bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving the quality control of drinking water in Nicaragua through proficiency testing in a metrological multilateral cooperation project
Authors: Molina-Castro Gabriel , Venegas-Padilla Jimmy , Molina-Marcia Junette , Scarioni Luciana , Calderón-Jiménez Bryan
Published: August 2021

The United Nations General Assembly explicitly recognized the human right to water and sanitation and acknowledged that drinking water is essential to the realization of all human rights in a 2010 resolution. Supporting and strengthening the quality infrastructure in countries throughout the world guarantees more reliable water quality analyses, thus reducing the risks to consumers’ health. The present paper describes a multilateral cooperation project developed in Nicaragua to improve the country's quality infrastructure and, in turn, the quality control of drinking water. The project was developed with the support of National Metrology Institutes (NMIs) from the Inter-American Metrology System (SIM), the Physikalisch Technische Bundesanstalt (PTB) and the participation of research institutes and laboratories in Nicaragua. Several mechanisms such as awareness seminars, workshops, metrological screenings, peer review of the laboratories’ quality systems, and organizing proficiency testing (PT) were used to successfully achieve the cooperation goal. As a result, technical infrastructure for the organization of PT rounds in Nicaragua was implemented to evaluate the relevant physicochemical parameters such as pH, chloride (Cl−), and nitrate (NO3−) in drinking water. The results from the PT rounds which took place during the two-year cooperation project showed substantial improvement in the performances of the participating laboratories, and therefore, in their measurement methods. Finally, this article shows how multilateral cooperation projects can strengthen the quality infrastructure, improving and ensuring the quality control of drinking water.
Green synthesis of 1,5-dideoxy-1,5-imino-ribitol and 1,5-dideoxy-1,5-imino-dl-arabinitol from natural d-sugars over Au/Al2O3 and SO42−/Al2O3 catalysts
Authors: Gao Hongjian , Fan Ao
Published: August 2021

A green synthetic route for the synthesis of some potential enzyme active hydroxypiperidine iminosugars including 1,5-dideoxy-1,5-imino-ribitol and 1,5-dideoxy-1,5-imino-dl-arabinitol, starting from commercially available d-ribose and d-lyxose was tested out. Heterogeneous catalysts including Au/Al2O3, SO42−/Al2O3 as well as environmentally friendly reagents were employed into several critical reaction of the route. The synthetic route resulted in good overall yields of 1,5-dideoxy-1,5-imino-ribitol of 54%, 1,5-dideoxy-1,5-imino-d-arabinitol of 48% and 1,5-dideoxy-1,5-imino-l-arabinitol of 46%. The Au/Al2O3 catalyst can be easily recovered from the reaction mixture and reused with no loss of activity.
Fish biodiversity and assemblages along the altitudinal gradients of tropical mountainous forest streams
Authors: Soo Chen-Lin , Nyanti Lee , Idris Nur Ezaimah , Ling Teck-Yee , Sim Siong-Fong , Grinang Jongkar , Ganyai Tonny , Lee Karen-Suan-Ping
Published: August 2021

Knowledge of the fundamental aspects of ecology such as the patterns of fish species distribution and biodiversity in the forest streams is the first and basic step to develop effective conservation strategies. Yet, studies on altitudinal changes of fish composition and assemblages in Bornean forest streams are scarce despite being one of the hotspots of biodiversity conservation. Hence, surveys on freshwater fish composition along the altitudinal gradients of the Baleh River Basin in Sarawak, Borneo were conducted from April 2014 to August 2015. The Baleh River Basin was divided into seven altitudinal groups with a total of 72 stations. Group elevation ranged from 53 to 269 m above sea level. The fish samples and environmental parameters were taken concurrently during samplings. A total of 3565 specimens belonging to six orders, 14 families, and 76 species were found in the present study. The most dominant family in the Baleh River Basin was Cyprinidae (74.4%), followed by Gastromyzontidae (16.2%) while the most dominant species wasTor tambra(12.9%), followed byLobocheilos ovalis(12.3%). Fish abundance significantly higher at high altitude sites than those at low altitude sites except for Mengiong River which has the lowest fish abundance despite with high elevation. Species richness was found significantly lower in midstream segment. Noticeable altitudinal gradient of fish assemblages was observed along the Baleh River except a discontinuity at the midstream segment which is attributable to the poorer quality inflow from the Mengiong River coupled with the meandering feature of the segment. Fish abundance was significantly and positively correlated with elevation, water pH and conductivity while negatively correlated with turbidity. Anthropogenic activities in the Baleh River Basin had altered the environmental variables thus disrupted the altitudinal gradient of fish assemblages. This phenomenon is apparent when the Canonical Correspondence Analysis (CCA) revealed that the first axis (CCA1) explained 42.5% of the variation and has positive loading on dissolved oxygen (DO) and negative loading on water conductivity; whereas CCA2 explained 37.5% of the variation and positively loaded on elevation, water pH, and DO. The results demonstrated thatGastromyzon fasciatuspreferred more oxygenated water thanProtomyzon sp., G. sp 1, andG. punctulatusalthough they are all from Gastromyzontidae family that inhabiting high altitude sites.Barbonymus schwanenfeldiiwas also found most abundant with elevated dissolved oxygen value. On the other hand,Rasbora volziiandR. hosiiinhabiting lower altitude sites with less oxygenated and more acidic water.
An example of DNA methylation as a means to quantify stress in wildlife using killer whales
Authors: Crossman Carla A. , Barrett-Lennard Lance G. , Frasier Timothy R.
Published: August 2021

The cumulative effects of non-lethal stressors on the health of biodiversity are a primary concern for conservation, yet difficulties remain regarding their quantification. In mammals, many stressors are processed through a common stress-response pathway, and therefore epigenetic changes in genes of this pathway may provide a powerful tool for quantifying cumulative effects. As a preliminary assessment of this approach, we investigated epigenetic manifestations of stress in two killer whale populations with different levels of exposure to anthropogenic stressors. We used bisulfite amplicon sequencing to compare patterns of DNA methylation at 25 CpG sites found in three genes involved in stress response and identified large differences in the level of methylation at two sites consistent with differential stress exposure between Northern and Southern Resident killer whale populations. DNA methylation patterns could therefore represent a useful method to assess the cumulative effects of non-lethal stressors in wildlife.
Tandem mass spectrometry of aqueous extract from Ficus dubia sap and its cell-based assessments for use as a skin antioxidant
Authors: Chansriniyom Chaisak , Nooin Rawiwan , Nuengchamnong Nitra , Wongwanakul Ratjika , Petpiroon Nalinrat , Srinuanchai Wanwisa , Chantarasuwan Bhanumas , Pitchakarn Pornsiri , Temviriyanukul Piya , Nuchuchua Onanong
Published: August 2021

Since 2006, Ficus dubia has been reported as a new Ficus species in Thailand. As per our recent report, the red-brown aqueous extract of F. dubia sap (FDS) has been determined to strongly exhibit in vitro anti-radicals. However, the phytochemicals in the FDS extract related to health-promoting antioxidation have not been explored. Thus, in this study, we aimed to investigate the chemical components of the F. dubia sap extract by liquid chromatography-electrospray ionization quadrupole time-of-flight mass spectrometry (LC–ESI–MS/QTOF-MS) and its potential use in cosmetics in terms of cellular antioxidation on keratinocytes (HaCaT), phototoxicity, and irritation on 3D skin cell models following standard tests suggested by the Organization for Economic Cooperation and Development (OECD). It was found that the sap extract was composed of quinic acid and caffeoyl derivatives (e.g., syringoylquinic acid, 3-O-caffeoylquinic acid, 4-O-caffeoylquinic acid, and dimeric forms of caffeoylquinic acids). The extract has significantly exhibited antioxidant activity against H2O2-induced oxidative stress in HaCaT cells. The cellular antioxidative effect of the FDS extract was remarkably dependent on the presence of 3- and 4-O-caffeoylquinic acid in the extract. Furthermore, the FDS extract showed negative results on skin phototoxicity and irritation. Overall, the results reveal that the FDS extract could be developed as a new antioxidant candidate for a skin healthcare product.
A novel D2D–MEC method for enhanced computation capability in cellular networks
Authors: Liu Xiangyan , Zheng Jianhong , Zhang Meng , Li Yang , Wang Rui , He Yun
Published: August 2021

Device-to-device (D2D) communications and mobile edge computing (MEC) used to resolve traffic overload problems is a trend in the cellular network. By jointly considering the computation capability and the maximum delay, resource-constrained terminals offload parts of their computation-intensive tasks to one nearby device via a D2D connection or an edge server deployed at a base station via a cellular connection. In this paper, a novel method of cellular D2D–MEC system is proposed, which enables task offloading and resource allocation meanwhile improving the execution efficiency of each device with a low latency. We consider the partial offloading strategy and divide the task into local and remote computing, both of which can be executed in parallel through different computational modes. Instead of allocating system resources from a macroscopic view, we innovatively study both the task offloading strategy and the computing efficiency of each device from a microscopic perspective. By taking both task offloading policy and computation resource allocation into consideration, the optimization problem is formulated as that of maximized computing efficiency. As the formulated problem is a mixed-integer non-linear problem, we thus propose a two-phase heuristic algorithm by jointly considering helper selection and computation resources allocation. In the first phase, we obtain the suboptimal helper selection policy. In the second phase, the MEC computation resources allocation strategy is achieved. The proposed low complexity dichotomy algorithm (LCDA) is used to match the subtask-helper pair. The simulation results demonstrate the superiority of the proposed D2D-enhanced MEC system over some traditional D2D–MEC algorithms.
Highly efficient evaporative cooling by all-day water evaporation using hierarchically porous biomass
Authors: Choi Jihun , Lee Hansol , Sohn Bokyeong , Song Minjae , Jeon Sangmin
Published: August 2021

We developed a 3D solar steam generator with the highest evaporation rate reported so far using a carbonized luffa sponge (CLS). The luffa sponge consisted of entangled fibers with a hierarchically porous structure; macropores between fibers, micro-sized pores in the fiber-thickness direction, and microchannels in the fiber-length direction. This structure remained after carbonization and played an important role in water transport. When the CLS was placed in the water, the microchannels in the fiber-length direction transported water to the top surface of the CLS by capillary action, and the micro-sized pores in the fiber-thickness direction delivered water to the entire fiber surface. The water evaporation rate under 1-sun illumination was 3.7 kg/m2/h, which increased to 14.5 kg/m2/h under 2 m/s wind that corresponded to the highest evaporation rate ever reported under the same condition. The high evaporation performance of the CLS was attributed to its hierarchically porous structure. In addition, it was found that the air temperature dropped by 3.6 °C when the wind passed through the CLS because of the absorption of the latent heat of vaporization. The heat absorbed by the CLS during water evaporation was calculated to be 9.7 kW/m2 under 1-sun illumination and 2 m/s wind, which was 10 times higher than the solar energy irradiated on the same area (1 kW/m2).
Genetic homogeneity, lack of larvae recruitment, and clonality in absence of females across western Mediterranean populations of the starfish Coscinasterias tenuispina
Authors: Pérez-Portela Rocío , Garcia-Cisneros Alex , Campos-Canet Marta , Palacín Creu
Published: August 2021

We here analysed the populations’ genetic structure ofCoscinasterias tenuispina,an Atlantic-Mediterranean fissiparous starfish,focusing on the western Mediterranean,to investigate: the distribution and prevalence of genetic variants, the relative importance of asexual reproduction, connectivity across the Atlantic-Mediterranean transition, and the potential recent colonisation of the Mediterranean Sea. Individuals from 11 Atlantic-Mediterranean populations of a previous study added to 172 new samples from five new W Mediterranean sites. Individuals were genotyped at 12 microsatellite loci and their gonads histologically analysed for sex determination. Additionally, four populations were genotyped at two-time points. Results demonstrated genetic homogeneity and low clonal richness within the W Mediterranean, due to the dominance of asuperclone, but large genetic divergence with adjacent areas. The lack of new genotypes recruitment over time, and the absence of females, confirmed that W Mediterranean populations were exclusively maintained by fission and reinforced the idea of its recent colonization. The existence of different environmental conditions among basins and/or density-depend processes could explain this lack of recruitment from distant areas. The positive correlation between clonal richness and heterozygote excess suggests that most genetic diversity is retained within individuals in the form of heterozygosity in clonal populations, which might increase their resilience.
Odours count: human olfactory ecology appears to be helpful in the improvement of the sense of smell
Authors: Oleszkiewicz Anna , Heyne Lena , Sienkiewicz-Oleszkiewicz Beata , Cuevas Mandy , Haehner Antje , Hummel Thomas
Published: August 2021

Odours modify human behaviour. Research in this field develops rapidly, providing more and more exciting discoveries. In this context, our daily odorous environment has been surprisingly poorly explored. The aim of our study was to quantify olfactory perception and preliminarily identify factors affecting the frequency of odorous experiences. We were also interested in knowing whether human olfactory ecology relates with olfactory performance. In this study, patients with olfactory deficits (n = 62) and healthy controls (n = 97) had their olfactory threshold and odour identification abilities measured before and after a two-week intervention comprising counting of conscious perception of odours naturally occurring in the environment. In both groups, we observed enhanced olfactory performance after the intervention suggesting that (1) the conscious focus on odours may change its perception, and that (2) social and physical environment can effectively stimulate the human olfactory system, presumably supporting the improvement of olfactory sensitivity.
The severity of malnutrition in children with epidermolysis bullosa correlates with disease severity
Authors: Manjunath Seema , Mahajan Rahul , De Dipankar , Handa Sanjeev , Attri Savita , Behera Banchha Nidhi , Bhasin Sadhna Lal , Bolia Rishi
Published: August 2021

WHO defines malnutrition as severe if the z-scores are less than − 3 Standard deviation (SD), moderate if between − 2 and − 3 SD and mild if between − 2 SD to – 1 SD. This study was aimed to assess nutritional aspects of Indian children suffering from EB and to evaluate the effect of severity of EB on the severity of malnutrition. In this study, pediatric EB patients were evaluated prospectively for baseline nutritional status using anthropometric parameters and WHO growth charts, and its correlation with disease severity using instrument for Scoring Clinical Outcomes for Research of Epidermolysis Bullosa-iscorEB. In second phase, an individualized diet chart was given to meet the energy, protein and micronutrients needs and its effects were observed after 6 months. The median age of participants was 3 years (IQR-9). Of 57 patients, malnutrition was seen in 40.35% patients (22.81%-moderate and 17.54%-severe), and significantly correlated with iscorEB (r = 0.45, p < 0.0001). On bivariate regression analysis, iscorEB was independently associated with moderate-to-severe malnutrition (p = 0.047; OR 1.038, CI 1.011–1.066). iscorEB enabled the identification of patients with moderate-to-severe malnutrition with an Area Under Receiver Operating Curve (AUROC) of 0.72 (95%CI 0.58–0.85; p < 0.005). In phase 2, there was significant improvement in nutritional status in children with recessive dystrophic EB (RDEB) and dominant dystrophic EB (DDEB) subtype (p < 0.0001). The severity of malnutrition in EB children significantly correlates with disease severity, and is an independent predictor of moderate-to-severe malnutrition.
Green synthesis of magnesium nanoparticles mediated from Rosa floribunda charisma extract and its antioxidant, antiaging and antibiofilm activities
Authors: Younis Inas Y. , El-Hawary Seham S. , Eldahshan Omayma A. , Abdel-Aziz Marwa M. , Ali Zeinab Y.
Published: August 2021

Flower based nanoparticles has gained a special attention as a new sustainable eco-friendly avenue. Rosa floribunda charisma belongs to modern roses with bright yellow, red flowers with marvellous rose scent. Different methods were used for the extraction of its floral scent such as hexane, microwave, and solid-phase micro-extraction. The latter was the most efficient method for the extraction of phenyl ethyl alcohol, the unique scent of roses. In the current study, magnesium nanoparticles (RcNps) have been synthesized using Rosa floribunda charisma petals that have privileges beyond chemical and physical routs. RcNps formation was confirmed using UV–Visible (UV–Vis) Spectroscopy, Fourier Transform Infrared Spectroscopy (FTIR), High Resolution-Transmission Electron Microscope (HR-TEM), Field Emission-Scanning Electron Microscope (FE-SEM), Energy dispersive X-ray (EDX), X-ray Diffractometer (XRD), and X-ray photoelectron spectroscopy (XPS). HR-TEM images detected the polyhedral shape of RcNps with a diverse size ranged within 35.25–55.14 nm. The resulting RcNps exhibited a high radical scavenging activity illustrated by inhibition of superoxide, nitric oxide, hydroxyl radical and xanthine oxidase by by IC50 values 26.2, 52.9, 31.9 and 15.9 µg/ml respectively as compared to ascorbic acid. Furthermore, RcNps at concentration of 100 µg/ml significantly reduced xanthine oxidase activity (15.9 ± 0.61 µg/ml) compared with ascorbic acid (12.80 ± 0.32 µg/ml) with p < 0.05. Moreover, RcNps showed an excellent antiaging activity demonstrated by inhibition of collagenase, elastase, hyaluronidase and tyrosinase enzymes in a dose-dependent manner with IC50 values of 58.7 ± 1.66 µg/ml, 82.5 ± 2.93 µg/ml, 191.4 ± 5.68 µg/ml and 158.6 ± 5.20 µg/ml as compared to EGCG respectively. RcNps also, exhibited a promising antibacterial activity against three skin pathogens delineate a significant threat to a public health, as Staphylococcus epidermidis, Streptococcus pyogenes, and Pseudomonas aeruginosa with MIC of 15.63, 7.81, 31.25 µg/ml as compared to ciprofloxacin (7.81, 3.9 and 15.63 µg/ml). Moreover, RcNps suppressed the formation of biofilms with minimum biofilm inhibitory concentrations 1.95, 1.95, 7.81 µg/ml against the fore mentioned strains, respectively. Overall, our findings indicate that Rosa floribunda nanoparticles could be used as a leading natural source in skin care cosmetic industry.
Effects of lipid emulsions on the formation of Escherichia coli–Candida albicans mixed-species biofilms on PVC
Authors: Li Shanshan , Duan Wanshi , Lei Yujie , Wang Zhonghui , Fu Chaojiang , He Liang , Shen Zhenghai , Li Minjie , Chen Ying , Huang Yunchao
Published: August 2021

Patients receiving lipid emulsions are at increased risk of contracting catheter-related bloodstream infections (CRBSIs) in the clinic. More than 15% of CRBSIs are polymicrobial. The objective of this study was to explore the effects of lipid emulsions on the formation of Escherichia coli (E. coli)–Candida albicans (C. albicans) mixed-species biofilms (BFs) on polyvinyl chloride (PVC) surfaces and the underlying mechanism. Mixed-species BFs were produced by coculturing E. coli and C. albicans with PVC in various concentrations of lipid emulsions. Crystal violet staining and XTT assays were performed to test the mixed-species BF biomass and the viability of microbes in the BFs. The microstructures of the BFs were observed by an approach that combined confocal laser scanning microscopy, fluorescence in situ hybridization, and scanning electron microscopy. The study found that lipid emulsions could promote the formation of E. coli–C. albicans mixed-species BFs, especially with 10% lipid emulsions. The mechanism by which lipid emulsions promote mixed-species BF formation may involve significant upregulation of the expression of the flhDC, iha, HTA1, and HWP1 genes, which are associated with bacterial motility, adhesion, and BF formation. The results derived from this study necessitate strict aseptic precautions when handling lipid emulsions and avoiding the use of high concentrations of lipid emulsions for as long as possible.
Morphological variability of the plantaris tendon in the human fetus
Authors: Waśniewska-Włodarczyk Anna , Paulsen Friedrich , Olewnik Łukasz , Polguj Michał
Published: August 2021

Muscular anatomy often differs between species and individuals. In particular, the plantaris muscle (PM) demonstrates great morphological variability in its course and its proximal and distal attachments. The aim of this study was to investigate the morphological variation of the PM tendon in human fetuses. Forty-six spontaneously aborted human fetuses (23 male, 23 female) aged 18–38 weeks of gestation were studied. Morphology of the attachment of the PM was assessed in both lower extremities (n = 92). The PM was present in 72 lower limbs (78.26%) and absent in 20 (21.74%). Eight types of PM distal attachment were identified. We propose an eight-fold classification of PM insertion in fetuses. Leg length, length of tendon, extension point (ExP) from the calcaneus, and ExP thickness differed significantly among types of PM insertion.
Salivary oxytocin, cognitive anxiety and self-confidence in pre-competition athletes
Authors: La Fratta Irene , Franceschelli Sara , Speranza Lorenza , Patruno Antonia , Michetti Carlo , D’Ercole Paolo , Ballerini Patrizia , Grilli Alfredo , Pesce Mirko
Published: August 2021

It is well known that soccer sport has the potential for high levels of stress and anxiety and that these are linked to Cortisol (C) variations. To date, much research has been devoted to understanding how Oxytocin (OT) can affect anxiety in response to a challenge. The aim of this study was to investigate, in 56 young male soccer players, the psychophysiological stress response 96 and 24 h before one soccer match of a tournament, in order to establish whether athletes who won or lost, show different levels of C and OT or expressions of competitive state anxiety subcomponents. We found that winners had significantly lower Cognitive anxiety and higher Self-confidence scores than losers. Also, significant differences between winners and losers in C and OT concentrations were observed, with higher OT levels in who has won and higher C levels in who has lost. Our results showed interesting associations between OT, C, anxiety feelings, and the outcome of competition.
Exercise interventions can improve muscle strength, endurance, and electrical activity of lumbar extensors in individuals with non-specific low back pain: a systematic review with meta-analysis
Authors: Clael Sacha , Campos Lorrane Freitas , Correia Karina Lisboa , de Lucena Joana Marcela Sales , Gentil Paulo , Durigan João Luiz , Ribeiro Alexandre Lima de Araújo , Martins Wagner Rodrigues
Published: August 2021

Exercise interventions have been recommended for people with non-specific low back pain. The literature is scarce regarding the effects of exercise on muscle strength, endurance, and electrical activity of lumbar extensor muscles. Electronic searches were carried out from May 2020 until August 2020 in the following databases: PUBMED, CENTRAL, EMBASE, PEDro, SPORTDiscus, Scielo, and LILACS. Only randomized controlled trials with passive and active control groups were included. The methodological quality of the included studies was performed using the Physiotherapy Evidence Database Scale. Eight studies, involving 508 participants, were included in metanalytical procedures. Exercise interventions demonstrated superior effects on muscle activity (Electromyography) when compared with active controls (p < 0.0001). Exercise interventions demonstrated superior effects on muscle endurance (Sorensen Test) when compared with passive (p = 0.0340) and active controls (p = 0.0276). Exercise interventions demonstrated superior effects on muscle strength (Machine) when compared with passive controls (p = 0.0092). Exercise interventions can improve muscle strength, endurance, and electrical activity in people with non-specific low back pain.
Short-term heat shock perturbation affects populations of Daphnia magna and Eurytemora carolleeae: a warning to the water thermal pollution
Authors: Nowakowski Kacper , Sługocki Łukasz
Published: August 2021

Thermal pollution leads to short-term heat shock in aquatic invertebrates; however, the modulation of tolerance and life history of these invertebrates by thermal stress varies among regions, phenology, species, and their acclimation. To assess the effect of thermal shock, we conducted experiments on Daphnia magna and Eurytemora carolleeae at 25 °C, 30 °C, 35 °C, and 40 °C (in relation to 20 °C) in a different exposure time of the stressor (10, 30, and 60 min). The results showed that short-term heat shock leads to increased mortality and reduced fertility of the studied planktonic crustaceans. D. magna was more resistant to thermal shock than E. carolleeae according to all variants of exposure based on the calculated LT50 values for 24, 48, and 72 h. Thermal shock decreased the potential of the Daphnia population in terms of the total number of births, however, with regard to individual reproductive abilities, the non-lethal heat shock did not reduce the birth rate. Although Eurytemora is more sensitive to thermal shock than Daphnia, the type of parental care in Eurytemora might be more favorable for offspring survival following thermal shock than in Daphnia. In Eurytemora, despite maternal deaths, a relatively high number of newborns who survived high temperatures were observed. The obtained results can help to understand the ecological processes occurring due to anthropogenic thermal pollution.
PD-L1 expression, EGFR and KRAS mutations and survival among stage III unresected non-small cell lung cancer patients: a Danish cohort study
Authors: Cronin-Fenton Deirdre , Dalvi Tapashi , Movva Naimisha , Pedersen Lars , Hansen Hanh , Fryzek Jon , Hedgeman Elizabeth , Mellemgaard Anders , Rasmussen Torben R. , Shire Norah , Hamilton-Dutoit Stephen , Nørgaard Mette
Published: August 2021

Programmed cell death receptor ligand-1 (PD-L1) expression, KRAS (KRASm) and EGFR (EGFRm) mutations may influence non-small cell lung cancer (NSCLC) prognosis. We aimed to evaluate PD-L1 expression, KRASm, and EGFRm and survival among stage III unresected NSCLC patients. Using Danish registries, we collected data on stage III unresected NSCLC patients diagnosed 2001–2012 and paraffin-embedded tumor tissue from pathology archives. We assessed PD-L1 expression in tumors and tumor-infiltrating immune cells (ICs) by immunohistochemistry ($$\ge$$
≥
 1% threshold for PD-L1+). We genotyped KRAS and EGFR. Follow-up extended from 120 days post-diagnosis to death, emigration, or 31/12/2014. We computed median survival using Kaplan–Meier methods, and hazard ratios (HRs) using Cox regression associating the biomarkers with death, adjusting for confounders. Among 305 patients, 48% had adenocarcinoma; 38% squamous cell carcinoma. Forty-nine percent had PD-L1+ tumors—51% stage IIIA and 26% KRASm. Few (2%) patients had EGFRm. Median survival in months was 14.7 (95% CI = 11.8–17.9) and 13.4 (95% CI = 9.5–16.3) in PD-L1+ and PD-L1− tumors, respectively. KRASm was not associated with death (HR = 1.06, 95% CI = 0.74–1.51 versus wildtype). PD-L1+ tumors yielded a HR = 0.83 (95% CI = 0.63–1.10); PD-L1+ ICs a HR = 0.51 (95% CI = 0.39–0.68). Tumor expression of PD-L1 did not influence survival. PD-L1+ ICs may confer survival benefit in stage III unresected NSCLC patients.
The effects of T-DXd on the expression of HLA class I and chemokines CXCL9/10/11 in HER2-overexpressing gastric cancer cells
Authors: Nakajima Shotaro , Mimura Kosaku , Matsumoto Takuro , Thar Min Aung Kyi , Ito Misato , Nakano Hiroshi , Neupane Prajwal , Kanke Yasuyuki , Okayama Hirokazu , Saito Motonobu , Momma Tomoyuki , Watanabe Yohei , Hanayama Hiroyuki , Hayase Suguru , Saze Zenichiro , Kono Koji
Published: August 2021

Trastuzumab deruxtecan (T-DXd), a HER2-targeting antibody–drug conjugate with a topoisomerase I inhibitor deruxtecan (DXd), exhibits an excellent anti-tumor effect in previously treated HER2-positive tumors. A recent study demonstrated that T-DXd not only suppressed tumor growth but also enhanced anti-tumor immunity through increasing the number of tumor-infiltrating CD8+ T cells and enhancement of major-histocompatibility-complex class I expression on tumor cells in a mouse model. However, the effect of T-DXd on anti-tumor immune responses in human cancers is largely unknown. We investigated the effect of T-DXd on the expression of HLA class I and CXCL9/10/11, T-cell chemoattractants, in HER2-positive human gastric cancer (GC) cells. We found that T-DXd significantly inhibited GC cell proliferation in a HER2-dependent manner, while it slightly increased the expression of HLA class I in HER2-positive GC cells. Moreover, we revealed that T-DXd significantly induced mRNA expression of CXCL9/10/11 in HER2-positive GC cells. T-DXd-triggered up-regulation of these chemokines was mediated through the activation of DNA damage signaling pathways. These results suggest that T-DXd triggers anti-tumor immune responses at least in part through induction of the expression of HLA class I and CXCL9/10/11 on HER2-positive GC cells, resulting in the enhancement of anti-tumor immunity in human GC.
Real-time cancer diagnosis of breast cancer using fluorescence lifetime endoscopy based on the pH
Authors: Lee Jooran , Kim Byungyeon , Park Byungjun , Won Youngjae , Kim Sang-Yeob , Lee Seungrag
Published: August 2021

A biopsy is often performed for the diagnosis of cancer during a surgical operation. In addition, pathological biopsy is required to discriminate the margin between cancer tissues and normal tissues in surgical specimens. In this study, we presented a novel method for discriminating between tumor and normal tissues using fluorescence lifetime endoscopy (FLE). We demonstrated the relationship between the fluorescence lifetime and pH in fluorescein using the proposed fluorescence lifetime measurement system. We also showed that cancer could be diagnosed based on this relationship by assessing differences in pH based fluorescence lifetime between cancer and normal tissues using two different types of tumor such as breast tumors (MDA-MB-361) and skin tumors (A375), where cancer tissues have ranged in pH from 4.5 to 7.0 and normal tissues have ranged in pH from 7.0 to 7.4. To support this approach, we performed hematoxylin and eosin (H&E) staining test of normal and cancer tissues within a certain area. From these results, we showed the ability to diagnose a cancer using FLE technique, which were consistent with the diagnosis of a cancer with H&E staining test. In summary, the proposed pH-based FLE technique could provide a real time, in vivo, and in-situ clinical diagnostic method for the cancer surgical and could be presented as an alternative to biopsy procedures.
Overview of Strategies for Solving ADMET Challenges
Authors: Schnider Patrick
Published: August 2021

This chapter provides a high-level overview of all the strategies for solving challenges related to the optimization of absorption, distribution, metabolism, excretion and toxicity (ADMET) properties in small molecule drug discovery, which are detailed within the chapters of this book. In the introductory section the need to apply a holistic view of molecular properties towards the identification of candidate drugs which meet the target pharmacokinetic–pharmacodynamic profile and possess an adequate therapeutic index for a given indication is discussed. The molecular properties which have the biggest influence on ADMET parameters and which are directly amenable to structural modifications are outlined. The effects of these are visualized in an overview table. The most promising mitigation strategies for each ADMET property described in this book in detail are summarized.
Aldehyde and Xanthine Oxidase Metabolism
Authors: Pryde David C. , Yadav Dharmendra B. , Ghosh Rajib
Published: August 2021

Aldehyde oxidase (AO) and xanthine oxidase (XO) are metabolizing enzymes contained within the cytosolic compartments of many tissues and species. In recent years, as drug discovery efforts have increasingly targeted new gene families and new chemotypes and applied decades of learning how to reduce P450-mediated metabolism, the role of non-P450 metabolism, such as by AO and XO, has become more prominent. In this chapter, we highlight the main features of this family of metabolising enzymes and support our view that this is an enzyme family of increasing importance in xenobiotic metabolism with several real-life examples.
Glucuronidation
Authors: Pan Yue
Published: August 2021

Glucuronidation catalyzed by uridine 5′-diphospho-glucuronosyltransferase (UGT) is the most common phase II metabolism. The UGTs can severely limit a drug's exposure and generate reactive metabolites, leading to toxicity. This chapter provides a brief overview of the current understanding of the UGT enzyme family, followed by various medicinal chemistry strategies to address this metabolic liability and select examples from the literature.
Genotoxicity
Authors: Kirchner Stephan , Schnider Patrick
Published: August 2021

The assessment of the potential of a new drug to cause genotoxicity is a prerequisite for its progression to clinical development. This chapter gives a concise overview of the major aspects relating to genotoxicity, which are relevant in small molecule drug discovery. Testing schemes and assays recommended by regulatory guidelines are outlined. The different ways by which small molecules and their metabolites can elicit genotoxicity by DNA-reactive (direct) or non-DNA-reactive (indirect) mechanisms are discussed. Strategies to mitigate the most prevalent mechanisms of small molecule induced genotoxicity are provided and illustrated by examples.
Drug-induced Phospholipidosis
Authors: Goracci Laura , Cruciani Gabriele
Published: August 2021

In the past decades, rising safety concerns about drug-induced phospholipidosis (DIPL) have induced scientists to develop novel strategies to detect the risk of DIPL early in drug discovery and drug development. An early detection of phospholipidosis (PL)-inducing potential of new chemical entities will contribute to the release of safer drugs, also reducing associated investments and time. This chapter focuses on concisely summarizing the current knowledge on DIPL, from the chemical features that are compatible with warnings to the proposed mechanisms behind phospholipid accumulation. In addition, strategies to mitigate the risk of DIPL are discussed.
Runge–Kutta analysis for optimizing the Zn-catalyzed transesterification conditions of MA and MMA with diols to maximize monoesterified products
Authors: Kato Taito , Akebi Shin-ya , Nagae Haruki , Yonehara Koji , Oku Tomoharu , Mashima Kazushi
Published: August 2021

Terminal hydroxylated acrylate derivatives were prepared by transesterification using zinc catalyst. The time to reach the equilibrium state was analyzed by curve-fitting analysis based on the Runge–Kutta method for optimizing the best conditions.
Flower-like 1T-MoS2/NiCo2S4on a carbon cloth substrate as an efficient electrocatalyst for the hydrogen evolution reaction
Authors: Zheng Meng , Chen Qianqiao , Zhong Qin
Published: August 2021

The 1T-MoS2/NiCo2S4/CC composite prepared by a hydrothermal method greatly increases the electron conduction rate and the number of active sites.
A theoretical chemistry-based strategy for the rational design of new luminescent lanthanide complexes: an approach from a multireference SOC-NEVPT2 method
Authors: Cantero-López Plinio , Santoyo-Flores Julián , Vega Andrés , Carreño Alexander , Fuentes Juan A. , Ramirez-Osorio Angélica , Ortiz Alejandro , Illicachi Luis Alberto , Sánchez Julio , Olea Andrés F. , Páez-Hernández Dayán
Published: August 2021

Theoretical methods of the SOC-NEVPT2 type combined with a molecular fragmentation scheme have been proven to be a powerful tool that allows explaining the luminescence mechanism in Ln(iii) compounds of the form Eu(R-phen)(BTA)3.
Ionic liquids as precursors for Fe–N doped carbon nanotube electrocatalysts for the oxygen reduction reaction
Authors: Mahmood Azhar , Zhao Bolin , Xie Nanhong , Niu Li
Published: August 2021

Iron and nitrogen codoped carbons (Fe–N–C) have emerged as promising noble-metal-free catalysts for the oxygen reduction reaction (ORR).
Supramolecular imaging of spermine in cancer cells
Authors: Tian Han-Wen , Chang Yu-Xuan , Hu Xin-Yue , Shah Muhammad Raza , Li Hua-Bin , Guo Dong-Sheng
Published: August 2021

A supramolecular imaging ensemble for spermine is developed by the complexation of amphiphilic sulfonatocalix[5]arene (SC5A12C) assembly with lucigenin.
Palladium-catalyzed difunctionalization/dearomatization of N-benzylacrylamides with α-carbonyl alkyl bromides: facile access to azaspirocyclohexadienones
Authors: Peng Chuan-Chong , Wu Li-Jun , Pi Shao-Feng
Published: August 2021

An efficient palladium-catalyzed difunctionalization/dearomatization of N-benzylacrylamides with α-carbonyl alkyl bromides for the preparation of azaspirocyclohexadienones has been disclosed.
Simple inorganic base promoted C–N and C–C formation: synthesis of benzo[4,5]imidazo[1,2-a]pyridines as functional AIEgens used for detecting picric acid
Authors: Yang Kai , Luo Shi-He , Chen Si-Hong , Cao Xi-Ying , Zhou Yong-Jun , Lin Yan-Lan , Huo Yan-Ping , Wang Zhao-Yang
Published: August 2021

Metal-free catalyzed intermolecular tandem Michael addition/cyclization is developed for the synthesis of benzo[4,5]imidazo[1,2-a]pyridines from α-bromocinnamaldehyde. The RIM of the benzene ring at the C1-position makes them a new class of AIE molecules.
Emissive semi-interpenetrating polymer networks for ink-jet printed multilayer OLEDs
Authors: Kunz Susanna V. , Cole Cameron M. , Baumann Thomas , Sonar Prashant , Yambem Soniya D. , Blasco Eva , Barner-Kowollik Christopher , Blinco James P.
Published: August 2021

Solution-processing of multi-layered Organic Light Emitting Diodes (OLEDs) remains challenging. Herein, we introduce a facile blending process of emitting polymers with photoreactive polymer strands, allowing for the generation of solvent resistant emissive layers.
Novel synthesis of in situ CeOx nanoparticles decorated on CoP nanosheets for highly efficient electrocatalytic oxygen evolution
Authors: Wu Xiaoxia , Wei Jiaxu , Zhang Tong , Yang Yuchen , Liu Qingyi , Yan Xingbin , Tang Yu
Published: August 2021

CoP nanosheets decorated by in-situ CeOx nanoparticles were designed through a novel two-step solvothermal-phosphating strategy, which act as an electrode exhibit excellent electrocatalytic performance toward OER in alkaline condition.
Sensitive magnetic-field-response magnetization dynamics in a one-dimensional dysprosium coordination polymer
Authors: Qu Yun-Xia , Ruan Ze-Yu , Huang Guo-Zhang , Chen Yan-Cong , Liu Yang , Jia Jian-Hua , Liu Jun-Liang , Tong Ming-Liang
Published: August 2021

A Dy(iii) coordination polymer shows significant single-molecule magnet behavior with a sensitive low-field response.
Reductive silylation of polyoxovanadate surfaces using Mashima's reagent
Authors: Chakraborty Sourav , Matson Ellen M.
Published: August 2021

Mechanistic insights into the reductive silylation of metal oxide surfaces.
A biomimetic synthesis-enabled stereochemical assignment of rhodotomentones A and B, two unusual caryophyllene-derived meroterpenoids from Rhodomyrtus tomentosa
Authors: Deng Lu-Ming , Hu Li-Jun , Tang Wei , Liu Jia-Xin , Huang Xiao-Jun , Li Yue-Yue , Li Yao-Lan , Ye Wen-Cai , Wang Ying
Published: August 2021

Rhodotomentones A and B (1 and 2), two unusual caryophyllene-derived meroterpenoids (CDMTs) featuring a rare 6/6/9/4/6/6 hexacyclic ring system, along with their biogenetically-related CDMTs 7 and 12–15, were isolated from Rhodomyrtus tomentosa.
NleB/SseK-catalyzed arginine-glycosylation and enteropathogen virulence are finely tuned by a single variable position contiguous to the catalytic machinery
Authors: García-García Ana , Hicks Thomas , El Qaidi Samir , Zhu Congrui , Hardwidge Philip R. , Angulo Jesús , Hurtado-Guerrero Ramon
Published: August 2021

The NleB and SseK glycosyltransferases glycosylate arginine residues of mammalian proteins with different substrate specificities. We uncover that these differences rely on a particular second-shell residue contiguous to the catalytic machinery.
Kust-I: a high-performance two-dimensional graphene-based material for seawater desalination
Authors: Yu Xiaohua , Hou Jincheng , Wu Haijun , Rong Ju , Wang Xiao , Xu Kui , Feng Jing
Published: August 2021

Na charge transfers to Kust-I with a nanometer pore size of 0.45 nm and the transfer value was quantified as 0.723 |e|, and this can explain why Kust-I displays a satisfactory desalination efficacy of nearly 100%.
A highly selective ratiometric molecular probe for imaging peroxynitrite during drug-induced acute liver injury
Authors: Gong Xiangyang , Cheng Dan , Li Wei , Shen Yang , Peng Rong , Shi Ling , He Longwei , Yuan Lin
Published: August 2021

Visualizing ONOO− fluctuations in the complex drug-induced acute liver injury process using a ratiometric fluorescent probe developed by using a molecular hybridization strategy with high selectivity and sensitivity.
Expanding Availability of Speech-Generating Device Evaluation and Treatment to People With Amyotrophic Lateral Sclerosis (pALS) Through Telepractice: Perspectives of pALS and Communication Partners
Authors: Roman Amy , Baylor Carolyn , Johnson Lindsay , Barton Maya
Published: August 2021

Purpose

To examine the experiences of people with ALS (pALS) and their communication partners (cALS) regarding receiving speech-generating device (SGD) evaluation and treatment via telepractice.

Method

Eight pALS along with a primary cALS participated in telepractice SGD evaluation and treatment with an augmentative and alternative communication (AAC) specialist and representatives from multiple SGD vendors. Participants were interviewed postevaluation and post-SGD training to examine their experiences. Mixed methods data were collected through Likert scale responses and qualitative interviews.

Results

Telepractice SGD evaluation and training were feasible and resulted in all pALS receiving SGDs they were able to use to communicate. In both Likert rating items and qualitative interviews, participants rated the telepractice experience very highly in terms of giving them access to AAC services via an AAC specialist that they would not have otherwise been able to access, and doing so in a format that was possible given their limitations in mobility, endurance, and caregiver availability. Suggestions for improving the telepractice experience were provided.

Conclusions

Telepractice should be considered as an option to provide vital SGD services to patients who are geographically remote, mobility impaired, unable to leave their home, experience fatigue with travel, or otherwise would not have access to these specialized services. Telepractice allows patients to preserve their time and energy for the assessment and treatment sessions, resulting in perhaps deeper and more frequent engagement in evaluation and training. Telepractice could serve as an alternative to outpatient, in-person evaluations, or be utilized in conjunction with in-person appointments.

Supplemental Material

https://doi.org/10.23641/asha.15094257
Measuring fracture toughness of human dental enamel at small scale using notched microcantilever beams
Authors: Chu Kangjie , Zhao Cancan , Ren Fuzeng
Published: August 2021

Dental enamel is the most mineralised hard tissue with a complex hierarchically organised anisotropic structure and it protects human teeth from mechanical damage during the dental function. Due to the sample size constraints, the available data for quantitative evaluation of the fracture toughness of human enamel is very limited. Here, on the basis of microstructural characterisation, the fracture toughness of human dental enamel at small scale with respect to orientation was measured using notched microcantilever beams fabricated by focussed ion beam. The fracture toughness of human enamel with perpendicular orientation was measured to be 1.244 ± 0.12 MPa · m1/2, 80% tougher than that of in‐plane parallel orientation (0.698 ± 0.18 MPa · m1/2). The present results are expected to provide deep insights into cusp fractures and the synthesis of enamel‐like restorative materials.
An innovative approach to partial discharge measurement and analysis in DC insulation systems during voltage transient and in steady state
Authors: Montanari Gian Carlo , Ghosh Riddhi
Published: August 2021

Measuring partial discharges in DC insulation systems is an issue due to the lack of a reference relating the voltage waveform to the physics of discharge phenomena. Also, DC is not always steady state, due to voltage and load transients that generate electric field profile variations inside an insulation system, which can affect partial discharge inception likelihood and characteristics. Partial discharge measurement technology must be able to separate discharge pulses from noise and identify the type of sources generating partial discharge, which is related to condition assessment and maintenance. Eventually, measurement and analysis should be automatic and unsupervised, in order to get rid, partially or totally, of expert support. This study addresses a new approach to partial discharge measurements in DC insulation systems, presenting algorithms for separation, recognition and identification, which are effective both in DC steady state and during voltage (and load) transients. These algorithms are automatic and do not require expert support. Various cases of algorithm application on test objects consisting of multilayer polymeric specimens with an internal cavity and defective cable models are presented and discussed. Their effectiveness is proved, at least at a laboratory level, with effective noise separation and identification of discharge typology.