bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutrient Deficiency Promotes the Entry of Helicobacter pylori Cells into Candida Yeast Cells
Authors: Sánchez-Alonzo Kimberly , Silva-Mieres Fabiola , Arellano-Arriagada Luciano , Parra-Sepúlveda Cristian , Bernasconi Humberto , Smith Carlos T. , Campos Víctor L. , García-Cancino Apolinaria
Published: May 2021

Helicobacter pylori, a Gram-negative bacterium, has as a natural niche the human gastric epithelium. This pathogen has been reported to enter into Candida yeast cells; however, factors triggering this endosymbiotic relationship remain unknown. The aim of this work was to evaluate in vitro if variations in nutrient concentration in the cultured medium trigger the internalization of H. pylori within Candida cells. We used H. pylori–Candida co-cultures in Brucella broth supplemented with 1%, 5% or 20% fetal bovine serum or in saline solution. Intra-yeast bacteria-like bodies (BLBs) were observed using optical microscopy, while intra-yeast BLBs were identified as H. pylori using FISH and PCR techniques. Intra-yeast H. pylori (BLBs) viability was confirmed using the LIVE/DEAD BacLight Bacterial Viability kit. Intra-yeast H. pylori was present in all combinations of bacteria–yeast strains co-cultured. However, the percentages of yeast cells harboring bacteria (Y-BLBs) varied according to nutrient concentrations and also were strain-dependent. In conclusion, reduced nutrients stresses H. pylori, promoting its entry into Candida cells. The starvation of both H. pylori and Candida strains reduced the percentages of Y-BLBs, suggesting that starving yeast cells may be less capable of harboring stressed H. pylori cells. Moreover, the endosymbiotic relationship between H. pylori and Candida is dependent on the strains co-cultured.
Effects of Propolis on Infectious Diseases of Medical Relevance
Authors: Rivera-Yañez Nelly , Rivera-Yañez C. Rebeca , Pozo-Molina Glustein , Méndez-Catalá Claudia F. , Reyes-Reali Julia , Mendoza-Ramos María I. , Méndez-Cruz Adolfo R. , Nieto-Yañez Oscar
Published: May 2021

Infectious diseases are a significant problem affecting the public health and economic stability of societies all over the world. Treatment is available for most of these diseases; however, many pathogens have developed resistance to drugs, necessitating the development of new therapies with chemical agents, which can have serious side effects and high toxicity. In addition, the severity and aggressiveness of emerging and re-emerging diseases, such as pandemics caused by viral agents, have led to the priority of investigating new therapies to complement the treatment of different infectious diseases. Alternative and complementary medicine is widely used throughout the world due to its low cost and easy access and has been shown to provide a wide repertoire of options for the treatment of various conditions. In this work, we address the relevance of the effects of propolis on the causal pathogens of the main infectious diseases with medical relevance; the existing compiled information shows that propolis has effects on Gram-positive and Gram-negative bacteria, fungi, protozoan parasites and helminths, and viruses; however, challenges remain, such as the assessment of their effects in clinical studies for adequate and safe use.
Luteogenesis and Embryo Implantation Are Enhanced by Exogenous hCG in Goats Subjected to an Out-of-Season Fixed-Time Artificial Insemination Protocol
Authors: Bustamante-Andrade Jorge A. , Meza-Herrera César A. , Rodríguez-Martínez Rafael , Santos-Jimenez Zurisaday , Ángel-García Oscar , Gaytán-Alemán Leticia R. , Gutierrez-Guzman Ulises N. , Esquivel-Romo Amaury , Véliz-Deras Francisco G.
Published: May 2021

The aim of this study was to evaluate the possible effect of two doses of hCG (100 and 300 IU) applied at two different times (7 and 14 d) after a fixed-time artificial insemination protocol (FTAI) upon some variables involved in the embryonic implantation rate in goats during the natural deep anestrous season (April, 25° north). The experimental units considered crossbred, multiparous, anovulatory goats (n = 69, Alpine, Saanen, Nubian x Criollo), with average body weight (43.6 ± 5.7 kg) and body condition score (1.86 ± 0.28 units) located in northern–semiarid Mexico (25° N, 103° W). Once the goat’s anestrus status was confirmed, goats were subjected to an estrus induction protocol. Upon estrus induction confirmation, goats (n = 61) were subjected to a FTAI procedure. Immediately after the FTAI, the goats were randomly distributed to five experimental groups: (1). G100-7 (n = 13) 100 IU, hCG 7 d post-FTAI, (2). G100-14 (n = 12) 100 IU hCG, 14 d post-FTAI, (3). G300-7 (n = 12) 300 IU, hCG, 7 d post-FTAI, (4). G300-14 (n = 12) 300 IU hCG 14 d post-FTAI, and (5). Control group, CONT (n = 12) 0.5 mL saline, 7 and 14 d post-FTAI. The response variables conception rate (39.36 ± 0.23), fertility rate (27.96%), prolificacy rate (1.1 ± 0.29 kids), ovulation rate (0.74 ± 0.20 corpus luteum) corpus luteum diameter (10.15 ± 0.59 mm), embryo number (1.58 ± 0.20), and embryo implantation rate (48.96%), did not differ between treatments. However, while the variables fecundity rate (67%), embryo efficiency index-1 (33.99 ± 0.20%), and embryo efficiency index-2 (27.94 ± 0.30%) were favored by the G300-14 treatment, the corpus luteum area was favored (p < 0.05) by both G300-7 (113.30 ± 0.19 mm2) and G300-14 (103.04 ± 0.17 mm2). Such reproductive strategy emerges as an interesting approach, not only to enhance the out-of-season reproductive outcomes, but also to boost one of the main rulers defining the global reproductive efficiency of a heard, namely, the embryo implantation efficiency.
Shorter Chain Triglycerides Are Negatively Associated with Symptom Improvement in Schizophrenia
Authors: Tkachev Anna , Stekolshchikova Elena , Anikanov Nickolay , Zozulya Svetlana , Barkhatova Aleksandra , Klyushnik Tatiana , Petrova Daria
Published: May 2021

Schizophrenia is a serious mental disorder requiring lifelong treatment. While medications are available that are effective in treating some patients, individual treatment responses can vary, with some patients exhibiting resistance to one or multiple drugs. Currently, little is known about the causes of the difference in treatment response observed among individuals with schizophrenia, and satisfactory markers of poor response are not available for clinical practice. Here, we studied the changes in the levels of 322 blood plasma lipids between two time points assessed in 92 individuals diagnosed with schizophrenia during their inpatient treatment and their association with the extent of symptom improvement. We found 20 triglyceride species increased in individuals with the least improvement in Positive and Negative Syndrome Scale (PANSS) scores, but not in those with the largest reduction in PANSS scores. These triglyceride species were distinct from the rest of the triglyceride species present in blood plasma. They contained a relatively low number of carbons in their fatty acid residues and were relatively low in abundance compared to the principal triglyceride species of blood plasma.
Antibiotic Therapy of Plague: A Review
Authors: Sebbane Florent , Lemaître Nadine
Published: May 2021

Plague—a deadly disease caused by the bacterium Yersinia pestis—is still an international public health concern. There are three main clinical forms: bubonic plague, septicemic plague, and pulmonary plague. In all three forms, the symptoms appear suddenly and progress very rapidly. Early antibiotic therapy is essential for countering the disease. Several classes of antibiotics (e.g., tetracyclines, fluoroquinolones, aminoglycosides, sulfonamides, chloramphenicol, rifamycin, and β-lactams) are active in vitro against the majority of Y. pestis strains and have demonstrated efficacy in various animal models. However, some discrepancies have been reported. Hence, health authorities have approved and recommended several drugs for prophylactic or curative use. Only monotherapy is currently recommended; combination therapy has not shown any benefits in preclinical studies or case reports. Concerns about the emergence of multidrug-resistant strains of Y. pestis have led to the development of new classes of antibiotics and other therapeutics (e.g., LpxC inhibitors, cationic peptides, antivirulence drugs, predatory bacteria, phages, immunotherapy, host-directed therapy, and nutritional immunity). It is difficult to know which of the currently available treatments or therapeutics in development will be most effective for a given form of plague. This is due to the lack of standardization in preclinical studies, conflicting data from case reports, and the small number of clinical trials performed to date.
Duplex On-Site Detection of Vibrio cholerae and Vibrio vulnificus by Recombinase Polymerase Amplification and Three-Segment Lateral Flow Strips
Authors: Wang Pei , Liao Lei , Ma Chao , Zhang Xue , Yu Junwei , Yi Longyu , Liu Xin , Shen Hui , Gao Song , Lu Qunwei
Published: May 2021

Vibrio cholerae and Vibrio vulnificus are two most reported foodborne Vibrio pathogens related to seafood. Due to global ocean warming and an increase in seafood consumption worldwide, foodborne illnesses related to infection of these two bacteria are growing, leading to food safety issues and economic consequences. Molecular detection methods targeting species-specific genes are effective tools in the fight against bacterial infections for food safety. In this study, a duplex detection biosensor based on isothermal recombinase polymerase amplification (RPA) and a three-segment lateral flow strip (LFS) has been established. The biosensor used lolB gene of Vibrio cholerae and empV gene of Vibrio vulnificus as the detection markers based on previous reports. A duplex RPA reaction for both targets were constructed, and two chemical labels, FITC and DIG, of the amplification products were carefully tested for effective and accurate visualization on the strip. The biosensor demonstrated good specificity and achieved a sensitivity of 101 copies per reaction or one colony forming unit (CFU)/10 g of spiked food for both bacteria. Validation with clinical samples showed results consistent with that of real-time polymerase chain reaction. The detection process was simple and fast with a 30-min reaction at 37 °C and visualization on the strip within 5 min. With little dependence on laboratory settings, this biosensor was suitable for on-site detection, and the duplex system enabled simultaneous detection of the two important foodborne bacteria. Moreover, the principle can be extended to healthcare and food safety applications for other pathogens.
How Consistent Are Consumers in Their Decisions? Investigation of Houseplant Purchasing
Authors: Knuth Melinda J. , Khachatryan Hayk , Hall Charles R.
Published: May 2021

This paper examines the impact of intrinsic consumer attributes on decision consistency in houseplant purchasing intentions. Subjects reported their likelihood to buy (LTB) for themselves and as a gift at perceived bargain and getting expensive price levels. The sample was analyzed according to those who switched their LTB ratings to relatively lower values versus subjects who did not by using their demographic characteristics and responses to plant buying behavior questions. Secondly, subjects who had high initial purchase intents were analyzed versus those who had low initial purchase intents. The results indicate that inconsistent purchase decisions are more likely to occur at the perceived getting expensive price level than the perceived bargain price points. Additionally, there are very few demographic differences among the plant buyers who are consistent with their purchase intent versus inconsistent, indicating that external environmental cues may have more of an influence on purchase consistency than intrinsic cues. This information can be utilized by greenhouse and retail firms to understand when a consumer is less likely to change their plant purchase decision with a high initial intent. These price points can help firms optimize their current price offerings within the market and create dialogues with partnering box stores.
A Framework for Developing Green Building Rating Tools Based on Pakistan’s Local Context
Authors: Khan Muhammad Afrasiab , Wang Cynthia Changxin , Lee Chyi Lin
Published: May 2021

Most countries have developed green building rating tools that are based on social, environmental, and economic dimensions. Pakistan followed a similar approach and has developed a rating tool known as Sustainability in Energy and Environmental Development (SEED). However, SEED is built on developed western countries’ rating tool standards which do not address Pakistan’s unique local context, especially from the cultural and governmental perspectives. This research aims to fill this research gap by developing a holistic framework of building rating tools that incorporates cultural and governmental dimensions. Based on an extensive literature review, a hypothetical framework, incorporating Pakistan’s unique local contexts and adding cultural and governmental dimensions to the widely adopted social, environmental, and economic dimensions of sustainability, was proposed in this paper. This framework was further validated by in-depth interviews with multiple stakeholders in Pakistan. A qualitative analysis of the interview results was carried out, and the final framework was proposed with key indicators, reflecting all five dimensions of sustainability. The verified sustainability framework can be used to improve or develop green building rating tools for Pakistan, and it can also inform other developing countries’ rating tool development.
Measuring Quality of Life Using Patient-Reported Outcomes in Real-World Metastatic Breast Cancer Patients: The Need for a Standardized Approach
Authors: Clarijs Marloes E. , Thurell Jacob , Kühn Friedrich , Uyl-de Groot Carin A. , Hedayati Elham , Karsten Maria M. , Jager Agnes , Koppert Linetta B.
Published: May 2021

Metastatic breast cancer (MBC) patients are almost always treated to minimize the symptom burden, and to prolong life without a curative intent. Although the prognosis of MBC patients has improved in recent years, the median survival after diagnosis is still only 3 years. Therefore, the health-related quality of life (HRQoL) should play a leading role in making treatment decisions. Heterogeneity in questionnaires used to evaluate the HRQoL in MBC patients complicates the interpretability and comparability of patient-reported outcomes (PROs) globally. In this review, we aimed to provide an overview of PRO instruments used in real-world MBC patients and to discuss important issues in measuring HRQoL. Routinely collecting symptom information using PROs could enhance treatment evaluation and shared decision-making. Standardizing these measures might help to improve the implementation of PROs, and facilitates collecting and sharing data to establish valid comparisons in research. This is a prerequisite to learn about how they could impact the clinical care pathway. In addition, the prognostic value of intensified PRO collection throughout therapy on survival and disease progression is promising. Future perspectives in the field of PROs and MBC are described.
Discontinuation of BRAF/MEK-Directed Targeted Therapy after Complete Remission of Metastatic Melanoma—A Retrospective Multicenter ADOReg Study
Authors: Stege Henner , Haist Maximilian , Schultheis Michael , Fleischer Maria Isabel , Mohr Peter , Meier Friedegund , Schadendorf Dirk , Ugurel Selma , Livingstone Elisabeth , Zimmer Lisa , Herbst Rudolf , Pföhler Claudia , Kähler Katharina , Weichenthal Michael , Terheyden Patrick , Nashan Dorothée , Debus Dirk , Kaatz Martin , Ziller Fabian , Haferkamp Sebastian , Forschner Andrea , Leiter Ulrike , Kreuter Alexander , Ulrich Jens , Kleemann Johannes , Bradfisch Fabienne , Grabbe Stephan , Loquai Carmen
Published: May 2021

The advent of BRAF/MEK inhibitors (BRAFi/MEKi) has significantly improved progression-free (PFS) and overall survival (OS) for patients with advanced BRAF-V600-mutant melanoma. Long-term survivors have been identified particularly among patients with a complete response (CR) to BRAF/MEK-directed targeted therapy (TT). However, it remains unclear which patients who achieved a CR maintain a durable response and whether treatment cessation might be a safe option in these patients. Therefore, this study investigated the impact of treatment cessation on the clinical course of patients with a CR upon BRAF/MEK-directed-TT. We retrospectively selected patients with BRAF-V600-mutant advanced non-resectable melanoma who had been treated with BRAFi ± MEKi therapy and achieved a CR upon treatment out of the multicentric skin cancer registry ADOReg. Data on baseline patient characteristics, duration of TT, treatment cessation, tumor progression (TP) and response to second-line treatments were collected and analyzed. Of 461 patients who received BRAF/MEK-directed TT 37 achieved a CR. TP after initial CR was observed in 22 patients (60%) mainly affecting patients who discontinued TT (n = 22/26), whereas all patients with ongoing TT (n = 11) maintained their CR. Accordingly, patients who discontinued TT had a higher risk of TP compared to patients with ongoing treatment (p < 0.001). However, our data also show that patients who received TT for more than 16 months and who discontinued TT for other reasons than TP or toxicity did not have a shorter PFS compared to patients with ongoing treatment. Response rates to second-line treatment being initiated in 21 patients, varied between 27% for immune-checkpoint inhibitors (ICI) and 60% for BRAFi/MEKi rechallenge. In summary, we identified a considerable number of patients who achieved a CR upon BRAF/MEK-directed TT in this contemporary real-world cohort of patients with BRAF-V600-mutant melanoma. Sustained PFS was not restricted to ongoing TT but was also found in patients who discontinued TT.
Natural Compounds in Glioblastoma Therapy: Preclinical Insights, Mechanistic Pathways, and Outlook
Authors: Zhai Kevin , Siddiqui Manaal , Abdellatif Basma , Liskova Alena , Kubatka Peter , Büsselberg Dietrich
Published: May 2021

Glioblastoma (GBM) is an aggressive, often fatal astrocyte-derived tumor of the central nervous system. Conventional medical and surgical interventions have greatly improved survival rates; however, tumor heterogeneity, invasiveness, and chemotherapeutic resistance continue to pose clinical challenges. As such, dietary natural substances—an integral component of the lifestyle medicine approach to chronic diseases—are examined as potential chemotherapeutic agents. These heterogenous substances exert anti-GBM effects by upregulating apoptosis and autophagy, inducing cell cycle arrest, interfering with tumor metabolism, and inhibiting proliferation, neuroinflammation, chemoresistance, angiogenesis, and metastasis. Although these beneficial effects are promising, natural substances’ efficacy in GBM is constrained by their bioavailability and blood–brain barrier permeability; various chemical formulations are proposed to improve their pharmacological properties. Many of the reviewed substances are available as over-the-counter dietary supplements, underscoring their viability as lifestyle interventions. However, clinical trials remain necessary to substantiate the in vitro and in vivo properties of natural substances.
Integration of Spatial PD-L1 Expression with the Tumor Immune Microenvironment Outperforms Standard PD-L1 Scoring in Outcome Prediction of Urothelial Cancer Patients
Authors: Weyerer Veronika , Strissel Pamela L. , Strick Reiner , Sikic Danijel , Geppert Carol I. , Bertz Simone , Lange Fabienne , Taubert Helge , Wach Sven , Breyer Johannes , Bolenz Christian , Erben Philipp , Schmitz-Draeger Bernd J. , Wullich Bernd , Hartmann Arndt , Eckstein Markus
Published: May 2021

Background: Immune therapy has gained significant importance in managing urothelial cancer. The value of PD-L1 remains a matter of controversy, thus requiring an in-depth analysis of its biological and clinical relevance. Methods: A total of 193 tumors of muscle-invasive bladder cancer patients (MIBC) were assessed with four PD-L1 assays. PD-L1 scoring results were correlated with data from a comprehensive digital-spatial immune-profiling panel using descriptive statistics, hierarchical clustering and uni-/multivariable survival analyses. Results: PD-L1 scoring algorithms are heterogeneous (agreements from 63.1% to 87.7%), and stems from different constellations of immune and tumor cells (IC/TC). While Ventana IC5% algorithm identifies tumors with high inflammation and favorable baseline prognosis, CPS10 and the TCarea25%/ICarea25% algorithm identify tumors with TC and IC expression. Spatially organized immune phenotypes, which correlate either with high PD-L1 IC expression and favorable prognosis or constitutive PD-L1 TC expression and poor baseline prognosis, cannot be resolved properly by PD-L1 algorithms. PD-L1 negative tumors with relevant immune infiltration can be detected by sTILs scoring on HE slides and digital CD8+ scoring. Conclusions: Contemporary PD-L1 scoring algorithms are not sufficient to resolve spatially distributed MIBC immune phenotypes and their clinical implications. A more comprehensive view of immune phenotypes along with the integration of spatial PD-L1 expression on IC and TC is necessary in order to stratify patients for ICI.
Tumor Extrinsic Factors Mediate Primary T-DM1 Resistance in HER2-Positive Breast Cancer Cells
Authors: Endo Yukinori , Wu Wen Jin
Published: May 2021

To explore if the tumor microenvironment contributes to the primary resistance of HER2-positive breast cancer cells to T-DM1, we examined whether Matrigel, a basement membrane matrix that provides a three-dimensional (3D) cell culture condition, caused the primary resistance of HER2-positive, T-DM1-sensitive breast cancer cells (JIMT1 and SKBR-3 cells) to T-DM1. This is different from the conventional approach such that the cells are exposed with escalated doses of drug to establish a drug-resistant cell line. We found that these cells were able to grow and form spheroids on the Matrigel in the presence of T-DM1. We further explored the molecular mechanisms that enables these cells to be primarily resistant to T-DM1 and found that EGFR was activated in the spheroids, leading to an increased HER2 tyrosine phosphorylation. This in turn enhances cell growth signaling downstream of EGFR/HER2 in the spheroids. HER2 tyrosine phosphorylation promotes receptor internalization and degradation in the spheroids, which limits T-DM1 access to HER2 on the cell surface of spheroids. Blocking EGFR activity by erlotinib reduces HER2 tyrosine phosphorylation and enhances HER2 cell surface expression. This enables T-DM1 to gain access to HER2 on the cell surface, resumes cell sensitivity to T-DM1, and exhibits synergistic activity with T-DM1 to inhibit the formation of spheroids on Matrigel. The discovery described in this manuscript reveals a novel approach to investigate the primary resistance of HER2-positive breast cancer cells and provides an opportunity to develop a therapeutic strategy to overcome primary resistance to T-DM1 by combing T-DM1 therapy with kinase inhibitors of EGFR.
Evaluation of the Preclinical Efficacy of Lurbinectedin in Malignant Pleural Mesothelioma
Authors: Anobile Dario P. , Bironzo Paolo , Picca Francesca , Lingua Marcello F. , Morena Deborah , Righi Luisella , Napoli Francesca , Papotti Mauro G. , Pittaro Alessandra , Di Nicolantonio Federica , Gigliotti Chiara , Bussolino Federico , Comunanza Valentina , Guerrera Francesco , Sandri Alberto , Leo Francesco , Libener Roberta , Aviles Pablo , Novello Silvia , Taulli Riccardo , Scagliotti Giorgio V. , Riganti Chiara
Published: May 2021

Background: Malignant pleural mesothelioma (MPM) is a highly aggressive cancer generally diagnosed at an advanced stage and characterized by a poor prognosis. The absence of alterations in druggable kinases, together with an immune-suppressive tumor microenvironment, limits the use of molecular targeted therapies, making the treatment of MPM particularly challenging. Here we investigated the in vitro susceptibility of MPM to lurbinectedin (PM01183), a marine-derived drug that recently received accelerated approval by the FDA for the treatment of patients with metastatic small cell lung cancer with disease progression on or after platinum-based chemotherapy. Methods: A panel of primary MPM cultures, resembling the three major MPM histological subtypes (epithelioid, sarcomatoid, and biphasic), was characterized in terms of BAP1 status and histological markers. Subsequently, we explored the effects of lurbinectedin at nanomolar concentration on cell cycle, cell viability, DNA damage, genotoxic stress response, and proliferation. Results: Stabilized MPM cultures exhibited high sensitivity to lurbinectedin independently from the BAP1 mutational status and histological classification. Specifically, we observed that lurbinectedin rapidly promoted a cell cycle arrest in the S-phase and the activation of the DNA damage response, two conditions that invariably resulted in an irreversible DNA fragmentation, together with strong apoptotic cell death. Moreover, the analysis of long-term treatment indicated that lurbinectedin severely impacts MPM transforming abilities in vitro. Conclusion: Overall, our data provide evidence that lurbinectedin exerts a potent antitumoral activity on primary MPM cells, independently from both the histological subtype and BAP1 alteration, suggesting its potential activity in the treatment of MPM patients.
Quantitative Multiplexed Proteomics Could Assist Therapeutic Decision Making in Non-Small Cell Lung Cancer Patients with Ambiguous ALK Test Results
Authors: An Ho Jung , An Eunkyung , Rabizadeh Shahrooz , Liao Wei-Li , Burrows Jon , Hembrough Todd , Kang Jin Hyung , Park Chan Kwon , Kim Tae-Jung
Published: May 2021

Therapeutic guidance in non-small cell lung cancer (NSCLC) tumors that are positive for anaplastic lymphoma kinase (ALK) fluorescent in situ hybridization (FISH), but negative for ALK immunohistochemistry, is still challenging. Parallel routine screening of 4588 NSCLC cases identified 22 discordant cases. We rechecked these samples using ALK antibodies and selected reaction monitoring (SRM) quantitative multiplexed proteomics screening multiple protein targets, including ALK and MET for the ALK tyrosine kinase inhibitor (TKI), and FR-alpha, hENT1, RRM1, TUBB3, ERCC1, and XRCC1 for chemotherapy. The presence of ALK (31.8%), MET (36.4%), FR-alpha (72.7%), hENT1 (18.2%), RRM1 (31.8%), TUBB3 (72.9%), ERCC1 (4.5%), and a low level of XRCC1 (54.4%) correlated with clinical outcomes. SRM was more sensitive than the ALK D5F3 assay. Among the eight cases receiving ALK TKI, four cases with ALK or MET detected by SRM had complete or partial responses, whereas four cases without ALK or MET showed progression. Twenty-seven treatment outcomes from 20 cases were assessed and cases expressing more than half of the specific predictive proteins were sensitive to matching therapeutic agents and showed longer progression-free survival than the other cases (p < 0.001). SRM showed a potential role in therapeutic decision making in NSCLC patients with ambiguous ALK test results.
A Review on the Catalytic Decomposition of NO by Perovskite-Type Oxides
Authors: Shen Qiuwan , Dong Shuangshuang , Li Shian , Yang Guogang , Pan Xinxiang
Published: May 2021

Direct catalytic decomposition of NO has the advantages of being a simple process, producing no secondary pollution, and being good for the economy, which has attracted extensive research in recent years. Perovskite-type mixed oxides, with an ABO3 or A2BO4 structure, are promising materials as catalysts for NO decomposition due to their low cost, high thermal stability, and, of course, their good catalytic performances. In this review, the influence factors, such as A-site substitution, B-site substitution and reaction conditions on the catalytic performance of catalysts have been expounded. The reaction mechanisms of direct NO decomposition are also discussed. Finally, major conclusions are drawn and some research challenges are highlighted.
Electrocatalysis for Oxygen Reduction Reaction on EDTAFeNa and Melamine co-Derived Self-Supported Fe-N-C Materials
Authors: Shen Mengfan , Meng Ziwei , Xue Tong , Shen Hongfang , Yan Xiang-Hui
Published: May 2021

To explore high-performing alternatives to platinum-based catalysts is highly desirable for lowering costs and thus promoting fuel cell commercialization. Herein, self-supported Fe-N-C materials were prepared by the pyrolysis of dual precursors including EDTA ferric sodium (EDTAFeNa) and melamine (MA), followed by acid-leaching and final annealing. Towards an oxygen reduction reaction (ORR) in 0.1 M KOH, the as-prepared MA/EDTAFeNa-HT2 delivered onset (Eonset) and half-wave (E1/2) potentials of 0.97 and 0.84 V vs. RHE, respectively, identical with that of a state-of-the-art Pt/C catalyst, accompanied with predominantly a four-electron pathway. The introduction of MA and extension of acid-leaching promoted a positive shift of 50 mV for E1/2 relative to that of only the EDTAFeNa-derived counterpart. It was revealed that the enhancement of ORR activity is attributed to a decrease in magnetic Fe species and increase in pyridinic/quanternary nitrogen content whilst nearly excluding effects of the graphitization degree, variety of crystalline iron species, and mesoscopic structure. The usage of dual precursors exhibited great potential for the large-scale production of inexpensive and efficient Fe-N-C materials.
Highly Efficient MOF Catalyst Systems for CO2 Conversion to Bis-Cyclic Carbonates as Building Blocks for NIPHUs (Non-Isocyanate Polyhydroxyurethanes) Synthesis
Authors: Benedito Adolfo , Acarreta Eider , Giménez Enrique
Published: May 2021

The present paper describes a greener sustainable route toward the synthesis of NIPHUs. We report a highly efficient solvent-free process to produce [4,4′-bi(1,3-dioxolane)]-2,2′-dione (BDC), involving CO2, as renewable feedstock, and bis-epoxide (1,3-butadiendiepoxide) using only metal–organic frameworks (MOFs) as catalysts and cetyltrimethyl-ammonium bromide (CTAB) as a co-catalyst. This synthetic procedure is evaluated in the context of reducing global emissions of waste CO2 and converting CO2 into useful chemical feedstocks. The reaction was carried out in a pressurized reactor at pressures of 30 bars and controlled temperatures of around 120–130 °C. This study examines how reaction parameters such as catalyst used, temperature, or reaction time can influence the molar mass, yield, or reactivity of BDC. High BDC reactivity is essential for producing high molar mass linear non-isocyanate polyhydroxyurethane (NIPHU) via melt-phase polyaddition with aliphatic diamines. The optimized Al-OH-fumarate catalyst system described in this paper exhibited a 78% GC-MS conversion for the desired cyclic carbonates, in the absence of a solvent and a 50 wt % chemically fixed CO2. The cycloaddition reaction could also be carried out in the absence of CTAB, although lower cyclic carbonate yields were observed.
Reticulated Platelets—Which Functions Have Been Established by In Vivo and In Vitro Data?
Authors: Hamad Muataz Ali , Schanze Nancy , Schommer Nicolas , Nührenberg Thomas , Duerschmied Daniel
Published: May 2021

Reticulated platelets (RP) are the youngest platelet fraction released into the circulation. These immature platelets have increased RNA content, a larger cell volume, more dense granules, higher levels of surface activation markers and are thought to be more reactive compared to their mature counterparts. RP have been associated with cardiovascular disease, diabetes and increased mortality. Yet only a few animal studies investigating RP have been conducted so far and further investigations are warranted. Established methods to count RP are flow cytometry (staining with thiazole orange or SYTO13) or fully automated hematology analyzers (immature platelet fraction, IPF). IPF has been established as a diagnostic parameter in thrombocytopenia, cardiovascular disease and, in particular, the response to antiplatelet therapy. This review seeks to provide an overview of the key features of RP as well as preanalytical and analytical aspects that need to be considered when working with this platelet population.
Culturing Keratinocytes on Biomimetic Substrates Facilitates Improved Epidermal Assembly In Vitro
Authors: Hunter-Featherstone Eve , Young Natalie , Chamberlain Kathryn , Cubillas Pablo , Hulette Ben , Wei Xingtao , Tiesman Jay P. , Bascom Charles C. , Benham Adam M. , Goldberg Martin W. , Saretzki Gabriele , Karakesisoglou Iakowos
Published: May 2021

Mechanotransduction is defined as the ability of cells to sense mechanical stimuli from their surroundings and translate them into biochemical signals. Epidermal keratinocytes respond to mechanical cues by altering their proliferation, migration, and differentiation. In vitro cell culture, however, utilises tissue culture plastic, which is significantly stiffer than the in vivo environment. Current epidermal models fail to consider the effects of culturing keratinocytes on plastic prior to setting up three-dimensional cultures, so the impact of this non-physiological exposure on epidermal assembly is largely overlooked. In this study, primary keratinocytes cultured on plastic were compared with those grown on 4, 8, and 50 kPa stiff biomimetic hydrogels that have similar mechanical properties to skin. Our data show that keratinocytes cultured on biomimetic hydrogels exhibited major changes in cellular architecture, cell density, nuclear biomechanics, and mechanoprotein expression, such as specific Linker of Nucleoskeleton and Cytoskeleton (LINC) complex constituents. Mechanical conditioning of keratinocytes on 50 kPa biomimetic hydrogels improved the thickness and organisation of 3D epidermal models. In summary, the current study demonstrates that the effects of extracellular mechanics on keratinocyte cell biology are significant and therefore should be harnessed in skin research to ensure the successful production of physiologically relevant skin models.
Diversity of Pod Shape in Pisum
Authors: Ellis Thomas Henry Noel , Hofer Julie M. I. , Vikeli Eleni , Ambrose Michael J. , Higuera-Poveda Paola , Wingen Luzie U. , Chayut Noam
Published: May 2021

The seed-containing pod is the defining structure of plants in the legume family, yet pods exhibit a wide range of morphological variation. Within a species pod characters are likely to be correlated with reproductive strategy, and within cultivated forms will correspond to aspects of yield determination and/or end use. Here variation in pod size, described as pod length: pod width ratio, has been analyzed in pea germplasm represented by 597 accessions. This pod size variation is discussed with respect to population structure and to known classical pod morphology mutants. Variability of the pod length: width ratio can be explained by allelic variation at two genetic loci that may correspond to organ-specific negative regulators of growth.
Blood–Brain Barrier Impairment in Patients Living with HIV: Predictors and Associated Biomarkers
Authors: Caligaris Giulia , Trunfio Mattia , Ghisetti Valeria , Cusato Jessica , Nigra Marco , Atzori Cristiana , Imperiale Daniele , Bonora Stefano , Di Perri Giovanni , Calcagno Andrea
Published: May 2021

Despite the substantial changes resulting from the introduction of combination antiretroviral therapy (cART), the prevalence of HIV-associated neurocognitive disorders (HAND) remains substantial. Blood–brain barrier impairment (BBBi) is a frequent feature in people living with HIV (PLWH) and it may persist despite effective antiretroviral treatment. A cross-sectional study was performed in PLWH who underwent lumbar puncture for clinical reasons or research protocols and several cerebrospinal fluid biomarkers were studied. BBBi was defined as cerebrospinal fluid-to-serum albumin ratio (CSAR) >6.5 (<40 years) or >8 (>40 years). We included 464 participants: 147 cART-naïve and 317 on cART. Male sex was prevalent in both groups (72.1% and 72.2% respectively); median age was 44 (38–52) years in naïve and 49 (43–57) years in treated subjects. BBBi was observed in 35.4% naïve and in 22.7% treated participants; the use of integrase inhibitors was associated with a lower prevalence (18.3 vs. 30.9%, p = 0.050). At multivariate binary logistic regression (including age and sex) nadir CD4 cell count (p = 0.034), presence of central nervous system (CNS) opportunistic infections (p = 0.024) and cerebrospinal fluid (CSF) HIV RNA (p = 0.002) in naïve participants and male sex (p = 0.021), a history of CNS opportunistic infections (p = 0.001) and CSF HIV RNA (p = 0.034) in treated patients were independently associated with BBBi. CSF cells and neopterin were significantly higher in participants with BBBi. BBBi was prevalent in naïve and treated PLWH and it was associated with CSF HIV RNA and neopterin. Systemic control of viral replication seems to be essential for BBB integrity while sex and treatment influence need further studies.
Prenatal Screening for Developmental Displacement of the Hip: The BUDDHA (Pre-Birth Ultrasound for Developmental Displacement of the Hip Assessment) Study
Authors: Contro Elena , Larcher Laura , Lenzi Jacopo , Benfenati Arianna , Massinissa Magini Giulia , Galeati Giulia , Terrone Maria , Galletti Silvia , Arcuri Santo , Seidenari Anna , Farina Antonio
Published: May 2021

Background: developmental dysplasia of the hip has an incidence of 3–5 out of 1000 children. Currently, only postnatal screening is available. Objective: to test the feasibility of a method based on Graf technique application at antenatal ultrasound in assessing the normal development of the hip in unselected term fetuses. Methods: a prospective cohort study in a single university tertiary hospital from January 2017 to January 2020. Single uncomplicated term pregnancies (37–40 weeks) attending our center for routine ultrasound were consecutively recruited for the purpose of the study. A 3D volume acquisition was launched on the coxofemoral joint of the fetus by a single expert operator, and offline analysis was then performed in the multiplanar mode by two operators (blinded to each other analysis) in order to measure the alpha and beta angles according to our modified Graf technique. Intra- and inter-observer variations were calculated. Reference charts for normal values of both angles were produced. Postnatal ultrasound was then performed to measure the Graf angles in newborns, confirming a normal development of the hip. Results: in the study period, 433 uncomplicated term pregnancies underwent 3D ultrasound for the assessment of the fetal hip. One case was subsequently excluded because of confirmed postnatal diagnosis of developmental dysplasia of the hip. The measurement of our modified Graf angles was feasible at prenatal ultrasound with a good reproducibility. The inter-rater and intra-rater reliability of both angles was substantial. Reference charts for normal values of both angles were produced. Conclusions: the evaluation of the coxofemoral joint in fetuses at term of gestation has never been attempted before. The Graf technique application, currently employed at postnatal ultrasound, may also be adapted to prenatal ultrasound with a substantial reproducibility. However, there was no evidence of a linear relationship between prenatal and postnatal alpha angles and beta angles. Further research is needed to establish if developmental dysplasia of the hip could be diagnosed antenatally.
Optical Diagnostics in Human Diseases
Authors: Dunaev Andrey
Published: May 2021

Light-based technologies provide unique opportunities for the diagnosis of various pathological disorders of biological tissues [...]
Stand-Alone Direct Current Power Network Based on Photovoltaics and Lithium-Ion Batteries for Reverse Osmosis Desalination Plant
Authors: Powar Vishwas , Singh Rajendra
Published: May 2021

Plummeting reserves and increasing demand of freshwater resources have culminated into a global water crisis. Desalination is a potential solution to mitigate the freshwater shortage. However, the process of desalination is expensive and energy-intensive. Due to the water-energy-climate nexus, there is an urgent need to provide sustainable low-cost electrical power for desalination that has the lowest impact on climate and related ecosystem challenges. For a large-scale reverse osmosis desalination plant, we have proposed the design and analysis of a photovoltaics and battery-based stand-alone direct current power network. The design methodology focusses on appropriate sizing, optimum tilt and temperature compensation techniques based on 10 years of irradiation data for the Carlsbad Desalination Plant in California, USA. A decision-tree approach is employed for ensuring hourly load-generation balance. The power flow analysis evaluates self-sufficient generation even during cloud cover contingencies. The primary goal of the proposed system is to maximize the utilization of generated photovoltaic power and battery energy storage with minimal conversions and transmission losses. The direct current based topology includes high-voltage transmission, on-the-spot local inversion, situational awareness and cyber security features. Lastly, economic feasibility of the proposed system is carried out for a plant lifetime of 30 years. The variable effect of utility-scale battery storage costs for 16–18 h of operation is studied. Our results show that the proposed design will provide low electricity costs ranging from 3.79 to 6.43 ¢/kWh depending on the debt rate. Without employing the concept of baseload electric power, photovoltaics and battery-based direct current power networks for large-scale desalination plants can achieve tremendous energy savings and cost reduction with negligible carbon footprint, thereby providing affordable water for all.
Numerical Modelling and Digitalization Analysis for a Photovoltaic Pumping System Placed in the South of Romania
Authors: Fara Laurentiu , Craciunescu Dan , Fara Silvian
Published: May 2021

The authors studied a working off-grid type photovoltaic (PV) pumping system for irrigation use. The methodology was based on digitalization analysis and numerical modeling as a preliminary stage. A mathematical model of the PV pumping installation considered the determination of the characteristic equations for all its components. These have been used together with the SISIFO simulation software to achieve the performances of the mechanical and electrical components of an advanced PV pumping system. Its global performance features, namely the monthly energy yield, monthly pumping yield, and monthly total performances (energy and flow rate) were introduced. Digital platform (DP) for PV systems characterized by three advanced technologies—machine learning (ML), digital twin (DT) and artificial intelligence (AI) was developed. The simulation results were discussed for a specific case study conducted for a location in the Southern Romania regarding the irrigation potential, taking into account the main meteorological parameters: solar irradiance and ambient temperature, related to the site. The AI approach was implemented to achieve an optimum operation of the PV pumping system by the use of the maximum power point tracking (MPPT) method and the MATLAB/Simulink software. A unified development of all the components of the PV pumping system using the SISIFO simulation software was established by the authors, with major implications in the development of solar PV installations on large-scale.
New Insights into the Therapeutic Applications of CRISPR/Cas9 Genome Editing in Breast Cancer
Authors: Ahmed Munazza , Daoud Grace Hope , Mohamed Asmaa , Harati Rania
Published: May 2021

Breast cancer is one of the most prevalent forms of cancer globally and is among the leading causes of death in women. Its heterogenic nature is a result of the involvement of numerous aberrant genes that contribute to the multi-step pathway of tumorigenesis. Despite the fact that several disease-causing mutations have been identified, therapy is often aimed at alleviating symptoms rather than rectifying the mutation in the DNA sequence. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 is a groundbreaking tool that is being utilized for the identification and validation of genomic targets bearing tumorigenic potential. CRISPR/Cas9 supersedes its gene-editing predecessors through its unparalleled simplicity, efficiency and affordability. In this review, we provide an overview of the CRISPR/Cas9 mechanism and discuss genes that were edited using this system for the treatment of breast cancer. In addition, we shed light on the delivery methods—both viral and non-viral—that may be used to deliver the system and the barriers associated with each. Overall, the present review provides new insights into the potential therapeutic applications of CRISPR/Cas9 for the advancement of breast cancer treatment.
Supporting Medical Staff from Psycho-Oncology with Smart Mobile Devices: Insights into the Development Process and First Results
Authors: Schobel Johannes , Volz Madeleine , Hörner Katharina , Kuhn Peter , Jobst Franz , Schwab Julian D. , Ikonomi Nensi , Werle Silke D. , Fürstberger Axel , Hoenig Klaus , Kestler Hans A.
Published: May 2021

Cancer is a very distressing disease, not only for the patients themselves, but also for their family members and relatives. Therefore, patients are regularly monitored to decide whether psychological treatment is necessary and applicable. However, such monitoring processes are costly in terms of required staff and time. Mobile data collection is an emerging trend in various domains. The medical and psychological field benefits from such an approach, which enables experts to quickly collect a large amount of individual health data. Mobile data collection applications enable a more holistic view of patients and assist psychologists in taking proper actions. We developed a mobile application, FeelBack, which is designed to support data collection that is based on well-known and approved psychological instruments. A controlled pilot evaluation with 60 participants provides insights into the feasibility of the developed platform and it shows the initial results. 31 of these participants received paper-based questionnaire and 29 followed the digital approach. The results reveal an increase of the overall acceptance by 58.5% in the mean when using a digital screening as compared to the paper-based. We believe that such a platform may significantly improve cancer patients’ and relatives’ psychological treatment, as available data can be used to optimize treatment.