bluuebunny/crossref_metadata_2025 huggingface dataset:
Canine squamous cell carcinoma: Electrochemotherapy association with surgery and correlation with overall survival
Authors: de Castro Cunha Rúbia Monteiro , Lavalle Gleidice Eunice , Nunes Fernanda Camargo , de Oliveira Ayisa Rodrigues , de Lima Santos Renato , de Araújo Roberto Baracat
Published: February 2023

Squamous cell carcinoma (SCC) is an important malignancy in dogs, due to its incidence and clinical presentation, which can be of locally aggressive single or multiple lesions with a metastatic potential. The objective of this investigation was to evaluate SCC response to treatment, anatomopathological and immunohistochemical characteristics, disease‐free interval and overall survival time. 54 dogs with histopathologically diagnosed SCC were included in this study. Their mean age was 9.16 years with a range of 1–14 years. Of the 54 animals in the study, 34 (65.4%) had white skin and white fur coats. There was a significant correlation between fur coat colour and the development of tumours in areas of sun exposure (p = .001). Animals with tumours in areas of the body exposed to the sun had longer overall survival time than animals with tumours in areas not associated with sun exposure (p = .001). Surgery combined with electrochemotherapy (ECT) yielded a survival rate 32% higher than using a surgical approach alone (HR = 0.32,p = .038, IC = 0.11–0.94). ECT, with or without surgery, had an objective response rate of 90.9%. Local lymph node and/or distant site metastasis at diagnosis, or at some point during follow‐up, occurred in 34.6% (18/52) of animals. Animals with tumours in sun exposed locations had more aggressive histopathological characteristics but had longer overall survival time. This is probably due to individualised therapeutic treatment with both surgery and ECT.
Potential determinants of low circulating glucagon‐like peptide 2 concentrations in Zambian children with non‐responsive stunting
Authors: Besa Ellen , Tembo Mizinga Jacqueline , Mulenga Chola , Mweetwa Monica , Choudhry Naheed , Chandwe Kanta , Storer Chad , Head Richard , Amadi Beatrice , Haritunians Talin , McGovern Dermot , Kwenda Geoffrey , Peiris Madusha , Kelly Paul
Published: February 2023

Nutrient sensing determines digestive and hormonal responses following nutrient ingestion. We have previously reported decreased levels of glucagon‐like peptide 2 (GLP‐2) in children with stunting. Here we demonstrate the presence of enteroendocrine cells in stunted children and explore potential pathways that may be involved in reduced circulating levels of GLP‐2. At the time of performing diagnostic endoscopies for non‐responsive stunted children, intestinal biopsies were collected for immunofluorescence staining of enteroendocrine cells and transcriptomic analysis. Circulating levels of GLP‐2 were also measured and correlated with transcriptomic data. An exploratory genome‐wide association study (GWAS) was conducted on DNA samples (n = 158) to assess genetic contribution to GLP‐2 variability. Intestinal tissue sections collected from non‐responsive stunted children stained positive for chromogranin A (88/89), alongside G‐protein‐coupled receptors G‐protein receptor 119 (75/87), free fatty acid receptor 3 (76/89) and taste 1 receptor 1 (39/45). Transcriptomic analysis found three pathways correlated with circulating GLP‐2: sugar metabolism, epithelial transport, and barrier function, which likely reflect downstream events following receptor–ligand interaction. GWAS analysis revealed potential genetic contributions to GLP‐2 half‐life and receptor binding. Enteroendocrine cell loss was not identified in stunted Zambian children as has been observed for goblet and Paneth cells. Transcriptomic analysis suggests that GLP‐2 has pleiotrophic actions on the intestinal mucosa in malnutrition, but further work is needed to dissect pathways leading to perturbations in nutrient sensing.
Evaluation of Heat Flux Distribution on Flat Plate Compound Parabolic Concentrator With Different Geometric Indices
Authors: Shanmugam Mathiyazhagan , Maganti Lakshmi Sirisha
Published: February 2023

The Compound Parabolic Concentrator (CPC), when coupled with the photovoltaic system, namely the Concentrated Photovoltaic Thermal System (CPVT), makes utilizing solar energy efficient. The major challenge that hinders the electrical and thermal performance of the CPC–CPVT system is the non-uniform heat flux distribution on the absorber surface. In the present paper, detailed ray-tracing simulations have been carried out to understand the heat flux distribution characteristics of CPC with different geometrical conditions, and those are concentration ratio, truncation ratio, incident angle, and average heat flux on the absorber surface. To have a thorough understanding, the analysis has been carried out in multiple steps. First, it is performed by analyzing the effect of concentration ratio and incident angle on heat flux distribution characteristics at a fixed truncation ratio. Second, investigations have been carried out to understand the heat flux distribution characteristics at different truncation ratios and different incident angles by keeping the concentration ratio constant. Local concentration ratio and non-uniformity index have been employed to quantify the non-uniformity of heat flux distribution on the absorber surface. It has been observed that the 0-deg incidence angle is the most effective angle to achieve uniform heat flux distribution on the absorber surface. This paper sheds insight into the heat flux distribution characteristics on the absorber surface of a CPC–CPVT system which can be used by the research community for designing an effective CPVT system from the perspective of uniform heat flux distribution on the absorber surface.
U.S. Physical Activity Para Report Card for Children and Adolescents With Disabilities
Authors: Stanish Heidi , Ross Samantha M. , Lai Byron , Haegele Justin A. , Yun Joonkoo , Healy Sean
Published: February 2023

The U.S. Report Card on Physical Activity for Children and Youth has tracked 10 physical activity (PA) indicators common to the Active Healthy Kids Global Matrix since 2014. This article expands on the U.S. report cards by presenting PA indicator assessments among children and adolescents with disabilities. Grades for indicators were assigned based on a search of peer-reviewed articles presenting nationally representative data. The Global Matrix 3.0 benchmarks and grading framework guided the process. Grades for overall PA, sedentary behaviors, organized sports, and school were F, D+, D+, and D, respectively. Insufficient evidence existed to assign grades to the remaining six indicators. There is a need in the United States for targeted PA promotion strategies that are specific to children and adolescents with disabilities. Without a commitment to this effort across sectors and settings, the low grades identified in this para report card are expected to remain.
Factors Associated With Physical Activity in Hospitalized Patients With Dementia
Authors: Drazich Brittany F. , Resnick Barbara , Boltz Marie , Galik Elizabeth , Kim Nayeon , McPherson Rachel , Ellis Jeanette , Phun Jasmine , Kuzmik Ashley
Published: February 2023

Older adults continue to spend little time engaged in physical activity when hospitalized. The purpose of this study was to (a) describe activity among hospitalized older adults with dementia and (b) identify the association between specific factors (gender, ambulation independence, comorbidities, race, and hospital setting) and their physical activity. This descriptive study utilized baseline data on the first 79 participants from the Function Focused Care for Acute Care using the Evidence Integration Triangle. Multiple linear regression models were run using accelerometry data from the first full day of hospitalization. The participants spent an average of 83.7% of their time being sedentary. Male gender, ambulation independence, and hospital setting (the hospital in which the patient was admitted) were associated with greater activity. This study reports on the limited time spent in activity for older adults with dementia when hospitalized and highlights patient profiles that are particularly vulnerable to sedentary behavior in the hospital setting.
Barriers, Facilitators, and Sustainers in Tai Ji Quan Practice: A Mixed-Methods RE-AIM Assessment of College Students Versus the General Population
Authors: Chen Sida , Tai Zixue , Liu Jianping
Published: February 2023

Background: Tai Ji Quan (TJQ) has broad appeal to people of all ages and backgrounds. This study aimed to examine a variety of individual and environmental factors in the dissemination of TJQ to diverse practicing communities in China. Methods: A mixed-methods approach was utilized in the research design. Quantitative data were collected via an online survey using a national sample (N = 737), whereas qualitative data came from focus groups and in-depth interviews. Analysis was performed along the RE-AIM dimensions of reach, efficacy, adoption, implementation, and maintenance. Results: We divided TJQ experience into 4 distinct categories (nonlearners, current learners, quitters, and retainers) and observed significant patterns of variation along lines of occupation groups and age cohorts. A significant male/female difference was detected in TJQ experience among college students but not the general public, and having practicing family members was an important predictor of personal TJQ history. Varied TJQ experience has a significant impact on perceptions of TJQ’s miscellaneous values as well as level of satisfaction with its health outcomes. Conclusions: Both individual (personal) and environmental (settings) factors are important in shaping personal decisions in TJQ engagement. An ecological approach coordinating individual factors and settings resources is essential in promoting TJQ to the general population.
Physical Activity and Its Association With Body Mass Index: A Cross-Sectional Analysis in Middle-Aged Adults From 4 Sub-Saharan African Countries
Authors: Muti Monica , Ware Lisa J. , Micklesfield Lisa K. , Ramsay Michele , Agongo Godfred , Boua Palwende R. , Kisiangani Isaac , Cook Ian , Gómez-Olivé Francesc Xavier , Crowther Nigel J. , Kabudula Chodziwadziwa , Norris Shane A. , Chikowore Tinashe
Published: February 2023

Background: This study aimed to explore association of self-reported physical activity domains of work, leisure, and transport-related physical activity and body mass index (BMI) in 9388 adult men and women from the Africa-Wits-INDEPTH partnership for Genomic (AWI-Gen) study in Africa. Africa-Wits-INDEPTH partnership for Genomic is a large, population-based cross-sectional cohort with participants from 6 sites from rural and urban areas in 4 sub-Saharan African countries. Methods: A sex-stratified meta-analysis of cross-sectional data from men and women aged 29–82 years was used to assess the association of physical activity with BMI. Results: Overall, meeting physical activity guidelines of at least 150 minutes per week was associated with 0.82 kg/m2 lower BMI in men (β = −0.80 kg/m2; 95% confidence interval [CI], −1.14 to −0.47) and 0.68 kg/m2 lower BMI in women (β = −0.68 kg/m2; 95% CI, −1.03 to −0.33). Sex and site-specific differences were observed in the associations between physical activity domains and BMI. Among those who met physical activity guidelines, there was an inverse association between transport-related physical activity and BMI in men from Nanoro (Burkina Faso) (β = −0.79 kg/m2; 95% CI, −1.25 to −0.33) as well as work-related physical activity and BMI in Navrongo men (Ghana) (β = −0.76 kg/m2; 95% CI, −1.25 to −0.27) and Nanoro women (β = −0.90 kg/m2; 95% CI, −1.44 to −0.36). Conclusions: Physical activity may be an effective strategy to curb rising obesity in Africa. More studies are needed to assess the impact of sex and geographic location-specific physical activity interventions on obesity.
Using
Entamoeba muris
To Model Fecal-Oral Transmission of
Entamoeba
in Mice
Authors: Mendoza Cavazos Carolina , Heredia Marienela Y. , Owens Leah A. , Knoll Laura J.
Published: February 2023

Infection with parasites from the
Entamoeba
genus are significantly underreported causes of diarrheal disease that disproportionally impact tropical regions. There are several species of
Entamoeba
that infect humans to cause a range of symptoms from asymptomatic colonization of the intestinal tract to invasive disease with dissemination.
Apoptosis or Antiapoptosis? Interrupted Regulated Cell Death of Host Cells by Ascovirus Infection
In Vitro
Authors: Yu Huan , Li Jin-Rong , Xiao Hua-Yan , Cao Sheng-Kai , Chen Bin , Li Ni , Chen Gong , Huang Guo-Hua
Published: February 2023

Clarifying the relationship between different types of viral infections and host regulation of cell death (RCD) can provide insights into the interaction between viruses and host cells. Ascoviruses are insect-specific viruses with apoptosis-utilizing-like infection cytopathology.
Plant-Pathogenic
Ralstonia
Phylotypes Evolved Divergent Respiratory Strategies and Behaviors To Thrive in Xylem
Authors: Truchon Alicia N. , Dalsing Beth L. , Khokhani Devanshi , MacIntyre April , McDonald Bradon R. , Ailloud Florent , Klassen Jonathan , Gonzalez-Orta Enid T. , Currie Cameron , Prior Philippe , Lowe-Power Tiffany M. , Allen Caitilyn
Published: February 2023

Plant-pathogenic
Ralstonia
spp. are a heterogeneous globally distributed group of bacteria that colonize plant xylem vessels.
Ralstonia
cells multiply rapidly in plants and obstruct water transport, causing fatal wilting and serious economic losses of many key food security crops. The virulence of these pathogens depends on their ability to grow to high cell densities in the low-oxygen xylem environment.
Developing a Temperature-Inducible Transcriptional Rheostat in Neurospora crassa
Authors: Tabilo-Agurto Cyndi , Del Rio-Pinilla Verónica , Eltit-Villarroel Valeria , Goity Alejandra , Muñoz-Guzmán Felipe , Larrondo Luis F.
Published: February 2023

A timely and dynamic response to strong temperature fluctuations is paramount for organismal biology. At the same time, inducible promoters are a powerful tool for fungal biotechnological and synthetic biology endeavors.
Comparative Genomic Study of Streptococcus anginosus Reveals Distinct Group of Urinary Strains
Authors: Prasad Ananya , Ene Adriana , Jablonska Sandra , Du Jingjie , Wolfe Alan J. , Putonti Catherine
Published: February 2023

Whole-genome analysis of
S. anginosus
strains provides greater insight into the diversity of this species than from marker genes alone. Our investigation of 166 publicly available
S. anginosus
genomes via average nucleotide identity and core genome analysis revealed two phylogenomically distinct groups of this species, with one group almost exclusively consisting of isolates from the urinary tract.
Host-Erythrocytic Sphingosine-1-Phosphate Regulates
Plasmodium
Histone Deacetylase Activity and Exhibits Epigenetic Control over Cell Death and Differentiation
Authors: Sah Raj Kumar , Anand Sakshi , Dar Waseem , Jain Ravi , Kumari Geeta , Madan Evanka , Saini Monika , Gupta Aashima , Joshi Nishant , Hada Rahul Singh , Gupta Nutan , Pati Soumya , Singh Shailja
Published: February 2023

Sphingolipid is an 18-carbon amino-alcohol-containing lipid with a sphingosine backbone, which when phosphorylated by sphingosine kinase 1 (SphK-1), generates sphingosine-1-phosphate (S1P), an essential lipid signaling molecule. Dysregulation of S1P function has been observed in a variety of pathologies, including severe malaria.
Effects of Salinity on Assembly Characteristics and Function of Microbial Communities in the Phyllosphere and Rhizosphere of Salt-Tolerant
Avicennia marina
Mangrove Species
Authors: Yang Xiangxia , Dai Zhian , Yuan Rongwei , Guo Zhenhua , Xi Hanxiao , He Zhili , Wei Mi
Published: February 2023

Avicennia marina
is a pioneer salt-tolerant plant in coastal intertidal mangroves, an efficient blue carbon ecosystem. It is of great importance to explore how salinity affects the phyllosphere and rhizosphere microbial communities of
A. marina.
This study showed that the microbial communities in the phyllosphere and rhizosphere of
A. marina
had different constitutive properties, adaptive network interactions, and potential stress-promoting functions.
Management of Black Root Disease-Causing Fungus Fusarium solani CRP1 by Endophytic Bacillus siamensis CNE6 through Its Metabolites and Activation of Plant Defense Genes
Authors: Gorai Pralay Shankar , Ghosh Ranjan , Ghosh Suvranil , Samanta Smriti , Sen Animesh , Panja Suraj , Gond Surendra Kumar , Mandal Narayan Chandra
Published: February 2023

The present work was undertaken to explore an effective biocontrol agent against the destructive black root rot disease of chickpea. We have used an efficient bacterial endophyte, CNE6, which can colonize in the chickpea root system, produce secondary metabolites and enzymes to degrade pathogenic cellular integrity, inhibit pathogenic establishment by rupturing biofilm formation, and induce host immunity upon treatment.
Epoxidation of Olefins in the Presence of Molybdenum Catalysts based on Porous Aromatic Frameworks
Authors: Yarchak V. A. , Kulikov L. A. , Maximov A. L. , Karakhanov E. A.
Published: February 2023

A porous aromatic framework, namely PAF-30, was structurally modified by the introduction of complexing groups based on dipyridylamine, dipicolylamine, and acetylacetone. The materials synthesized in this manner were used as supports of molybdenum catalysts for epoxidation: PAF-30-dpa-Mo, PAF-30-dpcl-Mo, and PAF-30-AA-Mo. All the materials were examined by various analytic methods, such as IR spectroscopy, low-temperature nitrogen adsorption/desorption, X-ray photoelectron spectroscopy, elemental analysis, and transmission electron microscopy. The catalytic activity was tested in epoxidation of cyclohexene, 1-hexene, 1-octene, and styrene. The reusability of the catalysts was assessed using the case of cyclohexene epoxidation.
Exploring predictors and moderators of response to multimodal obesity treatment in children
Authors: Aman-Braaksma Simone , Croker Helen , Viner Russell M , Nicholls Dasha
Published: February 2023

Objective

The aim of this study was to determine whether specific psychological factors influence intervention effects for children with severe obesity in a clinical setting.

Design

Secondary analyses of data about attention deficit/hyperactivity disorder (ADHD) characteristics, body satisfaction, social and emotional functioning, and the primary outcome, change in body mass index (BMI), were available for 41 out of 72 children and their families randomised to family-based behavioural treatment over 6 months or waiting list control. Regression analyses, with an interaction term for treatment condition, were performed to explore baseline factors and moderators of outcome.

Results

Parents reporting their child’s emotional well-being as high and high maternal education significantly predicted less weight loss for the total sample, with no effect of ethnicity, age, sex or baseline BMI. Children’s social functioning was a significant moderator of treatment effect; children with high social function showed a decrease in BMI after 6 months of therapy (R2=0.08–0.13), whereas an increase in BMI was observed in children with high social function who waited for treatment. For children with poor social function, no treatment effect was observed—subjects lost weight in both conditions. No significant moderation effect was found for body (dis)satisfaction, emotional status, comorbid depression or ADHD, adjusting for baseline BMI, age, sex and ethnicity.

Conclusions

These preliminary findings suggest directions for development of tailored obesity programmes. Professionals engaged in treatment of childhood obesity should consider a child’s emotional and social functioning when considering group obesity intervention, as well as the risks of no intervention.
Collagen type XII is undetectable in keratoconus Bowman’s layer
Authors: Rigi Mohammed , Son Hyeck-Soo , Moon Loren , Matthaei Mario , Srikumaran Divya , Jun Albert S , Eberhart Charles G , Soiberman Uri S
Published: February 2023

Purpose

Corneal biomechanical failure is the hallmark of keratoconus (KC); however, the cause of this failure remains elusive. Collagen type XII (COL12A1), which localises to Bowman’s layer (BL), is thought to function in stress-bearing areas, such as BL. Given the putative protective role ofCOL12A1in biomechanical stability, this study aims to characteriseCOL12A1expression in all corneal layers involved in KC.

Methods

TaqMan quantitative PCR was performed on 31 corneal epithelium samples of progressive KC and myopic control eyes. Tissue microarrays were constructed using full-thickness corneas from 61 KC cases during keratoplasty and 18 non-KC autopsy eyes and stained with an antibody specific to COL12A1. Additionally,COL12A1was knocked out in vitro in immortalised HEK293 cells.

Results

COL12A1expression was reduced at transcript levels in KC epithelium compared with controls (ratio: 0.58, p<0.03). Immunohistochemical studies demonstrated that COL12A1 protein expression in BL was undetectable, with reduced expression in KC epithelium, basement membrane and stroma.

Conclusions

The apparent absence of COL12A1 in KC BL, together with the functional importance thatCOL12A1is thought to have in stress bearing areas, suggests thatCOL12A1may play a role in the pathogenesis of KC. Further studies are necessary to investigate the mechanisms that lead toCOL12A1dysregulation in KC.
Association of arterial stiffness and neuropathy in diabetes: a systematic review and meta-analysis
Authors: Beros Angela , Sluyter John , Scragg Robert Keith Rhodes
Published: February 2023

Evidence is still emerging on the relationships of arterial stiffness with cardiac autonomic neuropathy (CAN) and peripheral neuropathy (PN). To our knowledge no systematic reviews or meta-analyses of these associations have been published. The purpose of our review was to assess the association of arterial stiffness with each type of neuropathy. Medline and Embase were systematically searched for observational studies of arterial stiffness and neuropathy.

The systematic review of 60 studies (25 for CAN and 37 for PN), 59 including people with diabetes, showed arterial stiffness overall was higher in people with neuropathy than people without neuropathy. Forty-three studies were included in the meta-analysis. For CAN (19 studies), arterial stiffness was increased in people with neuropathy compared with without, as measured by pulse wave velocity (PWV) (mean difference: 1.32 m/s, 95% CI 0.82 to 1.81, p<0.00001), pulse pressure (PP) (mean difference: 6.25 mmHg, 95% CI 4.51 to 7.99, p<0.00001) or augmentation index (mean difference: 5.52%, 95% CI 3.46 to 7.58, p<0.0001). For PN (26 studies), arterial stiffness was increased in people with neuropathy compared with those without, as measured by PWV (mean difference: 1.22 m/s, 95% CI 0.87 to 1.58, p<0.00001) or PP (mean difference: 4.59 mmHg, 95% CI 2.96 to 6.22, p<0.00001). Only two cohort studies were located so the temporality of the association between arterial stiffness and neuropathy remains unclear. Increased arterial stiffness is associated with CAN and PN.

PROSPERO registration number: CRD42019129563.
Social deprivation does not impact on acute pancreatitis severity and mortality: a single-centre study
Authors: Lim Wei Boon , Robertson Francis P , Nayar Manu K , Sharp Linda , Nandhra Sandip , Pandanaboyana Sanjay
Published: February 2023

Background and aims

The incidence of acute pancreatitis (AP) is increasing in the UK. Patients with severe AP require a significant amount of resources to support them during their admission. The ability to predict which patients will develop multiorgan dysfunction remains poor leading to a delay in the identification of these patients and a window of opportunity for early intervention is missed. Social deprivation has been linked with increased mortality across surgical specialties. Its role in predicting mortality in patients with AP remains unclear but would allow high-risk patients to be identified early and to focus resources on high-risk populations.

Methods

A prospectively collected single-centre database was analysed. English Index of Multiple Deprivation (IMD) was calculated based on postcode. Patients were grouped according to their English IMD quintile. Outcomes measured included all-cause mortality, Intestive care unit (ITU) admission, overall length of stay (LOS) and local pancreatitis-specific complications.

Results

398 patients with AP between 2018 and 2021 were identified. There were significantly more patients with AP in Q1 (IMD 1–2) compared with Q5 (IMD 9–10) (156 vs 38, p<0.001). Patients who were resident in the most deprived areas were significantly younger (52.4 in Q1 vs 65.2 in Q5, p<0.001), and more often smokers (39.1% in Q1 vs 23.7% in Q5, p=0.044) with IHD (95.0% vs 92.1% in Q5, p<0.001). In multivariate modelling, there was no significance difference in pancreatitis-related complications, number of ITU visits, number of organs supported and overall, LOS by IMD quintile.

Conclusions

Although there was a significantly higher number of patients admitted to our unit with AP from the most socially deprived quintiles, there was no correlation between social economic deprivation and mortality following AP.
Does COVID-19 infection significantly affect liver transplantation? Results of liver transplantation in the COVID-19 era at a single, high-volume centre
Authors: Moradi Alimohammad , Hadizadeh Alireza , Ghiasvand Fereshte , Ahmadinejad Zahra , Toosi Mohsen Nasiri , Ghazi Samrand , Jafarian Ali , Ahmadi-Tafti Mohsen , Ayati Aryan
Published: February 2023

Background

Liver transplantation is a proven management method for end-stage cirrhosis and is estimated to have increased life expectancy by 15 years. The COVID-19 pandemic posed a challenge to patients who were candid for a solid-organ transplant. It has been suggested that the outcomes of liver transplants could be adversely affected by the infection, as immunosuppression makes liver transplant candidates more susceptible to adverse effects while predisposing them to higher thrombotic events.

Material and methods

In this retrospective study, the cases who received liver transplants from January 2018 to March 2022 were assessed regarding early postoperative mortality rate and hepatic artery thrombosis (HAT) with COVID-19 infection. This study included 614 cases, of which 48 patients were infected.

Results

This study shows that the early COVID-19-related early postoperative mortality rates substantially increased in the elective setting (OR: 2.697), but the results for the acute liver failure were insignificant. The average model for end-stage liver disease score increased significantly during the pandemic due to new regulations. Although mortality rates increased during the pandemic, the data for the vaccination period show that mortality rates have equalised with the prepandemic era. Meanwhile, COVID-19 infection is assumed to have increased HAT by 1.6 times in the elective setting.

Conclusion

This study shows that COVID-19 infection in an acute liver failure poses comparatively little risk; hence transplantation should be considered in such cases. Meanwhile, the hypercoagulative state induced by the infection predisposes this group of patients to higher HAT rates.
Phase 1 first-in-human study of dalutrafusp alfa, an anti–CD73-TGF-β-trap bifunctional antibody, in patients with advanced solid tumors
Authors: Tolcher Anthony W , Gordon Michael , Mahoney Kathleen M , Seto Anna , Zavodovskaya Marianna , Hsueh Chia-Hsiang , Zhai Shuyan , Tarnowski Thomas , Jürgensmeier Juliane M , Stinson Susanna , Othman Ahmed A , Chen Tianling , Strauss James
Published: February 2023

Background

Cluster of differentiation (CD)73-adenosine and transforming growth factor (TGF)-β pathways are involved in abrogated antitumor immune responses and can lead to protumor conditions. This Phase 1 study (NCT03954704) evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of dalutrafusp alfa (also known as GS-1423 and AGEN1423), a bifunctional, humanized, aglycosylated immunoglobulin G1 kappa antibody that selectively inhibits CD73-adenosine production and neutralizes active TGF-β signaling in patients with advanced solid tumors.

Methods

Dose escalation started with an accelerated titration followed by a 3+3 design. Patients received dalutrafusp alfa (0.3, 1, 3, 10, 20, 30, or 45 mg/kg) intravenously every 2 weeks (Q2W) up to 1 year or until progressive disease (PD) or unacceptable toxicity.

Results

In total, 21/22 patients received at least one dose of dalutrafusp alfa. The median number of dalutrafusp alfa doses administered was 3 (range 1–14). All patients had at least one adverse event (AE), most commonly fatigue (47.6%), nausea (33.3%), diarrhea (28.6%), and vomiting (28.6%). Nine (42.9%) patients had a Grade 3 or 4 AE; two had Grade 5 AEs of pulmonary embolism and PD, both unrelated to dalutrafusp alfa. Target-mediated drug disposition appears to be saturated at dalutrafusp alfa doses above 20 mg/kg. Complete CD73 target occupancy on B cells and CD8+ T cells was observed, and TGF-β 1/2/3 levels were undetectable at dalutrafusp alfa doses of 20 mg/kg and higher. Free soluble (s)CD73 levels and sCD73 activity increased with dalutrafusp alfa treatment. Seventeen patients reached the first response assessment, with complete response, partial response, stable disease, and PD in 0, 1 (4.8%), 7 (33.3%), and 9 (42.9%) patients, respectively.

Conclusions

Dalutrafusp alfa doses up to 45 mg/kg Q2W were well tolerated in patients with advanced solid tumors. Additional evaluation of dalutrafusp alfa could further elucidate the clinical utility of targeting CD73-adenosine and TGF-β pathways in oncology.
Progression from suspected to definite systemic sclerosis and the role of anti-topoisomerase I antibodies
Authors: Liem Sophie I E , Neppelenbroek Sam , Fehres Cynthia M , Wevers Brigitte A , Toes René E M , Allaart Cornelia F , Huizinga Tom W J , Scherer Hans Ulrich , De Vries-Bouwstra Jeska K
Published: February 2023

Introduction

Early diagnosis of systemic sclerosis (SSc) is important to start therapeutic interventions timely. Important risk factors for progression to SSc are the SSc-specific autoantibodies, of whom anti-centromere antibodies (ACA) and anti-topoisomerase I antibodies (ATA) are the most frequent. ATA is associated with a severe disease course. A more detailed characterisation of the ATA-response in SSc might increase insights in preclinical disease stages and improve prognostication. To address this we identified all patients with suspected very early ATA-positive SSc, defined as all patients who are ATA-positive not fulfilling American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) 2013 criteria, in the Leiden Combined Care in Systemic Sclerosis (CCISS)-cohort and found very low numbers.

Methods

This triggered us to search the literature on the ATA prevalence in patients with suspected very early SSc and contribution of the SSc-specific autoantibodies to progression from suspected very early to definite SSc. To increase insights on the ATA-response in suspected very early SSc, we then evaluated the association between the ATA-response and time between onset of Raynaud’s phenomenon (RP) and first non-RP symptom, as a proxy for progressing to definite SSc, in all patients with ATA-positive SSc from the Leiden CCISS-cohort.

Results

In short, included studies show that prevalence of ATA is much lower in suspected very early SSc than in populations fulfilling ACR/EULAR 2013 criteria. After 1–15 years of follow-up, only 52% of the patients with suspected very early SSc progress to definite SSc. ATA-IgG levels tend to be higher in patients with ATA-positive SSc with more rapid disease progression.

Conclusion

Although a role of ATA in disease progression is suggested, more studies on the ATA response in suspected very early SSc are warranted.
Susceptibility of endangeredCornus florida(eastern flowering dogwood) to the introduced fungal pathogenDiscula destructiva(dogwood anthracnose) in the Canadian Carolinian forest: insights from environmental, ecological, and population genetics assessments
Authors: Mitchell Emily , Fleming Sage , Dorken Marcel , Freeland Joanna
Published: February 2023

Forest fragmentation and introduced pathogens are negatively impacting trees and forests globally, including the Carolinian forest of southern Ontario, Canada. Multiple species at risk live in this threatened but biodiverse forest, including the endangered Cornus florida (eastern flowering dogwood), which is now limited to fragmented woodlots, and has been decimated by the introduced fungal pathogen Discula destructiva (dogwood anthracnose). Ongoing management of C. florida in Canada is challenged by multiple knowledge gaps, two of which we aimed to address in this study. We first evaluated the association between anthracnose disease prevalence and a suite of ecological and environmental variables across 21 sites. Across our sites, larger trees tended to have the highest disease incidence, and trees on shallow slopes had the most crown dieback. We then quantified genetic diversity and gene flow, and found that genetic structure has not been substantially impacted by habitat fragmentation, although dispersal typically covers short distances. However, genetic diversity is relatively low in smaller populations and in younger trees. Localized dispersal and eroding genetic diversity may limit future adaptation and hence exacerbate population declines. We recommend that managers prioritize plantings in small populations, avoid shallow slopes, and track younger trees to evaluate age-related mortality.
The carbon star mystery: 40 years later
Authors: Straniero Oscar , Abia Carlos , Domínguez Inma
Published: February 2023

In 1981 Icko Iben Jr published a paper entitled “The carbon star mystery: why do the low mass ones become such, and where have all the high mass ones gone?”, where he discussed the discrepancy between the theoretical expectation and its observational counterpart about the luminosity function of AGB carbon stars. After more than 40 years, our understanding of this longstanding problem is greatly improved, also thanks to more refined stellar models and a growing amount of observational constraints. In this paper we review the state of the art of these studies and we briefly illustrate the future perspectives.
Exploration of trace anomaly contribution to proton mass based on light vector meson photoproduction
Authors: Dong Chen , Zhang Jiyuan , Bu Jingxuan , Zhou Huifang , Wang Xiao-Yun
Published: February 2023

In the quantum chromodynamics, the mass source of the proton is decomposed into four parts by the energy momentum tensor: quark energy term, gluon energy term, quark mass term and trace anomaly term. And the trace anomaly term is the most crucial contribution for studying the internal structure of the proton. In this work, under the definition of the vector meson dominant model, the trace anomaly contribution of the proton is extracted from the experimental data of light vector mesons $$\rho $$
ρ
, $$\omega $$
ω
and $$\phi $$
ϕ
photoproduction at the near-threshold, which are ($$0.53\pm 0.15$$

0.53
±
0.15

)$$\%$$
%
, ($$1.47\pm 0.48$$

1.47
±
0.48

)$$\%$$
%
and ($$2.73\pm 0.54$$

2.73
±
0.54

)$$\%$$
%
, respectively. Further, combined with the results extracted from the heavy vector meson $$J/\psi $$

J
/
ψ

photoproduction, the distribution of the trace anomaly contribution with the vector meson mass is given for the first time. These results may provide important theoretical information for determining the range of the trace anomaly contribution and for further understanding the origin of the proton mass.
Quantum codes from constacyclic codes over $S_{k}$
Authors: Kong Bo , Zheng Xiying
Published: February 2023

Let $S_{k}={\mathbb{F}}_{q}[u_{1},u_{2},\ldots ,u_{k}]/\langle u^{3}_{i}=u_{i},u_{i}u_{j}=u_{j}u_{i}=0 \rangle $

S
k

=

F
q

[

u
1

,

u
2

,
…
,

u
k

]
/
〈

u
i
3

=

u
i

,

u
i

u
j

=

u
j

u
i

=
0
〉
, where $1\leq i,j\leq k$
1
≤
i
,
j
≤
k
, $q=p^{m}$
q
=

p
m

, p is an odd prime. First, we define two new Gray maps $\phi _{k}$

ϕ
k

and $\varphi _{k}$

φ
k

, and study their Gray images. Further, we determine the structure of constacyclic codes and their dual codes, and give a necessary and sufficient conditions of constacyclic codes to contain their duals. Finally, we obtain some new quantum codes over $\mathbb{F}_{q}$

F
q

by using CSS construction, and compare the constructed codes better than the existing literature.
BOUNDED STRATEGIES FOR MAXIMIZING THE SHARPE RATIO
Authors: YE JIANG , WANG YIWEI , RAZA MUHAMMAD WAJID
Published: February 2023

Bernard et al. [(2019) Optimal strategies under omega ratio, European Journal of Operational Research 275 (2), 755–767] use convex ordering arguments to determine the bounded payoff for maximizing the omega ratio. However, it appears difficult to apply such reasoning to estimate the bounded payoff for maximizing the Sharpe ratio. As a proposed solution, this paper uses a Lagrange multiplier method to derive the bounded payoff for maximizing the Sharpe ratio. In contrast to the optimal strategy in Bernard & Vanduffel [(2014) Mean–variance optimal portfolios in the presence of a benchmark with applications to fraud detection, European Journal of Operational Research 234 (2), 469–480], the optimal strategy in this paper is bounded from below. It can protect investors from substantial losses when they invest in payoffs with a maximized Sharpe ratio.
Microwave synthesis of cationic ABAB di-imidazolyl fluorinated porphyrins and manganese complexes
Authors: Teixeira Daniela S.S. , Aroso Rafael T. , Almeida Joseany M. S. , Brett Christopher M.A. , Calvete Mário J.F. , Pinto Sara M.A. , Pereira Mariette M.
Published: February 2023

ABAB porphyrins are promising platforms for potential use in several applications, particularly in medical imaging. Herein, the synthetic optimization studies for preparing such porphyrins via the statistical condensation of 4-trifluoromethylphenyl and 1-methylimidazol-2-yl aldehydes with pyrrole, are described, with emphasis on the use of microwave irradiation as heating source, against conventional heating. Then, the preparation of the corresponding Mn(III) complex and cationization of the imidazole groups, using microwave irradiation, were also carried out and the photophysical, photochemical, and electrochemical properties were further assessed. The compounds revealed interesting features, including adequate log P, singlet oxygen yield, redox potentials, and excellent photostability, which pave the way for potential use as imaging probes in MRI or PET, or as photosensitizing molecules.
Interaction between DNA and cationic metalloporphyrins in ionic liquid solutions
Authors: Nobuoka Kaoru , Sumi Kensuke , Kitagawa Eri , Sato Kenta , Nakamura Ayumi , Kitaoka Satoshi
Published: February 2023

We studied the interaction of water-soluble cationic metalloporphyrins, [Formula: see text]Py and TMPyP, with the DNA double helix in ionic liquid solutions using CD and absorption spectra. The dispersibility of their porphyrin complexes was improved by electrostatic interactions of the anions of the ionic liquid. In the case of Cu(II) and Zn(II) complexes, the [Formula: see text]Py complexes with pyridinium cations attached to the meso-phenyl groups via methylene groups intercalated into the DNA double helix, while the compact TMPyP complexes with pyridinium cations at the meso-position could not interact with DNA. Thus, it was suggested that the solvation behavior by ionic liquids depends on the structure of the porphyrin and also affects its interaction with DNA. Neither Mn(III) complexes with axial ligands could interact with DNA, regardless of the presence of the ionic liquids, due to their steric hindrance.
The Skeleton Counts! A study of the porphyrinoid structure’s influence on sensing properties
Authors: Magna Gabriele , Nardis Sara , Di Natale Corrado , Perdigón Victor Mariãs , Torres Tomás , Paolesse Roberto
Published: February 2023

A series of porphyrinoids has been tested as sensing layers for the development of nanogravimetric chemical sensors using quartz crystal microbalances (QMB) as transducers. The macrocycles have been studied as Ni complexes, Cu in the case of corrole, to elucidate the influence of the molecular skeleton on the sensing properties of the related sensors. For the first time, subphthalocyanines have been tested in sensor applications. The study has been carried out by testing different volatile organic compounds chosen as model analytes. The results obtained demonstrate that the exploitation of different porphyrinoids offers useful insights for the development of cross-sensitive sensor arrays and can open novel perspectives for their applications in the sensor field.
HOW FORMALISATION AND CONNECTEDNESS MODERATE THE EFFECT OF FORESIGHT ON RADICAL INNOVATION: EMPIRICAL EVIDENCE FROM EUROPEAN COMPANIES
Authors: PINTER DJORDJE , LEITNER KARL-HEINZ , SCHWEITZER FIONA MARIA
Published: February 2023

While strategic foresight is relevant for radical innovation, many companies fail to produce radical innovation despite blown-up foresight units. We take into consideration the extent of formalisation and social connectedness in a firm to consider how they moderate the effect of strategic foresight on a firm’s ability to produce radical innovations. In a multi-industry study among 212 European companies, we find that formalisation and connectedness interact to enhance the effect of strategic foresight on radical innovation. When formalisation and connectedness are both high, they jointly improve a firm’s ability to use strategic foresight to produce radical innovation. When social connectedness is low, high formalisation, however, reduces a firm’s ability to turn foresight action into radical innovation. We discuss these findings relative to the controversial role of formalisation in radical innovation and provide managerial advice based on our findings.
Digitization, Ageing Population and Bank Profitability: Evidence in Light of Two Global Crises
Authors: Ramlall Indranarain
Published: February 2023

Despite the prevalence of a rich literature on bank profitability, yet, none of it analyzes the simultaneous effects of GFC and COVID-19 on bank profitability. We attempt to fulfil this gap by using a model which factors in digitization, ageing population, endogenous and predetermined variables, let alone control for G-SIBs. Findings show that the impacts of COVID-19 were twice as much deleterious as those hailing from the GFC in the case of NIM and four times as harmful in the case of ROE, with ageing population exerting bearish forces on bank profitability. Mobile usage interacted with COVID-19 crisis dummy and is found to leverage on ROE, underscoring the significance of technology-driven sources of activities during the pandemic. Overall, our paper justifies the significantly larger bailout package launched by the authorities during the pandemic compared to that triggered during the GFC with the critical role of technology being underscored in securing banks’ profits during the pandemic.
Edge-enhanced Global Disentangled Graph Neural Network for Sequential Recommendation
Authors: Li Yunyi , Hao Yongjing , Zhao Pengpeng , Liu Guanfeng , Liu Yanchi , Sheng Victor S. , Zhou Xiaofang
Published: February 2023

Sequential recommendation has been a widely popular topic of recommender systems. Existing works have contributed to enhancing the prediction ability of sequential recommendation systems based on various methods, such as recurrent networks and self-attention mechanisms. However, they fail to discover and distinguish various relationships between items, which could be underlying factors which motivate user behaviors. In this article, we propose an Edge-Enhanced Global Disentangled Graph Neural Network (EGD-GNN) model to capture the relation information between items for global item representation and local user intention learning. At the global level, we build a global-link graph over all sequences to model item relationships. Then a channel-aware disentangled learning layer is designed to decompose edge information into different channels, which can be aggregated to represent the target item from its neighbors. At the local level, we apply a variational auto-encoder framework to learn user intention over the current sequence. We evaluate our proposed method on three real-world datasets. Experimental results show that our model can get a crucial improvement over state-of-the-art baselines and is able to distinguish item features.
Hybrid Representation and Decision Fusion towards Visual-textual Sentiment
Authors: Yin Chunyong , Zhang Sun , Zeng Qingkui
Published: February 2023

The rising use of online media has changed social customs of the public. Users have become gradually accustomed to sharing daily experiences and publishing personal opinions on social networks. Social data carrying with emotions and attitudes have provided significant decision support for numerous tasks in sentiment analysis. Conventional sentiment analysis methods only concern about textual modality and are vulnerable to the multimodal scenario, while common multimodal approaches only focus on the interactive relationship between modalities without considering unique intra-modal information. A hybrid fusion network is proposed in this work to capture both the inter-modal and intra-modal features. First, in the intermediate fusion stage, a multi-head visual attention is proposed to extract accurate semantic and sentimental information from textual embedding representations with the assistance of visual features. Then, multiple base classifiers are trained to learn independent and diverse discriminative information from different modal representations in the late fusion stage. The final decision is determined based on fusing the decision supports from base classifiers via a decision fusion method. To improve the generalization of our hybrid fusion network, a similarity loss is employed to inject decision diversity into the whole model. Empirical results on multimodal datasets have demonstrated the proposed model achieves a higher accuracy and better generalization compared with baselines for multimodal sentiment analysis.
Cross-link Degree Dependence of Electronic, Water Uptakes and Thermal-mechanical Properties of Epoxy Resin Polymers: Molecular Simulations
Authors: Li Shuang Cui , Hao Chun Cheng , Sun Wei Feng
Published: February 2023

Epoxy resin (EP) is a widely used polymer matrix. A deep understanding of the structure/property relationship of EP at the molecular level is critical to realizing the materials’ full potential. Here, molecular simulations are used to calculate and compare the electronic, water uptakes and thermal-mechanical properties of EP dependent on different cross-link degrees, bisphenol A diglygde ether (DGEBA) cross-linked with methyl-tetrahydro phthalic anhydride (MTHPA), revealing these inter-relationships. The results show that they have the same energetic spectrum character of electronic states, which is determined by compositions and bonding configurations of chemical groups in EP polymers, only with the different magnitudes of the density of states which are proportional to the number of cross-link points or curing agents and monomers. Furthermore, the van der Waals forces, not the cross-link chemical bonds, dominate the molecular chain interactions and motions in EP polymers below the glass transition temperature, while cross-link structure determines the configuration of the aggregated molecular chains and thermal properties of EP polymers above the glass transition temperature. Meanwhile, the hydrostatic mechanical modulus of EP material is primarily derived from cross-link structure even below the glass transition temperature. These results lay the foundation for designing and manufacturing customized EP with desirable electric and thermal-mechanical properties.