bluuebunny/crossref_metadata_2025 huggingface dataset:
Designing Effective Multi-Target Drugs and Identifying Biomarkers in Recurrent Pregnancy Loss (RPL) Using In Vivo, In Vitro, and In Silico Approaches
Authors: Ramírez-Coronel Andrés Alexis , Rostami Amirabbas , Younus Laith A. , Arias Gonzáles José Luis , Lafta Methaq Hadi , Amin Ali H. , Saadoon Mohammed Abdulkadhim , Salman Hayder Mahmood , Bahrami Abolfazl , Feilei Rossa , Akhavan-Sigari Reza
Published: March 2023

Recurrent pregnancy loss (RPL) occurs in approximately 5% of women. Despite an abundance of evidence, the molecular mechanism of RPL’s pathology remains unclear. Here, we report the protective role of polo-like kinase 1 (PLK1) during RPL. We aimed to construct an RPL network utilizing GEO datasets and identified hub high-traffic genes. We also investigated whether the expressions of PLK1 were altered in the chorionic villi collected from women with RPL compared to those from healthy early pregnant women. Gene expression differences were evaluated using both pathway and gene ontology (GO) analyses. The identified genes were validated using in vivo and in vitro models. Mice with PLK1-overexpression and PLK1-knockdown in vitro models were produced by transfecting certain plasmids and si-RNA, respectively. The apoptosis in the chorionic villi, mitochondrial function, and NF-κB signaling activity was evaluated. To suppress the activation of PLK1, the PLK1 inhibitor BI2536 was administered. The HTR-8/SVneo and JEG-3 cell lines were chosen to establish an RPL model in vitro. The NF-κB signaling, Foxo signaling, PI3K/AKT, and endometrial cancer signaling pathways were identified via the RPL regulatory network. The following genes were identified: PLK1 as hub high-traffic gene and MMP2, MMP9, BAX, MFN1, MFN2, FOXO1, OPA1, COX15, BCL2, DRP1, FIS1, TRAF2, and TOP2A. Clinical samples were examined, and the results demonstrated that RPL patients had tissues with decreased PLK1 expression in comparison to women with normal pregnancies (p < 0.01). In vitro, PLK1 knockdown induced the NF-κB signaling pathway and apoptosis activation while decreasing cell invasion, migration, and proliferation (p < 0.05). Furthermore, the in vivo model proved that cell mitochondrial function and chorionic villi development are both hampered by PLK1 suppression. Our findings revealed that the PLK1/TRAF2/NF-κB axis plays a crucial role in RPL-induced chorionic villi dysfunction by regulating mitochondrial dynamics and apoptosis and might be a potential therapeutic target in the clinic.
Total Chemical Synthesis of LC3A and LC3B Activity-Based Probes
Authors: Huppelschoten Yara , Buchardt Jens , Nielsen Thomas E. , Sapmaz Aysegul , van der Heden van Noort Gerbrand J.
Published: March 2023

Autophagy is a conserved cellular process involved in the degradation of intercellular materials. During this process, double-membrane vesicles called autophagosomes engulf cytoplasmic components ready for degradation. A key component in the formation of autophagosomes are the autophagy-related (Atg) proteins, including microtubule-associated protein light chain 3A (LC3A) and 3B (LC3B). After the C-terminus of LC3 is conjugated to a phospholipid, it promotes the elongation of the phagosome and provides a docking station for the delivery of proteins ready for degradation. Since dysregulation of the autophagy pathway has been associated with a variety of human diseases, components of this process have been considered as potential therapeutic targets. However, the mechanistic details of LC3-specific ligases and deconjugation enzymes are far from unraveled and chemical tools for activity profiling could aid in affording more insights into this process. Herein, we describe a native chemical ligation approach for the synthesis of two LC3 activity-based probes (ABPs). Initial studies show that the probes covalently interact with the cysteine protease ATG4B, showcasing the potential of these probes to unravel mechanistic and structural details.
Pancreatic Cancer Organoids: An Emerging Platform for Precision Medicine?
Authors: Sereti Evangelia , Papapostolou Irida , Dimas Konstantinos
Published: March 2023

Despite recent therapeutic advances, pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive malignancies, with remarkable resistance to treatment, poor prognosis, and poor clinical outcome. More efficient therapeutic approaches are urgently needed to improve patients’ survival. Recently, the development of organoid culture systems has gained substantial attention as an emerging preclinical research model. PDAC organoids have been developed to study pancreatic cancer biology, progression, and treatment response, filling the translational gap between in vitro and in vivo models. Here, we review the rapidly evolving field of PDAC organoids and their potential as powerful preclinical tools that could pave the way towards precision medicine for pancreatic cancer.
Improving the Accuracy of Single-Nucleotide Variant Diagnosis Using On–Off Discriminating Primers
Authors: Shin Juny , Jung Cheulhee
Published: March 2023

Early detection of rare mutations through liquid biopsy can provide real-time information related to cancer diagnosis, prognosis, and treatment outcomes. Cell-free DNA samples used in liquid biopsies contain single-nucleotide variants (SNVs) with a variant allele frequency (VAF) of approximately ≤1%. Droplet digital polymerase chain reaction (ddPCR) is considered the gold standard of sequencing using liquid samples, generating amplicons from samples containing mutations with 0.001–0.005% VAF; however, it requires expensive equipment and time-consuming protocols. Therefore, various PCR methods for discriminating SNVs have been developed; nonetheless, non-specific amplification cannot be avoided even in the absence of mutations, which hampers the accurate diagnosis of SNVs. In this study, we introduce single-nucleotide variant on–off discrimination–PCR (Soo-PCR), a highly accurate and practical method that uses a 3′-end tailing primer for the on–off discrimination of low-abundance mutant-type targets, including SNVs. Soo-PCR minimizes the chance of incorrect judgments owing to its high discriminating power. Cancer markers, such as KRAS G12D, EGFR L858R, and EGFR T790M mutations, containing 0.1% VAF, were clearly detected in under 2 h with a high reliability comparable with that of ddPCR. This new method serves as a practical approach to accurately detect and evaluate low-abundance mutations in a user-friendly manner.
The Influencing Mechanism of Incidental Emotions on Risk Perception: Evidence from Event-Related Potential
Authors: Zhang Shu , Yu Xinrou , Shi Xiuzhi , Zhang Yan
Published: March 2023

Incidental emotions would lead to accidents by influencing risk perception. However, few works of research further studied how incidental emotions affect risk perception at the neurological level. Before the experimental task, we used video clips for emotion elicitation. Then, the event-related potential (ERP) technique was used to obtain data on the risk perception process. The results showed that: compared to neutral emotion, the participants’ average reaction time was significantly shorter in positive and negative incidental emotion. Under negative incidental emotion, individuals overestimated risk and had a more significant deviation in risk perception; the amplitude of P2 and N2 components increased, and the amplitude of LPP component decreased under negative incidental emotion. Under positive incidental emotion, individuals’ correct-response rate was higher. These findings indicated that incidental emotions affected the mid-term risk analysis stage and the late risk judgment stage of risk perception. In the mid-term risk analysis stage, individuals processed high-risk information with a negativity bias which led to stronger cognitive conflict, while individuals assessed risks more accurately due to a larger attentional span under positive incidental emotions. In the late risk judgment stage, individuals under negative incidental emotion devoted few attentional resources to risk information which led to a risk judgment deviation. In contrast, individuals had a more detailed cognitive process of risk information under positive incidental emotion. On these bases, this paper confirmed the influence of incidental emotions on risk perception and established an emotional information-processing model. This study provided a reference for emotional interventions to facilitate accident prevention.
Role of Adjuvant Chemotherapy in Stage I Pure Ovarian Immature Teratoma: A Systematic Review and Meta-Analysis
Authors: Li Sijian , Wang Yuelin , Zhang Xinyue , Zhang Tianyu , Yin Min , Yang Jiaxin
Published: March 2023

To determine the role of adjuvant chemotherapy in stage IA G2-3 and stage IB-IC pure ovarian immature teratoma (POIT), we performed a systematic review and meta-analysis by searching PubMed, Embase, Cochrane library, Web of Science, and ClinicalTrials.gov. Randomized controlled trials or cohort studies on stage IA G2-G3 or stage IB-IC POIT between 1 January 1970 and 15 December 2022 were enrolled. The recurrence rate and mortality rate were the primary outcomes, and subgroup analysis based on the tumor stage and grade was also conducted. In total, 15 studies with 707 patients were included. Compared with surveillance, adjuvant chemotherapy significantly decreased the mortality rate (RR 0.31, 95% CI 0.11–0.88, p = 0.03), but not recurrence (RR 0.74, 95% CI 0.39–1.42, p = 0.37), in the overall population. Subgroup analysis showed no statistical difference in the recurrence rate and mortality rate between patients who received adjuvant chemotherapy and surveillance in pediatric POIT, stage IA G2-3 POIT, stage IB-IC POIT, and stage IA-IC G3 POIT (all with p > 0.05). However, patients who underwent adjuvant chemotherapy appeared to have a lower risk of both recurrence (RR 0.17, 95% CI 0.03–0.83, p = 0.03) and death (RR 0.04, 95% CI 0.00–1.00, p = 0.05) in adult POIT. Adjuvant chemotherapy significantly decreased the mortality rate in patients with stage I POIT and lowered the risk of recurrence in the adult subgroup. Surveillance administered in stage I POIT over IA G1 should be cautious, especially in adult patients.
Refining the Characterization and Outcome of Pathological Complete Responders after Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: Lessons from the Randomized Phase III VESPER (GETUG-AFU V05) Trial
Authors: Culine Stéphane , Harter Valentin , Krucker Clémentine , Gravis Gwenaelle , Fléchon Aude , Chevreau Christine , Mahammedi Hakim , Laguerre Brigitte , Guillot Aline , Joly Florence , Fontugne Jacqueline , Allory Yves , Pfister Christian
Published: March 2023

Neoadjuvant cisplatin-based chemotherapy (NAC) followed by radical cystectomy and pelvic lymph node dissection is the optimal treatment for patients with muscle-invasive bladder cancer. In recent years, the VESPER trial showed a statistically significant higher progression-free survival with dd-MVAC (dose dense methotrexate, vinblastine, doxorubicin, and cisplatin) compared to GC (gemcitabine and cisplatin). In the present report, we refine the characterization and outcome of patients whose cystectomy specimens were pathologically free of cancer (pathological complete response, pCR). We confirm that these patients portend a better outcome as compared to patients with invasive disease (≥pT1N0) at cystectomy. Nested variant and lymphovascular invasion were identified as adverse predictive factors of pCR. Progression-free survival probability three years after pCR on cystectomy was about 85%, regardless of the NAC regimen. A lower creatinine clearance and the delivery of less than four cycles were associated with a higher risk of relapse. Predicting the efficacy of NAC remains a major challenge. The planned analysis of molecular subtypes in the VESPER trial could help predict which patients may achieve complete response and better outcome.
Addressing Natural Killer Cell Dysfunction and Plasticity in Cell-Based Cancer Therapeutics
Authors: Coyle Kassandra M. , Hawke Lindsey G. , Ormiston Mark L.
Published: March 2023

Natural killer (NK) cells are cytotoxic group 1 innate lymphoid cells (ILC), known for their role as killers of stressed, cancerous, and virally infected cells. Beyond this cytotoxic function, NK cell subsets can influence broader immune responses through cytokine production and have been linked to central roles in non-immune processes, such as the regulation of vascular remodeling in pregnancy and cancer. Attempts to exploit the anti-tumor functions of NK cells have driven the development of various NK cell-based therapies, which have shown promise in both pre-clinical disease models and early clinical trials. However, certain elements of the tumor microenvironment, such as elevated transforming growth factor (TGF)-β, hypoxia, and indoalemine-2,3-dioxygenase (IDO), are known to suppress NK cell function, potentially limiting the longevity and activity of these approaches. Recent studies have also identified these factors as contributors to NK cell plasticity, defined by the conversion of classical cytotoxic NK cells into poorly cytotoxic, tissue-resident, or ILC1-like phenotypes. This review summarizes the current approaches for NK cell-based cancer therapies and examines the challenges presented by tumor-linked NK cell suppression and plasticity. Ongoing efforts to overcome these challenges are discussed, along with the potential utility of NK cell therapies to applications outside cancer.
Second Primary Cancers in a Population-Based Mesothelioma Registry
Authors: Mensi Carolina , Stella Simona , Dallari Barbara , Rugarli Sabrina , Pesatori Angela Cecilia , Ceresoli Giovanni Luca , Consonni Dario
Published: March 2023

Background: The presence of a second primary cancer (SPC) in patients with pleural mesothelioma (PM) may impact overall survival and suggest a common mechanism of carcinogenesis or an underlying germline genetic alteration. Methods: We evaluated the occurrence of SPCs within PM cases collected from 2000 to 2018 by the Lombardy Mesothelioma Registry and their prognostic implications. Kaplan–Meier analysis was performed to estimate median survival times, together with univariate and multivariate Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) of death. Results: The median overall survival (OS) of the entire study population (N = 6646) was 10.9 months (95% CI: 10.4–11.2); patient age and histotype were the strongest prognostic factors. No substantial survival difference was observed by the presence of an SPC (10.5 months in 1000 patients with an SPC vs. 10.9 months in 5646 patients in the non-SPC group, HR 1.03, p = 0.40). Shorter OS in the SPC group was only observed in 150 patients with the non-epithelioid subtype (median OS of 5.4 vs. 7.1 months, HR 1.21, p = 0.03). Conclusions: The diagnosis of an SPC did not influence the outcome of PM patients in the overall study population but was associated with shorter OS in non-epithelioid cases. Further studies are needed to clarify the role of SPCs as markers of genetic susceptibility in mesothelioma.
Long-Term Follow-Up of Bridging Therapies Prior to CAR T-Cell Therapy for Relapsed/Refractory Large B Cell Lymphoma
Authors: Ladbury Colton , Dandapani Savita , Hao Claire , Fabros Mildred , Amini Arya , Sampath Sagus , Glaser Scott , Sokolov Karen , Yeh Jekwon , Baird John , Thiruvengadam Swetha , Herrera Alex , Mei Matthew , Nikolaenko Liana , Shouse Geoffrey , Budde Lihua
Published: March 2023

Background: Bridging therapy (BT) with systemic therapy (ST), radiation therapy (RT), or combined-modality therapy (CMT) is increasingly being utilized prior to chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL). We report the long-term outcomes of the patients who received commercial CAR T-cell therapy with or without BT. Methods: The patients with LBCL who underwent infusion of a commercial CD19 CAR T product were eligible. The radiation was stratified as comprehensive or focal. The efficacy outcomes and toxicity were analyzed. Results: In total, 156 patients were included and, of them, 52.5% of the patients received BT. The median progression-free survival (PFS) was 0.65 years in the BT cohort compared to 1.45 years in the non-BT cohort. The median overall survival (OS) was 3.16 years in the BT cohort and was not reached in the non-BT cohort. The patients who received comprehensive radiation (versus focal) had significantly improved PFS and OS, achieving a 1-year PFS of 100% vs. 9.1% and 1-year OS of 100% vs. 45.5%. There was no difference in the severe toxicity between any of the nonbridging or BT cohorts. Conclusions: BT did not appear to compromise outcomes with respect to response rates, disease control, survival, and toxicity. The patients with limited disease treated with RT had favorable outcomes.
Machine Learning of Multi-Modal Tumor Imaging Reveals Trajectories of Response to Precision Treatment
Authors: Mansouri Nesrin , Balvay Daniel , Zenteno Omar , Facchin Caterina , Yoganathan Thulaciga , Viel Thomas , Herraiz Joaquin Lopez , Tavitian Bertrand , Pérez-Liva Mailyn
Published: March 2023

The standard assessment of response to cancer treatments is based on gross tumor characteristics, such as tumor size or glycolysis, which provide very indirect information about the effect of precision treatments on the pharmacological targets of tumors. Several advanced imaging modalities allow for the visualization of targeted tumor hallmarks. Descriptors extracted from these images can help establishing new classifications of precision treatment response. We propose a machine learning (ML) framework to analyze metabolic–anatomical–vascular imaging features from positron emission tomography, ultrafast Doppler, and computed tomography in a mouse model of paraganglioma undergoing anti-angiogenic treatment with sunitinib. Imaging features from the follow-up of sunitinib-treated (n = 8, imaged once-per-week/6-weeks) and sham-treated (n = 8, imaged once-per-week/3-weeks) mice groups were dimensionally reduced and analyzed with hierarchical clustering Analysis (HCA). The classes extracted from HCA were used with 10 ML classifiers to find a generalized tumor stage prediction model, which was validated with an independent dataset of sunitinib-treated mice. HCA provided three stages of treatment response that were validated using the best-performing ML classifier. The Gaussian naive Bayes classifier showed the best performance, with a training accuracy of 98.7 and an average area under curve of 100. Our results show that metabolic–anatomical–vascular markers allow defining treatment response trajectories that reflect the efficacy of an anti-angiogenic drug on the tumor target hallmark.
A Handheld Visible Resonance Raman Analyzer Used in Intraoperative Detection of Human Glioma
Authors: Zhang Liang , Zhou Yan , Wu Binlin , Zhang Shengjia , Zhu Ke , Liu Cheng-Hui , Yu Xinguang , Alfano Robert R.
Published: March 2023

There is still a lack of reliable intraoperative tools for glioma diagnosis and to guide the maximal safe resection of glioma. We report continuing work on the optical biopsy method to detect glioma grades and assess glioma boundaries intraoperatively using the VRR-LRRTM Raman analyzer, which is based on the visible resonance Raman spectroscopy (VRR) technique. A total of 2220 VRR spectra were collected during surgeries from 63 unprocessed fresh glioma tissues using the VRR-LRRTM Raman analyzer. After the VRR spectral analysis, we found differences in the native molecules in the fingerprint region and in the high-wavenumber region, and differences between normal (control) and different grades of glioma tissues. A principal component analysis–support vector machine (PCA-SVM) machine learning method was used to distinguish glioma tissues from normal tissues and different glioma grades. The accuracy in identifying glioma from normal tissue was over 80%, compared with the gold standard of histopathology reports of glioma. The VRR-LRRTM Raman analyzer may be a new label-free, real-time optical molecular pathology tool aiding in the intraoperative detection of glioma and identification of tumor boundaries, thus helping to guide maximal safe glioma removal and adjacent healthy tissue preservation.
Hyperinsulinemic and Pro-Inflammatory Dietary Patterns and Metabolomic Profiles Are Associated with Increased Risk of Total and Site-Specific Cancers among Postmenopausal Women
Authors: Jin Qi , Shi Ni , Lee Dong Hoon , Rexrode Kathryn M. , Manson JoAnn E. , Balasubramanian Raji , Zhang Xuehong , Neuhouser Marian L. , Lopez-Pentecost Melissa , Thomson Cynthia A. , Zick Suzanna M. , Felix Ashley S. , Stover Daniel G. , Sardesai Sagar D. , Esnakula Ashwini , Mo Xiaokui , Clinton Steven K. , Tabung Fred K.
Published: March 2023

We evaluated associations of the Empirical Dietary Index for Hyperinsulinemia (EDIH), Empirical Dietary Inflammatory Pattern (EDIP) and Healthy Eating Index (HEI2015) and their metabolomics profiles with the risk of total and site-specific cancers. We used baseline food frequency questionnaires to calculate dietary scores among 112,468 postmenopausal women in the Women’s Health Initiative. We used multivariable-adjusted Cox regression to estimate hazard ratios (HR) and 95% confidence intervals for cancer risk estimation. Metabolomic profile scores were derived using elastic-net regression with leave-one-out cross validation. In over 17.8 years, 18,768 incident invasive cancers were adjudicated. Higher EDIH and EDIP scores were associated with greater total cancer risk, and higher HEI-2015 with lower risk: HRQ5vsQ1(95% CI): EDIH, 1.10 (1.04–1.15); EDIP, 1.08 (1.02–1.15); HEI-2015, 0.93 (0.89–0.98). The multivariable-adjusted incidence rate difference(Q5vsQ1) for total cancer was: +52 (EDIH), +41 (EDIP) and −49 (HEI-2015) per 100,000 person years. All three indices were associated with colorectal cancer, and EDIH and EDIP with endometrial and breast cancer risk. EDIH was further associated with luminal-B, ER-negative and triple negative breast cancer subtypes. Dietary patterns contributing to hyperinsulinemia and inflammation were associated with greater cancer risk, and higher overall dietary quality, with lower risk. The findings warrant the testing of these dietary patterns in clinical trials for cancer prevention among postmenopausal women.
Catalytic Reduction of N2O by CO on Single-Atom Catalysts Au/C2N and Cu/C2N: A First-Principles Study
Authors: Su Shengyang , Ma Junmei , Liu Zhenhua , Holiharimanana Domoina , Sun Hao
Published: March 2023

The catalytic conversion of greenhouse gases, such as N2O, is a promising way to mitigate global warming. In this work, density functional theory (DFT) studies were performed to study N2O reduction by CO over single-atom catalysts (SACs) and compare the performance of noble (Au/C2N) and non-noble (Cu/C2N) SACs. The computational results indicated that catalytic N2O reduction on both catalysts occurs via two mechanisms: (I) the N2O adsorption mechanism—starting from the adsorption on the catalysts, N2O decomposes to a N2 molecule and O-M/C2N intermediate, and then CO reacts with O atom on the O-M/C2N intermediate to form CO2; and (II) the CO adsorption mechanism—CO and N2O are adsorbed on the catalyst successively, and then a synergistic reaction occurs to produce N2 and CO2 directly. The computational results show that mechanism I exhibits an obvious superiority over mechanism II for both catalysts due to the lower activation enthalpy. The activation enthalpies of the rate-determining step in mechanism I are 1.10 and 1.26 eV on Au/C2N and Cu/C2N, respectively. These results imply that Cu/C2N, an abundant-earth SAC, can be as active as expensive Au/C2N. Herein, our research provides a theoretical foundation for the catalytic reduction of N2O and broadens the application of non-noble-metal SACs.
Constructing Z-Scheme 0D/2D TiO2 Nanoparticles/Bi2O3 Nanosheet Heterojunctions with Enhanced Visible Light Induced Photocatalytic Antibiotics Degradation and Hydrogen Evolution
Authors: Xie Lijia , Wu Piaopiao , Lei Qiong , Xu Chong , Huang Weiya , Chen Xunjun , Yang Kai , He Hua
Published: March 2023

Photocatalysis has been regarded as a promising technology for degrading organic pollutants in wastewater and producing hydrogen. In this paper, TiO2 nanoparticles (NPs) were synthesized to improve the visible light absorption of TiO2, which were further combined with Bi2O3 nanosheets to synthesize a series of 0D/2D TiO2 NPs/Bi2O3 nanosheet heterojunctions. The visible light induced photocatalytic activities of the as-synthesized TiO2/Bi2O3 heterojunctions were studied. The optimized catalyst TB-3 with 15 wt% of Bi2O3/TiO2 exhibited the best photocatalytic degradation of tetracycline hydrochloride (TC). The degradation rate constant k of TC over TB-3 was approximately eight times and 39 times greater than that of P25 and Bi2O3, respectively. Additionally, TB-3 showed the highest amount of hydrogen evolution, while that of Bi2O3 was almost zero. The enhancement of photocatalytic performances was ascribed to the improved visible light absorption and the Z-scheme charge transfer path of the TiO2/Bi2O3 heterojunctions, which enhanced the separation efficiency and reduced recombination of photogenerated charge carries, as evidenced by UV–Visible diffuse reflectance spectroscopy (DRS), photoluminescence spectroscopy (PL), and electrochemistry measurements. The active species trapping experiments and the electron spin resonance (ESR) results revealed that ·O2− was the main active substance in the photocatalytic degradation. The possible degradation pathway and intermediate products of TC have been proposed. This work provides experimental evidence supporting the construction of Z-scheme heterojunctions to achieve excellent visible light induced photocatalytic activity.
Development and In Vitro/In Vivo Comparative Characterization of Cryopreserved and Decellularized Tracheal Grafts
Authors: Stocco Elena , Barbon Silvia , Mammana Marco , Trojan Diletta , Bianchin Alice , Favaretto Francesca , Contran Martina , Zambello Giovanni , Vogliardi Andrea , Confalonieri Marta , Todros Silvia , Pavan Piero G. , Romanato Filippo , Conconi Maria Teresa , Macchi Veronica , De Caro Raffaele , Rea Federico , Porzionato Andrea
Published: March 2023

Tracheal reconstruction represents a challenge when primary anastomosis is not feasible. Within this scenario, the study aim was to develop a new pig-derived decellularized trachea (DecellT) to be compared with the cryopreserved counterpart (CryoT) for a close predictive analysis. Tracheal segments underwent decellularization by a physical + enzymatic + chemical method (12 cycles); in parallel, cryopreserved samples were also prepared. Once decellularized (histology/DNA quantification), the two groups were characterized for Alpha-Gal epitopes/structural proteins (immunohistochemistry/histology/biochemical assays/second harmonic generation microscopy)/ultrastructure (Scanning Electron Microscopy (SEM))/mechanical behaviour. Cytotoxicity absence was assessed in vitro (extract-test assay/direct seeding, HM1SV40 cell line) while biocompatibility was verified in BALB/c mice, followed by histological/immunohistochemical analyses and SEM (14 days). Decellularization effectively removed Alpha-Gal epitopes; cartilage histoarchitecture was retained in both groups, showing chondrocytes only in the CryoT. Cryopreservation maintained few respiratory epithelium sparse cilia, not detectable in DecellT. Focusing on ECM, preserved structural/ultrastructural organization and collagen content were observed in the cartilage of both; conversely, the GAGs were significantly reduced in DecellT, as confirmed by mechanical study results. No cytotoxicity was highlighted by CryoT/DecellT in vitro, as they were also corroborated by a biocompatibility assay. Despite some limitations (cells presence/GAGs reduction), CryoT/DecellT are both appealing options, which warrant further investigation in comparative in vivo studies.
The Anti-Snow Behaviour of Icephobic Coatings: Laboratory and In-Field Testing
Authors: Balordi Marcella , Santucci de Magistris Giorgio , Casali Alessandro , Pini Francesco , Cammi Andrea , Lacavalla Matteo , Rotella Vincenzo
Published: March 2023

Overhead power line conductors and ground wires are affected by ice and snow accretion which can easily adhere to their surface, causing the breakage of cables and the collapse of pylons due to excessive weight. In Italy, the main concern is about wet snow: this phenomenon occurs close to zero degrees Celsius with snow density reaching up to 350 Kg/m3. Anti-icing and anti-snow coatings represent a possible strategy to mitigate ice accretion on overhead power line structures. Many works are oriented to achieve anti-icing properties, starting from superhydrophobic coatings or slippery coatings; however, there is a lack of knowledge about the anti-snow behaviour of these surfaces. In this work, aluminium alloy conductor and ground-wire samples were prepared with different coatings, which include hydrophobic, superhydrophobic and slippery surfaces prepared in the laboratory. Characterisations of sample wettability at room and low temperatures and ice adhesion strength were carried out in the laboratory. Anti-snow behaviour was studied in outdoor test facilities in the Italian Alps during several snowfall events. Furthermore, the environmental parameters were also recorded. Two figures of merit were developed to quantify anti-snow behaviour of the samples: one describing the fraction of surfaces covered by snow during the snowfall event and the other representing the maximum accretion load reached on the samples. Results of laboratory and field testing are compared and discussed. Field testing evidenced a promising snowphobic behaviour for all the samples, despite the different anti-icing and wettability properties measured in the laboratory. The mitigation of the phenomenon was found to occur mainly with two different mechanisms: the delay in snow accretion on the surface and/or the early shedding of the snow-sleeve.
Research on the Fracture Characteristics of Asphalt Mixtures in High Altitude and Cold Regions with Large Temperature Differences
Authors: Wang Shuangjie , Cao Haibo , Chen Tuanjie , Ke Wenhao , Bo Wu
Published: March 2023

Due to the harsh climatic conditions in high altitude and cold regions with large temperature differences, asphalt pavement is generally prone to cracking, and the cracks propagate rapidly, which reduces the service life and service level of the road. The factors influencing the fracture characteristics of asphalt mixtures were analyzed in this paper, and the mixtures with different aggregate gradations from various types of asphalt were prepared. The fracture characteristics were explored using the thermal stress restrained specimen test (TSRST) and low-temperature bending test, and the good consistency of the low-temperature fracture performance was identified according to the results of frost-break temperature, flexural strength, and fracture toughness. The frost-break temperature was confirmed as the best indicator of the material crack resistance and could be used as the index to evaluate the performance of asphalt mixtures at low temperatures. The frost-break temperature of matrix asphalt mixture is 8–10 °C higher than that of modified asphalt mixture, and AC asphalt mixture is 2–4 °C higher than that of SMA asphalt mixture. The excellent asphalt performance has a more important influence on the fracture characteristics of asphalt mixture. The asphalt mixture of the same type had similar fracture toughness at varying notch depths, the most deviation is 3.78% which shows that the initial crack depth has little effect on the fracture toughness of asphalt mixture at low temperature. The results of the study can provide a basis for the selection of asphalt pavement surface materials and the optimization of mixtures in high altitude and cold regions with large temperature differences.
Structural, Optical and Dielectric Properties of Holmium-Doped Nickel-Cadmium Ferrite Nanoparticles Synthesized by Sol-Gel Auto-Combustion Method
Authors: Ahmad Danyal , Ali Asad , Abbas Zahid , Zaman Abid , Alsuhaibani Amnah Mohammed , Tirth Vineet , Sarker Mahidur R. , Kamari Nor Azwan Mohamed , Algahtani Ali , Aljohani Mohammed
Published: March 2023

Nanoparticles where holmium was substituted with nickel-cadmium Ni0.5Cd0.5HoxFe2-xO4 (X = 0, 0.02, and 0.04) ferrites were synthesized through a sol-gel auto-combustion process to reveal their structural and physical properties. The synthesized nanoparticles were characterized using X-ray diffraction (XRD), a scanning electron microscope (SEM), Fourier transform infrared ray (FTIR) spectroscopy, and impedance spectroscopy techniques. XRD revealed the formation of the cubic crystal structure had a preferential orientation along (311). By including holmium, the lattice constant was reduced, while the average crystallite size was increased. SEM analysis revealed that the nanoparticles exhibited regular shapes, and the average grain size increased with the holmium content. FTIR spectroscopy determined that all the organic and inorganic materials had an absorption range of 400 to 4000 cm−1. The dielectric properties were measured between the frequency ranges of 1 kHz and 2 MHz. This shows that the tangent loss and the dielectric constant were raised when the concentration of holmium was increased.
Isothermal Evaporations of the Brine from Tibet’s Laguocuo Salt Lake at 15 °C: Experiment and UNIQUAC Simulations
Authors: Zhang Yongming , Li Wu
Published: March 2023

The original composition of Laguocuo Salt Lake was found in the mirabilite area of the 15 °C isothermal phase diagrams of the Li+, Na+, K+//Cl−, SO42−-H2O system. Four phases comprise the isothermal evaporation procedure. The first stage is the unsaturated stage except for carbonate. The second stage is made up of sodium chloride, mirabilite, and borax precipitate simultaneously, where the halogenation rate is 31.58%, and the water loss rate is 68.32%. The penultimate step is the lithium salt precipitation section, where primarily NaCl, Na2SO4·10H2O, and Li2SO4·3Na2SO4·12H2O are formed, where the water loss rate is 91.38%, the halogenation rate is 7.42%, and the salt precipitation rate is 1.20%. The final stage is the eutectoid stage of lithium and potassium salts, where primarily NaCl, Li2SO4·3Na2SO4·12H2O, and 3K2SO4·Na2SO4 precipitate simultaneously. The rates of water loss, halogenation, and salt precipitation are 93.60%, 5.73%, and 0.67%, respectively. NaCl, Li2SO4·3Na2SO4·12H2O, and 3K2SO4·Na2SO4 were all precipitated through dispersion precipitation of borax with the evaporation process following precipitation. The UNIQUAC model was employed to predict the isothermal evaporation at 15 °C. The theoretical calculation and the experimental were in good agreement. The present work can offer a fundamental theoretical framework for the development and use of Laguocuo Salt Lake resources at 15 °C.
Forest Fragmentation and Developmental Stability of Wood Mice Apodemus sylvaticus: A Food-Mediated Effect?
Authors: Díaz Mario , Morán-López Teresa
Published: March 2023

Generalist mice are key species for the long-term dynamics of fragmented forests due to their dual role as seed dispersers or predators of the dominant trees. Wood mice, Apodemus sylvaticus, usually act as a net predator in woodlots due to higher winter densities and earlier winter reproduction than in forests. Here we analyze the recruitment expectations of young mice born in woodlots in relation to food availability through an index of developmental stability that combined values of fluctuating asymmetry (FA) for six traits of the lower mandibles. FA was measured in young and adult mice caught at the end of the winter in control woodlots, food-supplemented woodlots and in a nearby large forest. Despite low sample sizes (n = 9 for young and n = 74 for adults), FA in young mice born in control woodlots were significantly higher than in those from food-supplemented woodlots and the forest and in all adults. Food limitation in woodlots was thus associated with increased developmental instability of young mice, but it had no effect on adults. Instability likely reduced the survival prospects of young mice through increased mortality, and this should be compensated by yearly recolonization of woodlots by adults from the agricultural matrix in autumn and winter. Future work analyzing mechanisms suggested here but using non-lethal methods will be important to clarify the impacts of FA on the population dynamics of wood mice.
The Revision of the Crustacea Collection of the Museum of Zoology “P. Doderlein” under the Framework of the National Biodiversity Future Center
Authors: Pipitone Carlo , Innocenti Gianna , Pepe Paola , Tumbiolo Maria , Lo Brutto Sabrina
Published: March 2023

The collection of Crustacea preserved in the Museum of Zoology “P. Doderlein” in Palermo (Italy) has been revised in the framework of the activities of the National Biodiversity Future Center. The main part of the collection is composed of Decapoda, while a smaller part includes Stomatopoda, Isopoda, Amphipoda, and Cirripedia. Overall the collection includes common species, some of which are now protected.
Historical Landscape Evolution Shaped the Phylogeography and Population History of the Cyprinid Fishes of Acrossocheilus (Cypriniformes: Cyprinidae) According to Mitochondrial DNA in Zhejiang Province, China
Authors: Zhou Mu-Yang , Wang Jun-Jie , Ren Jian-Feng , Li Fan , Wu Jin-Xian , Zhou Jia-Jun , Li Jia-Le , Yang Jin-Quan , Lin Hung-Du
Published: March 2023

Geological events and landscape features, as well as changes in the climate during the Pliocene period, have shaped the distribution of genetic diversity and demographic history of freshwater fish in mainland China. In this study, we investigated the phylogeny and population genetic structure of Acrossocheilus species (A. fasciatus, A. kreyenbergii and A. wenchowensis) in the Zhejiang region by the mitochondrial cytochrome b (cyt-b) and control (D-loop) region s. Mitochondrial phylogenetic analysis revealed three major lineages (lineages A, B and C), which may represent A. fasciatus, A. wenchowensis and A. kreyenbergii, respectively. Our results revealed that A. fasciatus and A. wenchowensis diverged from A. kreyenbergii in the Zhejiang region. The uplift of the Wuyi Mountains and the Xianxia Mountains served as an important geographic barrier in the diversification of the three Acrossocheilus species. The most recent common ancestors (TMRCAs) of the three lineages and lineages A + B were dated to 1.859 and 1.614 myr, respectively. Our results indicate that the effective population sizes of A. fasciatus and A. wenchowensis remained constant from the past to the present, as supported by ABC analysis. For conservation and protection, a strategy is required because of their genetic uniqueness, and we suggest that the two regions divided by the Xianxia Mountains be regarded as different management units (Mus), conforming to the major zoological regions of the Zhejiang region.
Management of a Globally Imperiled and Fire-Dependent Ecosystem in the Urban Matrix of Miami–Dade County, Florida: A Case Study of the Richmond Tract Pine Rocklands
Authors: Figueroa Adrian , Heinen Joel T. , Ridgley Frank N. , Whitfield Steven M. , Liu Hong
Published: March 2023

Pine rockland habitat of South Florida is among the most highly threatened terrestrial ecosystems in the neo-subtropics and is among the rarest worldwide. With only 1.2% of its original extent remaining outside Everglades National Park, fewer than 780 hectares of this ecosystem remains across all of South Florida. This fire-dependent ecosystem—habitat for many rare, endemic species—has experienced substantial deforestation and defaunation due to urbanization, land use change, habitat fragmentation, fire suppression, and exotic plant invasions. Owing to the small size of remaining fragments, and the fact that most are surrounded by urbanization, adequate burning regimes are suppressed. The Richmond Tract, a complex of twelve separate parcels under multiple private and public ownership partially surrounding Zoo Miami, is the largest tract of pine rockland outside the federal protection of Everglades National Park. In this article, we take inventory of the threatened biodiversity at the Richmond Tract and focus on the policy and management landscape. We take a close look at threats to the pine rockland’s persistence here and review approaches that either help maintain the health of this ecosystem or those that may need to be reconsidered. We end by discussing coordination among multiple stakeholder groups, the potential use for incentive-based conservation practices, and suggesting ways to improve management in highly urbanized South Florida.
The Role of MRI in the Diagnosis of Solid Pseudopapillary Neoplasm of the Pancreas and Its Mimickers: A Case-Based Review with Emphasis on Differential Diagnosis
Authors: Kovac Jelena Djokic , Djikic-Rom Aleksandra , Bogdanovic Aleksandar , Jankovic Aleksandra , Grubor Nikica , Djuricic Goran , Dugalic Vladimir
Published: March 2023

Solid pseudopapillary neoplasm (SPN) is rare pancreatic tumor occurring most commonly in young females. The typical imaging appearance of SPN is of well-defined, encapsulated, and large heterogeneous tumors, consisting of solid and cystic components due to various degrees of intralesional hemorrhage and necrosis. However, atypical imaging presentation in the form of small solid tumors or uniformly cystic lesions might also be seen, which can be explained by specific pathological characteristics. Other imaging features such as a round shape, the absence of main pancreatic duct dilatation, and slow growth, in combination with vague symptoms, favor the diagnosis of SPNs. Nevertheless, the radiological findings of SPN might overlap with other solid and cystic pancreatic neoplasms, such as neuroendocrine tumors, serous and mucinous neoplasms, and even small pancreatic adenocarcinomas. In addition, a few benign non-tumorous conditions including walled-of-necrosis, and intrapancreatic accessory spleen may also pose diagnostic dilemmas simulating SPNs on imaging studies. The aim of this manuscript is to provide a comprehensive overview of the typical and atypical imaging features of SPNs and to describe useful tips for differential diagnosis with its potential mimickers.
Common Mental Disorders in Smart City Settings and Use of Multimodal Medical Sensor Fusion to Detect Them
Authors: Alwakeel Ahmed , Alwakeel Mohammed , Zahra Syed Rameem , Saleem Tausifa Jan , Hijji Mohammad , Alwakeel Sami S. , Alwakeel Abdullah M. , Alzorgi Sultan
Published: March 2023

Cities have undergone numerous permanent transformations at times of severe disruption. The Lisbon earthquake of 1755, for example, sparked the development of seismic construction rules. In 1848, when cholera spread through London, the first health law in the United Kingdom was passed. The Chicago fire of 1871 led to stricter building rules, which led to taller skyscrapers that were less likely to catch fire. Along similar lines, the COVID-19 epidemic may have a lasting effect, having pushed the global shift towards greener, more digital, and more inclusive cities. The pandemic highlighted the significance of smart/remote healthcare. Specifically, the elderly delayed seeking medical help for fear of contracting the infection. As a result, remote medical services were seen as a key way to keep healthcare services running smoothly. When it comes to both human and environmental health, cities play a critical role. By concentrating people and resources in a single location, the urban environment generates both health risks and opportunities to improve health. In this manuscript, we have identified the most common mental disorders and their prevalence rates in cities. We have also identified the factors that contribute to the development of mental health issues in urban spaces. Through careful analysis, we have found that multimodal feature fusion is the best method for measuring and analysing multiple signal types in real time. However, when utilizing multimodal signals, the most important issue is how we might combine them; this is an area of burgeoning research interest. To this end, we have highlighted ways to combine multimodal features for detecting and predicting mental issues such as anxiety, mood state recognition, suicidal tendencies, and substance abuse.
Mathematical Modelling of Cervical Precancerous Lesion Grade Risk Scores: Linear Regression Analysis of Cellular Protein Biomarkers and Human Papillomavirus E6/E7 RNA Staining Patterns
Authors: Bumrungthai Sureewan , Ekalaksananan Tipaya , Kleebkaow Pilaiwan , Pongsawatkul Khajohnsilp , Phatnithikul Pisit , Jaikan Jirad , Raumsuk Puntanee , Duangjit Sureewan , Chuenchai Datchani , Pientong Chamsai
Published: March 2023

The current practice of determining histologic grade with a single molecular biomarker can facilitate differential diagnosis but cannot predict the risk of lesion progression. Cancer is caused by complex mechanisms, and no single biomarker can both make accurate diagnoses and predict progression risk. Modelling using multiple biomarkers can be used to derive scores for risk prediction. Mathematical models (MMs) may be capable of making predictions from biomarker data. Therefore, this study aimed to develop MM–based scores for predicting the risk of precancerous cervical lesion progression and identifying precancerous lesions in patients in northern Thailand by evaluating the expression of multiple biomarkers. The MMs (Models 1–5) were developed in the test sample set based on patient age range (five categories) and biomarker levels (cortactin, p16INK4A, and Ki–67 by immunohistochemistry [IHC], and HPV E6/E7 ribonucleic acid (RNA) by in situ hybridization [ISH]). The risk scores for the prediction of cervical lesion progression (“risk biomolecules”) ranged from 2.56–2.60 in the normal and low–grade squamous intraepithelial lesion (LSIL) cases and from 3.54–3.62 in cases where precancerous lesions were predicted to progress. In Model 4, 23/86 (26.7%) normal and LSIL cases had biomolecule levels that suggested a risk of progression, while 5/86 (5.8%) cases were identified as precancerous lesions. Additionally, histologic grading with a single molecular biomarker did not identify 23 cases with risk, preventing close patient monitoring. These results suggest that biomarker level–based risk scores are useful for predicting the risk of cervical lesion progression and identifying precancerous lesion development. This multiple biomarker–based strategy may ultimately have utility for predicting cancer progression in other contexts.
The Effect of a Bioactive Oral System and CO2 Laser on Enamel Susceptibility to Acid Challenge
Authors: Shubbar Mustafa , Addie Ali , Al-Taee Lamis
Published: March 2023

This study evaluated the structural changes of enamel treated by the Regenerate system and carbon dioxide (CO2) laser against acid challenge. Thirty human enamel slabs were prepared and assigned into three groups: Group I: untreated (control); Group II: treated with the Regenerate system; and Group III exposed to CO2 laser. All specimens were subjected to an acid challenge (pH 4.5–7.0) for 14 days. Specimens were evaluated and compared at 120 points using five Raman microspectroscopic peaks; the phosphate vibrations ν1, ν2, ν3, and ν4 at 960, 433, 1029, and 579 cm−1, respectively, and the carbonate at 1070 cm−1, followed by Vickers microhardness test. The ratio of carbonate to phosphate was correlated to the equivalent microhardness numbers. The intensities of phosphate peaks ν1, ν2, and ν4 were reduced in all groups post-acid challenge, while the carbonate and ν3 were significantly increased (p < 0.000). Surfaces treated by Regenerate exhibited higher peak intensity of phosphate and carbonate before and after pH-cycling (p < 0.05). The mineral content in enamel had a direct effect on tissue microhardness, and the CO2-lased surfaces showed a reduced carbonate content and higher microhardness values. Both approaches induced surface changes that can protect enamel against acid challenge resulting in a significant benefit for dental healthcare.