bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of Fatigue by Specific Anthracycline Cancer Drugs through Disruption of the Circadian Pacemaker
Authors: Wang Yumeng , Zanden Sabina Y. van der , van Leerdam Suzanne , Tersteeg Mayke M. H. , Kastelein Anneke , Michel Stephan , Neefjes Jacques , Meijer Johanna H. , Deboer Tom
Published: May 2022

Cancer-related fatigue (CRF) is the most devastating long-term side effect of many cancer survivors that confounds the quality of life for months to years after treatment. However, the cause of CRF is poorly understood. As a result, cancer survivors, at best, receive psychological support. Chemotherapy has been shown to increase the risk of CRF. Here, we study therapy-induced fatigue in a non-tumor-bearing mouse model with three different topoisomerase II-poisoning cancer drugs. These drugs either induce DNA damage and/or chromatin damage. Shortly before and several weeks after treatment, running wheel activity and electroencephalographic sleep were recorded. We show that doxorubicin, combining DNA damage with chromatin damage, unlike aclarubicin or etoposide, induces sustained CRF in this model. Surprisingly, this was not related to changes in sleep. In contrast, our data indicate that the therapy-induced CRF is associated with a disrupted circadian clock. The data suggest that CRF is probably a circadian clock disorder that influences the quality of waking and that the development of CRF depends on the type of chemotherapy provided. These findings could have implications for selecting and improving chemotherapy for the treatment of cancer in order to prevent the development of CRF.
HER-2-Targeted Nanoparticles for Breast Cancer Diagnosis and Treatment
Authors: Sitia Leopoldo , Sevieri Marta , Signati Lorena , Bonizzi Arianna , Chesi Arianna , Mainini Francesco , Corsi Fabio , Mazzucchelli Serena
Published: May 2022

Human epidermal growth factor receptor-2 (HER-2) overexpressing breast cancer is a breast cancer subtype characterized by high aggressiveness, high frequency of brain metastases and poor prognosis. HER-2, a glycoprotein belonging to the ErbB receptor family, is overexpressed on the outer membrane of cancer cells and has been an important therapeutic target for the development of targeted drugs, such as the monoclonal antibodies trastuzumab and pertuzumab. These therapies have been available in clinics for more than twenty years. However, despite the initial enthusiasm, a major issue emerged limiting HER-2 targeted therapy efficacy, i.e., the evolution of drug resistance, which could be tackled by nanotechnology. The aim of this review is to provide a first critical update on the different types of HER-2-targeted nanoparticles that have been proposed in the literature in the last decade for therapeutic purposes. We focus on the different targeting strategies that have been explored, their relative outcomes and current limitations that still need to be improved. Then, we review the nanotools developed as diagnostic kits, focusing on the most recent techniques, which allow accurate quantification of HER-2 levels in tissues, with the aim of promoting more personalized medicinal approaches in patients.
Clinical Impact of Pathogenic Variants in DNA Damage Repair Genes beyond BRCA1 and BRCA2 in Breast and Ovarian Cancer Patients
Authors: Espinel Whitney , Champine Marjan , Hampel Heather , Jeter Joanne , Sweet Kevin , Pilarski Robert , Pearlman Rachel , Shane Kate , Brock Pamela , Westman Judith , Kipnis Lindsay , Sotelo Jilliane , Chittenden Anu , Culver Samantha , Stopfer Jill , Schneider Katherine , Sacca Rosalba , Koeller Diane , Gaonkar Shraddha , Vaccari Erica , Kane Sarah , Michalski Scott , Yang Shan , Nielsen Sarah , Bristow Sara , Lincoln Stephen , Nussbaum Robert , Esplin Edward
Published: May 2022

Consensus guidelines for hereditary breast and ovarian cancer include management recommendations for pathogenic/likely pathogenic (P/LP) variants in ATM, CHEK2, PALB2, and other DNA damage repair (DDR) genes beyond BRCA1 or BRCA2. We report on clinical management decisions across three academic medical centers resulting from P/LP findings in DDR genes in breast/ovarian cancer patients. Among 2184 patients, 156 (7.1%) carried a P/LP variant in a DDR gene. Clinical follow-up information was available for 101/156 (64.7%) patients. Genetic test result-based management recommendations were made for 57.8% (n = 59) of patients and for 64.7% (n = 66) of patients’ family members. Most recommendations were made for moderate-to-high risk genes and were consistent with guidelines. Sixty-six percent of patients (n = 39/59) implemented recommendations. This study suggests that P/LP variants in DDR genes beyond BRCA1 and BRCA2 can change clinical management recommendations for patients and their family members, facilitate identification of new at-risk carriers, and impact treatment decisions. Additional efforts are needed to improve the implementation rates of genetic-testing-based management recommendations for patients and their family members.
Concordance, Correlation, and Clinical Impact of Standardized PD-L1 and TIL Scoring in SCCHN
Authors: De Keukeleire Stijn Jeroen , Vermassen Tijl , Deron Philippe , Huvenne Wouter , Duprez Fréderic , Creytens David , Van Dorpe Jo , Ferdinande Liesbeth , Rottey Sylvie
Published: May 2022

Background: The clinical significance of tumor-infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PD-L1) expression has been thoroughly researched in squamous cell carcinoma of the head and neck (SCCHN). To address the impact of intra- and intertumoral heterogeneity in these biomarkers, we explored the concordance of PD-L1 combined positive score (CPS) and stromal TILs in different paired tissue sample types, while evaluating their internal relationship and prognostic impact. Methods: A total of 165 tissue blocks from 80 SCCHN patients were reviewed for TILs and PD-L1 CPS. Concordance between paired tissue samples was evaluated, and their association with several clinicopathological variables, overall survival (OS), and disease-free survival (DFS) was determined. Results: Biopsies and paired resection material were severely discordant in 39% and 34% of samples for CPS and TIL count, respectively, of which CPS was underscored in 27% of biopsies. In paired primary tumor–metastatic lesions, the disagreement was lower for CPS (19%) but not for TIL count (44%). PD-L1 CPS was correlated with prolonged OS when calculated from tissue acquirement, while extended OS and DFS were observed for high TIL density. Conclusion: Intertumoral and, especially, intratumoral heterogeneity were confounding factors when determining PD-L1 CPS and TIL count on paired tissue samples, indicating the increasing necessity of assessing both biomarkers on representative tissue material. Although TILs hold valuable prognostic information in SCCHN, the robustness of PD-L1 as a biomarker in SCCHN remains ambiguous.
Cold Atmospheric Plasma Reduces Vessel Density and Increases Vascular Permeability and Apoptotic Cell Death in Solid Tumors
Authors: Kugler Philipp , Becker Sven , Welz Christian , Wiesmann Nadine , Sax Jonas , Buhr Christoph R. , Thoma Markus H. , Brieger Juergen , Eckrich Jonas
Published: May 2022

Cold atmospheric plasma (CAP) has demonstrated promising anti-cancer effects in numerous in vitro and in vivo studies. Despite their relevance for the treatment of solid tumors, effects of CAP on tumor vasculature and microcirculation have only rarely been investigated. Here, we report the reduction of vessel density and an increase in vascular permeability and tumor cell apoptosis after CAP application. Solid tumors in the chorioallantoic membrane of chicken embryos were treated with CAP and evaluated with respect to effects of CAP on embryo survival, tumor size, and tumor morphology. Furthermore, intratumoral blood vessel density, apoptotic cell death and the tumor-associated microcirculation were investigated and compared to sham treatment. Treatment with CAP significantly reduced intratumoral vessel density while increasing the rate of intratumoral apoptosis in solid tumors. Furthermore, CAP treatment increased vascular permeability and attenuated the microcirculation by causing vessel occlusions in the tumor-associated vasculature. These effects point out the potential of CAP as a promising and yet underrated therapeutic modality for addressing the tumor vasculature in the treatment of solid tumors.
MET Expression Level in Lung Adenocarcinoma Loosely Correlates with MET Copy Number Gain/Amplification and Is a Poor Predictor of Patient Outcome
Authors: Yin Wei , Guo Ming , Tang Zhenya , Toruner Gokce A. , Cheng Joanne , Medeiros L. Jeffrey , Tang Guilin
Published: May 2022

MET amplification has been associated with shorter survival in cancer patients, however, the potential correlation of MET overexpression with either MET amplification or patient outcome is controversial. The aim of this study was to address these questions by correlating MET expression level with MET copy number and patient outcome in a cohort of 446 patients who had a lung adenocarcinoma: 88 with MET amplification, 118 with polysomy 7, and 240 with negative results by fluorescence in situ hybridization. MET expression assessed by immunohistochemistry was semi-quantified by expression level: absent (0+), weak (1+), moderate (2+) and strong (3+); or by H-score: 0–99, 100–199, and ≥200. MET expression level or H-score was positively but weakly correlated with MET copy number or MET/CEP7 ratio. Strong expression of MET (3+ or H-score ≥ 200) was associated with a shorter overall survival, but it was not an independent hazard for survival by multivariant analysis. We conclude that MET expression is loosely correlated with MET copy number gain/amplification. Strong expression of MET does not independently predict patient outcome.
Are We Moving the Needle for Patients with TP53-Mutated Acute Myeloid Leukemia?
Authors: Shallis Rory M. , Bewersdorf Jan P. , Stahl Maximilian F. , Halene Stephanie , Zeidan Amer M.
Published: May 2022

The currently available therapeutic options for patients with TP53-mutated acute myeloid leukemia (AML) are insufficient, as they translate to a median overall of only 6–9 months, and less than 10% of patients undergoing the most aggressive treatments, such as intensive induction therapy and allogeneic hematopoietic stem cell transplantation, will be cured. The lack of clear differences in outcomes with different treatments precludes the designation of a standard of care. Recently, there has been growing attention on this critical area of need by way of better understanding the biology of TP53 alterations and the disparities in outcomes among patients in this molecular subgroup, reflected in the development and testing of agents with novel mechanisms of action. Promising preclinical and efficacy data exist for therapies that are directed at the p53 protein rendered dysfunctional via mutation or that inhibit the CD47/SIRPα axis or other immune checkpoints such as TIM-3. In this review, we discuss recently attractive and emerging therapeutic agents, their preclinical rationale and the available clinical data as a monotherapy or in combination with the currently accepted backbones in frontline and relapsed/refractory settings for patients with TP53-mutated AML.
Large-Scale Profiling of Extracellular Vesicles Identified miR-625-5p as a Novel Biomarker of Immunotherapy Response in Advanced Non-Small-Cell Lung Cancer Patients
Authors: Pantano Francesco , Zalfa Francesca , Iuliani Michele , Simonetti Sonia , Manca Paolo , Napolitano Andrea , Tiberi Simone , Russano Marco , Citarella Fabrizio , Foderaro Simone , Vulpis Elisabetta , Zingoni Alessandra , Masuelli Laura , Bei Roberto , Ribelli Giulia , Del Re Marzia , Danesi Romano , Vincenzi Bruno , Perrone Giuseppe , Tonini Giuseppe , Santini Daniele
Published: May 2022

Immune checkpoint inhibitors (ICIs) are largely used in the treatment of patients with advanced non-small-cell lung cancer (NSCLC). Novel biomarkers that provide biological information that could be useful for clinical management are needed. In this respect, extracellular vesicles (EV)-associated microRNAs (miRNAs) that are the principal vehicle of intercellular communication may be important sources of biomarkers. We analyzed the levels of 799 EV-miRNAs in the pretreatment plasma of 88 advanced NSCLC patients who received anti-PD-1 therapy as single agent. After data normalization, we used a two-step approach to identify candidate biomarkers associated to both objective response (OR) by RECIST and longer overall survival (OS). Univariate and multivariate analyses including known clinicopathologic variables and new findings were performed. In our cohort, 24/88 (27.3%) patients showed OR by RECIST. Median OS in the whole cohort was 11.5 months. In total, 196 EV-miRNAs out 799 were selected as expressed above background. After multiplicity adjustment, abundance of EV-miR-625-5p was found to be correlated with PD-L1 expression and significantly associated to OR by RECIST (p = 0.0366) and OS (p = 0.0031). In multivariate analysis, PD-L1 staining and EV-miR-625-5p levels were constantly associated to OR and OS. Finally, we showed that EV-miR-625-5p levels could discriminate patients with longer survival, in particular in the class expressing PD-L1 ≥50%. EV-miRNAs represent a source of relevant biomarkers. EV-miR-625-5p is an independent biomarker of response and survival in ICI-treated NSCLC patients, in particular in patients with PD-L1 expression ≥50%.
Peripheral Blood Mononuclear Cell Populations Correlate with Outcome in Patients with Metastatic Breast Cancer
Authors: Larsson Anna-Maria , Nordström Olle , Johansson Alexandra , Rydén Lisa , Leandersson Karin , Bergenfelz Caroline
Published: May 2022

Local tumor-associated immune cells hold prognostic and predictive value in various forms of malignancy. The role of systemic, circulating leukocytes is, however, not well-characterized. In this prospective and explorative study, we aim to delineate the clinical relevance of a broad panel of circulating immune cells in 32 patients with newly diagnosed metastatic breast cancer (MBC) before the start of systemic treatment. Freshly isolated peripheral blood mononuclear cells (PBMCs) were analyzed by flow cytometry and evaluated for potential associations to clinicopathological variables and patient outcome. We show that the levels of specific circulating leukocyte populations are associated with clinical parameters such as hormone receptor status, histological subtype, number of circulating tumor cells (CTCs) and metastatic burden. Importantly, high levels of CD8+ cytotoxic T lymphocytes (CTLs) are significantly linked to improved overall survival (OS). In patients with estrogen receptor (ER)-positive primary tumors, high levels of circulating CTLs and non-classical (CD14+CD16++) monocytes were associated with improved OS, whereas in patients with ER-negative tumors low levels of circulating natural killer (NK) cells potentially associate with improved OS. We propose that the levels of specific circulating immune cell populations, such as CD8+ CTLs, may be used to predict clinical outcomes in MBC patients. Thus, larger studies are warranted to validate these findings.
Modelling α-Synuclein Aggregation and Neurodegeneration with Fibril Seeds in Primary Cultures of Mouse Dopaminergic Neurons
Authors: Tourville Aurore , Akbar David , Corti Olga , Prehn Jochen H. M. , Melki Ronald , Hunot Stéphane , Michel Patrick P.
Published: May 2022

To model α-Synuclein (αS) aggregation and neurodegeneration in Parkinson’s disease (PD), we established cultures of mouse midbrain dopamine (DA) neurons and chronically exposed them to fibrils 91 (F91) generated from recombinant human αS. We found that F91 have an exquisite propensity to seed the aggregation of endogenous αS in DA neurons when compared to other neurons in midbrain cultures. Until two weeks post-exposure, somal aggregation in DA neurons increased with F91 concentrations (0.01–0.75 μM) and the time elapsed since the initiation of seeding, with, however, no evidence of DA cell loss within this time interval. Neither toxin-induced mitochondrial deficits nor genetically induced loss of mitochondrial quality control mechanisms promoted F91-mediated αS aggregation or neurodegeneration under these conditions. Yet, a significant loss of DA neurons (~30%) was detectable three weeks after exposure to F91 (0.5 μM), i.e., at a time point where somal aggregation reached a plateau. This loss was preceded by early deficits in DA uptake. Unlike αS aggregation, the loss of DA neurons was prevented by treatment with GDNF, suggesting that αS aggregation in DA neurons may induce a form of cell death mimicking a state of trophic factor deprivation. Overall, our model system may be useful for exploring PD-related pathomechanisms and for testing molecules of therapeutic interest for this disorder.
Endocannabinoid and Nitric Oxide-Dependent IGF-I-Mediated Synaptic Plasticity at Mice Barrel Cortex
Authors: Noriega-Prieto José Antonio , Maglio Laura Eva , Ibáñez-Santana Sara , de Sevilla David Fernández
Published: May 2022

Insulin-like growth factor-I (IGF-I) signaling plays a key role in learning and memory. IGF-I increases the spiking and induces synaptic plasticity in the mice barrel cortex (Noriega-Prieto et al., 2021), favoring the induction of the long-term potentiation (LTP) by Spike Timing-Dependent Protocols (STDP) (Noriega-Prieto et al., 2021). Here, we studied whether these IGF-I effects depend on endocannabinoids (eCBs) and nitric oxide (NO). We recorded both excitatory postsynaptic currents (EPSCs) and inhibitory postsynaptic currents (IPSCs) evoked by stimulation of the basal dendrites of layer II/III pyramidal neurons of the Barrel Cortex and analyzed the effect of IGF-I in the presence of a CB1R antagonist, AM251, and inhibitor of the NO synthesis, L-NAME, to prevent the eCBs and the NO-mediated signaling. Interestingly, L-NAME abolished any modulatory effect of the IGF-I-induced excitatory and inhibitory transmission changes, suggesting the essential role of NO. Surprisingly, the inhibition of CB1Rs did not only block the potentiation of EPSCs but reversed to a depression, highlighting the remarkable functions of the eCB system. In conclusion, eCBs and NO play a vital role in deciding the sign of the effects induced by IGF-I in the neocortex, suggesting a neuromodulatory interplay among IGF-I, NO, and eCBs.
Brain Organization and Human Diseases
Authors: Sapir Tamar , Sela-Donenfeld Dalit , Karlinski Maayan , Reiner Orly
Published: May 2022

The cortex is a highly organized structure that develops from the caudal regions of the segmented neural tube. Its spatial organization sets the stage for future functional arealization. Here, we suggest using a developmental perspective to describe and understand the etiology of common cortical malformations and their manifestation in the human brain.
Stable Integration of Inducible SPLICS Reporters Enables Spatio-Temporal Analysis of Multiple Organelle Contact Sites upon Modulation of Cholesterol Traffic
Authors: Giamogante Flavia , Barazzuol Lucia , Poggio Elena , Tromboni Marta , Brini Marisa , Calì Tito
Published: May 2022

The study of organelle contact sites has received a great impulse due to increased interest in the understanding of their involvement in many disease conditions. Split-GFP-based contact sites (SPLICS) reporters emerged as essential tools to easily detect changes in a wide range of organelle contact sites in cultured cells and in vivo, e.g., in zebrafish larvae. We report here on the generation of a new vector library of SPLICS cloned into a piggyBac system for stable and inducible expression of the reporters in a cell line of interest to overcome any potential weakness due to variable protein expression in transient transfection studies. Stable HeLa cell lines expressing SPLICS between the endoplasmic reticulum (ER) and mitochondria (MT), the ER and plasma membrane (PM), peroxisomes (PO) and ER, and PO and MT, were generated and tested for their ability to express the reporters upon treatment with doxycycline. Moreover, to take advantage of these cellular models, we decided to follow the behavior of different membrane contact sites upon modulating cholesterol traffic. Interestingly, we found that the acute pharmacological inhibition of the intracellular cholesterol transporter 1 (NPC1) differently affects membrane contact sites, highlighting the importance of different interfaces for cholesterol sensing and distribution within the cell.
The RAL Enigma: Distinct Roles of RALA and RALB in Cancer
Authors: Richardson Dillon S. , Spehar Jonathan M. , Han David T. , Chakravarthy Prathik A. , Sizemore Steven T.
Published: May 2022

RALA and RALB are highly homologous small G proteins belonging to the RAS superfamily. Like other small GTPases, the RALs are molecular switches that can be toggled between inactive GDP-bound and active GTP-bound states to regulate diverse and critical cellular functions such as vesicle trafficking, filopodia formation, mitochondrial fission, and cytokinesis. The RAL paralogs are activated and inactivated by a shared set of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) and utilize similar sets of downstream effectors. In addition to their important roles in normal cell biology, the RALs are known to be critical mediators of cancer cell survival, invasion, migration, and metastasis. However, despite their substantial similarities, the RALs often display striking functional disparities in cancer. RALA and RALB can have redundant, unique, or even antagonistic functions depending on cancer type. The molecular basis for these discrepancies remains an important unanswered question in the field of cancer biology. In this review we examine the functions of the RAL paralogs in normal cellular physiology and cancer biology with special consideration provided to situations where the roles of RALA and RALB are non-redundant.
Cyanide Anion Determination Based on Nucleophilic Addition to 6-[(E)-(4-Nitrophenyl)diazenyl]-1′,3,3′,4-tetrahydrospiro[chromene-2,2′-indole] Derivatives
Authors: Dagilienė Miglė , Markuckaitė Giedrė , Krikštolaitytė Sonata , Šačkus Algirdas , Martynaitis Vytas
Published: May 2022

This work provides a novel approach for the instant detection of CN− anions based on chromogenic 6-[(E)-(4-nitrophenyl)diazenyl]-1′,3,3′,4-tetrahydrospiro[chromene-2,2′-indole] derivatives. New colorimetric detectors were synthesized and characterized. These compounds exhibited a substantial color change from orange to magenta and blue when treated with cyanide ions in a CH3CN solution buffered with sodium phosphate and demonstrated high selectivity to CN− anions. Common anions were tested, and they did not interfere with cyanide detection, except for carbonates and hydrosulfites. The simple preparation of a molecular sensor and the easily noticeable color change makes this a practical system for the monitoring of CN− ions. This color change is explained by nucleophilic substitution of the pyrane ring oxygen atom at the indoline C-2 atom by the cyanide anion. This generates the appearance of intensively colored 4-(4-nitrophenylazo)phenolate chromophore and allows for determining very low levels of CN− anion.
The Influence of Different Rope Jumping Methods on Adolescents’ Lower Limb Biomechanics during the Ground-Contact Phase
Authors: Lin Yi , Lu Zhenghui , Cen Xuanzhen , Thirupathi Anand , Sun Dong , Gu Yaodong
Published: May 2022

As a simple and beneficial way of exercise, rope skipping is favored by the majority of teenagers, but incorrect rope skipping may lead to the risk of injury. In this study, 16 male adolescent subjects were tested for bounced jump skipping and alternating jump rope skipping. The kinematic data of the hip, knee, ankle and metatarsophalangeal joint of lower extremities and the kinetics data of lower extremity touching the ground during rope skipping were collected, respectively. Moreover, the electromyography (EMG) data of multiple muscles of the lower extremity were collected by Delsys wireless surface EMG tester. Results revealed that bounced jump (BJ) depicted a significantly smaller vertical ground reaction force (VGRF) than alternate jump (AJ) during the 11–82% of the ground-contact stage (p < 0.001), and the peak ground reaction force and average loading rate were significantly smaller than AJ. From the kinematic perspective, in the sagittal plane, when using BJ, the flexion angle of the hip joint was comparably larger at 12–76% of the ground-contact stage (p < 0.01) and the flexion angle of the knee joint was significantly larger at 13–72% of the ground-contact stage (p < 0.001). When using two rope skipping methods, the minimum dorsal extension angle of the metatarsophalangeal joint was more than 25°, and the maximum was even higher than 50°. In the frontal plane, when using AJ, the valgus angle of the knee joint was significantly larger during the whole ground-contact stage (p < 0.001), and the adduction angle of the metatarsophalangeal joint (MPJ) was significantly larger at 0–97% of the ground-contact stage (p = 0.001). EMG data showed that the standardized value of root mean square amplitude of the tibialis anterior and gastrocnemius lateral head of BJ was significantly higher than AJ. At the same time, that of semitendinosus and iliopsoas muscle was significantly lower. According to the above results, compared with AJ, teenagers receive less GRF and have a better landing buffer strategy to reduce load, and have less risk of injury during BJ. In addition, in BJ rope skipping, the lower limbs are more inclined to the calf muscle group force, while AJ is more inclined to the thigh muscle group force. We also found that in using two ways of rope skipping, the extreme metatarsophalangeal joint back extension angle could be a potential risk of injury for rope skipping.
The Effect of Interlayer Microstructure on the Thermal Boundary Resistance of GaN-on-Diamond Substrate
Authors: Jia Xin , Huang Lu , Sun Miao , Zhao Xia , Wei Junjun , Li Chengming
Published: May 2022

Diamond has the highest thermal conductivity of any natural material. It can be used to integrate with GaN to dissipate heat from AlGaN/GaN high electron mobility transistor (HEMT) channels. Much past work has investigated the thermal properties of GaN-on-diamond devices, especially the thermal boundary resistance between the diamond and GaN (TBReff,Dia/GaN). However, the effect of SiNx interlayer structure on the thermal resistance of GaN-on-diamond devices is less investigated. In this work, we explore the role of different interfaces in contributing to the thermal boundary resistance of the GaN-on-diamond layers, specifically using 100 nm layer of SiNx, 80 nm layer of SiNx, 100 nm layer of SiNx with a 20 nm × 20 nm periodic structure. Through combination with time-domain thermoreflectance measurement and microstructural analysis, we were able to determine that a patterning SiNx interlayer provided the lower thermal boundary resistance (32.2 ± 1.8 m2KGW−1) because of the diamond growth seeding and the diamond nucleation surface. In addition, the patterning of the SiNx interlayer can effectively improve the interface bonding force and diamond nucleation density and reduce the thermal boundary resistance of the GaN-on-diamond. This enables significant improvement in heat dissipation capability of GaN-on-diamond with respect to GaN wafers.
Novel Micronized Mica Modified Casein–Aluminum Hydroxide as Fire Retardant Coatings for Wood Products
Authors: Uddin Mezbah , Alabbad Maitham , Li Ling , Orell Olli , Sarlin Essi , Haapala Antti
Published: May 2022

Sustainable coating solutions that function as a fire retardant for wood are still a challenging topic for the academic and industrial sectors. In this study, composite coatings of casein protein mixed with mica and aluminum trihydroxide (ATH) were tested as fire retardants for wood and plywood; coating degradation and fire retardancy performance were assessed with a cone calorimeter, and a thermogravimeter was used for the thermal stability measurement. The results indicated that casein–mica composites were beneficial as coatings. The heat release rate (HRR) and the total heat released (THR) of the sample coated with casein–mica composite were reduced by 55% and 37%, respectively; the time to ignition was increased by 27% compared to the untreated sample. However, the TTI of the sample coated with the casein–mica–ATH composite was increased by 156%; the PHR and THR were reduced by 31% and 28%, respectively. This is attributed to the yielded insulating surface layer, active catalytic sites, and the crosslink from mica and endothermic decomposition of ATH and casein producing different fragments which create multiple modes of action, leading to significant roles in suppressing fire spread. The multiple modes of action involved in the prepared composites are presented in detail. Coating wear resistance was investigated using a Taber Abrader, and adhesion interaction between wood and a coated composite were investigated by applying a pull-off test. While the addition of the three filler types to casein caused a decrease in the pull-off adhesion strength by up to 38%, their abrasion resistance was greatly increased by as much as 80%.
Effect of Fine Aggregate Gradation on Macro and Micro Properties of Cold Recycling Mixture Using Emulsified Asphalt
Authors: Li Zhigang , Li Kexin , Zhang Jianmin , Ren Ruibo , Du Pinru , Zhao Pinhui , Zhao Quanman , Geng Litao
Published: May 2022

In order to explore the influence of fine aggregate on the macro and micro properties of cold recycling mixture using emulsified asphalt (CRME), mechanical and microscopic property tests were carried out. The indirect tensile strength (ITS), unconfined compressive strength (UCS) and triaxial shear strength of different fine aggregate gradation was measured for analyzing the effects of fine aggregate on the mechanical strength, triaxial shear resistance and fracture energy of CRME. Meanwhile, the surface morphologies and air voids distribution of different CRME were observed by scanning electron microscopy (SEM) and X-ray computed tomography (X-ray CT). The results show that fine aggregate has a significant effect on the mechanical strength and shear resistance of CRME. With the same water and asphalt content, the fracture energy and failure strain of the mixture with less fine aggregate (G3-2) decreased by 16.2% and 18.2%, respectively. The less content of powder there was, the fewer cement hydration products there were due to some cement being coated by emulsified asphalt and the “cement hydration products fiber” length being shorter. Approximately 70% of the AFt hydration products in the G3-2 mixture were in the range of 1–4 μm, while those in the G1 mixture were in the range of 4–8 μm. With the increase in filler content, the number of air voids in the volume range of 0.5 mm3 ≤ V < 5 mm3 in CRME decreased, and the number of air voids in the volume range of V < 0.5 mm3 significantly increased, while the equivalent radius of air voids decreased slightly with the increase in filler content.
Evaluation of Infiltrant Application in the Course of Root Cementum Caries with Different Methods of Surface Preparation—An In Vitro Study
Authors: Nowak-Wachol Anna , Korytkowska-Wałach Anna , Chmiela Bartosz , Wachol Kacper , Wyszyńska Magdalena , Łopaciński Maciej , Mostafavi Sayedamirreza , Morawiec Tadeusz , Skucha-Nowak Małgorzata
Published: May 2022

The aim of this study is to evaluate the depth of penetration of an experimental preparation with the characteristics of a dental infiltrant into the decalcified root cementum tissue and observation of the root cementum tissue subjected to a single and repeated twice hydrochloric acid etching process. The study material consisted of 20 human teeth (the study group—12 demineralised teeth, the control group—8 teeth). A commercially available Icon preparation and an experimental preparation were used for the study with addition 2% of YF3 (yttrium trifluoride) added as an indicator to facilitate microscopic observation. Each tooth was divided into two zones, blue (Icon) and red (experimental preparation). The teeth were divided into two subgroups—in the first subgroup, the etching preparation was applied once, in the second subgroup twice, and at the end the teeth were infiltrated with the experimental preparation and the Icon preparation. The study of tooth longitudinal section morphology and chemical composition was performed with the use of a Hitachi S-3400N scanning electron microscope. Microscopic observations show that the applied YF3 tracer in most cases agglomerates and remains in the form of conglomerates on the surface of the root cementum. Single particles of YF3 are visible, penetrating through the cementum tissues into the root dentine structure. The degree of tissue infiltration with the resin (depth of penetration into decalcified tissues) is visible at a depth of approx. 80–120 μm. In the test group subjected to a single etching process, good penetration of both resins was noticeable, however, excessive erosion of the root surface was evident in several of the specimens—indicating that damage occurred as a result of the etching process. In the test group subjected to two etching processes, excessive erosion of the cementum is visible in each deposit.
The Evolution of Geometric Structures, Electronic Properties, and Chemical Bonding of Small Phosphorus-Boron Clusters
Authors: Wen Limei , Li Qingshan , Song Bingyi , Yang Liming , Ganz Eric
Published: May 2022

We report a comprehensive theoretical investigation on phosphorus–boron mixed neutral, anionic, and cationic clusters P2Bn/P2Bn−/P2Bn+ (n = 3–7) with two phosphorus atoms and three to seven boron atoms. We reveal the common character of all the structures (i.e., the phosphorus atoms choose to occupy the peripheral position), whereas the boron atoms tend to be in the central and inside position of the ground state phosphorus—boron mixed clusters at each stoichiometry. Any three atoms preferentially form a stable triangle and grow with zigzag shape in a planar network. Interestingly, a series of planar motifs (including tetra-, penta-, and hexa-coordination) have been discovered in the phosphorus–boron clusters. The large binding energies (3.6 to 4.6 eV/atom) and quite large HOMO–LUMO gaps (5 to 10 eV) indicate the high stability of the clusters. The energy differences Δ1E, Δ2E, and energy gaps display oscillating behavior with increasing numbers of boron atoms. The electron affinity (EA) and ionization potential (IP) generally have small variations, with the EA values ranging from 2 to 3 eV, and the IP values ranging from 7 to 9 eV. Chemical bond analysis shows that the existence of multi-center delocalized bonds stabilize the clusters.
In Silico Investigation of the Impact of Hole-Transport Layers on the Performance of CH3NH3SnI3 Perovskite Photovoltaic Cells
Authors: Omarova Zhansaya , Yerezhep Darkhan , Aldiyarov Abdurakhman , Tokmoldin Nurlan
Published: May 2022

Perovskite solar cells represent one of the recent success stories in photovoltaics. The device efficiency has been steadily increasing over the past years, but further work is needed to enhance the performance, for example, through the reduction of defects to prevent carrier recombination. SCAPS-1D simulations were performed to assess efficiency limits and identify approaches to decrease the impact of defects, through the selection of an optimal hole-transport material and a hole-collecting electrode. Particular attention was given to evaluation of the influence of bulk defects within light-absorbing CH3NH3SnI3 layers. In addition, the study demonstrates the influence of interface defects at the TiO2/CH3NH3SnI3 (IL1) and CH3NH3SnI3/HTL (IL2) interfaces across the similar range of defect densities. Finally, the optimal device architecture TiO2/CH3NH3SnI3/Cu2O is proposed for the given absorber layer using the readily available Cu2O hole-transporting material with PCE = 27.95%, FF = 84.05%, VOC = 1.02 V and JSC = 32.60 mA/cm2, providing optimal performance and enhanced resistance to defects.
WAXS and SAXS Investigation of Collagen-Rich Diet Effect on Multiscale Arrangement of Type I Collagen in Tilapia Skin Fed in Aquaponics Plant
Authors: Terzi Alberta , Sibillano Teresa , De Caro Liberato , Altamura Davide , Gallo Nunzia , Natali Maria Lucia , Sannino Alessandro , Salvatore Luca , Blasi Federica Stella , Corallo Angelo , Giannini Cinzia
Published: May 2022

Type I collagen is the main component of the extracellular matrix that acts as the physical and biochemical support of tissues. Thanks to its characteristics, collagen is widely employed as a biomaterial for implantable device fabrication and as antiaging food supplementation. Because of the BSE transmission in the 1990s, aquatic animals have become a more suitable extraction source than warm-blooded animals. Moreover, as recently demonstrated, a supplementing diet with fish collagen can increase the body’s collagen biosynthesis. In this context, Tilapia feeding was supplemented with hydrolyzed collagen in order to enhance the yield of extracted collagen. Tilapia skin was investigated with wide and small angle scattering techniques, analyzing the collagen structure from the submolecular to the nanoscale and correlated with Differential Scanning Calorimetry (DSC) measurements. Our studies demonstrated that the supplementation appears to have an effect at the nanoscale in which fibrils appear more randomly oriented than in fish fed with no supplemented feed. Conversely, no effect of a collagen-rich diet was observed at the submolecular scale.
Marrying Story with Science: The Impact of Outdated and Inconsistent Breast Cancer Screening Practices in Canada
Authors: Dale Jennie , Di Tomaso Michelle , Gay Victoria
Published: May 2022

Behind the science of breast cancer in Canada, as well as globally, are the stories of thousands of women, their families, and their communities. These include stories from those who have died or those suffering from the realities of stage III and stage IV breast cancer due to late detection, misinformation, and dismissal. The reality for these women is that, whilst grateful for the latest developments in cancer research, much of this knowledge is not reflected in policy and practice. Canadian guidelines do not reflect the recommended screening by experts within the field and inequities in screening practices and practitioner knowledge exist in different areas within Canada. Told through the stories of women with lived experiences of late-stage breast cancer and supported by scientific evidence, this paper explores the impact of outdated breast cancer screening practices on the lives of women. Recent patient advocacy is driving changes, such as notifying women of their breast density in a few jurisdictions in Canada, but we call for the whole medical community to take responsibility and ensure breast screening is optimised to save more lives.
Diatom Red List Species Reveal High Conservation Value and Vulnerability of Mountain Lakes
Authors: Ossyssek Stefan , Hofmann Andrea Maria , Geist Juergen , Raeder Uta
Published: May 2022

Mountain lakes are unique and often isolated freshwater habitats that harbour a rich biotic diversity. This high conservation value may be reflected by diatoms, a group of algae that is known for its reliability as a bioindicator, but which has not been studied extensively in mountain lakes of the northern European Alps. In this study, the conservation value of these lakes was assessed by characterizing the number, share, and abundance of diatom Red List (RL) taxa and their relationship with environmental variables, diatom α and β diversity (assemblage uniqueness). For this purpose, linear regression models, generalized linear models, and generalized additive models were fitted and spatial descriptors were included when relevant. Of the 560 diatom taxa identified, 64% were on the RL and half of these were assigned a threat status. As hypothesized, a decreasing share of RL species in sediment and littoral samples at higher trophic levels was reflected by higher total phosphorous content and lower Secchi depth, respectively. Species-rich lakes contained a high number of RL taxa, contrasting our hypothesis of a logarithmic relationship. In turn, RL abundance increased with uniqueness, confirming our initial hypothesis. However, some of the most unique sites were degraded by fish stocking and contained low abundances of RL species. The results demonstrate the importance of oligotrophic mountain lakes as habitats for rare freshwater biota and their vulnerability in light of human impact through cattle herding, tourism, damming, and fish stocking. Additional conservation efforts are urgently needed for mountain lakes that are still underrepresented within legal conservation frameworks. Species richness and uniqueness reflect complementary aspects of RL status and thus should be applied jointly. Uniqueness can indicate both pristine and degraded habitats, so that including information on human impacts facilitates its interpretation.
Datasets on Energy Simulations of Standard and Optimized Buildings under Current and Future Weather Conditions across Europe
Authors: D’Agostino Delia , Parker Danny , Epifani Ilenia , Crawley Dru , Lawrie Linda
Published: May 2022

The building sector has a strategic role in the clean energy transition towards a fully decarbonized stock by mid-century. This data article investigates the use of different weather datasets in building energy simulations across Europe. It focuses on a standard performing building optimized to a nearly-zero level accounting for climate projections towards 2060. The provided data quantify the building energy performance in the current and future scenarios. The article investigates how heating and cooling loads change depending on the location and climate scenario. Hourly weather datasets frequently used in building energy simulations are analyzed to investigate how climatic conditions have changed over recent decades. The data give insight into the implications of the use of weather datasets on buildings in terms of energy consumption, efficiency measures (envelope, appliances, systems), costs, and renewable production. Due to the ongoing changing climate, basing building energy simulations and design optimization on obsolete weather data may produce inaccurate results and related building designs with an increased energy consumption in the coming decades. Energy efficiency will become more crucial in the future when cooling and overheating will have to be controlled with appropriate measures used in combination with renewable energy sources.
Left Ventricle Outflow Tract Velocity-Time Index and Right Ventricle to Left Ventricle Ratio as Predictors for in Hospital Outcome in Intermediate-Risk Pulmonary Embolism
Authors: Babes Elena Emilia , Stoicescu Manuela , Bungau Simona Gabriela , Uivarosan Diana , Tit Delia Mirela , Toma Mirela Marioara , Bungau Alexa Florina , Bustea Cristiana
Published: May 2022

Accurate estimation of risk with both imaging and biochemical parameters in intermediate risk pulmonary embolism (PE) remains challenging. The aim of the study was to evaluate echocardiographic parameters that reflect right and left heart hemodynamic as predictors of adverse events in intermediate risk PE. This was a retrospective observational study on patients with computed tomography pulmonary angiography diagnosis of PE admitted at Cardiology department of the Clinical Emergency Hospital of Oradea, Romania between January 2018—December 2021. Echocardiographic parameters obtained at admission were studied as predictors of in hospital adverse events. The following adverse outcomes were registered: death, resuscitated cardiac arrest, hemodynamic deterioration and need of rescue thrombolysis. An adverse outcome was present in 50 patients (12.62%). PE related death was registered in 17 patients (4.3%), resuscitated cardiac arrest occurred in 6 patients (1.51%). Another 20 patients (5.05%) required escalation of therapy with thrombolysis and 7 (1.76%) patients developed haemodynamic instability. Echocardiographic independent predictors for in hospital adverse outcome were RV/LV ≥ 1 (HR = 3.599, 95% CI 1.378–9.400, p = 0.009) and VTI ≤ 15 mm (HR = 11.711, 95% CI 4.336–31.633, p < 0.001). The receiver operator curve renders an area under curve for LVOT VTI ≤ 15 mm of 0.792 (95% CI 0.719–0.864, p < 0.001) and for a RV/LV ≥ 1 of 0.746 (95% CI 0.671–0.821, p < 0.001). A combined criterion (LVOT VTI ≤ 15 and RV/LV ≥ 1) showed a positive predictive value of 75% and a negative predictive value of 95% regarding in hospital adverse outcomes. Low LVOT VTI and increased RV/LV are useful for identifying normotensive patients with PE at risk for short term adverse outcomes. Combining an LVOT VTI ≤ 15 cm with a RV/LV ≥ 1 can identify with increased accuracy PE patients with impending risk of clinical deterioration.
Quality Improvement Initiatives in Renal Biopsy for Patient-Centered Communication by Shared Decision Making
Authors: Chen Cheng-Hsu , Hsu Chia-Tien , Wu Ming-Ju , Tsai Shang-Feng
Published: May 2022

Background: Renal biopsy is the gold standard for diagnosing renal disease. The major concern is bleeding. Shared decision making (SDM) has been reported to improve communication but has never been used regarding renal biopsy. Methods: We launched a 5-year project on SDM for renal biopsy. We collected cases of renal biopsy and bleeding, and cases of SDM. The process of quality improvement (QI) for SDM is also shared. Results: Taichung Veterans General Hospital has the largest number of renal biopsy cases, and the lowest bleeding rate in Taiwan. We enlisted a core team for this QI project and conducted stakeholder mapping. In 2017, we conducted a small pilot study for SDM based on printed material as a decision aid. The satisfaction rate was 95.5%. From 2018 to 2019, we improved SDM patients’ decision aid from printed material to four videos, designing questions to consolidate their understanding, and a unique information platform. The above improvements facilitated the utilization of SDM for renal biopsy (81.27% in 2020 and 100% in 2021). Even with higher bleeding complications in 2019 and 2020, patients remained satisfied when we launched SDM prior to renal biopsy. Conclusion: This is the first study regarding SDM on renal biopsy. Through SDM, patients had time to understand renal biopsy, including risk and benefit. We recommend SDM to elaborate renal biopsy in clinical practice.
Frailty Network in an Acute Care Setting: The New Perspective for Frail Older People
Authors: Salini Sara , Giovannini Silvia , Covino Marcello , Barillaro Christian , Acampora Nicola , Gravina Ester Manes , Loreti Claudia , Damiano Francesco Paolo , Franceschi Francesco , Russo Andrea
Published: May 2022

The incidence of elderly patients who come to the emergency room is progressively increasing. The specialization of the physician units might not be adequate for the evaluation of this complexity. The present study aimed to present a standard procedure, called ‘The Geriatric Frailty Network’, operating at the Policlinico Gemelli IRCCS Foundation, which is configured specifically for the level II assessment of frail elderly patients. This was a retrospective study in 1191 patients aged over 65, who were evaluated by the Geriatric Frailty Unit directly after emergency department admission for one year. All patients underwent multidimensional geriatric evaluation. Data were collected on demographics, co-morbidity, disease severity, and Clinical Frailty Scale. Among all patients, 723 were discharged directly from the emergency room with early identification of continuity of care path. Globally, 468 patients were hospitalized with an early assessment of frailty that facilitated the discharge process. The geriatric frailty network model aims to assist the emergency room and ward doctor in the prevention of the most common geriatric syndromes and reduce the number of incongruous hospitalizations.