bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Analysis of the Effect of the Evolution of Energy Saving Regulations on the Indoor Summer Comfort of Five Homes on the Coast of the Basque Country
Authors: Otaegi Jorge , Hernández Rufino J. , Oregi Xabat , Martín-Garín Alexander , Rodríguez-Vidal Iñigo
Published: July 2022

In the last decade, several European directives have been established to contribute to the 2020, 2030 and 2050 energy saving targets and impose energy efficiency requirements for new construction, existing buildings and building renovation operations. One of the ways to achieve said objectives is to rely on the most demanding energy efficiency labels existing in Europe, such as Passivhaus, and to implement similar concepts into the national energy regulations of European countries based on a high-performance thermal envelope (high insulation and high-performance windows), high airtightness and high-performance heat-recovery ventilation systems, and solar heat harvesting. This energy conservation concept has shown to be effective for houses with low-density occupation in cold climates, but may cause severe overheating problems in denser collective housing in temperate and hot climates with higher solar radiation. To assess this impact, five flats in three developments from different periods that range from no insulation at all to a nZEB, Passivhaus-certified high-rise are compared in this paper, using data from a monitoring campaign during the summer of 2020. The results show and quantify the strong impact the evolution of the energy saving regulatory trend has had on summer indoor comfort, which may in some cases lead to previously unnecessary air conditioning for cooling and, ultimately, be counterproductive towards the end goals of reducing energy consumption and greenhouse-effect gas emissions and mitigating climate change.
Study on an Integrated LCA-LCC Model for Assessment of Highway Engineering Technical Schemes
Authors: Hou Yunfei , Qian Xiaojing , Zhang Rui , Gu Fan , Feng Ping
Published: July 2022

This paper proposes an integrated life cycle assessment-life cycle cost (LCA-LCC) model of environmental and economic factors for highway engineering technical schemes to problems such as the limitations of single-dimensional assessment, their narrow scope, the difficulty in tracing sources, and the conflicts of various dimensions in existing integrated assessment methods. The latest documents issued by the Ministry of Ecology and Environment and the Ministry of Transport of China used as an integrated assessment database. Air pollution, water pollution, solid waste pollution, noise pollution, energy consumption, pre-project cost, project construction cost, project operation cost, and post-project cost were used to construct the integrated assessment index system of environmental and economic factors. An improved entropy method was adopted in the LCA-LCC model to overcome the problems of ambiguous results of the previous entropy due to too few assessment schemes, the inoperability of the method when it encounters a negative value or zero value, and unbalanced multi-angle assessments. This model was applied to the assessment of two asphalt pavement maintenance schemes of Highway US280 in Alabama and two improvement schemes of high liquid limit soil subgrade of Highway G360 in Hainan. The results show that the LCA-LCC model overcomes the limitations and imbalances of a single LCA or LCC. The gravel improved scheme and the cold recycling scheme were identified through quantitative assessment as more sustainable. This paper can provide a reference for the comprehensive quantitative assessment of environmental and economic benefits of highway engineering technical schemes.
Architectural Systemic Approach: The Serpentine Gallery 2005, a Reciprocal Frame Case Study
Authors: del Río-Calleja Beatriz , Grau Enguix Joaquín , García-Santos Alfonso
Published: July 2022

The application of the systemic approach in architecture aims to promote an integral, holistic view of the architectural design process. The literature reviewed calls for models with systemic behavior, and for these models to be applied in concrete cases. This paper proposes an original approach, using the foundation matrix and the constructive logic matrix. Both matrices are part of a developing model that is being tested on a case study. The work presented here had two objectives: to check this part of the model and gain more knowledge about the model itself. The selected case study, the 2005 Serpentine Gallery Pavilion, is a contemporary ephemeral construction of significant architectural interest. It is a reciprocal frame structure, linked to the construction history. The methodology used was a systemic analysis. In the first phase of the analysis, the reciprocal structures documented historically in the West were reviewed. The other two phases corresponded to the application of the two model matrices. Conceptual diagramming was used in all phases of the process. The results show the importance of the study of historical building solutions. The use of matrices facilitates the identification and understanding of the operations carried out in the design process of the case study. Matrices favor the organization of concepts and relationships from through a systemic approach. Understanding generation operations in an integrated way leads to a type of knowledge (relational knowledge) that allows architecture to be thought about in a holistic way. This makes the systemic view of art and technology as a unit possible, attending to the whole complexity of architectural thinking.
Machine Learning Models and Multiparametric Magnetic Resonance Imaging for the Prediction of Pathologic Response to Neoadjuvant Chemotherapy in Breast Cancer
Authors: Herrero Vicent Carmen , Tudela Xavier , Moreno Ruiz Paula , Pedralva Víctor , Jiménez Pastor Ana , Ahicart Daniel , Rubio Novella Silvia , Meneu Isabel , Montes Albuixech Ángela , Santamaria Miguel Ángel , Fonfria María , Fuster-Matanzo Almudena , Olmos Antón Santiago , Martínez de Dueñas Eduardo
Published: July 2022

Background: Most breast cancer (BC) patients fail to achieve pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). The aim of this study was to evaluate whether imaging features (perfusion/diffusion imaging biomarkers + radiomic features) extracted from pre-treatment multiparametric (mp)MRIs were able to predict, alone or in combination with clinical data, pCR to NAC. Methods: Patients with stage II-III BC receiving NAC and undergoing breast mpMRI were retrospectively evaluated. Imaging features were extracted from mpMRIs performed before NAC. Three different machine learning models based on imaging features, clinical data or imaging features + clinical data were trained to predict pCR. Confusion matrices and performance metrics were obtained to assess model performance. Statistical analyses were conducted to evaluate differences between responders and non-responders. Results: Fifty-eight patients (median [range] age, 52 [45–58] years) were included, of whom 12 showed pCR. The combined model improved pCR prediction compared to clinical and imaging models, yielding 91.5% of accuracy with no false positive cases and only 17% false negative results. Changes in different parameters between responders and non-responders suggested a possible increase in vascularity and reduced tumour heterogeneity in patients with pCR, with the percentile 25th of time-to-peak (TTP), a classical perfusion parameter, being able to discriminate both groups in a 75% of the cases. Conclusions: A combination of mpMRI-derived imaging features and clinical variables was able to successfully predict pCR to NAC. Specific patient profiles according to tumour vascularity and heterogeneity might explain pCR differences, where TTP could emerge as a putative surrogate marker for pCR.
Genetic Polymorphisms Associated with Vincristine Pharmacokinetics and Vincristine-Induced Peripheral Neuropathy in Pediatric Oncology Patients
Authors: van de Velde Mirjam E. , Uittenboogaard Aniek , Yang Wenjian , Bonten Erik , Cheng Cheng , Pei Deqing , van den Berg Marleen H. , van der Sluis Inge M. , van den Bos Cor , Abbink Floor C. H. , van den Heuvel-Eibrink Marry M. , Segers Heidi , Chantrain Christophe , van der Werff ten Bosch Jutte , Willems Leen , Evans William E. , Kaspers Gertjan J. L.
Published: July 2022

Vincristine (VCR) is an important component of curative chemotherapy for many childhood cancers. Its main side effect is VCR-induced peripheral neuropathy (VIPN), a dose limiting toxicity. Some children are more susceptible to VIPN, which is at least partially dependent on genetic factors and pharmacokinetics (PK). In this study, we identify and replicate genetic variants associated with VCR PK and VIPN. Patient samples from a randomized clinical trial studying the effect of administration duration of VCR on VIPN in 90 patients were used. PK sampling was conducted on between one and five occasions at multiple time points. A linear two-compartment model with first-order elimination was used, and targeted next-generation DNA sequencing was performed. Genotype–trait associations were analyzed using mixed-effect models or logistic regression analysis for repeated measures, or Poisson regression analysis in which the highest VIPN score per patient was included. Nine single-nucleotide polymorphisms (SNPs) in seven genes (NDRG1, GARS, FIG4, FGD4, SEPTIN9, CEP72, and ETAA1) were associated with VIPN. Furthermore, three SNPs in three genes (MTNR1B, RAB7A and SNU13) were associated with PK of VCR. In conclusion, PK of VCR and VIPN are influenced by SNPs; upfront identification of those that lead to an altered susceptibility to VIPN or VCR exposure could help individualize VCR treatment.
Perioperative Complications and Oncologic Outcomes after Radical Cystectomy in End-Stage Renal Disease Patients with Bladder Cancer Obtained Using a Standardized Reporting System
Authors: Liu Yu-Liang , Wu Chun-Te , Hsu Yu-Chao , Chen Miao-Fen , Chen Chih-Shou , Shi Chung-Sheng , Huang Yun-Ching
Published: July 2022

Background: We investigated the use of a standardized reporting system to study perioperative complications and oncologic outcomes after radical cystectomy in end-stage renal disease (ESRD) patients with bladder cancer. Methods: We reviewed retrospective outcomes in 141 ESRD patients with bladder cancer who underwent radical cystectomy between 2004 and 2015. Complications were graded using the Clavien–Dindo classification system with 0–2 classified as “No Major Complications” and Clavien 3–5 as “Major Complications”. Low-volume surgeons were classified as those performing fewer than nine cases during the study. Fisher’s exact test along with the chi-squared test, two-tailed t tests, logistic regression, and the Cox proportional hazard model were used to evaluate all clinically meaningful covariates. Results: Ninety-nine (99, 70.2%) patients had no major complications, and forty-two (29.8%) patients had major complications. Patients in the major complications group were older, had a higher Charlson comorbidity index (CCI), and had a longer hospitalization duration than those in the no major complications group (all, p < 0.05). Major complications were also more common when the procedure was performed by low-volume surgeons (p = 0.003). In multivariate logistic regression models, CCI ≥ 5 (p = 0.006) and low-volume surgeon (p = 0.004) were independent predictors of major complications. According to multivariate analysis with the Cox hazards regression, male sex, age > 70 years, CCI ≥ 5, bladder cancer stage ≥ 3, lymphovascular invasion, and experiencing major complications were significant poor prognostic factors for overall survival (all, p < 0.05). Conclusions: Accurate reporting of complications is necessary for preoperative counseling, identifying modifiable risk factors, and planning risk mitigation strategies. High comorbidity and low-volume surgeons were interrelated as notable risk factors for major complications. In addition to tumor-related factors, male sex, older age, and major complications significantly influence overall survival.
Inflammation-Driven Regulation of PD-L1 and PD-L2, and Their Cross-Interactions with Protective Soluble TNFα Receptors in Human Triple-Negative Breast Cancer
Authors: Baram Tamir , Oren Nino , Erlichman Nofar , Meshel Tsipi , Ben-Baruch Adit
Published: July 2022

Pro-inflammatory cytokines play key roles in elevating cancer progression in triple-negative breast cancer (TNBC). We demonstrate that specific combinations between TNFα, IL-1β and IFNγ up-regulated the proportion of human TNBC cells co-expressing the inhibitory immune checkpoints PD-L1 and PD-L2: TNFα + IL-1β in MDA-MB-231 cells and IFNγ + IL-1β in BT-549 cells; in the latter cells, the process depended entirely on STAT1 activation, with no involvement of p65 (CRISPR-Cas9 experiments). Highly significant associations between the pro-inflammatory cytokines and PD-L1/PD-L2 expression were revealed in the TCGA dataset of basal-like breast cancer patients. In parallel, we found that the pro-inflammatory cytokines regulated the expression of the soluble receptors of tumor necrosis factor α (TNFα), namely sTNFR1 and sTNFR2; moreover, we revealed that sTNFR1 and sTNFR2 serve as anti-metastatic and protective factors in TNBC, reducing the TNFα-induced production of inflammatory pro-metastatic chemokines (CXCL8, CXCL1, CCL5) by TNBC cells. Importantly, we found that in the context of inflammatory stimulation and also without exposure to pro-inflammatory cytokines, elevated levels of PD-L1 have down-regulated the production of anti-tumor sTNFR1 and sTNFR2. These findings suggest that in addition to its immune-suppressive activities, PD-L1 may promote disease course in TNBC by inhibiting the protective effects of sTNFR1 and sTNFR2.
Delta-Radiomics Based on Dynamic Contrast-Enhanced MRI Predicts Pathologic Complete Response in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy
Authors: Guo Liangcun , Du Siyao , Gao Si , Zhao Ruimeng , Huang Guoliang , Jin Feng , Teng Yuee , Zhang Lina
Published: July 2022

Objective: To investigate the value of delta-radiomics after the first cycle of neoadjuvant chemotherapy (NAC) using dynamic contrast-enhanced (DCE) MRI for early prediction of pathological complete response (pCR) in patients with breast cancer. Methods: From September 2018 to May 2021, a total of 140 consecutive patients (training, n = 98: validation, n = 42), newly diagnosed with breast cancer who received NAC before surgery, were prospectively enrolled. All patients underwent DCE-MRI at pre-NAC (pre-) and after the first cycle (1st-) of NAC. Radiomic features were extracted from the postcontrast early, peak, and delay phases. Delta-radiomics features were computed in each contrast phases. Least absolute shrinkage and selection operator (LASSO) and a logistic regression model were used to select features and build models. The model performance was assessed by receiver operating characteristic (ROC) analysis and compared by DeLong test. Results: The delta-radiomics model based on the early phases of DCE-MRI showed a highest AUC (0.917/0.842 for training/validation cohort) compared with that using the peak and delay phases images. The delta-radiomics model outperformed the pre-radiomics model (AUC = 0.759/0.617, p = 0.011/0.047 for training/validation cohort) in early phase. Based on the optimal model, longitudinal fusion radiomic models achieved an AUC of 0.871/0.869 in training/validation cohort. Clinical-radiomics model generated good calibration and discrimination capacity with AUC 0.934 (95%CI: 0.882, 0.986)/0.864 (95%CI: 0.746, 0.982) for training and validation cohort. Delta-radiomics based on early contrast phases of DCE-MRI combined clinicopathology information could predict pCR after one cycle of NAC in patients with breast cancer.
External Beam Accelerated Partial Breast Irradiation in Early Breast Cancer and the Risk for Radiogenic Pneumonitis
Authors: Ott Oliver J. , Stillkrieg Wilhelm , Lambrecht Ulrike , Sauer Tim-Oliver , Schweizer Claudia , Lamrani Allison , Strnad Vratislav , Hack Carolin C. , Beckmann Matthias W. , Uder Michael , Fietkau Rainer , Distel Luitpold
Published: July 2022

In order to evaluate the risk for radiation-associated symptomatic pneumonitis in a prospective external beam accelerated partial breast irradiation (APBI) trial, between 2011 and 2021, 170 patients with early stage breast cancer were enclosed in the trial. Patients were eligible for study participation if they had a histologically confirmed breast cancer or an exclusive ductal carcinoma in situ (DCIS), a tumor size ≤3 cm, free safety margins ≥2 mm, no involved axillary lymph nodes, tumor bed clips, and were ≥50 years old. Patients received APBI with 38 Gy with 10 fractions in 10 consecutive working days. The trial was registered at the German Clinical Trials Registry, DRKS-ID: DRKS00004417. Median follow-up was 56 (1–129) months. Ipsilateral lung MLD, V20, and V30 were 4.3 ± 1.4 Gy, 3.0 ± 2.0%, and 1.0 ± 1.0%, respectively. Radiogenic pneumonitis grade 2 appeared in 1/170 (0.6%) patients two months after radiotherapy. Ipsilateral MLD, V20, and V30 were 6.1 Gy, 7, and 3% in this patient. Additionally, individual radiosensitivity was increased in this specific patient. Compared to WBI, APBI leads to lower lung doses. Using APBI, the risk of symptomatic radiogenic pneumonitis is very low and may be limited, with an ipsilateral V20 < 3% to very exceptional cases associated with innate risk factors with an increased radiation susceptibility.
Humoral Responses to Repetitive Doses of COVID-19 mRNA Vaccines in Patients with CAR-T-Cell Therapy
Authors: Gössi Simona , Bacher Ulrike , Haslebacher Claudia , Nagler Michael , Suter Franziska , Staehelin Cornelia , Novak Urban , Pabst Thomas
Published: July 2022

Background: Due to B-cell aplasia following CAR-T-cell therapy, patients are at risk of severe SARS-CoV-2 course. Methods: COVID-19 vaccines were assessed by IgG antibody tests against SARS-CoV-2 spike protein (anti-S1/S2). Vaccination procedures: group (1): CAR-T-cells followed by two to four vaccine doses; group (2): Two vaccine doses prior to CAR-T-cells, followed by doses 3 or 4. Results: In group 1 (n = 32), 7/30 patients (23.2%) had positive antibody tests after a second dose, 9/23 (39.1%) after a third dose, and 3/3 patients after a fourth dose. A third dose led to seroconversion in 5 of 21 patients (23.8%) with available data, while a fourth dose did so in 2/3 patients. Higher B-cells (AUC: 96.2%, CI: 89–100, p = 0.0006) and lower CAR-T-cell copies (AUC: 77.3%, CI: 57–97, p = 0.0438) were predictive of positive humoral vaccine response. In group 2 (n = 14), 6/14 patients (42.9%) had a positive antibody test after a second dose, 3/8 patients (37.5%) after a third dose, and 3/4 patients after a fourth dose. A third dose led to seroconversion in 1/8 patients (12.5%), while a fourth dose did so in 3/4 patients. Conclusion: Additional vaccine doses increased seroconversion rates whilst high B-cell counts and low CAR-T-cell copy numbers were associated with positive antibody response.
Recent Application of Artificial Intelligence in Non-Gynecological Cancer Cytopathology: A Systematic Review
Authors: Thakur Nishant , Alam Mohammad Rizwan , Abdul-Ghafar Jamshid , Chong Yosep
Published: July 2022

State-of-the-art artificial intelligence (AI) has recently gained considerable interest in the healthcare sector and has provided solutions to problems through automated diagnosis. Cytological examination is a crucial step in the initial diagnosis of cancer, although it shows limited diagnostic efficacy. Recently, AI applications in the processing of cytopathological images have shown promising results despite the elementary level of the technology. Here, we performed a systematic review with a quantitative analysis of recent AI applications in non-gynecological (non-GYN) cancer cytology to understand the current technical status. We searched the major online databases, including MEDLINE, Cochrane Library, and EMBASE, for relevant English articles published from January 2010 to January 2021. The searched query terms were: “artificial intelligence”, “image processing”, “deep learning”, “cytopathology”, and “fine-needle aspiration cytology.” Out of 17,000 studies, only 26 studies (26 models) were included in the full-text review, whereas 13 studies were included for quantitative analysis. There were eight classes of AI models treated of according to target organs: thyroid (n = 11, 39%), urinary bladder (n = 6, 21%), lung (n = 4, 14%), breast (n = 2, 7%), pleural effusion (n = 2, 7%), ovary (n = 1, 4%), pancreas (n = 1, 4%), and prostate (n = 1, 4). Most of the studies focused on classification and segmentation tasks. Although most of the studies showed impressive results, the sizes of the training and validation datasets were limited. Overall, AI is also promising for non-GYN cancer cytopathology analysis, such as pathology or gynecological cytology. However, the lack of well-annotated, large-scale datasets with Z-stacking and external cross-validation was the major limitation found across all studies. Future studies with larger datasets with high-quality annotations and external validation are required.
The “Balloon-Like” Sign: Differential Diagnosis between Postoperative Air Leak and Residual Pleural Space: Radiological Findings and Clinical Implications of the Young–Laplace Equation
Authors: Petrella Francesco , Rizzo Stefania , Bertolaccini Luca , Casiraghi Monica , Girelli Lara , Lo Iacono Giorgio , Mazzella Antonio , Spaggiari Lorenzo
Published: July 2022

In this paper, we propose a radiological sign for an appropriate differential diagnosis between postoperative pleural space and active air leak after lung resection. In the case of residual pleural space without any active air leak, the lung takes the form of a round balloon due to the hyperinflation condition, which is governed by the Young–Laplace equation describing the capillary pressure difference sustained across the interface between two static fluids, such as water and air, due to the phenomenon of wall tension. The two principal mechanisms by which a lung forms a spherical image are shear-controlled detachment induced by shear stress on the membrane surface, and spontaneous detachment induced by a gradient in Young–Laplace pressure. On the contrary, the lung maintains its tapered shape in the case of an active air leak because the continuous air refill does not allow a complete parenchyma re-expansion.
LncRNA HOXC-AS1 Sponges miR-99a-3p and Upregulates MMP8, Ultimately Promoting Gastric Cancer
Authors: Jiang Yue , Li Xiangpan , Yang Yu , Luo Jiajun , Ren Xunshan , Yuan Jingwen , Tong Qiang
Published: July 2022

Gastric cancer (GC) is among the most lethal tumors worldwide. Long noncoding RNAs (lncRNAs) are reported to be critical during the occurrence and progression of malignancies. The HOXC cluster antisense RNA 1 (HOXC-AS1) has been suggested to participate in the genesis and development of GC. Therefore, we examined GC cells and tissues for the expression of HOXC-AS1 and correlated the expression levels with the disease specific survival of the patients, finding that HOXC-AS1 was overexpressed and probably had a tendency of leading to a poor prognosis. The Cell Counting Kit-8 assay and colony formation assay were then performed under knockdown of HOXC-AS1, revealing that cell proliferation of GC was distinctly decreased. Afterwards, miR-99a-3p was predicted to bind with HOXC-AS1 by DIANA tools. We carried out dual-luciferase reporter gene assays to identify the interaction between them. After knockdown of HOXC-AS1, miR-99a-3p was clearly overexpressed in GC cells. In addition, matrix metalloproteinase 8 (MMP8) was shown to be combined with miR-99a-3p using TargetScan. Similar experiments, along with western blot, were conducted to validate the correlation between miR-99a-3p and MMP8. Finally, rescue experiments for CCK-8 were completed, disclosing that HOXC-AS1 promoted cell progression of GC through sponging miR-99a-3p followed by subsequent upregulation of MMP8.
3D Bioprinting: An Enabling Technology to Understand Melanoma
Authors: Fernandes Samantha , Vyas Cian , Lim Peggy , Pereira Rúben F. , Virós Amaya , Bártolo Paulo
Published: July 2022

Melanoma is a potentially fatal cancer with rising incidence over the last 50 years, associated with enhanced sun exposure and ultraviolet radiation. Its incidence is highest in people of European descent and the ageing population. There are multiple clinical and epidemiological variables affecting melanoma incidence and mortality, such as sex, ethnicity, UV exposure, anatomic site, and age. Although survival has improved in recent years due to advances in targeted and immunotherapies, new understanding of melanoma biology and disease progression is vital to improving clinical outcomes. Efforts to develop three-dimensional human skin equivalent models using biofabrication techniques, such as bioprinting, promise to deliver a better understanding of the complexity of melanoma and associated risk factors. These 3D skin models can be used as a platform for patient specific models and testing therapeutics.
Silica Bifunctional Supports for the Direct Synthesis of H2O2: Optimization of Br/Acid Sites and Pd/Br Ratio
Authors: Blanco-Brieva Gema , Desmedt Frederique , Miquel Pierre , Campos-Martin Jose , Fierro Jose
Published: July 2022

We have studied the direct synthesis of hydrogen peroxide using a catalytic system consisting of palladium supported on silica bifunctionalized with sulfonic acid groups and bromide in the absence of acid and halide promoters in solution. Catalysts with several bromide substituents were employed in the catalyst synthesis. The prepared samples were characterized by TXRF, XPS, and hydrogen peroxide decomposition. Catalysts characterization indicated the presence of only palladium (II) species in all of the samples, with similar values for surface and bulk of Pd/Br atomic ratio. The catalysts were tested via direct synthesis, and all samples were able to produce hydrogen peroxide at 313 K and 5.0 MPa. The hydrogen peroxide yield and selectivity changed with the Pd/Br ratio. A decrease in the Pd/Br ratio increases the final hydrogen peroxide concentration, and the selectivity for H2O2 reaches a maximum at a Pd/Br ratio around 0.16 and then decreases. However, the maximum hydrogen peroxide concentration and selectivity occur at slightly different Pd/Br ratios, i.e., resp. 0.4 vs. 0.16.
Sn(IV) Porphyrin-Based Ionic Self-Assembled Nanostructures and Their Application in Visible Light Photo-Degradation of Malachite Green
Authors: Shee Nirmal Kumar , Kim Hee-Joon
Published: July 2022

A series of porphyrin-based ionic complexes were prepared through the reaction of two porphyrin precursors, 5,10,15,20-tetrakis(4-(2-pyridyl)phenyl)porphyrin H2TPhPyP (1) and trans-dihydroxo [5,10,15,20-tetrakis(4-(2-pyridyl)phenyl)porphyrinato]tin(IV) Sn(OH)2TPhPyP (2), with various acids (HCl, HNO3, CF3COOH, H2SO4, H2CO3, and H3PO4). The complexes were characterized via elemental analysis, 1H nuclear magnetic resonance spectroscopy, electrospray ionization mass spectrometry, Fourier transform infrared (FT-IR) spectroscopy, ultraviolet (UV)-visible spectroscopy, fluorescence spectroscopy, and field-emission scanning electron microscopy (FE-SEM). Each compound exhibited different results for UV-visible, fluorescence, FT-IR, and FE-SEM studies depending on the counter anions. The complexes possessed different self-assembled nanostructures based on electronic interactions between the cations of compounds 1 and 2 with different counter anions. These aggregated species are stabilized by electrostatic forces and the π-π stacking interactions between the two porphyrin rings, in which the counter anions play an important bridging role. The counter anions also play an important role in controlling the morphology and photocatalytic properties of the as-developed materials. The complexes were then used for the photocatalytic degradation of the malachite green (MG) dye in aqueous media under visible light irradiation for up to 70 min. A morphology-dependent photocatalytic degradation of the MG dye was observed for all the ionic complexes, with efficiencies ranging from 50% to 95%.
Muramyl Dipeptide Administration Delays Alzheimer’s Disease Physiopathology via NOD2 Receptors
Authors: Piec Pierre-Alexandre , Pons Vincent , Préfontaine Paul , Rivest Serge
Published: July 2022

Alzheimer’s disease (AD) is the most common form of dementia in the world. The prevalence is steadily increasing due to an aging population and the lack of effective treatments. However, modulation of innate immune cells is a new therapeutic avenue, which is quite effective at delaying disease onset and improving cognitive decline. Methods: We studied the effect of the NOD2 receptor ligand muramyl dipeptide (MDP) on the modulation of the innate immune cells, namely patrolling monocytes and microglia. We administrated MDP once a week for 3 months in an APPswe/PS1 mouse model in both sexes. We started the treatment at 3 months before plaque formation and evaluated its effects at 6 months. Results: We showed that the MDP injections delay cognitive decline in both sexes via different mechanisms and protect the blood brain barrier (BBB). In males, MDP triggers the sink effect from the BBB, leading to a diminution in the amyloid load in the brain. This phenomenon is underlined by the increased expression of phagocytosis markers such as TREM2, CD68, and LAMP2 and a higher expression of ABCB1 and LRP1 at the BBB level. The beneficial effect seems more restricted to the brain in females treated with MDP, where microglia surround amyloid plaques and prevent the spreading of amyloid peptides. This phenomenon is also associated with an increase in TREM2 expression. Interestingly, both treated groups showed an increase in Arg-1 expression compared to controls, suggesting that MDP modulates the inflammatory response. Conclusion: These results indicate that stimulation of the NOD2 receptor in innate immune cells is a promising therapeutic avenue with potential different mechanisms between males and females.
Compensatory Upregulation of LPA2 and Activation of the PI3K-Akt Pathway Prevent LPA5-Dependent Loss of Intestinal Epithelial Cells in Intestinal Organoids
Authors: Liang Zhongxing , Yun C. Chris
Published: July 2022

Renewal of the intestinal epithelium is orchestrated by regenerative epithelial proliferation within crypts. Recent studies have shown that lysophosphatidic acid (LPA) can maintain intestinal epithelial renewal in vitro and conditional deletion of Lpar5 (Lpar5iKO) in mice ablates the intestinal epithelium and increases morbidity. In contrast, constitutive Lpar5 deletion (Lpar5cKO) does not cause a defect in intestinal crypt regeneration. In this study, we investigated whether another LPA receptor (LPAR) compensates for constitutive loss of LPA5 function to allow regeneration of intestinal epithelium. In Lpar5cKO intestinal epithelial cells (IECs), Lpar2 was upregulated and blocking LPA2 function reduced proliferation and increased apoptosis of Lpar5cKO IECs. Similar to Lpar5cKO mice, the absence of Lpar2 (Lpar2−/−) resulted in upregulation of Lpar5 in IECs, indicating that LPA2 and LPA5 reciprocally compensate for the loss of each other. Blocking LPA2 in Lpar5cKO enteroids reduced phosphorylation of Akt, indicating that LPA2 maintains the growth of Lpar5cKO enteroids through activation of the PI3K-Akt pathway. The present study provides evidence that loss of an LPAR can be compensated by another LPAR. This ability to compensate needs to be considered in studies aimed to define receptor functions or test the efficacy of a LPAR-targeting drug using genetically engineered animal models.
A Drug Repurposing Screen Identifies Fludarabine Phosphate as a Potential Therapeutic Agent for N-MYC Overexpressing Neuroendocrine Prostate Cancers
Authors: Elhasasna Hussain , Khan Raymond , Bhanumathy Kalpana K. , Vizeacoumar Frederick S. , Walke Prachi , Bautista Maricris , Dahiya Dinesh K. , Maranda Vincent , Patel Hardikkumar , Balagopal Amrutha , Alli Nezeka , Krishnan Anand , Freywald Andrew , Vizeacoumar Franco J.
Published: July 2022

Neuroendocrine prostate cancer (NEPC) represents a highly aggressive form of prostate tumors. NEPC results from trans-differentiated castration-resistant prostate cancer (CRPC) with increasing evidence indicating that the incidence of NEPC often results from the adaptive response to androgen deprivation therapy. Recent studies have shown that a subset of NEPC exhibits overexpression of the MYCN oncogene along with the loss of tumor suppressing TP53 and RB1 activities. N-MYC is structurally disordered with no binding pockets available on its surface and so far, no clinically approved drug is available. We adopted a drug-repurposing strategy, screened ~1800 drug molecules, and identified fludarabine phosphate to preferentially inhibit the proliferation of N-MYC overexpressing NEPC cells by inducing reactive oxygen species (ROS). We also show that fludarabine phosphate affects N-MYC protein levels and N-MYC transcriptional targets in NEPC cells. Moreover, enhanced ROS production destabilizes N-MYC protein by inhibiting AKT signaling and is responsible for the reduced survival of NEPC cells and tumors. Our results indicate that increasing ROS production by the administration of fludarabine phosphate may represent an effective treatment option for patients with N-MYC overexpressing NEPC tumors.
Evidence for a Hepatitis B Virus Short RNA Fragment Directly Targeting the Cellular RRM2 Gene
Authors: Broennimann Karin , Ricardo-Lax Inna , Adler Julia , Shaul Yosef
Published: July 2022

The hepatitis B virus (HBV) is one of the smallest but most highly infectious human pathogens. With a DNA genome of only 3.2 kb and only four genes, HBV successfully completes its life cycle by using intricate processes to hijack the host machinery. HBV infects non-dividing liver cells in which dNTPs are limited. As a DNA virus, HBV requires dNTPs for its replication. HBV induces the ATR-mediated cellular DNA damage response pathway to overcome this constraint. This pathway upregulates R2 (RRM2) expression in generating an active RNR holoenzyme catalyzing de novo dNTP synthesis. Previously we reported that ERE, a small RNA fragment within the HBx ORF, is sufficient to induce R2 upregulation. Interestingly, there is high sequence similarity between ERE and a region within the R2 5′UTR that we named R2-box. Here, we established a mutant cell line in the R2-box region of the R2 gene using CRISPR-Cas9 technology to investigate the R2 regulation by ERE. This cell line expresses a much lower R2 level than the parental cell line. Interestingly, the HBV infection and life cycle were severely impaired. These cells became permissive to HBV infection upon ectopically R2 expression. These results validate the requirement of the R2 gene expression for HBV replication. Remarkably, the R2-box mutated cells became ERE refractory, suggesting that the homology region between ERE and R2 gene is critical for ERE-mediated R2 upregulation. Thus, along with the induction of the ATR pathway of the DNA damage response, ERE might also directly target the R2 gene via the R2-box.
Optical Multisensor System Based on Lanthanide(III) Complexes as Near-Infrared Light Sources for Analysis of Milk
Authors: Surkova Anastasiia , Bogomolov Andrey , Paderina Aleksandra , Khistiaeva Viktoria , Boichenko Ekaterina , Grachova Elena , Kirsanov Dmitry
Published: July 2022

Optical multisensor systems are easy-to-use and inexpensive analytical devices. In this work, we propose an optical multisensor system based on the luminescence of Nd(III) and Yb(III) complexes in the near-infrared (NIR) spectral region. The observed emission bands play the role of secondary light sources for further analysis of milk—for the determination of fat content and for the recognition of adulteration. The samples for analysis were prepared by putting a drop of milk upon a thin glass covering the powdered mixture of lanthanide complexes, which were excited by a light-emitting diode (LED) in the ultraviolet region (the maximum intensity at 365 nm). The diffuse-reflectance spectra of samples were acquired in the short-wave NIR range 750–1100 nm using a portable NIR spectrometer. The developed optical system was tested using two sets of milk samples with varying concentration levels of fat and added urea. The obtained spectral data were analyzed using a number of multivariate prediction and classification methods of chemometrics and the results were statistically compared. The regression and classification model performances achieved in this proof-of-concept study illustrate the feasibility of the optical multisensor analysis based on luminescent light sources in the short-wave NIR range, in particular, for their application in the dairy.
Inequities in Availability of Evidence-Based Birth Supports to Improve Perinatal Health for Socially Vulnerable Rural Residents
Authors: Basile Ibrahim Bridget , Interrante Julia D. , Fritz Alyssa H. , Tuttle Mariana S. , Kozhimannil Katy Backes
Published: July 2022

Rural residents in the United States (US) have disproportionately high rates of maternal and infant mortality. Rural residents who are Black, Indigenous, and People of Color (BIPOC) face multiple social risk factors and have some of the worst maternal and infant health outcomes in the U.S. The purpose of this study was to determine the rural availability of evidence-based supports and services that promote maternal and infant health. We developed and conducted a national survey of a sample of rural hospitals. We determined for each responding hospital the county-level scores on the 2018 CDC Social Vulnerability Index (SVI). The sample’s (n = 93) median SVI score [IQR] was 0.55 [0.25–0.88]; for majority-BIPOC counties (n = 29) the median SVI score was 0.93 [0.88–0.98] compared with 0.38 [0.19–0.64] for majority-White counties (n = 64). Among counties where responding hospitals were located, 86.2% located in majority-BIPOC counties ranked in the most socially vulnerable quartile of counties nationally (SVI ≥ 0.75), compared with 14.1% of majority-White counties. In analyses adjusted for geography and hospital size, certified lactation support (aOR 0.36, 95% CI 0.13–0.97), midwifery care (aOR 0.35, 95% CI 0.12–0.99), doula support (aOR 0.30, 95% CI 0.11–0.84), postpartum support groups (aOR 0.25, 95% CI 0.09–0.68), and childbirth education classes (aOR 0.08, 95% CI 0.01–0.69) were significantly less available in the most vulnerable counties compared with less vulnerable counties. Residents in the most socially vulnerable rural counties, many of whom are BIPOC and thus at higher risk for poor birth outcomes, are significantly less likely to have access to evidence-based supports for maternal and infant health.
Old and New Aspects of H. pylori-Associated Inflammation and Gastric Cancer
Authors: Dincă Andreea Ligia , Meliț Lorena Elena , Mărginean Cristina Oana
Published: July 2022

H. pylori is involved in the development of 80% of gastric cancers and 5.5% of all malignant conditions worldwide. Its persistence within the host’s stomach causes chronic inflammation, which is a well-known hallmark of carcinogenesis. A wide range of cytokines was reported to be involved in the initiation and long-term persistence of this local and systemic inflammation. IL-8 was among the first cytokines described to be increased in patients with H. pylori infection. Although, this cytokine was initially identified to exert a chemoattracting effect that represents a trigger for the activation of inflammatory cells within H.-pylori-infected mucosa, more recent studies failed in encountering any association between IL-8 and H. pylori infection. IL-6 is a multifunctional, pleiotropic and multipotent cytokine involved in mediating the interaction between innate and adaptive immunity with a dichotomous role acting as both a proinflammatory and an anti-inflammatory cytokine depending on the signaling pathway. IL-1α functions as a promoter of angiogenesis and vascular endothelial cell proliferation in gastric carcinoma since it is closely related to H.-pylori-induced inflammation in children. IL-1β is an essential trigger and enhancer of inflammation. The association between a low IL-1β level and an increased TNF-α level might be considered a risk factor for peptic ulcer disease in the setting of H. pylori infection. IL-10 downregulates both cytotoxic inflammatory responses and cell-mediated immune responses. H. pylori uses the immunosuppressive role of IL-10 to favor its escape from the host’s immune system. TGFβ is a continuous inflammatory mediator that promotes the adherence of H. pylori to the host’s cells and their subsequent colonization. The role of H.-pylori-induced inflammatory responses in the onset of gastric carcinogenesis seems to represent the missing puzzle piece for designing effective preventive and therapeutic strategies in patients with H.-pylori-associated gastric cancer.
Analysis of Minor Proteins Present in Breast Milk by Using WGA Lectin
Authors: Hernández-Caravaca Iván , Cabañas Andrés , López-Úbeda Rebeca , González-Brusi Leopoldo , Guillén-Martínez Ascensión , Izquierdo-Rico Mª José , Muñoz-Rodríguez Mª Nieves , Avilés Manuel , Ruiz García Mª Jesús
Published: July 2022

Breast milk is a complex and dynamic biological fluid and considered an essential source of nutrition in early life. In its composition, the proteins have a relevant biological activity and are related to the multiple benefits demonstrated when compared with artificial milks derived from cow’s milk. Understanding human milk composition provides an important tool for health care providers toward the management of infant feeding and the establishment of breastfeeding. In this work, a new technique was developed to increase the knowledge of human milk, because many of the components remain unknown. To isolate minor proteins present in breast milk by using WGA lectin, breast milk was centrifuged to remove cells and separate the fat phase from the serum phase. The serum obtained was separated into two groups: control (n = 3; whole serum sample from mature milk) and WGA lectin (n = 3; sample processed with WGA lectin to isolate glycosylated proteins). The samples were analyzed by high-performance liquid chromatography coupled to mass spectrometry (HPLC/MS). A total of 84 different proteins were identified from all of the samples. In the WGA lectin group, 55 different proteins were isolated, 77% of which had biological functions related to the immune response. Of these proteins, there were eight WGA lectin group exclusives, and two had not previously been described in breast milk (polyubiquitin-B and POTE ankyrin domain family member F). Isolation by WGA lectin is a useful technique to detect minor proteins in breast milk and to identify proteins that could not be observed in whole serum.
Assessment of an Axially Loaded Self-Sensing Concrete Element with Recycled Steel Residuals
Authors: Scott David B. , Chen Shen-En
Published: July 2022

This paper describes the fundamental evaluation of a self-sensing concrete column using recycled steel residuals (RSR) as functional fill and the testing of the column under slow-rate cyclic loading. The RSR modified concrete has the advantage of sustainably using the otherwise waste material from steel fabrication process. Two columns (one without and one with 2% of RSR by volume) were fabricated in the lab and load-tested in cyclic axial compression. The columns are connected to an alternating current power source and have three electrode sets each for electric property measurements. The results indicate that the 2% specimen can accurately detect the loading and unloading processes using electric-based measurements to calculate resistivity. Based on the test results, empirical linear equations are derived to correlate the mechanical and electrical behaviors.
Mechanical Properties and Thermal Stability of CrZrN/CrZrSiN Multilayer Coatings with Different Bilayer Periods
Authors: Kim Hoe-Kun , Kim Sung-Min , Lee Sang-Yul
Published: July 2022

The CrZrN/CrZrSiN multilayer coatings at a bilayer period range decreasing from 1.35 μm to 0.45 μm were synthesized on a Si (100) wafer and WC-6 wt.% Co substrate using a closed-field unbalanced magnetron sputter, and the thickness effects on the mechanical properties and thermal stability were investigated. The CrZrN/CrZrSiN multilayer coatings showed high hardness and elastic modulus in the ranges of 28 to 33 GPa and 255 to 265 GPa, respectively, and the friction coefficient showed the lowest value of 0.24 on the multilayer coating with a bilayer period of 0.54 μm. The bilayer periods affected the adhesion strength of the multilayer coatings. From the scratch test, the critical load (Lc2) steadily increased with the decreasing of the bilayer period, and the CrZrN/CrZrSiN multilayer coating with a bilayer period of 0.45 μm showed the highest critical load (Lc2) of 79 N. In the case of the annealing test, the bilayer periods affected the thermal stability of the multilayer coatings, and the CrZrN/CrZrSiN multilayer coatings with 0.54 μm showed a maximum hardness value of approximately 30 GPa up to 800 °C.
Special Issue: Biofilm Composition and Applications
Authors: Subhadra Bindu
Published: July 2022

Biofilms can be formed on both biotic and abiotic surfaces, including on living tissues, indwelling medical devices, industrial or portable water system piping, and natural aquatic systems [...]
Mitigation of Black-Box Attacks on Intrusion Detection Systems-Based ML
Authors: Alahmed Shahad , Alasad Qutaiba , Hammood Maytham M. , Yuan Jiann-Shiun , Alawad Mohammed
Published: July 2022

Intrusion detection systems (IDS) are a very vital part of network security, as they can be used to protect the network from illegal intrusions and communications. To detect malicious network traffic, several IDS based on machine learning (ML) methods have been developed in the literature. Machine learning models, on the other hand, have recently been proved to be effective, since they are vulnerable to adversarial perturbations, which allows the opponent to crash the system while performing network queries. This motivated us to present a defensive model that uses adversarial training based on generative adversarial networks (GANs) as a defense strategy to offer better protection for the system against adversarial perturbations. The experiment was carried out using random forest as a classifier. In addition, both principal component analysis (PCA) and recursive features elimination (Rfe) techniques were leveraged as a feature selection to diminish the dimensionality of the dataset, and this led to enhancing the performance of the model significantly. The proposal was tested on a realistic and recent public network dataset: CSE-CICIDS2018. The simulation results showed that GAN-based adversarial training enhanced the resilience of the IDS model and mitigated the severity of the black-box attack.