bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining Primary Care Physicians' Intention to Perform Cervical Cancer Screening Services Using a Theory of Planned Behavior: A Structural Equation Modeling Approach
Authors: Hu Zhiqing , Sun Yanjun , Ma Yuhao , Chen Kejin , Lv Ling , Wang Lingling , He Yuan
Published: May 2022

Background

Promoting cervical cancer screening (CCS) is undoubtedly effective in combating severe public health problems in developing countries, but there are challenges to its implementation. Understanding the factors influencing primary care physicians' intentions to provide CCSs to rural women is crucial for the future implementation of screening programs. The aim of this study was to assess the intentions of primary care physicians to provide cervical cancer screening services (CCSSs) to rural women and their determinants.

Methods

This cross-sectional study included 1,308 primary care physicians in rural primary health care, and the data collection tool was developed based on the theory of planned behavior (TPB), which included demographic characteristics, the basic constructs of TPB, and the degree of knowledge of CCSSs as an extended variable of the TPB model. Structural equation modeling was used to analyze the relationships between each factor.

Results

Pathway analysis found that TPB is an appropriate theoretical basis for predicting primary care physicians' intent to provide CCSSs (χ2/df = 2.234 < 3, RMSEA = 0.035, and SRMR = 0.034). Meanwhile, the structural equation model showed that attitude (β = 0.251, p < 0.001), subjective norm (β = 0.311, p < 0.001), perceived behavioral control (β = 0.162, p < 0.001), and knowledge level (β = 0.152, p < 0.01) positively predicted primary care physicians' intention to provide CCSSs.

Conclusions

TPB model, with the addition of knowledge, was useful in predicting primary care physicians' intention to provide CCSSs for rural Chinese women. The findings of this study provide a reference for the government and hospitals to develop strategies to improve the intent of primary care physicians to provide CCSSs.
Coronavirus Disease 2019 (COVID-19) Lockdown: Morbidity, Perception, Behaviors, and Attitudes in French Families From the PARIS Birth Cohort
Authors: Citerne Antoine , Rancière Fanny , Roda Célina , Momas Isabelle
Published: May 2022

Background

Few studies have examined the overall experience of adolescents and their families during COVID-19 lockdowns. This study describes COVID-19-related morbidity in the PARIS birth cohort families during the first lockdown in France and identifies family profiles in terms of morbidity, perception, behaviors, and attitudes.

Methods

Online questionnaires were sent to adolescents of the PARIS birth cohort and their parents. Possible COVID-19 was defined by symptoms using the ECDC definition. Household transmission was estimated by calculating the observed clinical secondary attack rates. Perception, behaviors and attitudes were assessed by levels of stress, degree of satisfaction regarding levels of information about COVID-19, degree of agreement with the lockdown and preventive measures. COVID-19 morbidity in adolescents and parents was compared using chi-squared or Student's t-tests. Within each family, perception, behaviors, and attitudes were compared between adolescents and parents using matched-pairs tests. To identify contrasting family profiles, a K-means cluster analysis was implemented.

Results

Of 1,549 families contacted, 1,051 (68%) participated. Adolescents were less affected by possible COVID-19 than their parents (138.7 vs. 192.7 per 1,00,000 person-days). Household transmission of possible COVID-19 was higher when possible COVID-19 came from adults than from adolescents. Most families implemented preventive measures. Adolescents and parents generally shared the same attitudes, but adolescents were less compliant with restrictive measures. Four family profiles were identified which differed mainly regarding family stress, COVID-19 in the household, and compliance with preventive measures.

Conclusion

Improving information dissemination to parents and adolescents, including dedicated adolescent messages, would increase adherence to preventive measures.
Beyond the Benchmarks: Toward Human-Like Lexical Representations
Authors: Stevenson Suzanne , Merlo Paola
Published: May 2022

To process language in a way that is compatible with human expectations in a communicative interaction, we need computational representations of lexical properties that form the basis of human knowledge of words. In this article, we concentrate on word-level semantics. We discuss key concepts and issues that underlie the scientific understanding of the human lexicon: its richly structured semantic representations, their ready and continual adaptability, and their grounding in crosslinguistically valid conceptualization. We assess the state of the art in natural language processing (NLP) in achieving these identified properties, and suggest ways in which the language sciences can inspire new approaches to their computational instantiation.
Follow Your Nose: Extended Arm Reach After Pinocchio Illusion in Virtual Reality
Authors: Berger Christopher C. , Lin Baihan , Lenggenhager Bigna , Lanier Jaron , Gonzalez-Franco Mar
Published: May 2022

In this study, we recreate the Pinocchio Illusion—a bodily illusion whereby the perceived length of one’s nose is extended—in Virtual Reality. Participants (n = 38) self-administered tapping on the tip of the nose of a virtual avatar seen from the first-person perspective (using a hand-held controller) while the nose of the avatar slowly grew with each tap. The stimulating virtual arm and the virtual nose were linked such that while the nose grew the arm extended, and then also grew up to 50%. This produced an extension of the perceived reach of the stimulating arm, and an outward drift in the participants’ real arm. A positive correlation between the extent of the outward drift of the participants’ arm and the perceived reachability of distal objects was observed. These results were found both with synchronous tactile stimulation on the participants’ real nose, and without, but not for control conditions in which the visuomotor synchrony or body schema were violated. These findings open new avenues for hand grasp interactions with virtual objects out of arm’s-reach in immersive setups and are discussed in the context of theories of body ownership, body schema, and touch perception.
Sex Differences and Cognitive Maps: Studies in the Lab don’t Always Reflect Cognitive Map Accuracy in Everyday Life
Authors: Cocquyt Chantelle M. , Youngson Nicole , Sutton Jennifer E.
Published: May 2022

The ability to create an accurate mental survey representation, orcognitive map, when moving through an environment varies widely across individuals, and we are still trying to understand the origins of these individual differences. Non-immersive virtual environments used to test for cognitive map accuracy in the laboratory have shown sex differences with a performance advantage for men in some studies but not others. When sex differences are demonstrated, it is unclear whether women’s performance generalizes to familiar and unfamiliar real-world environments. In Experiment 1, 98 participants explored the virtual environment Silcton and afterwards estimated directions between the landmarks in Silcton and arranged landmarks found in Silcton on a map. In addition, they reported frequently visited real-world locations and then estimated directions between them and drew a map of the locations. Men were more accurate on tests of Silcton than women were, although there was no difference between sexes for accuracy with real-world locations. Within sexes, women were more accurate with the real-world locations than Silcton, while men showed the opposite pattern. In Experiment 2, 21 women were tested with Silcton and their familiar real-world locations as in Experiment 1 but were also walked through an unfamiliar real-world area on campus and completed direction estimation and map drawing tests for the new environment. Overall, women were more accurate with the two real-world environments than Silcton, with some evidence that accuracy with the new real-world environment was more accurate than the familiar real-world locations. Overall, women’s ability to create a cognitive map of a virtual environment in the laboratory does not seem to be indicative of their ability to do the same in the real world, and care should be taken when generalizing lab results with virtual environments.
Earth-Fixed Books Reduce Motion Sickness When Reading With a Head-Mounted Display
Authors: Sato Hikaru , Sato Yuki , Takamatsu Atsushi , Makita Mitsuhiro , Wada Takahiro
Published: May 2022

There are concerns that viewing two-dimensional (2D) content such as web pages on a head-mounted display (HMD) in the car may aggravate motion sickness. This is because when 2D content is fixed to a head-fixed coordinate system, the appearance of the content does not change even when the body moves; therefore, it is impossible to visually perceive the movement of one’s body, resulting in a sensory conflict between the visual and vestibular senses. A method for reducing motion sickness when displaying 3D content on an HMD has been investigated; however, when displaying 2D content, no such method has been investigated. Therefore, this study aims to verify to the possibility of reducing motion sickness from the change of appearance caused by fixing 2D content to the earth-fixed coordinate system when viewing it with an HMD in a moving environment. Participants sat on a seat that was mounted on a vibrating device and moved in the pitch direction while reading a book on the HMD. Consequently, the severity of motion sickness was significantly lower when the book was fixed to the earth-fixed coordinate system than when fixed to the head-fixed coordinate system. This result suggests that by fixing the content to the earth-fixed coordinate system, motion sickness can be reduced because the movement of one’s body can be perceived through changes in the appearance of the content, and the sensory conflict between visual and vestibular sensations can be resolved.
The Role of Surgery in Patients with COVID-19-Related Thoracic Complications
Authors: Raveglia Federico , Scarci Marco , Rimessi Arianna , Orlandi Riccardo , Rebora Paola , Cioffi Ugo , Guttadauro Angelo , Ruffini Enrico , Benvenuti Mauro , Cardillo Giuseppe , Patrini Davide , Vannucci Fernando , Yusuf Nasser , Jindal Pramoj , Cerfolio Robert
Published: May 2022

Objective

Patients with several thoracic complications induced by SARS-CoV-2 infection may benefit from surgery, but its role in this condition is largely unknown, and many surgeons’ advice against any surgical referrals. Our aim is to investigate the efficacy and safety of surgery in COVID-19 patients with thoracic complications requiring surgery.

Methods

We designed a multicenter observational study, involving nine thoracic surgery departments, evaluating patients who developed thoracic complications in hospital, surgically managed from March 1, 2020, to May 31, 2021. An overall 30-day mortality was obtained by using the Kaplan–Meier method. Multivariable Cox regression model and logistic models were applied to identify the variables associated with mortality and postoperative complications.

Results

Among 83 patients, 33 (40%) underwent surgery for complicated pneumothorax, 17 (20.5%) for pleural empyema, 13 (15.5%) for hemothorax, 8 (9.5%) for hemoptysis, 5 patients (6%) for lung abscess, 4 (5%) for infected pneumatoceles, and 3 (3.5%) for other causes. Within 30 days of surgery, 60 patients (72%) survived. At multivariable analysis, age (HR 1.05 [95% CI, 1.01, 1.09], p = 0.022), pulmonary hypertension (HR 3.98 [95% CI, 1.09, 14.5], p = 0.036), renal failure (HR 2.91 [95% CI, 1.19, 7.10], p-value 0.019), thoracotomy (HR 4.90 [95% CI, 1.84, 13.1], p-value 0.001) and infective affections (HR 0.17 [95% CI, 0.05, 0.58], p-value 0.004) were found to be independent prognostic risk factors for 30-day mortality. Age (OR 1.05 [95% CI, 1.01, 1.10], p = 0.023) and thoracotomy (OR 3.85 [95% CI, 1.35, 12.0] p = 0.014) became significant predictors for 30-day morbidity.

Conclusion

Surgical management of COVID-19-related thoracic complications is affected by high mortality and morbidity rates, but a 72% survival rate still seems to be satisfactory with a rescue intent. Younger patients without pulmonary hypertension, without renal insufficiency and undergoing surgery for infectious complications appear to have a better prognosis.
Safety Evaluation of Porcine Bile Acids in Laying Hens: Effects on Laying Performance, Egg Quality, Blood Parameters, Organ Indexes, and Intestinal Development
Authors: Yang Bowen , Huang Shimeng , Li Shupeng , Feng Zhihua , Zhao Guoxian , Ma Qiugang
Published: May 2022

Bile acids (BAs) have long been known to facilitate digestion, transport, and absorption of lipids in the small intestine as well as regulate host lipid metabolic homeostasis. However, excessive BAs may lead to long-term damage to tissue. Also, it is unknown whether different levels of porcine BAs supplementation could improve performance, host metabolism, intestinal functions in laying hens. Hence, this study was aimed to investigate the potential effects of BAs addition on laying performance, egg quality, blood parameters, organ indexes, and intestinal histopathology of hens in the late phase. A total of 300 58-week-old Hy-line Gray hens were randomly divided into five groups which fed a basal diet (control) or basal diets supplemented with 60, 300, 600, and 3,000 mg/kg BAs for 56 days. Compared with the control group, no significant differences (P > 0.05) were observed in egg production, egg weight, ADFI, and FCR of hens in 60, 300, 600, and 3,000 mg/kg BAs groups. Dietary 60 mg/kg BAs supplementation resulted in a significant increase (P < 0.05) in egg mass. Meanwhile, no significant differences were observed in egg quality, including eggshell strength, eggshell thickness, albumen height, and Haugh unit among any treatment groups (P > 0.05). Dramatically, dietary 3,000 mg/kg BAs supplement decreased yolk color (P < 0.05). There was no significant difference in the blood parameters such as WBC, RBC, HGB, HCT, and PLT among any treatments. However, in 3,000 mg/kg BAs group, ovary coefficient was lower than the control (P < 0.05), and serum urea and creatinine were higher than the control (P < 0.05). Also, kidney and oviduct injury appeared in 3,000 mg/kg BAs group. These results indicated that a porcine BAs concentration of 3,000 mg/kg may cause harmful effects while 600 mg/kg was non-deleterious to laying hens after a daily administration for 56 days, namely that dietary supplement of up to 10 times the recommended dose of BAs was safely tolerated by laying hens.
Fumonisin B1 Induces Immunotoxicity and Apoptosis of Chicken Splenic Lymphocytes
Authors: Zhu Fenghua , Wang Yang
Published: May 2022

Fumonisin B1 (FB1), produced by Fusarium, is among the most abundant and toxic mycotoxin contaminations in feed, causing damages to the health of livestock. However, the mechanisms of FB1 toxicity in chickens are less understood. As splenic lymphocytes play important roles in the immune system, the aim of this study was to investigate the immunotoxic effects and mechanisms of FB1 on chicken splenic lymphocytes. In the present study, the chicken primary splenic lymphocytes were harvested and treated with 0, 2.5, 5, 10, 20 and 40 μg/mL FB1. Then, the cell proliferation, damage, ultrastructure, inflammation and apoptosis were evaluated. Results showed that the proliferation rate of splenic lymphocytes was decreased by FB1 treatments. The activity of lactate dehydrogenase (LDH) was increased by FB1 treatments in a dose-dependent manner, implying the induction of cell damage. Consistently, the ultrastructure of splenic lymphocytes showed that FB1 at all the tested concentrations caused cell structure alterations, including nuclear vacuolation, mitochondrial swelling and mitochondrial crest fracture. Besides, immunosuppressive effects of FB1 were observed by the decreased concentrations of interleukin-2 (IL-2), IL-4, IL-12 and interferon-γ (IFN-γ) in the cell culture supernatant. Furthermore, apoptosis was observed in FB1-treated cells by flow cytometry. The mRNA expressions of apoptosis-related genes showed that the expression of Bcl-2 was decreased, while the expressions of the P53, Bax, Bak-1, and Caspase-3 were increased with FB1 treatment. Similar results were found in the concentrations of apoptosis-related proteins in the cell supernatant by ELISA assay. Moreover, regression analysis indicated that increasing FB1 concentration increased LDH activity, concentrations of Bax, Bak-1 and mRNA expression of Bak-1 linearly, increased M1 area percentage quadratically, decreased concentration of IFN-γ, mRNA expression of Bcl-2 linearly, and decreased concentrations of IL-2 and IL-4 quadratically. Besides, regression analysis also showed reciprocal relationships between IL-12 concentration, Caspase-3 mRNA expression and increasing FB1 concentration. The increasing FB1 concentration could decrease IL-12 concentration and increase Caspase-3 mRNA expression. Altogether, this study reported that FB1 induced the immunotoxicity of chicken splenic lymphocytes and caused splenic lymphocytes apoptosis by the Bcl-2 family-mediated mitochondrial pathway of caspase activation.
Prognostic Analysis of Differentially Expressed DNA Damage Repair Genes in Bladder Cancer
Authors: Yang Yong , Yu Jieqing , Xiong Yuanping , Xiao Jiansheng , Dai Daofeng , Zhang Feng
Published: May 2022

Bladder cancer (BCa) is the tenth most common tumor in humans. DNA damage repair genes (DDRGs) play important roles in many malignant tumors; thus, their functions in BCa should also be explored. We performed a comprehensive analysis of the expression profiles of DDRGs in 410 BCa tumors and 19 normal tissues from The Cancer Genome Atlas database. We identified 123 DDRGs differentially expressed between BCa tumors and normal tissues, including 95 upregulated and 28 downregulated genes. We detected 22 DDRGs associated with overall survival (OS) of patients with BCa by performing univariate Cox regression analysis. To explore the interactions between OS-associated DDRGs, we constructed a PPI network, which showed that the top six DDRGs (CDCA2, FOXM1, PBK, RRM2, ORC1, and HDAC4) with the highest scores in the PPI network might play significant roles in OS of BCa. Moreover, to investigate the latent regulatory mechanism of these OS-associated DDRGs, we analyzed the transcription factors (TFs)-DDRGs regulatory network. The core seven TFs (NCAPG, DNMT1, LMNB1, BRCA1, E2H2, CENPA, and E2F7) were shown to be critical regulators of the OS-related DDRGs. The 22 DDRGs were incorporated into a stepwise multivariable Cox analysis. Then, we built the index of risk score based on the expression of 8 DDRGs (CAD, HDAC10, JDP2, LDLR, PDGFRA, POLA2, SREBF1, and STAT1). The p-value < 0.0001 in the Kaplan–Meier survival plot and an area under the ROC curve (AUC) of 0.771 in TCGA-BLCA training dataset suggested the high specificity and sensitivity of the prognostic index. Furthermore, we validated the risk score in the internal TCGA-BLCA and an independent GSE32894 dataset, with AUC of 0.743 and 0.827, respectively. More importantly, the multivariate Cox regression and stratification analysis demonstrated that the predictor was independent of various clinical parameters, including age, tumor stage, grade, and number of positive tumor lymph nodes. In summary, a panel of 8 DNA damage repair genes associated with overall survival in bladder cancer may be a useful prognostic tool.
In Vitro Antifungal Antibacterial Activity of Partitions from Euphorbia tirucalli L.
Authors: Heya Michel Stéphane , Verde-Star María Julia , Galindo-Rodríguez Sergio Arturo , Rivas-Morales Catalina , Robledo-Leal Efrén , García-Hernández David Gilberto
Published: May 2022

We determined the antifungal and antimicrobial sensitivity of Euphorbia tirucalli extracts in vitro. Antifungal and antibacterial activity was determined based on the M38-A and M26-A protocols, respectively. The methanolic and ethanolic partitions demonstrated antidermatophytic activity against Trichophyton rubrum (MIC 125 µg/mL for ethanol and MIC 125 µg/mL for methanol) and T. interdigitalis (MIC 500 µg/mL for ethanol; 125 µg/mL for methanol). These partitions also showed antibacterial activity—the ethanolic partition had an MIC of 1.56 ± 0.02 mg/mL against methicillin-resistant Staphylococcus aureus (clinical isolate), 6.25 ± 0.04 mg/mL against Staphylococcus aureus BAA-44, 3.13 ± 0.13 mg/mL against Pseudomonas aeruginosa 27853, and 3.13 ± 0.15 mg/mL against Escherichia coli ATCC 25922; the methanolic partition showed an MIC of 1.56 ± 0.02 mg/mL against P. aeruginosa 27853 and 1.56 ± 0.043 mg/mL against E. coli ATCC 25922. These partitions show promise as antimicrobial agents or adjuvants in the treatment of infections caused by these microorganisms.
Combined PK/PD Index May Be a More Appropriate PK/PD Index for Cefoperazone/Sulbactam against Acinetobacter baumannii in Patients with Hospital-Acquired Pneumonia
Authors: Zhou Yingjie , Zhang Jing , Chen Yuancheng , Wu Jufang , Guo Beining , Wu Xiaojie , Zhang Yingyuan , Wang Minggui , Ya Ru , Huang Hao
Published: May 2022

Cefoperazone/sulbactam (CPZ/SUL) is a β-lactam and β-lactamase inhibitor combination therapy for the treatment of respiratory tract infections. Using data from a prospective, multiple-center, open-label clinical trial in 54 patients with hospital-acquired pneumonia or ventilator-associated pneumonia caused by multidrug-resistant Acinetobacter baumannii (Ab), we showed that a combined PK/PD index %(T > MICcpz*T > MICsul) is a more appropriate PK/PD index against Ab, compared to the PK/PD index (%T > MIC) for a single drug. For a 2 h infusion, the PK/PD cutoff of CPZ/SUL (2 g/1 g, q8h) for clinical and microbiological efficacy was 4/2 and 1/0.5 mg/L, respectively. The corresponding cumulative fraction of response was 46.5% and 25.3%, respectively. Results based on the combined PK/PD index were quite similar to that based on the joint probability of target attainment. The two drugs have interaction from the viewpoint of PK/PD. When the dose of one drug was too high, the PK/PD cutoff was often determined by another drug in which the dose was maintained. In most cases, sulbactam exerted the main effect against infection by Ab in the complex CPZ/SUL, which was similar to the literature reports. When the MIC of CPZ was 8, 16, or 32 mg/L, a CPZ/SUL 2 g/1 g (q8h), 2 g/2 g (q8h), or 2 g/2 g (q6h) (infusion was all 3 h) was recommended, respectively. A clinical efficacy and safety study to confirm simulation results is warranted.
Plant- and Animal-Based Antioxidants’ Structure, Efficacy, Mechanisms, and Applications: A Review
Authors: Abeyrathne Edirisinghe Dewage Nalaka Sandun , Nam Kichang , Huang Xi , Ahn Dong Uk
Published: May 2022

Antioxidants are compounds that normally prevent lipid and protein oxidation. They play a major role in preventing many adverse conditions in the human body, including inflammation and cancer. Synthetic antioxidants are widely used in the food industry to prevent the production of adverse compounds that harm humans. However, plant- and animal-based antioxidants are more appealing to consumers than synthetic antioxidants. Plant-based antioxidants are mainly phenolic compounds, carotenoids, and vitamins, while animal-based antioxidants are mainly whole protein or the peptides of meat, fish, egg, milk, and plant proteins. Plant-based antioxidants mainly consist of aromatic rings, while animal-based antioxidants mainly consist of amino acids. The phenolic compounds and peptides act differently in preventing oxidation and can be used in the food and pharmaceutical industries. Therefore, compared with animal-based antioxidants, plant-based compounds are more practical in the food industry. Even though plant-based antioxidant compounds are good sources of antioxidants, animal-based peptides (individual peptides) cannot be considered antioxidant compounds to add to food. However, they can be considered an ingredient that will enhance the antioxidant capacity. This review mainly compares plant- and animal-based antioxidants’ structure, efficacy, mechanisms, and applications.
Poly(3-mercapto-2-methylpropionate), a Novel α-Methylated Bio-Polythioester with Rubber-like Elasticity, and Its Copolymer with 3-hydroxybutyrate: Biosynthesis and Characterization
Authors: Ceneviva Lucas Vinicius Santini , Mierzati Maierwufu , Miyahara Yuki , Nomura Christopher T. , Taguchi Seiichi , Abe Hideki , Tsuge Takeharu
Published: May 2022

A new polythioester (PTE), poly(3-mercapto-2-methylpropionate) [P(3M2MP)], and its copolymer with 3-hydroxybutyrate (3HB) were successfully biosynthesized from 3-mercapto-2-methylpropionic acid as a structurally-related precursor. This is the fourth PTE of biological origin and the first to be α-methylated. P(3M2MP) was biosynthesized using an engineered Escherichia coli LSBJ, which has a high molecular weight, amorphous structure, and elastomeric properties, reaching 2600% elongation at break. P(3HB-co-3M2MP) copolymers were synthesized by expressing 3HB-supplying enzymes. The copolymers were produced with high content in the cells and showed a high 3M2MP unit incorporation of up to 77.2 wt% and 54.8 mol%, respectively. As the 3M2MP fraction in the copolymer increased, the molecular weight decreased and the polymers became softer, more flexible, and less crystalline, with lower glass transition temperatures and higher elongations at break. The properties of this PTE were distinct from those of previously biosynthesized PTEs, indicating that the range of material properties can be further expanded by introducing α-methylated thioester monomers.
Phospholipid Membrane Transport and Associated Diseases
Authors: Ventura Raúl , Martínez-Ruiz Inma , Hernández-Alvarez María Isabel
Published: May 2022

Phospholipids are the basic structure block of eukaryotic membranes, in both the outer and inner membranes, which delimit cell organelles. Phospholipids can also be damaged by oxidative stress produced by mitochondria, for instance, becoming oxidized phospholipids. These damaged phospholipids have been related to prevalent diseases such as atherosclerosis or non-alcoholic steatohepatitis (NASH) because they alter gene expression and induce cellular stress and apoptosis. One of the main sites of phospholipid synthesis is the endoplasmic reticulum (ER). ER association with other organelles through membrane contact sites (MCS) provides a close apposition for lipid transport. Additionally, an important advance in this small cytosolic gap are lipid transfer proteins (LTPs), which accelerate and modulate the distribution of phospholipids in other organelles. In this regard, LTPs can be established as an essential point within phospholipid circulation, as relevant data show impaired phospholipid transport when LTPs are defected. This review will focus on phospholipid function, metabolism, non-vesicular transport, and associated diseases.
The Four-Feature Prognostic Models for Cancer-Specific and Overall Survival after Surgery for Localized Clear Cell Renal Cancer: Is There a Place for Inflammatory Markers?
Authors: Zapała Łukasz , Ślusarczyk Aleksander , Wolański Rafał , Kurzyna Paweł , Garbas Karolina , Zapała Piotr , Radziszewski Piotr
Published: May 2022

We aimed at a determination of the relevance of comorbidities and selected inflammatory markers to the survival of patients with primary non-metastatic localized clear cell renal cancer (RCC). We retrospectively analyzed data from a single tertiary center on 294 patients who underwent a partial or radical nephrectomy in the years 2012–2018. The following parameters were incorporated in the risk score: tumor stage, grade, size, selected hematological markers (SIRI—systemic inflammatory response index; SII—systemic immune-inflammation index) and a comorbidities assessment tool (CCI—Charlson Comorbidity Index). For further analysis we compared our model with existing prognostic tools. In a multivariate analysis, tumor stage (p = 0.01), tumor grade (p = 0.03), tumor size (p = 0.006) and SII (p = 0.02) were significant predictors of CSS, while tumor grade (p = 0.02), CCI (p = 0.02), tumor size (p = 0.01) and SIRI (p = 0.03) were significant predictors of OS. We demonstrated that our model was characterized by higher accuracy in terms of OS prediction compared to the Leibovich and GRANT models and outperformed the GRANT model in terms of CSS prediction, while non-inferiority to the VENUSS model was revealed. Four different features were included in the predictive models for CSS (grade, size, stage and SII) and OS (grade, size, CCI and SIRI) and were characterized by adequate or even superior accuracy when compared with existing prognostic tools.
Docosahexaenoic Acid and Melatonin Prevent Impaired Oligodendrogenesis Induced by Intrauterine Growth Restriction (IUGR)
Authors: Kühne Britta Anna , Vázquez-Aristizabal Paula , Fuentes-Amell Mercè , Pla Laura , Loreiro Carla , Gómez-Catalán Jesús , Gratacós Eduard , Illa Miriam , Barenys Marta
Published: May 2022

In this study, our aims were to characterize oligodendrogenesis alterations in fetuses with intrauterine growth restriction (IUGR) and to find therapeutic strategies to prevent/treat them using a novel rabbit in vitro neurosphere culture. IUGR was surgically induced in one uterine horn of pregnant rabbits, while the contralateral horn served as a control. Neural progenitor cells (NPCs) were obtained from pup’s whole brain and cultured as neurospheres mimicking the basic processes of brain development including migration and cell differentiation. Five substances, chosen based on evidence provided in the literature, were screened in vitro in neurospheres from untreated rabbits: Docosahexaenoic acid (DHA), melatonin (MEL), zinc, 3,3′,5-Triiodo-L-thyronine (T3), and lactoferrin (LF) or its metabolite sialic acid (SA). DHA, MEL and LF were further selected for in vivo administration and subsequent evaluation in the Neurosphere Assay. In the IUGR culture, we observed a significantly reduced percentage of oligodendrocytes (OLs) which correlated with clinical findings indicating white matter injury in IUGR infants. We identified DHA and MEL as the most effective therapies. In all cases, our in vitro rabbit neurosphere assay predicted the outcome of the in vivo administration of the therapies and confirmed the reliability of the model, making it a powerful and consistent tool to select new neuroprotective therapies.
Associations of Physical Activity and Handgrip Strength with Different Domains of Quality of Life in Pediatric Cancer Survivors
Authors: Cheung Ankie , Li William , Ho Laurie , Xia Wei , Luo Yuanhui , Chan Godfrey , Chung Joyce
Published: May 2022

There is a paucity of evidence about the associations of physical activity (PA) and handgrip strength (HGS) within different domains of quality of life (QoL) in Chinese pediatric cancer survivors. We, therefore, conducted this multicenter cross-sectional study aimed to investigate whether increased PA level and HGS are associated with higher scores in different QoL domains (i.e., physical, emotional, social, and school functioning) in pediatric cancer survivors. PA was assessed with a validated self-reported PA rating scale. In total, 191 Chinese pediatric cancer survivors aged 9 to 16 years were included in the analysis. Results showed that engaging in a higher level of PA was significantly associated with improved QoL in different domains, including physical (β = 0.543, p < 0.001), emotional (β = 0.449, p < 0.001), social (β = 0.434, p < 0.001), and school functioning (β = 0.407, p < 0.001). Greater HGS was also associated with better physical (β = 0.230, p ≤ 0.001) and emotional (β = 0.261, p ≤ 0.001) functioning. Findings from this study provide evidence of the significant beneficial impact of regular PA on pediatric cancer survivors’ QoL along their survivorship trajectory.
Glutathione Peroxidase GPX1 and Its Dichotomous Roles in Cancer
Authors: Zhao Yangjing , Wang Hui , Zhou Jingdong , Shao Qixiang
Published: May 2022

As the first identified selenoprotein, glutathione peroxidase 1 (GPX1) is a widely and abundantly expressed antioxidant enzyme. GPX1 utilizes glutathione as a substrate to catalyze hydrogen peroxide, lipid peroxide, and peroxynitrite, thereby reducing intracellular oxidative stress. The GPX1 gene is regulated at transcriptional, post-transcriptional, and translational levels. Numerous case-control studies and meta-analyses have assessed the association between a functional genetic polymorphism of the GPX1 gene, named Pro198Leu (rs1050450 C>T), and cancer susceptibility in different populations. GPX1 polymorphism has type-specific effects as a candidate marker for cancer risk, but the association between GPX1 variants and cancer susceptibility remains controversial in different studies. GPX1 is abnormally elevated in most types of cancer but has complex dichotomous roles as tumor suppressor and promoter in different cancers. GPX1 can participate in various signaling pathways to regulate tumor biological behaviors, including cell proliferation, apoptosis, invasion, immune response, and chemoresistance. In this review, we comprehensively summarize the controversial associations between GPX1 polymorphism and cancer risks and further discuss the relationships between the aberrant expressions of GPX1 and tumorigenesis. Further studies are needed to elucidate the clinical significance of GPX1 as a potential prognostic biomarker and novel therapeutic target in various malignancies.
Homologous Recombination Repair in Biliary Tract Cancers: A Prime Target for PARP Inhibition?
Authors: Yin Chao , Kulasekaran Monika , Roy Tina , Decker Brennan , Alexander Sonja , Margolis Mathew , Jha Reena C. , Kupfer Gary M. , He Aiwu R.
Published: May 2022

Biliary tract cancers (BTCs) are a heterogeneous group of malignancies that make up ~7% of all gastrointestinal tumors. It is notably aggressive and difficult to treat; in fact, >70% of patients with BTC are diagnosed at an advanced, unresectable stage and are not amenable to curative therapy. For these patients, chemotherapy has been the mainstay treatment, providing an inadequate overall survival of less than one year. Despite the boom in targeted therapies over the past decade, only a few targeted agents have been approved in BTCs (i.e., IDH1 and FGFR inhibitors), perhaps in part due to its relatively low incidence. This review will explore current data on PARP inhibitors (PARPi) used in homologous recombination deficiency (HRD), particularly with respect to BTCs. Greater than 28% of BTC cases harbor mutations in genes involved in homologous recombination repair (HRR). We will summarize the mechanisms for PARPi and its role in synthetic lethality and describe select genes in the HRR pathway contributing to HRD. We will provide our rationale for expanding patient eligibility for PARPi use based on literature and anecdotal evidence pertaining to mutations in HRR genes, such as RAD51C, and the potential use of reliable surrogate markers of HRD.
GDF15 Is an Eribulin Response Biomarker also Required for Survival of DTP Breast Cancer Cells
Authors: Bellio Chiara , Emperador Marta , Castellano Pol , Gris-Oliver Albert , Canals Francesc , Sánchez-Pla Alex , Zamora Esther , Arribas Joaquín , Saura Cristina , Serra Violeta , Tabernero Josep , Littlefield Bruce A. , Villanueva Josep
Published: May 2022

Drug tolerant persister (DTP) cells enter into a reversible slow-cycling state after drug treatment. We performed proteomic characterization of the breast cancer (BC) DTP cell secretome after eribulin treatment. We showed that the growth differentiation factor 15 (GDF15) is a protein significantly over-secreted upon eribulin treatment. The biomarker potential of GDF15 was confirmed in 3D-cell culture models using BC cells lines and PDXs, as well as in a TNBC in vivo model. We also found that GDF15 is required for survival of DTP cells. Direct participation of GDF15 and its receptor GFRAL in eribulin-induction of DTPs was established by the enhanced cell killing of DTPs by eribulin seen under GDF15 and GFRAL loss of function assays. Finally, we showed that combination therapy of eribulin plus an anti-GDF15 antibody kills BC-DTP cells. Our results suggest that targeting GDF15 may help eradicate DTP cells and block the onset of acquired resistance.
Use of Thiazide Diuretics and Risk of All Types of Skin Cancers: An Updated Systematic Review and Meta-Analysis
Authors: Nochaiwong Surapon , Chuamanochan Mati , Ruengorn Chidchanok , Noppakun Kajohnsak , Awiphan Ratanaporn , Phosuya Chabaphai , Tovanabutra Napatra , Chiewchanvit Siri , Sood Manish M. , Hutton Brian , Thavorn Kednapa , Knoll Greg A.
Published: May 2022

Background: The use of thiazide diuretics is associated with skin cancer risk; however, whether this applies to all skin cancer types is unclear. Methods: In this meta-analysis, we searched multiple electronic databases and gray literature up to 10 April 2022, with no language restrictions, to identify relevant randomized controlled trials (RCTs) and non-randomized studies (cohort, case-control) that investigated the association between thiazide diuretics and skin cancer. The primary outcomes of interest were malignant melanoma and non-melanoma skin cancer (basal cell carcinoma [BCC], squamous cell carcinoma [SCC]). Secondary outcomes included other skin cancers (lip cancer, Merkel cell carcinoma, malignant adnexal skin tumors, oral cavity cancer, and precursors of skin cancer). We used a random-effects meta-analysis to estimate pooled adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results: Thirty non-randomized studies (17 case-control, 13 cohort, no RCTs) were included. Thiazide diuretic users had a higher risk of malignant melanoma (17 studies; n = 10,129,196; pooled adjusted OR, 1.10; 95% CI, 1.04–1.15; p < 0.001; strength of evidence, very low; very small harmful effect), BCC (14 studies; n = 19,780,476; pooled adjusted OR, 1.05; 95% CI, 1.02–1.09; p = 0.003; strength of evidence, very low; very small harmful effect), and SCC (16 studies; n = 16,387,862; pooled adjusted OR, 1.35; 95% CI, 1.22–1.48; p < 0.001; strength of evidence, very low; very small harmful effect) than non-users. Thiazide diuretic use was also associated with a higher risk of lip cancer (5 studies; n = 161,491; pooled adjusted OR, 1.92; 95% CI, 1.52–2.42; p < 0.001; strength of evidence, very low; small harmful effect), whereas other secondary outcomes were inconclusive. Conclusions: Thiazide diuretics are associated with the risk of all skin cancer types, including malignant melanoma; thus, they should be used with caution in clinical practice.
Simultaneous Care in Oncology: A 7-Year Experience at ESMO Designated Centre at Veneto Institute of Oncology, Italy
Authors: Brunello Antonella , Galiano Antonella , Schiavon Stefania , Nardi Mariateresa , Feltrin Alessandra , Pambuku Ardi , De Toni Chiara , Dal Col Alice , Lamberti Evelina , Pittarello Chiara , Bergamo Francesca , Basso Umberto , Maruzzo Marco , Finotto Silvia , Bolshinsky Maital , Stragliotto Silvia , Procaccio Letizia , Rizzato Mario Domenico , Formaglio Fabio , Lombardi Giuseppe , Lonardi Sara , Zagonel Vittorina
Published: May 2022

Benefits of early palliative care referral in oncology are well-validated. At the Veneto Institute of Oncology-IRCCS, a simultaneous-care outpatient clinic (SCOC) has been active since 2014, where patients with advanced cancer are evaluated by an oncologist together with a palliative care team. We prospectively assessed SCOC patients’ characteristics and SCOC outcomes through internal procedure indicators. Data were retrieved from the SCOC prospectively maintained database. There were 753 eligible patients. The median age was 68 years; primary tumor sites were gastrointestinal (75.2%), genitourinary (15.0%) and other sites (9.8%). Predominant symptoms were psychological issues (69.4%), appetite loss (67.5%) and pain (65.9%). Dyspnea was reported in 53 patients (7%) in the referral form, while it was detected in 226 patients (34.2%) during SCOC visits (p < 0.0001). Median survival of patients after the SCOC visit was 7.3 months. Survival estimates by the referring oncologist were significantly different from the actual survival. Psychological intervention was deemed necessary and undertaken in 34.6% of patients, and nutritional support was undertaken in 37.9% of patients. Activation of palliative care services was prompted for 77.7% of patients. Out of 357 patients whose place of death is known, 69.2% died at home, in hospice or residential care. With regard to indicators’ assessment, the threshold was reached for 9 out of 11 parameters (81.8%) requested by the procedure. This study confirmed the importance of close collaboration between oncologists and palliative care teams in responding properly to cancer patients’ needs. The introduction of a procedure with indicators allowed punctual assessment of a team’s performance.
Breast Cancer—Epidemiology, Classification, Pathogenesis and Treatment (Review of Literature)
Authors: Smolarz Beata , Nowak Anna Zadrożna , Romanowicz Hanna
Published: May 2022

Breast cancer is the most-commonly diagnosed malignant tumor in women in the world, as well as the first cause of death from malignant tumors. The incidence of breast cancer is constantly increasing in all regions of the world. For this reason, despite the progress in its detection and treatment, which translates into improved mortality rates, it seems necessary to look for new therapeutic methods, and predictive and prognostic factors. Treatment strategies vary depending on the molecular subtype. Breast cancer treatment is multidisciplinary; it includes approaches to locoregional therapy (surgery and radiation therapy) and systemic therapy. Systemic therapies include hormone therapy for hormone-positive disease, chemotherapy, anti-HER2 therapy for HER2-positive disease, and quite recently, immunotherapy. Triple negative breast cancer is responsible for more than 15–20% of all breast cancers. It is of particular research interest as it presents a therapeutic challenge, mainly due to its low response to treatment and its highly invasive nature. Future therapeutic concepts for breast cancer aim to individualize therapy and de-escalate and escalate treatment based on cancer biology and early response to therapy. The article presents a review of the literature on breast carcinoma—a disease affecting women in the world.
Enucleation Is a Feasible Procedure for Well-Differentiated pNEN—A Matched Pair Analysis
Authors: Nießen Anna , Bechtiger Fabiola A. , Hinz Ulf , Lewosinska Magdalena , Billmann Franck , Hackert Thilo , Büchler Markus W. , Schimmack Simon
Published: May 2022

The extent of surgical resection in the treatment of pancreatic neuroendocrine neoplasms (pNEN) is still controversial. This study aimed to evaluate the outcomes of enucleation for well-differentiated non-functional (nf) pNEN. Patients undergoing enucleation (2001–2020) were analyzed. Clinicopathological parameters, perioperative outcomes and survival were assessed. The analysis was performed as a nested case-control study and matched-pair analysis with formal resection. Sixty-one patients undergoing enucleation were identified. Compared to patients undergoing formal resection, enucleation was associated with a significantly shorter median length of operative time (128 (IQR 95–170) versus 263 (172–337) minutes, p < 0.0001) and a significantly lower rate of postoperative diabetes (2% versus 21%, p = 0.0020). There was no significant difference in postoperative pancreatic fistula rate (18% versus 16% type B/C, p = 1.0), Clavien−Dindo ≥ III complications (20% versus 26%, p = 0.5189), readmission rate (12% versus 15%, p = 0.6022) or length of hospital stay (8 (7–11) versus 10 (8–17) days, p = 0.0652). There was no 30-day mortality after enucleation compared to 1.6% (n = 1) after formal resection. 10-year overall survival (OS) and disease-free survival (DFS) was similar between the two groups (OS: 89% versus 77%, p = 0.2756; DFS: 98% versus 91%, p = 0.0873). Enucleation presents a safe surgical approach for well-differentiated nf-pNEN with good long-term outcomes for selected patients.
Reassessment of Reliability and Reproducibility for Triple-Negative Breast Cancer Subtyping
Authors: Yu Xinjian , Liu Yongjing , Chen Ming
Published: May 2022

Triple-negative breast cancer (TNBC) is a heterogeneous disease with diverse, often poor prognoses and treatment responses. In order to identify targetable biomarkers and guide personalized care, scientists have developed multiple molecular classification systems for TNBC based on transcriptomic profiling. However, there is no consensus on the molecular subtypes of TNBC, likely due to discrepancies in technical and computational methods used by different research groups. Here, we reassessed the major steps for TNBC subtyping, validated the reproducibility of established TNBC subtypes, and identified two more subtypes with a larger sample size. By comparing results from different workflows, we demonstrated the limitations of formalin-fixed, paraffin-embedded samples, as well as batch effect removal across microarray platforms. We also refined the usage of computational tools for TNBC subtyping. Furthermore, we integrated high-quality multi-institutional TNBC datasets (discovery set: n = 457; validation set: n = 165). Performing unsupervised clustering on the discovery and validation sets independently, we validated four previously discovered subtypes: luminal androgen receptor, mesenchymal, immunomodulatory, and basal-like immunosuppressed. Additionally, we identified two potential intermediate states of TNBC tumors based on their resemblance with more than one well-characterized subtype. In summary, we addressed the issues and limitations of previous TNBC subtyping through comprehensive analyses. Our results promote the rational design of future subtyping studies and provide new insights into TNBC patient stratification.
High-Fat Diet Enhances the Liver Metastasis Potential of Colorectal Cancer through Microbiota Dysbiosis
Authors: Yu Yina , Cai Yangke , Yang Bin , Xie Siyuan , Shen Wenjuan , Wu Yaoyi , Sui Ziqi , Cai Jianting , Ni Chao , Ye Jun
Published: May 2022

Obesity, metabolic changes, and intestinal microbiota disruption significantly affect tumorigenesis and metastasis in colorectal cancer (CRC). However, the relationships among these factors remain poorly understood. In this study, we found that a high-fat diet (HFD) promoted gut barrier dysfunction and inflammation in the colorectum and liver. We further investigated gut microbiota changes through 16S rRNA sequencing of faecal samples from HFD-fed rats and CRC hepatic metastasis patients and found an abundance of Desulfovibrio (DSV). DSV could also induce barrier dysfunction in the colorectum and inflammation in the colorectum and liver, suggesting that it contributes to the formation of a microenvironment conducive to CRC tumorigenesis and metastasis. These findings highlight that HFD-induced microbiota dysbiosis, especially DSV abundance, could promote CRC initiation and metastasis.