bluuebunny/crossref_metadata_2025 huggingface dataset:
A Clinical and Pathophysiological Overview of Intestinal and Systemic Diseases Associated with Pancreatic Disorders: Causality or Casualty?
Authors: Conti Bellocchi Maria Cristina , Crinò Stefano Francesco , De Marchi Giulia , De Pretis Nicolò , Ofosu Andrew , Caldart Federico , Ciccocioppo Rachele , Frulloni Luca
Published: May 2023

The relationship between chronic intestinal disease, including inflammatory bowel disease (IBD) and celiac disease (CelD), and pancreatic disorders has been little investigated. Although an increased risk of acute pancreatitis (AP), exocrine pancreatic insufficiency with or without chronic pancreatitis, and chronic asymptomatic pancreatic hyperenzymemia have been described in these patients, the pathogenetic link remains unclear. It may potentially involve drugs, altered microcirculation, gut permeability/motility with disruption of enteric-mediated hormone secretion, bacterial translocation, and activation of the gut-associated lymphoid tissue related to chronic inflammation. In addition, the risk of pancreatic cancer seems to be increased in both IBD and CelD patients with unknown pathogenesis. Finally, other systemic conditions (e.g., IgG4-related disease, sarcoidosis, vasculitides) might affect pancreatic gland and the intestinal tract with various clinical manifestations. This review includes the current understandings of this enigmatic association, reporting a clinical and pathophysiological overview about this topic.
Time-Updated Phenotypic Guidance of Corticosteroids and Antibiotics in COPD: Rationale, Perspective and a Proposed Method
Authors: Jordan Alexander , Sivapalan Pradeesh , Rømer Valdemar , Jensen Jens-Ulrik
Published: May 2023

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with distinct phenotypes, each having distinct treatment needs. Eosinophilic airway inflammation is present in a subset of COPD patients in whom it can act as a driver of exacerbations. Blood eosinophil counts are a reliable way to identify patients with an eosinophilic phenotype, and these measurements have proven to be successful in guiding the use of corticosteroids in moderate and severe COPD exacerbations. Antibiotic use in COPD patients induces a risk of Clostridium difficile infection, diarrhea, and antibiotic resistance. Procalcitonin could possibly guide antibiotic treatment in patients admitted with AECOPD. Current studies in COPD patients were successful in reducing exposure to antibiotics with no changes in mortality or length of stay. Daily monitoring of blood eosinophils is a safe and effective way to reduce oral corticosteroid exposure and side effects for acute exacerbations. No evidence on time-updated treatment guidance for stable COPD exists yet, but a current trial is testing an eosinophil-guided approach on inhaled corticosteroid use. Procalcitonin-guided antibiotic treatment in AECOPD shows promising results in safely and substantially reducing antibiotic exposure both in time-independent and time-updated algorithms.
An Insight into Cellular and Molecular Mechanisms Underlying the Pathogenesis of Neurodegeneration in Alzheimer’s Disease
Authors: Ratan Yashumati , Rajput Aishwarya , Maleysm Sushmita , Pareek Aaushi , Jain Vivek , Pareek Ashutosh , Kaur Ranjeet , Singh Gurjit
Published: May 2023

Alzheimer’s disease (AD) is the most prominent neurodegenerative disorder in the aging population. It is characterized by cognitive decline, gradual neurodegeneration, and the development of amyloid-β (Aβ)-plaques and neurofibrillary tangles, which constitute hyperphosphorylated tau. The early stages of neurodegeneration in AD include the loss of neurons, followed by synaptic impairment. Since the discovery of AD, substantial factual research has surfaced that outlines the disease’s causes, molecular mechanisms, and prospective therapeutics, but a successful cure for the disease has not yet been discovered. This may be attributed to the complicated pathogenesis of AD, the absence of a well-defined molecular mechanism, and the constrained diagnostic resources and treatment options. To address the aforementioned challenges, extensive disease modeling is essential to fully comprehend the underlying mechanisms of AD, making it easier to design and develop effective treatment strategies. Emerging evidence over the past few decades supports the critical role of Aβ and tau in AD pathogenesis and the participation of glial cells in different molecular and cellular pathways. This review extensively discusses the current understanding concerning Aβ- and tau-associated molecular mechanisms and glial dysfunction in AD. Moreover, the critical risk factors associated with AD including genetics, aging, environmental variables, lifestyle habits, medical conditions, viral/bacterial infections, and psychiatric factors have been summarized. The present study will entice researchers to more thoroughly comprehend and explore the current status of the molecular mechanism of AD, which may assist in AD drug development in the forthcoming era.
Electrophysiological and Behavioral Effects of Alpha-Band Sensory Entrainment: Neural Mechanisms and Clinical Applications
Authors: Gallina Jessica , Marsicano Gianluca , Romei Vincenzo , Bertini Caterina
Published: May 2023

Alpha-band (7–13 Hz) activity has been linked to visuo-attentional performance in healthy participants and to impaired functionality of the visual system in a variety of clinical populations including patients with acquired posterior brain lesion and neurodevelopmental and psychiatric disorders. Crucially, several studies suggested that short uni- and multi-sensory rhythmic stimulation (i.e., visual, auditory and audio-visual) administered in the alpha-band effectively induces transient changes in alpha oscillatory activity and improvements in visuo-attentional performance by synchronizing the intrinsic brain oscillations to the external stimulation (neural entrainment). The present review aims to address the current state of the art on the alpha-band sensory entrainment, outlining its potential functional effects and current limitations. Indeed, the results of the alpha-band entrainment studies are currently mixed, possibly due to the different stimulation modalities, task features and behavioral and physiological measures employed in the various paradigms. Furthermore, it is still unknown whether prolonged alpha-band sensory entrainment might lead to long-lasting effects at a neural and behavioral level. Overall, despite the limitations emerging from the current literature, alpha-band sensory entrainment may represent a promising and valuable tool, inducing functionally relevant changes in oscillatory activity, with potential rehabilitative applications in individuals characterized by impaired alpha activity.
Viral Coinfection of Children Hospitalized with Severe Acute Respiratory Infections during COVID-19 Pandemic
Authors: Malveste Ito Célia Regina , Moreira André Luís Elias , Silva Paulo Alex Neves da , Santos Mônica de Oliveira , Santos Adailton Pereira dos , Rézio Geovana Sôffa , Brito Pollyanna Neta de , Rezende Alana Parreira Costa , Fonseca Jakeline Godinho , Peixoto Fernanda Aparecida de Oliveira , Wastowski Isabela Jubé , Goes Viviane Monteiro , Estrela Mariely Cordeiro , Souza Priscila Zanette de , Carneiro Lilian Carla , Avelino Melissa Ameloti Gomes
Published: May 2023

The main pathogens of severe respiratory infection in children are respiratory viruses, and the current molecular technology allows for a rapid and simultaneous detection of a wide spectrum of these viral pathogens, facilitating the diagnosis and evaluation of viral coinfection. Methods: This study was conducted between March 2020 and December 2021. All children admitted to the ICU with a diagnosis of SARI and who were tested by polymerase chain reaction on nasopharyngeal swabs for SARS-CoV-2 and other common respiratory viral pathogens were included in the study. Results: The result of the viral panel identified 446 children, with one infected with a single virus and 160 co-infected with two or more viruses. This study employed descriptive analyses, where a total of twenty-two coinfections among SARI-causing viruses were identified. Thus, the five most frequent coinfections that were selected for the study are: hRV/SARS-CoV-2 (17.91%), hRV/RSV (14.18%), RSV/SARS-CoV-2 (12.69%), hRV/BoV (10.45%), and hRV/AdV (8.21%). The most significant age group was 38.1%, representing patients aged between 24 and 59 months (61 individuals). Patients older than 59 months represented a total of 27.5%, comprising forty-four patients. The use of oxygen therapy was statistically significant in coinfections with Bocavirus, other CoVs, Metapneumovirus, and RSV. Coinfections with SARS-CoV-2 and the other different coinfections presented a similar time of use of oxygen therapy with a value of (p > 0.05). In the year 2020, hRV/BoV was more frequent in relation to other types of coinfections, representing a total of 35.1%. The year 2021 presented a divergent profile, with hRV/SARS-CoV-2 coinfection being the most frequent (30.8%), followed by hRV/RSV (28.2%). Additionally, 25.6% and 15.4% represented coinfections between RSV/SARS-CoV-2 and hRV/AdV, respectively. We saw that two of the patients coinfected with hRV/SARS-CoV-2 died, representing 9.52% of all deaths in the study. In addition, both hRV/hBoV and hRV/RSV had death records for each case, representing 8.33% and 6.67% of all deaths, respectively. Conclusion: Coinfections with respiratory viruses, such as RSV and hBoV, can increase the severity of the disease in children with SARI who are admitted to the ICU, and children infected with SARS-CoV-2 have their clinical condition worsened when they have comorbidities.
A Numerical Modelling Framework for Investigating the Ballistic Performance of Bio-Inspired Body Armours
Authors: Ghazlan Abdallah , Ngo Tuan , Tan Ping , Tran Phuong , Xie Yi
Published: May 2023

Biological structures possess excellent damage tolerance, which makes them attractive for ballistic protection applications. This paper develops a finite element modelling framework to investigate the performance of several biological structures that are most relevant for ballistic protection, including nacre, conch, fish scales, and crustacean exoskeleton. Finite element simulations were conducted to determine the geometric parameters of the bio-inspired structures that can survive projectile impact. The performances of the bio-inspired panels were benchmarked against a monolithic panel with the same 4.5 mm overall thickness and projectile impact condition. It was found that the biomimetic panels that were considered possessed better multi-hit resistant capabilities compared to the selected monolithic panel. Certain configurations arrested a fragment simulating projectile with an initial impact velocity of 500 m/s, which was similar to the performance of the monolithic panel.
L-DOPA Improves Ventilation but Not the Ventilatory Response to Hypercapnia in a Reserpine Model of Parkinson’s Disease
Authors: Jampolska Monika , Andrzejewski Kryspin , Boguszewski Paweł M. , Kaczyńska Katarzyna
Published: May 2023

Parkinson’s disease (PD) is a neurological disorder characterized by progressive degeneration of the substantia nigra that affects mainly movement control. However, pathological changes associated with the development of PD may also alter respiration and can lead to chronic episodes of hypoxia and hypercapnia. The mechanism behind impaired ventilation in PD is unclear. Therefore, in this study, we explore the hypercapnic ventilatory response in a reproducible reserpine-induced (RES) model of PD and parkinsonism. We also investigated how dopamine supplementation with L-DOPA, a classic drug used to treat PD, would affect the breathing and respiratory response to hypercapnia. Reserpine treatment resulted in decreased normocapnic ventilation and behavioral changes manifested as low physical activity and exploratory behavior. The respiratory rate and the minute ventilation response to hypercapnia were significantly higher in sham rats compared to the RES group, while the tidal volume response was lower. All of this appears to be due to reduced baseline ventilation values produced by reserpine. L-DOPA reversed reduced ventilation, indicating a stimulatory effect of DA on breathing, and showed the potency of DA supplementation in restoring normal respiratory activity.
Impulsivity and Alcohol-Drinking Behavior: Evidence from Japan
Authors: Fukuda Sayaka , Katauke Takuya , Hattori Saki , Tanaka Soma , Kurushima Yu , Arakawa Yoichi , Ikeda Nao , Kinoshita Haruka , Urayama Mikito , Shimizu Ryota , Anan Tomohide , Ifuku Shinya , Shiwaku Yuta , Khan Mostafa Saidur Rahim , Kadoya Yoshihiko
Published: May 2023

Despite the attempt by the Japanese government to reduce alcohol consumption, reduction of alcohol consumption requires improvement. We explore this issue from the impulsivity perspective and investigate whether a causal relationship exists between impulsivity and drinking behavior. We used data from the Preference Parameter Study of Osaka University to capture respondents’ drinking status. Our probit regression showed that procrastination, a proxy measure of impulsivity, was significantly associated with drinking behavior, while hyperbolic discounting, a direct measure of impulsivity, was insignificant. Our findings suggest that impulsive people will discount their health in the future; thus, the government should consider impulsivity in policymaking. For example, awareness programs should focus more on future healthcare costs from alcohol-related problems so that impulsive drinkers can understand how much they may need to spend in the future compared to current satisfaction with alcohol drinking.
A Semi-Explicit Practical Coding Method for Prefabricated Building Component Parts in China
Authors: Shan Zhi , Fu Dingkang , Qiu Lijie , Liang Yuling , Huang Chao
Published: May 2023

In the context of building industrialization, the dissemination and transmission of information related to prefabricated building component parts are of paramount importance throughout the building’s life cycle and the entire industry chain, necessitating high standards of information integration. At present, the development of information coding for prefabricated building component parts in China is hindered by various challenges, such as the lack of uniform norms and standards across different regions, as well as significant differences in the composition and character length of coded information categories. Through reviewing academic papers and society, group, and local standards related to the coding of prefabricated building component parts, this article identifies the importance of component part coding information categories. Considering the readability of codes, a practical coding system is adopted for the coding design, proposing a semi-implicit practical coding method for prefabricated building component parts. This method has strong flexibility and wide applicability. Additionally, a common coding system for component parts is devised to address the issue of missing information caused by the limited characters of component parts codes. This system enables comprehensive life cycle information management of component parts of prefabricated buildings and promotes the application of prefabricated buildings in China.
Occupational Road Safety Management: A Preliminary Insight for a Landfill Remediation Site
Authors: Lombardi Mara , Mauro Francesca , Berardi Davide , Galuppi Marta
Published: May 2023

Road crashes have been internationally recognized as one of the main causes of death. On one hand, in Europe, many governments are struggling with the ambitious target of zero road deaths by 2050. On the other hand, they are facing remediation of illegal waste dumps, subject to European infringement procedures and involving a lot of workers and heavy materials transportation. With the aim to further explore occupational health and safety (OHS) issues related to the remediation of such contaminated sites close to urban areas, we decided to focus our attention on road crashes involving people while working in the transport of materials and goods (i.e., occupational road safety). In the scientific literature, it is considered an emerging matter of concern, but no significant contribution nor specific procedures have been provided in this research field for workers in charge of contaminated sites. With the aim to fill such a gap, we decided to, first, investigate the impacts of a landfill remediation site (Malagrotta landfill, near Rome—Italy) on road safety in the surrounding context. Then, road safety management measures for workers driving heavy vehicles from and toward the reference site were suggested through the means of cluster analysis. The main road accident determinants (road safety signs and traffic conditions) for heavy vehicles in the Rome municipality, derived from a sample of 166 events, occurred in the period 2017–2021 on target road infrastructures for the case study. The events were finally grouped with a k-means three-centroid solution. Overall, despite the intrinsic limits related to the data’s details, this paper provides a specific and data-driven methodology to address occupational road safety near a landfill remediation site and encourages further research in this field.
Interventional Treatment Strategies in Intrahepatic Cholangiocarcinoma and Perspectives for Combined Hepatocellular-Cholangiocarcinoma
Authors: Auer Timo Alexander , Collettini Federico , Segger Laura , Pelzer Uwe , Mohr Raphael , Krenzien Felix , Gebauer Bernhard , Geisel Dominik , Hosse Clarissa , Schöning Wenzel , Fehrenbach Uli
Published: May 2023

cHCC-CCA is an uncommon type of liver cancer that exhibits clinical and pathological characteristics of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), which are the two main forms of primary liver cancer. The similarity to HCC and CCA makes therapeutical strategies challenging. The poor prognosis of CCA in general, as well as for cHCC-CCA, is mainly attributable to the fact that diagnosis is often at an advanced stage of disease. During the last decade, locoregional therapies usually performed by interventional radiologists and its established role in HCC treatment have gained an increasing role in CCA treatment as well. These comprise a wide range of options from tumor ablation procedures such as radiofrequency ablation (RFA), microwave ablation (MWA), computed tomography high-dose rate brachytherapy (CT-HDRBT), and cryoablation to transarterial chemoembolization (TACE), including the option of intra-arterial administration of radioactive spheres (transarterial radioembolization—TARE), and much attention has focused on the potential of individual concepts in recent years. The purpose of this review is to provide an overview of current radiologic interventions for CCA (excluding options for eCCA), to review and appraise the existing literature on the topic, and to provide an outlook on whether such interventions may have a role as treatment for cHCC-CCA in the future.
Preoperative Arterial Embolization of Musculoskeletal Tumors: A Tertiary Center Experience
Authors: Kedra Alice , Dohan Anthony , Biau David , Belbachir Anissa , Dautry Raphael , Lucas Alexandre , Aissaoui Mathilde , Feydy Antoine , Soyer Philippe , Barat Maxime
Published: May 2023

The purpose of this study was to report the effectiveness of preoperative transcatheter arterial embolization (TAE) of musculoskeletal tumors in terms of blood loss and functional outcomes. Patients who underwent preoperative TAE of hypervascular musculoskeletal tumors between January 2018 and December 2021 were retrospectively included. The patients’ characteristics, TAE procedure details, degree of post-TAE devascularization, surgical outcomes in terms of red blood cell transfusion and functional results were collected. The degree of devascularization was compared between patients who had peri-operative transfusion and those who did not. Thirty-one patients were included. The 31 TAE procedures led to complete (58%) or near-complete (42%) tumor devascularization. Twenty-two patients (71%) had no blood transfusion during surgery. Nine patients (29%) had a blood transfusion, with a median number of red blood cell packs of three (q1, 2; q3, 4; range: 1–4). Eight patients (27%) had complete improvement of the initial musculoskeletal symptoms at the end of the follow-up, 15 (50%) had partially satisfying improvement, 4 (13%) had partially unsatisfying improvement and 3 (10%) had no improvement. Our study suggests that preoperative TAE of hypervascular musculoskeletal tumors allowed for bloodless surgery in 71% of patients and minimal transfusion needs for the remaining 29%.
Clinical Significance of microRNAs in Hematologic Malignancies and Hematopoietic Stem Cell Transplantation
Authors: Sevcikova Aneta , Fridrichova Ivana , Nikolaieva Nataliia , Kalinkova Lenka , Omelka Radoslav , Martiniakova Monika , Ciernikova Sona
Published: May 2023

Hematologic malignancies are a group of neoplastic conditions that can develop from any stage of the hematopoiesis cascade. Small non-coding microRNAs (miRNAs) play a crucial role in the post-transcriptional regulation of gene expression. Mounting evidence highlights the role of miRNAs in malignant hematopoiesis via the regulation of oncogenes and tumor suppressors involved in proliferation, differentiation, and cell death. In this review, we provide current knowledge about dysregulated miRNA expression in the pathogenesis of hematological malignancies. We summarize data about the clinical utility of aberrant miRNA expression profiles in hematologic cancer patients and their associations with diagnosis, prognosis, and the monitoring of treatment response. Moreover, we will discuss the emerging role of miRNAs in hematopoietic stem cell transplantation (HSCT), and severe post-HSCT complications, such as graft-versus-host disease (GvHD). The therapeutical potential of the miRNA-based approach in hemato-oncology will be outlined, including studies with specific antagomiRs, mimetics, and circular RNAs (circRNAs). Since hematologic malignancies represent a full spectrum of disorders with different treatment paradigms and prognoses, the potential use of miRNAs as novel diagnostic and prognostic biomarkers might lead to improvements, resulting in a more accurate diagnosis and better patient outcomes.
Efficacy of Lymph Node Location-Number Hybrid Staging System on the Prognosis of Gastric Cancer Patients
Authors: Wu Junpeng , Wang Hao , Yin Xin , Wang Xibo , Wang Yufei , Lu Zhanfei , Zhang Jiaqi , Zhang Yao , Xue Yingwei
Published: May 2023

Background: Lymph node metastasis location and number significantly affects the prognosis of patients with gastric cancer (GC). This study was designed to examine a new lymph node hybrid staging (hN) system to increase the predictive ability for patients with GC. Methods: This study analyzed the gastrointestinal treatment of GC at the Harbin Medical University Cancer Hospital from January 2011 to December 2016, and selected 2598 patients from 2011 to 2015 as the training cohort (hN) and 756 patients from 2016 as the validation cohort (2016-hN). The study utilized the receiver operating characteristic curve (ROC), c-index, and decision curve analysis (DCA) to compare the prognostic performance of the hN with the 8th edition of AJCC pathological lymph node (pN) staging for GC patients. Results: The ROC verification of the training cohort and validation cohort based on each hN staging and pN staging showed that for each N staging, the hN staging had a training cohort with an AUC of 0.752 (0.733, 0.772) and a validation cohort with an AUC of 0.812 (0.780, 0.845). In the pN staging, the training cohort had an AUC of 0.728 (0.708, 0.749), and the validation cohort had an AUC of 0.784 (0.754, 0.824). c-Index and DCA also showed that hN staging had a higher prognostic ability than pN staging, which was confirmed in the training cohort and the verification cohort, respectively. Conclusion: Lymph node location-number hybrid staging can significantly improve the prognosis of patients with GC.
Roles of the PARP Inhibitor in BRCA1 and BRCA2 Pathogenic Mutated Metastatic Prostate Cancer: Direct Functions and Modification of the Tumor Microenvironment
Authors: Inoue Takahiro , Sekito Sho , Kageyama Takumi , Sugino Yusuke , Sasaki Takeshi
Published: May 2023

Cancer cells frequently exhibit defects in DNA damage repair (DDR), leading to genomic instability. Mutations in DDR genes or epigenetic alterations leading to the downregulation of DDR genes can result in increased dependency on other DDR pathways. Therefore, DDR pathways could be a treatment target for various cancers. In fact, polyadenosine diphosphatase ribose polymerase (PARP) inhibitors, such as olaparib (Lynparza®), have shown remarkable therapeutic efficacy against BRCA1/2-mutant cancers through synthetic lethality. Recent genomic analytical advancements have revealed that BRCA1/BRCA2 pathogenic variants are the most frequent mutations among DDR genes in prostate cancer. Currently, the PROfound randomized controlled trial is investigating the efficacy of a PARP inhibitor, olaparib (Lynparza®), in patients with metastatic castration-resistant prostate cancer (mCRPC). The efficacy of the drug is promising, especially in patients with BRCA1/BRCA2 pathogenic variants, even if they are in the advanced stage of the disease. However, olaparib (Lynparza®) is not effective in all BRCA1/2 mutant prostate cancer patients and inactivation of DDR genes elicits genomic instability, leading to alterations in multiple genes, which eventually leads to drug resistance. In this review, we summarize PARP inhibitors’ basic and clinical mechanisms of action against prostate cancer cells and discuss their effects on the tumor microenvironment.
Intraoperative Assessment of Breast Cancer Tissues after Breast-Conserving Surgery Based on Mapping the Attenuation Coefficients in 3D Cross-Polarization Optical Coherence Tomography
Authors: Gubarkova Ekaterina , Kiseleva Elena , Moiseev Alexander , Vorontsov Dmitry , Kuznetsov Sergey , Plekhanov Anton , Karabut Maria , Sirotkina Marina , Gelikonov Grigory , Gamayunov Sergey , Vorontsov Alexey , Krivorotko Petr , Gladkova Natalia
Published: May 2023

Intraoperative differentiation of tumorous from non-tumorous tissue can help in the assessment of resection margins in breast cancer and its response to therapy and, potentially, reduce the incidence of tumor recurrence. In this study, the calculation of the attenuation coefficient and its color-coded 2D distribution was performed for different breast cancer subtypes using spectral-domain CP OCT. A total of 68 freshly excised human breast specimens containing tumorous and surrounding non-tumorous tissues after BCS was studied. Immediately after obtaining structural 3D CP OCT images, en face color-coded attenuation coefficient maps were built in co-(Att(co)) and cross-(Att(cross)) polarization channels using a depth-resolved approach to calculating the values in each A-scan. We determined spatially localized signal attenuation in both channels and reported ranges of attenuation coefficients to five selected breast tissue regions (adipose tissue, non-tumorous fibrous connective tissue, hyalinized tumor stroma, low-density tumor cells in the fibrotic tumor stroma and high-density clusters of tumor cells). The Att(cross) coefficient exhibited a stronger gain contrast of studied tissues compared to the Att(co) coefficient (i.e., conventional attenuation coefficient) and, therefore, allowed improved differentiation of all breast tissue types. It has been shown that color-coded attenuation coefficient maps may be used to detect inter- and intra-tumor heterogeneity of various breast cancer subtypes as well as to assess the effectiveness of therapy. For the first time, the optimal threshold values of the attenuation coefficients to differentiate tumorous from non-tumorous breast tissues were determined. Diagnostic testing values for Att(cross) coefficient were higher for differentiation of tumor cell areas and tumor stroma from non-tumorous fibrous connective tissue: diagnostic accuracy was 91–99%, sensitivity—96–98%, and specificity—87–99%. Att(co) coefficient is more suitable for the differentiation of tumor cell areas from adipose tissue: diagnostic accuracy was 83%, sensitivity—84%, and specificity—84%. Therefore, the present study provides a new diagnostic approach to the differentiation of breast cancer tissue types based on the assessment of the attenuation coefficient from real-time CP OCT data and has the potential to be used for further rapid and accurate intraoperative assessment of the resection margins during BCS.
HER2 Intratumoral Heterogeneity in Breast Cancer, an Evolving Concept
Authors: Hou Yanjun , Nitta Hiroaki , Li Zaibo
Published: May 2023

Amplification and/or overexpression of human epidermal growth factor receptor 2 (HER2) in breast cancer is associated with an adverse prognosis. The introduction of anti-HER2 targeted therapy has dramatically improved the clinical outcomes of patients with HER2-positive breast cancer. Unfortunately, a significant number of patients eventually relapse and develop distant metastasis. HER2 intratumoral heterogeneity (ITH) has been reported to be associated with poor prognosis in patients with anti-HER2 targeted therapies and was proposed to be a potential mechanism for anti-HER2 resistance. In this review, we described the current definition, common types of HER2 ITH in breast cancer, the challenge in interpretation of HER2 status in cases showing ITH and the clinical applications of anti-HER2 agents in breast cancer showing heterogeneous HER2 expression. Digital image analysis has emerged as an objective and reproducible scoring method and its role in the assessment of HER2 status with ITH remains to be demonstrated.
Sex- and Co-Mutation-Dependent Prognosis in Patients with SMARCA4-Mutated Malignancies
Authors: Pan Minggui , Jiang Chen , Zhang Zheyang , Achacoso Ninah , Solorzano-Pinto Aleyda V. , Tse Pam , Chung Elaine , Suga Jennifer Marie , Thomas Sachdev , Habel Laurel A.
Published: May 2023

Background: Whether sex and co-mutations impact prognosis of patients with SMARCA4-mutated (mutSMARCA4) malignancies is not clear. Methods: This cohort included patients from Northern California Kaiser Permanente with next-generation sequencing (NGS) performed from August 2020 to October 2022. We used Cox regression modeling to examine the association between sex and overall survival (OS), adjusting for demographics, performance status, Charlson comorbidity index, receipt of treatment, tumor mutation burden (TMB), and TP53, KRAS, CDKN2A, STK11, and Keap1 co-mutations. Results: Out of 9221 cases with NGS performed, 125 cases (1.4%) had a mutSMARCA4. The most common malignancies with a mutSMARCA4 were non-small cell lung cancer (NSCLC, 35.2%), esophageal and stomach adenocarcinoma (12.8%), and cancer of unknown primary (11.2%). The most common co-mutations were p53 (mutp53, 59.2%), KRAS (mutKRAS, 28.8%), CDKN2A (mutCDKN2A, 31.2%), STK11 (mutSTK11, 12.8%), and Keap1 (mutKeap1, 8.8%) mutations. Male patients had substantially worse OS than female patients both among the entire mutSMARCA4 cohort (HR = 1.71, [95% CI 0.92–3.18]) with a median OS of 3.0 versus 43.3 months (p < 0.001), and among the NSCLC subgroup (HR = 14.2, [95% CI 2.76–73.4]) with a median OS of 2.75 months versus un-estimable (p = 0.02). Among all patients with mutSMARCA4, mutp53 versus wtp53 (HR = 2.12, [95% CI 1.04–4.29]) and mutSTK11 versus wtSTK11 (HR = 2.59, [95% CI 0.87–7.73]) were associated with worse OS. Among the NSCLC subgroup, mutp53 versus wtp53 (HR = 0.35, [0.06–1.97]) and mutKRAS versus wtKRAS (HR = 0.04, [0.003-.45]) were associated with better OS, while mutCDKN2A versus wtCDKN2A (HR = 5.04, [1.12–22.32]), mutSTK11 versus wtSTK11 (HR = 13.10, [95% CI 1.16–148.26]), and mutKeap1 versus wtKeap1 (HR = 5.06, [95% CI 0.89–26.61}) were associated with worse OS. Conclusion: In our cohort of patients with mutSMARCA4, males had substantially worse prognosis than females, while mutTP53, mutKRAS, mutCDKN2A, mutSTK11 and mutKeap1were differentially associated with prognosis among all patients and among the NSCLC subgroup. Our results, if confirmed, could suggest potentially unidentified mechanisms that underly this sex and co-mutation-dependent prognostic disparity among patients whose tumor bears a mutSMARCA4.
The Current Treatment Trends and Survival Patterns in Melanoma Patients with Positive Sentinel Lymph Node Biopsy (SLNB): A Multicenter Nationwide Study
Authors: Ziętek Marcin , Teterycz Paweł , Wierzbicki Jędrzej , Jankowski Michał , Las-Jankowska Manuela , Zegarski Wojciech , Piekarski Janusz , Nejc Dariusz , Drucis Kamil , Cybulska-Stopa Bożena , Łobaziewicz Wojciech , Galwas Katarzyna , Kamińska-Winciorek Grażyna , Zdzienicki Marcin , Sryukina Tatsiana , Ziobro Anna , Kluz Agnieszka , Czarnecka Anna M. , Rutkowski Piotr
Published: May 2023

Background: In melanoma treatment, an approach following positive sentinel lymph node biopsy (SLNB) has been recently deescalated from completion lymph node dissection (CLND) to active surveillance based on phase III trials data. In this study, we aim to evaluate treatment strategies in SLNB-positive melanoma patients in real-world practice. Methods: Five-hundred-fifty-seven melanoma SLNB-positive patients from seven comprehensive cancer centers treated between 2017 and 2021 were included. Kaplan–Meier methods and the Cox Proportional-Hazards Model were used for analysis. Results: The median follow-up was 25 months. Between 2017 and 2021, the percentage of patients undergoing CLND decreased (88–41%), while the use of adjuvant treatment increased (11–51%). The 3-year OS and RFS rates were 77.9% and 59.6%, respectively. Adjuvant therapy prolonged RFS (HR:0.69, p = 0.036)), but CLND did not (HR:1.22, p = 0.272). There were no statistically significant differences in OS for either adjuvant systemic treatment or CLND. Lower progression risk was also found, and time-dependent hazard ratios estimation in patients treated with systemic adjuvant therapy was confirmed (HR:0.20, p = 0.002 for BRAF inhibitors and HR:0.50, p = 0.015 for anti-PD-1 inhibitors). Conclusions: Treatment of SLNB-positive melanoma patients is constantly evolving, and the role of surgery is currently rather limited. Whether CLND has been performed or not, in a group of SLNB-positive patients, adjuvant systemic treatment should be offered to all eligible patients.
An Image-Based Identification of Aggressive Breast Cancer Circulating Tumor Cell Subtypes
Authors: Kamal Mohamed , Wang Yiru Jess , Plummer Sarai , Dickerson Amber , Yu Min
Published: May 2023

Using previously established CTC lines from breast cancer patients, we identified different morphometric subgroups of CTCs with one of them having the highest tumorigenic potential in vivo despite the slowest cell proliferation in vitro. This subgroup represents 32% of all cells and contains cells with small cell volume, large nucleus to cell, dense nuclear areas to the nucleus, mitochondria to cell volume ratios and rough texture of cell membrane and termed “Small cell, Large mitochondria, Rough membrane” (SLR). RNA-seq analyses showed that the SLR group is enriched in pathways and cellular processes related to DNA replication, DNA repair and metabolism. SLR upregulated genes are associated with poor survival in patients with ER+ breast cancer based on the KM Plotter database. The high tumorigenic potential, slow proliferation, and enriched DNA replication/repair pathways suggest that the SLR subtype is associated with stemness properties. Our new findings provide a simple image-based identification of CTC subpopulations with elevated aggressiveness, which is expected to provide a more accurate prediction of patient survival and therapy response than total CTC numbers. The detection of morphometric and transcriptomic profiles related to the SLR subgroup of CTCs also opens opportunities for potential targeted cancer treatment.
Re-Evaluating the Role of PTHrP in Breast Cancer
Authors: Kane Jeremy F. , Johnson Rachelle W.
Published: May 2023

Parathyroid-hormone-related protein (PTHrP) is a protein with a long history of association with bone metastatic cancers. The paracrine signaling of PTHrP through the parathyroid hormone receptor (PTHR1) facilitates tumor-induced bone destruction, and PTHrP is known as the primary driver of humoral hypercalcemia of malignancy. In addition to paracrine signaling, PTHrP is capable of intracrine signaling independent of PTHR1 binding, which is essential for cytokine-like functions in normal physiological conditions in a variety of tissue types. Pre-clinical and clinical studies evaluating the role of PTHrP in breast cancer have yielded contradictory conclusions, in some cases indicating the protein is tumor suppressive, and in other studies, pro-growth. This review discusses the possible molecular basis for the disharmonious prognostic indications of these studies and highlights the implications of the paracrine, intracrine, and nuclear functions of the protein. This review also examines the current understanding of the functional domains of PTHrP and re-evaluates their role in the unique context of the breast cancer environment. This review will expand on the current understanding of PTHrP by attempting to reconcile the functional domains of the protein with its intracrine signaling in cancer.
Visible-Light-Driven GO/Rh-SrTiO3 Photocatalyst for Efficient Overall Water Splitting
Authors: Zhang Shuai , Jiang Enhui , Wu Ji , Liu Zhonghuan , Yan Yan , Huo Pengwei , Yan Yongsheng
Published: May 2023

The combining of the heterostructure construction and active sites modification to remodel the traditional wide-band-gap semiconductor SrTiO3 for improving visible light absorption capacity and enhancing photocatalytic performance is greatly desired. Herein, we research a novel GO/Rh-SrTiO3 nanocomposite via a facile hydrothermal method. The champion GO/Rh-SrTiO3 nanocomposite exhibits the superior photocatalytic overall water splitting performance with an H2 evolution rate of 55.83 μmol∙g−1∙h−1 and O2 production rate of 23.26 μmol∙g−1∙h−1, realizing a breakthrough from zero with respect to the single-phased STO under visible light (λ ≥ 420 nm). More importantly, a series of characterizations results showed that significantly improving photocatalytic performance originated mainly from the construction of heterostructure and more active sites rooted in Rh metal. In addition, the possible photocatalytic reaction mechanisms and the transport behavior of photogenerated carriers have been revealed in deeper detail. This work provides an effective strategy for heterostructure construction to improve solar utilization through vastly expanding visible light response ranges from traditional UV photocatalysts.
Bioprocessing and Screening of Indigenous Wastes for Hyper Production of Fungal Lipase
Authors: Ali Usman , Anwar Zahid , Hasan Shoaib , Zafar Muddassar , Ain Noor ul , Afzal Fareed , Khalid Waseem , Rahim Muhammad Abdul , Mrabti Hanae Naceiri , AL-Farga Ammar , Eljeam Hamdi Abdel Rasool Abdelsamad
Published: May 2023

Background: Lipase is one of the most important enzymes produced from microbial fermentation. Agricultural wastes are a good source of enzyme production because they are cost-effective and production rates are also higher. Method: In this study, eight lignolitic substrates were screened for lipase production. Results: Out of these substrates, guava leaves showed maximum activity of 9.1 U/mL from Aspergillus niger by using the solid-state fermentation method. Various factors such as temperature, pH, incubation period, moisture content, inoculum size, and substrate size that influence the growth of fungi were optimized by response surface methodology (RSM), and then characterization was performed. When all physical and nutritional parameters were optimized by RSM, the maximum lipase activity obtained was 12.52 U/mL after 4 days of incubation, at pH 8, 40 °C temperature, 3 mL inoculum size, 20% moisture content, and 6 g substrate concentration. The enzyme was partially purified through 70% ammonium sulfate precipitation. After purification, it showed 34.291 U/mg enzyme activity, increasing the purification fold to 1.3. The enzyme was then further purified by dialysis, and the purification fold increased to 1.83 having enzyme activity of 48.03 U/mg. Furthermore, activity was increased to 132.72 U/mg after column chromatography. A purification fold of 5.07 was obtained after all purification steps.
Research Progress in Gas Separation and Purification Based on Zeolitic Materials
Authors: Qi Kai , Gao Lili , Li Xuelian , He Feng
Published: May 2023

The characteristics and preparation methods of zeolite-based adsorbents and membranes were reviewed and their applications in gas separation and purification were introduced according to classification. The effects of framework structure, equilibrium cations and pore size of zeolites as well as temperature and pressure of the system on gas adsorption and separation were discussed, and the separation mechanisms were also summarized. The main defects and improved methods of zeolite-based adsorbents and membranes were briefly described, and their future trend for gas separation and purification was finally prospected.
Lignin Hydrogenolysis over Bimetallic Ni–Ru Nanoparticles Supported on SiO2@HPS
Authors: Stepacheva Antonina A. , Manaenkov Oleg V. , Markova Mariia E. , Sidorov Alexander I. , Bykov Alexsey V. , Sulman Mikhail G. , Kiwi-Minsker Lioubov
Published: May 2023

Lignin obtained by hydrogenolysis of lignocellulose biomass is a prospective source of valuable green fuels and chemicals such as monophenols. One of the key factors in the chemical decomposition of lignin to monophenols is an efficient catalyst. Inert porous materials such as hypercrosslinked polymers are suitable catalytic supports for the immobilization of noble and transition metal nanoparticles. However, such polymers do not have acidic properties, which are crucial for catalyzing hydrolysis. In this work, we report novel, efficient catalysts for lignin hydrogenolysis to produce valuable monophenolic compounds. The synthesized catalysts contained Ni, Ru, and Ni–Ru nanoparticles supported on SiO2-coated hypercrosslinked polystyrene (SiO2@HPS). Ni-Ru/SiO2@HPS demonstrated remarkable stability without any loss of the metallic phase and a high yield of monophenols (>42 wt.%) at close to full lignin conversion (>95 wt.%). This result was attributed to the synergy between the two metals and the support’s surface acidity. All catalysts were fully characterized by a series of physico-chemical methods.
The Construction of p/n-Cu2O Heterojunction Catalysts for Efficient CO2 Photoelectric Reduction
Authors: Zhou Qianqian , Chen Yanxin , Shi Haoyan , Chen Rui , Ji Minghao , Li Kexian , Wang Hailong , Jiang Xia , Lu Canzhong
Published: May 2023

Cu2O is a p-type direct bandgap semiconductor with a band gap of 2~2.2 eV, which has excellent visible light absorption and utilization. However, slow charge transfer and poor stability hinder its practical application. In this paper, a facile electrodeposition approach successfully synthesized the heterostructure of p-Cu2O and n-Cu2O. The protective layer of n-Cu2O on the surface of p-Cu2O nanoparticles forms a p/n heterojunction. Due to the p/n heterojunction, the PEC performance of p/n-Cu2O is enhanced significantly. The charge separation efficiency of photogenerated electron/hole pairs in p/n-Cu2O is greatly improved. Therefore, p/n-Cu2O shows superior photoelectrochemical (PEC) CO2 reduction reaction (CO2RR) efficiency when used as a photocathode.
Improving the Kinetics of H2-Fueled Biological Methanation with Quinone-Based Redox Mediators
Authors: Tucci Matteo , Colantoni Simone , Cruz Viggi Carolina , Aulenta Federico
Published: May 2023

The biomethanation process involves the conversion of CO2 into a valuable energy carrier (i.e., methane) by methanogenic archaea. Since it can be operated at mild conditions, it is more sustainable than traditional chemical approaches. Nevertheless, the efficacy of biomethanation is limited by the low kinetics of the microbiological reaction and the poor solubility of H2 in water. Herein, the effect of soluble (i.e., AQDS) and insoluble (i.e., biochar) quinone-based redox mediators on the kinetics of H2-fueled biological methanation in bench-scale microcosms was investigated. Microcosms were set up in 120 mL serum bottles and were initially inoculated with a methanogenic sludge deriving from a lab-scale anaerobic digester treating food waste. As a result, the kinetics of H2 consumption and CH4 generation were greatly increased (p < 0.05) in presence of AQDS as compared to the control, accounting for up to +160% and +125% in the last experimental cycle, respectively. These findings could be explained by a two-step mechanism, whereby microbes used H2 to quickly reduce AQDS into the highly soluble AH2QDS, which in turn served as a more efficient electron donor for methanogenesis. In contrast, the used biochar had apparently an adverse effect on the biomethanation process.
Microvascular Leakage as Therapeutic Target for Ischemia and Reperfusion Injury
Authors: Kloka Jan Andreas , Friedrichson Benjamin , Wülfroth Petra , Henning Rainer , Zacharowski Kai
Published: May 2023

Reperfusion injury is a very common complication of various indicated therapies such as the re-opening of vessels in the myocardium or brain as well as reflow in hemodynamic shutdown (cardiac arrest, severe trauma, aortic cross-clamping). The treatment and prevention of reperfusion injury has therefore been a topic of immense interest in terms of mechanistic understanding, the exploration of interventions in animal models and in the clinical setting in major prospective studies. While a wealth of encouraging results has been obtained in the lab, the translation into clinical success has met with mixed outcomes at best. Considering the still very high medical need, progress continues to be urgently needed. Multi-target approaches rationally linking interference with pathophysiological pathways as well as a renewed focus on aspects of microvascular dysfunction, especially on the role of microvascular leakage, are likely to provide new insights.
Activated Carbon from Sugarcane Bagasse: A Low-Cost Approach towards Cr(VI) Removal from Wastewater
Authors: Ahmed Rana , Block Inga , Otte Fabian , Günter Christina , Duarte-Rodrigues Alysson , Hesemann Peter , Banerji Amitabh , Taubert Andreas
Published: May 2023

The potential of pretreated sugarcane bagasse (SCB) as a low-cost and renewable source to yield activated carbon (AC) for chromate CrO42− removal from an aqueous solution has been investigated. Raw sugarcane bagasse was pretreated with H2SO4, H3PO4, HCl, HNO3, KOH, NaOH, or ZnCl2 before carbonization at 700 °C. Only pretreatments with H2SO4 and KOH yield clean AC powders, while the other powders still contain non-carbonaceous components. The point of zero charge for ACs obtained from SCB pretreated with H2SO4 and KOH is 7.71 and 2.62, respectively. Batch equilibrium studies show that the most effective conditions for chromate removal are a low pH (i.e., below 3) where >96% of the chromate is removed from the aqueous solution.