 2023

Table S2: Protein phosphorylation events distinct in αEPHA2-Cond and cIgG-Tr cells.
Supplementary Table S1 from A Multipronged Unbiased Strategy Guides the Development of an Anti-EGFR/EPHA2–Bispecific Antibody for Combination Cancer Therapy
Authors: El Zawily Amr , Vizeacoumar Frederick S. , Dahiya Renuka , Banerjee Sara L. , Bhanumathy Kalpana K. , Elhasasna Hussain , Hanover Glinton , Sharpe Jessica C. , Sanchez Malkon G. , Greidanus Paul , Stacey R. Greg , Moon Kyung-Mee , Alexandrov Ilya , Himanen Juha P. , Nikolov Dimitar B. , Fonge Humphrey , White Aaron P. , Foster Leonard J. , Wang Bingcheng , Toosi Behzad M. , Bisson Nicolas , Mirzabekov Tajib A. , Vizeacoumar Franco J. , Freywald Andrew
Published: March 2023

Table S1: Phosphorylated proteins expressed differently in αEPHA2-Cond and cIgG-Tr cells.
Supplementary Table S2 from Durvalumab plus Cetuximab in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: An Open-label, Nonrandomized, Phase II Clinical Trial
Authors: Gulati Shuchi , Crist McKenzie , Riaz Muhammed Kashif , Takiar Vinita , Lehn Maria , Monroe Ilaina , Palackdharry Sarah , Kurtzweil Nicky , Jandarov Roman , Harun Nusrat , Wise-Draper Trisha M.
Published: March 2023

All treatment-related adverse events on trial
Supplementary Figure S6 from Durvalumab plus Cetuximab in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: An Open-label, Nonrandomized, Phase II Clinical Trial
Authors: Gulati Shuchi , Crist McKenzie , Riaz Muhammed Kashif , Takiar Vinita , Lehn Maria , Monroe Ilaina , Palackdharry Sarah , Kurtzweil Nicky , Jandarov Roman , Harun Nusrat , Wise-Draper Trisha M.
Published: March 2023

Supplementary Figure 6. Comparison of outcomes between patients that were p16 positive vs. negative A) Progression-free survival and B) Overall survival comparison
Data from Tumor Mutational Burden as a Predictor of Survival with Durvalumab and/or Tremelimumab Treatment in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Authors: Wildsmith Sophie , Li Weimin , Wu Song , Stewart Ross , Morsli Nassim , Raja Rajiv , Zhang Qu , Ye Jiabu , He Philip , Shetty Jagdish , Yovine Alejandro , Holoweckyj Nicholas , Real Katia , Walker Jill , Wrona Magdalena , de los Reyes Melissa , Barker Craig , Whiteley Jessica , Haddad Robert , Licitra Lisa , Ferris Robert , Fayette Jérôme , Zandberg Dan P. , Siu Lillian L. , Mesía Ricard
Published: March 2023

AbstractPurpose:
Biomarkers that predict response to immune checkpoint inhibitors (ICI) in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) are needed. This retrospective study assessed tumor mutational burden (TMB) and outcomes in the phase II HAWK and CONDOR and phase III EAGLE studies of durvalumab with or without tremelimumab in platinum-resistant R/M HNSCC.
Patients and Methods:
Tumor samples from HAWK/CONDOR (N = 153) and blood samples from EAGLE (N = 247) were analyzed for TMB. Associations with survival were evaluated for tissue TMB (tTMB) at cutoffs from 10 to 20 mutations/megabase (mut/Mb) and for blood plasma TMB (bTMB) at cutoffs from 8 to 24 mut/Mb.
Results:
In HAWK/CONDOR, overall survival (OS) with durvalumab with or without tremelimumab was longer for high versus low tTMB: statistically significant differences were observed with durvalumab plus tremelimumab at tTMB ≥ 10 mut/Mb [HR, 0.52 (95% confidence interval, CI, 0.28–0.98)] and tTMB ≥ 12 mut/Mb [HR, 0.46 (95% CI, 0.24–0.86)]. In EAGLE, a significant OS benefit versus chemotherapy was observed with durvalumab and durvalumab plus tremelimumab at bTMB≥16 mut/Mb [HR, 0.39 (95% CI, 0.20–0.76) and 0.38 (95% CI, 0.19–0.78), respectively] but not bTMB < 16 mut/Mb [HR, 0.92 (0.61–1.37) and 0.92 (95% CI, 0.62–1.36), respectively]. A significant progression-free survival benefit was also observed in the ICI arms versus chemotherapy at bTMB ≥ 16 mut/Mb.
Conclusions:
Findings support TMB as a biomarker for predicting survival in patients with platinum-resistant R/M HNSCC treated with ICIs. The analysis of EAGLE demonstrated that bTMB was predictive of survival with ICI treatment versus chemotherapy in a large, randomized controlled study population.
Data from A Multipronged Unbiased Strategy Guides the Development of an Anti-EGFR/EPHA2–Bispecific Antibody for Combination Cancer Therapy
Authors: El Zawily Amr , Vizeacoumar Frederick S. , Dahiya Renuka , Banerjee Sara L. , Bhanumathy Kalpana K. , Elhasasna Hussain , Hanover Glinton , Sharpe Jessica C. , Sanchez Malkon G. , Greidanus Paul , Stacey R. Greg , Moon Kyung-Mee , Alexandrov Ilya , Himanen Juha P. , Nikolov Dimitar B. , Fonge Humphrey , White Aaron P. , Foster Leonard J. , Wang Bingcheng , Toosi Behzad M. , Bisson Nicolas , Mirzabekov Tajib A. , Vizeacoumar Franco J. , Freywald Andrew
Published: March 2023

AbstractPurpose:
Accumulating analyses of pro-oncogenic molecular mechanisms triggered a rapid development of targeted cancer therapies. Although many of these treatments produce impressive initial responses, eventual resistance onset is practically unavoidable. One of the main approaches for preventing this refractory condition relies on the implementation of combination therapies. This includes dual-specificity reagents that affect both of their targets with a high level of selectivity. Unfortunately, selection of target combinations for these treatments is often confounded by limitations in our understanding of tumor biology. Here, we describe and validate a multipronged unbiased strategy for predicting optimal co-targets for bispecific therapeutics.
Experimental Design:
Our strategy integrates ex vivo genome-wide loss-of-function screening, BioID interactome profiling, and gene expression analysis of patient data to identify the best fit co-targets. Final validation of selected target combinations is done in tumorsphere cultures and xenograft models.
Results:
Integration of our experimental approaches unambiguously pointed toward EGFR and EPHA2 tyrosine kinase receptors as molecules of choice for co-targeting in multiple tumor types. Following this lead, we generated a human bispecific anti-EGFR/EPHA2 antibody that, as predicted, very effectively suppresses tumor growth compared with its prototype anti-EGFR therapeutic antibody, cetuximab.
Conclusions:
Our work not only presents a new bispecific antibody with a high potential for being developed into clinically relevant biologics, but more importantly, successfully validates a novel unbiased strategy for selecting biologically optimal target combinations. This is of a significant translational relevance, as such multifaceted unbiased approaches are likely to augment the development of effective combination therapies for cancer treatment.

See related commentary by Kumar, p. 2570
Supplementary Table S1 from Metabolomic, DNA Methylomic, and Transcriptomic Profiling of Suberoylanilide Hydroxamic Acid Effects on LPS-Exposed Lung Epithelial Cells
Authors: Chou Pochung Jordan , Sarwar Md Shahid , Wang Lujing , Wu Renyi , Li Shanyi , Hudlikar Rasika R. , Wang Yujue , Su Xiaoyang , Kong Ah-Ng
Published: March 2023

Supplementary Table S1 shows the primer sequences of the genes used in the qPCR assay.
Data from Metabolomic, DNA Methylomic, and Transcriptomic Profiling of Suberoylanilide Hydroxamic Acid Effects on LPS-Exposed Lung Epithelial Cells
Authors: Chou Pochung Jordan , Sarwar Md Shahid , Wang Lujing , Wu Renyi , Li Shanyi , Hudlikar Rasika R. , Wang Yujue , Su Xiaoyang , Kong Ah-Ng
Published: March 2023

Abstract
Suberoylanilide hydroxamic acid (SAHA) is a histone deacetylase (HDAC) inhibitor with anticancer effects via epigenetic and non-epigenetic mechanisms. The role of SAHA in metabolic rewiring and epigenomic reprogramming to inhibit pro-tumorigenic cascades in lung cancer remains unknown. In this study, we aimed to investigate the regulation of mitochondrial metabolism, DNA methylome reprogramming, and transcriptomic gene expression by SAHA in lipopolysaccharide (LPS)-induced inflammatory model of lung epithelial BEAS-2B cells. LC/MS was used for metabolomic analysis, while next-generation sequencing was done to study epigenetic changes. The metabolomic study reveals that SAHA treatment significantly regulated methionine, glutathione, and nicotinamide metabolism with alteration of the metabolite levels of methionine, S-adenosylmethionine, S-adenosylhomocysteine, glutathione, nicotinamide, 1-methylnicotinamide, and nicotinamide adenine dinucleotide in BEAS-2B cells. Epigenomic CpG methyl-seq shows SAHA revoked a list of differentially methylated regions in the promoter region of the genes, such as HDAC11, miR4509–1, and miR3191. Transcriptomic RNA sequencing (RNA-seq) reveals SAHA abrogated LPS-induced differentially expressed genes encoding proinflammatory cytokines, including interleukin 1α (IL1α), IL1β, IL2, IL6, IL24, and IL32. Integrative analysis of DNA methylome-RNA transcriptome displays a list of genes, of which CpG methylation correlated with changes in gene expression. qPCR validation of transcriptomic RNA-seq data shows that SAHA treatment significantly reduced the LPS-induced mRNA levels of IL1β, IL6, DNA methyltransferase 1 (DNMT1), and DNMT3A in BEAS-2B cells. Altogether, SAHA treatment alters the mitochondrial metabolism, epigenetic CpG methylation, and transcriptomic gene expression to inhibit LPS-induced inflammatory responses in lung epithelial cells, which may provide novel molecular targets to inhibit the inflammation component of lung carcinogenesis.
Prevention Relevance:
Inflammation increases the risk of lung cancer and blocking inflammation could reduce the incidence of lung cancer. Herein, we demonstrate that histone deacetylase inhibitor suberoylanilide hydroxamic acid regulates metabolic rewiring and epigenetic reprogramming to attenuate lipopolysaccharide-driven inflammation in lung epithelial cells.
Supplemental Figure S3. TMB distributions of different ancestries. from Probabilistic Mixture Models Improve Calibration of Panel-derived Tumor Mutational Burden in the Context of both Tumor-normal and Tumor-only Sequencing
Authors: Anaya Jordan , Sidhom John-William , Cummings Craig A. , Baras Alexander S.
Published: March 2023

Tumor-normal TMB distributions for panel and exome.
Figure S5 from Systemic LRG1 expression in melanoma is associated with disease progression and recurrence
Authors: Hoefsmit Esmee P. , Völlmy Franziska , Rozeman Elisa A. , Reijers Irene L. M. , Versluis Judith M. , Hoekman Liesbeth , van Akkooi Alexander C. J. , Long Georgina V. , Schadendorf Dirk , Dummer Reinhard , Altelaar Maarten , Blank Christian U.
Published: March 2023

Figure S5 shows that complement factor B (CFB), component 7 (C7) and alpha-1B-glycoportein (A1BG) expression are increased upon melanoma progression and recurrence.
Figure S3 from Systemic LRG1 expression in melanoma is associated with disease progression and recurrence
Authors: Hoefsmit Esmee P. , Völlmy Franziska , Rozeman Elisa A. , Reijers Irene L. M. , Versluis Judith M. , Hoekman Liesbeth , van Akkooi Alexander C. J. , Long Georgina V. , Schadendorf Dirk , Dummer Reinhard , Altelaar Maarten , Blank Christian U.
Published: March 2023

Figure S3 shows that SAA1, CRP and LDHB are associated with melanoma disease progression.
Data from Systemic LRG1 Expression in Melanoma is Associated with Disease Progression and Recurrence
Authors: Hoefsmit Esmee P. , Völlmy Franziska , Rozeman Elisa A. , Reijers Irene L.M. , Versluis Judith M. , Hoekman Liesbeth , van Akkooi Alexander C.J. , Long Georgina V. , Schadendorf Dirk , Dummer Reinhard , Altelaar Maarten , Blank Christian U.
Published: March 2023

The response rates upon neoadjuvant immune checkpoint blockade (ICB) in stage III melanoma are higher as compared with stage IV disease. Given that successful ICB depends on systemic immune response, we hypothesized that systemic immune suppression might be a mechanism responsible for lower response rates in late-stage disease, and also potentially with disease recurrence in early-stage disease. Plasma and serum samples of cohorts of patients with melanoma were analyzed for circulating proteins using mass spectrometry proteomic profiling and Olink proteomic assay. A cohort of paired samples of patients with stage III that progressed to stage IV disease (n = 64) was used to identify markers associated with higher tumor burden. Baseline patient samples from the OpACIN-neo study (n = 83) and PRADO study (n = 49; NCT02977052) were used as two independent cohorts to analyze whether the potential identified markers are also associated with disease recurrence after neoadjuvant ICB therapy. When comparing baseline proteins overlapping between patients with progressive disease and patients with recurrent disease, we found leucine-rich alpha-2-glycoprotein 1 (LRG1) to be associated with worse prognosis. Especially nonresponder patients to neoadjuvant ICB (OpACIN-neo) with high LRG1 expression had a poor outcome with an estimated 36-month event-free survival of 14% as compared with 83% for nonresponders with a low LRG1 expression (P = 0.014). This finding was validated in an independent cohort (P = 0.0021). LRG1 can be used as a biomarker to identify patients with high risk for disease progression and recurrence, and might be a target to be combined with neoadjuvant ICB.
Significance:
LRG1 could serve as a potential target and as a biomarker to identify patients with high risk for disease recurrence, and consequently benefit from additional therapies and intensive follow-up.
Survival Trends in Sorafenib for Advanced Hepatocellular Carcinoma: A Reconstructed Individual Patient Data Meta-Analysis of Randomized Trials
Authors: Tan Darren Jun Hao , Tang Ansel Shao Pin , Lim Wen Hui , Ng Cheng Han , Nah Benjamin , Fu Clarissa , Xiao Jieling , Koh Benjamin , Tay Phoebe Wen Lin , Tan Eunice X , Teng Margaret , Syn Nicholas , Muthiah Mark D , Tamaki Nobuharu , Lee Sung Won , Kim Beom Kyung , Yau Thomas , Vogel Arndt , Loomba Rohit , Huang Daniel Q.
Published: March 2023

Background: Emerging data suggest that outcomes for advanced hepatocellular carcinoma (HCC) treated with sorafenib may have improved over time. We aimed to provide robust, time-to-event estimates of survival outcomes for sorafenib in advanced HCC. Summary: In this systematic review and individual patient data meta-analysis of randomized-controlled trials (RCTs), we searched MEDLINE and Embase from inception till September 2022 for RCTs that provided data for overall survival (OS) and progression-free survival (PFS) for sorafenib monotherapy as first-line systemic therapy for advanced HCC. We performed a pooled analysis using reconstructed individual participant data from published Kaplan-Meier curves to obtain robust estimates for OS and PFS. Of 1,599 articles identified, 29 studies (5,525 patients) met the inclusion criteria. Overall, the median OS was 10.4 (95% CI: 9.6–11.4) months. Median OS increased over time, from 9.8 (95% CI: 8.8–10.7) months in studies before 2015 to 13.4 (95% CI: 11.03–15.24) months in studies from 2015 onwards (p < 0.001). OS did not differ by trial phase, geographical region, or study design. The overall median PFS was 4.4 (95% CI: 3.9–4.8) months, but PFS did not improve over time. Sensitivity analysis of studies from 2015 and onwards to account for the introduction of direct-acting antivirals determined that hepatitis C virus was associated with reduced mortality (p < 0.001). There was minimal heterogeneity in the estimates for OS (all I2 ≤ 33). Key Messages: Survival outcomes for sorafenib in advanced HCC have improved over time. These data have important implications for clinical trial design.