bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of Life among Mothers of High Functioning Autism Spectrum Disorder (HFASD)Adolescents
Authors: Mohamad Aun Nur Saadah , Zakaria Siti Marziah , Ahmad Badayai Abdul Rahman , Idris Idayu Badilla , Mohd Daud Tuti Iryani , Mohd Fazree Shima Dyana
Published: May 2022

Autism Spectrum Disorder (ASD) has become more prevalent globally. The disorder is predominantly characterised by low social skills noted explicitly in people with High Functioning Autism Spectrum Disorder (HFASD). The individuals usually possess a normal or superior intelligence quotient (IQ) but the disability impedes the achievement of their actual high potential, hence compromising their quality of life (QoL). Managing adversities encountered by children with HFASD often compromises the QoL of the entire family. Thus, this study aimed to identify specific domains of QoL among mothers of high-functioning autistic adolescents. The study assessed seven mothers of adolescents with HFASD using a semi-structured interview format. A thematic qualitative analysis was conducted to analyse the data. The results suggested that mothers perceived their QoL based on physical and emotional well-being, material well-being, interpersonal relationship, and environmental well-being. Intervention for HFASD is multidisciplinary, which targets a broad spectrum of symptoms and skills deficits and customises the programme to meet each individual’s different needs. Nonetheless, intervention facilities in Malaysia are seriously limited, particularly in supporting QoL for children with HFASD. Therefore, by identifying the domains of QoL would improve the mothers’ resilience in raising their children with HFASD.
Survey of Airborne Microorganisms in an Arcade-Type Traditional Market in Anseong, South Korea
Authors: Song Chan-Geun , Park Jang-Hyun , Lee Pum-Mook , Jung Myeong-Gyu
Published: May 2022

We aimed to analyze airborne microorganisms and assess air quality, temperature, and relative humidity at “J” Market, an arcade-type traditional market in Anseong (South Korea). Measurements were taken 16 times, twice per quarter (January, April, July, and October), at both the entrance and intersection of the market in 2020. The concentrations of airborne bacteria and fungi at the entrance and intersection were highest in October and lowest in April; however, they were below the recommended indoor levels (airborne bacteria: <800 CFU/m3, airborne fungi: <500 CFU/m3) in January (second measurement) and April (first and second measurements). The concentrations of microbes during the first measurement in January and both measurements in July and October exceeded the allowed limits. The concentration of microorganisms exceeded the acceptable levels at relative humidity ≥60%. At all time points, except during the eighth survey, when the microorganisms were too numerous to count, microbial concentrations were higher at the intersection than at the entrance. It was confirmed that the microorganisms detected in this experiment were 26 species of bacteria and 21 species of fungi. Three of the four species of bacteria and fungi detected in more than 50% of the 16 experimental results were pathogenic. Our findings suggest that air purification systems must be installed in the market to improve sanitary conditions.
Psychological and Social Impact of HIV on Women Living with HIV and Their Families in Low- and Middle-Income Asian Countries: A Systematic Search and Critical Review
Authors: Fauk Nelsensius Klau , Mwanri Lillian , Hawke Karen , Mohammadi Leila , Ward Paul Russell
Published: May 2022

Human Immunodeficiency Virus (HIV) infection adds a significant burden to women in Low- and Middle-Income Countries (LMICs), often leading to severe detrimental impact, not only on themselves, but also on their families and communities. Given that more than half of all people living with HIV globally are females (53%), this review seeks to understand the psychological and social impact of HIV infection on Women Living with HIV (WLHIV) and their families in LMICs in Asia, and the interrelationships between one impact and another. A systematic review was conducted to find literature using the following databases: Medline, PsycINFO, CINAL, Emcare, Scopus and ProQuest. Research articles included in this review were selected based on the following inclusion criteria: conducted in LMICs in Asia, published in English language between 1 January 2004 and 31 December 2021, had full text available, involved WLHIV (married and unmarried) and explored the psychological and social impacts of HIV on these women and their families. Critical appraisal tools developed by Joanna Briggs Institute (JBI) were used to assess the methodological quality of the studies, and thematic narrative synthesis was used to analyse the findings. A total of 17 articles met the inclusion criteria. The review showed that HIV has a range of negative psychological consequences on WLHIV, such as stress, fear, worry, anxiety and depression, as well as social impacts on the women and their families, including stigma, discrimination and family separation. The findings indicate the need for targeted interventions—specific to WLHIV—that address the psychological challenges, stigma and discrimination these women and their families face. These interventions should also incorporate education and sustainable support structures for WLHIV and their families.
Strengthening Australia’s Chemical Regulation
Authors: Gabriela Arlene , Leong Sarah , Ong Philip S. W. , Weinert Derek , Hlubucek Joe , Tait Peter W.
Published: May 2022

Humans are exposed to a myriad of chemicals every day, some of which have been established to have deleterious effects on human health. Regulatory frameworks play a vital role in safeguarding human health through the management of chemicals and their risks. For this review, we focused on agricultural and veterinary (Agvet) chemicals and industrial chemicals, which are regulated, respectively, by the Australian Pesticides and Veterinary Medicines Authority (APVMA), and the Australian Industrial Chemicals Introduction Scheme (AICIS). The current frameworks have been considered fragmented, inefficient, and most importantly, unsafe in prioritizing human health. We evaluated these frameworks, identified gaps, and suggested improvements that would help bring chemical regulation in Australia in line with comparative regulations in the EU, US, and Canada. Several weaknesses in the Australian frameworks include the lack of a national program to monitor chemical residues, slow pace in conducting chemical reviews, inconsistent risk management across states and territories, a paucity of research efforts on human health impacts, and inadequate framework assessment systems. Recommendations for Australia include establishing a national surveillance and chemical residue monitoring system, harmonizing risk assessment and management across jurisdictions, improving chemical review efficiency, and developing regular performance review mechanisms to ensure that human health is protected.
Associative and Physical Mapping of Markers Related to Fusarium in Maize Resistance, Obtained by Next-Generation Sequencing (NGS)
Authors: Sobiech Aleksandra , Tomkowiak Agnieszka , Nowak Bartosz , Bocianowski Jan , Wolko Łukasz , Spychała Julia
Published: May 2022

On the basis of studies carried out in the last few years, it is estimated that maize diseases cause yield losses of up to 30% each year. The most dangerous diseases are currently considered to be caused by fungi of the genus Fusarium, which are the main culprits of root rot, ear rots, and stalk rot. Early plant infection causes grain diminution, as well as a significant deterioration in nutritional value and fodder quality due to the presence of harmful mycotoxins. Therefore, the aim of the research was to identify new markers of the SilicoDArT and SNP type, which could be used for the mass selection of varieties resistant to fusarium. The plant material consisted of 186 inbred maize lines. The lines came from experimental plots belonging to two Polish breeding companies: Plant Breeding Smolice Ltd., (Co., Kobylin, Poland). Plant Breeding and Acclimatization Institute—National Research Institute Group (51°41′23.16″ N, 17°4′18.241″ E), and Małopolska Plant Breeding Kobierzyce, Poland Ltd., (Co., Kobierzyce, Poland) (50°58′19.411″ N, 16°55′47.323″ E). As a result of next-generation sequencing, a total of 81,602 molecular markers were obtained, of which, as a result of the associative mapping, 2962 (321 SilicoDArT and 2641 SNP) significantly related to plant resistance to fusarium were selected. Out of 2962 markers significantly related to plant resistance in the fusarium, seven markers (SilicoDArT, SNP) were selected, which were significant at the level of 0.001. They were used for physical mapping. As a result of the analysis, it was found that two out of seven selected markers (15,097—SilicoDArT and 58,771—SNP) are located inside genes, on chromosomes 2 and 3, respectively. Marker 15,097 is anchored to the gene encoding putrescine N-hydroxycinnamoyltransferase while marker 58,771 is anchored to the gene encoding the peroxidase precursor 72. Based on the literature data, both of these genes may be associated with plant resistance to fusarium. Therefore, the markers 15,097 (SilicoDArT) and 58,771 (SNP) can be used in breeding programs to select lines resistant to fusarium.
A MZB Cell Activation Profile Present in the Lacrimal Glands of Sjögren’s Syndrome-Susceptible C57BL/6.NOD-Aec1Aec2 Mice Defined by Global RNA Transcriptomic Analyses
Authors: Peck Ammon B. , Nguyen Cuong Q. , Ambrus Julian L.
Published: May 2022

The C57BL/6.NOD-Aec1Aec2 mouse has been extensively studied to define the underlying cellular and molecular basis for the onset and development of Sjögren’s syndrome (SS), a human systemic autoimmune disease characterized clinically as the loss of normal lacrimal and salivary gland functions leading respectively to dry eye and dry mouth pathologies. While an overwhelming majority of SS studies in both humans and rodent models have long focused primarily on pathophysiological events and the potential role of T lymphocytes in these events, recent studies in our murine models have indicated that marginal zone B (MZB) lymphocytes are critical for both development and onset of SS disease. Although migration and function of MZB cells are difficult to study in vivo and in vitro, we have carried out ex vivo investigations that use temporal global RNA transcriptomic analyses to track early cellular and molecular events in these exocrine glands of C57BL/6.NOD-Aec1Aec2 mice. In the present report, genome-wide transcriptome analyses of lacrimal glands indicate that genes and gene-sets temporally upregulated during early onset of disease define the Notch2/NF-kβ14 and Type1 interferon signal transduction pathways, as well as identify chemokines, especially Cxcl13, and Rho-GTPases, including DOCK molecules, in the cellular migration of immune cells to the lacrimal glands. We discuss how the current results compare with our recently published salivary gland data obtained from similar studies carried out in our C57BL/6.NOD-Aec1Aec2 mice, pointing out both similarities and differences in the etiopathogeneses underlying the autoimmune response within the two glands. Overall, this study uses the power of transcriptomic analyses to identify temporal molecular bioprocesses activated during the preclinical covert pathogenic stage(s) of SS disease and how these findings may impact future intervention therapies as the disease within the two exocrine glands may not be identical.
Curvicollide D Isolated from the Fungus Amesia sp. Kills African Trypanosomes by Inhibiting Transcription
Authors: Ortiz-Gonzalez Matilde , Pérez-Victoria Ignacio , Ramirez-Macias Inmaculada , de Pedro Nuria , Linde-Rodriguez Angel , González-Menéndez Víctor , Sanchez-Martin Victoria , Martín Jesús , Soriano-Lerma Ana , Genilloud Olga , Perez-Carrasco Virginia , Vicente Francisca , Maceira José , Rodrígues-Poveda Carlos A. , Navarro-Marí José María , Reyes Fernando , Soriano Miguel , Garcia-Salcedo Jose A.
Published: May 2022

Sleeping sickness or African trypanosomiasis is a serious health concern with an added socio-economic impact in sub-Saharan Africa due to direct infection in both humans and their domestic livestock. There is no vaccine available against African trypanosomes and its treatment relies only on chemotherapy. Although the current drugs are effective, most of them are far from the modern concept of a drug in terms of toxicity, specificity and therapeutic regime. In a search for new molecules with trypanocidal activity, a high throughput screening of 2000 microbial extracts was performed. Fractionation of one of these extracts, belonging to a culture of the fungus Amesia sp., yielded a new member of the curvicollide family that has been designated as curvicollide D. The new compound showed an inhibitory concentration 50 (IC50) 16-fold lower in Trypanosoma brucei than in human cells. Moreover, it induced cell cycle arrest and disruption of the nucleolar structure. Finally, we showed that curvicollide D binds to DNA and inhibits transcription in African trypanosomes, resulting in cell death. These results constitute the first report on the activity and mode of action of a member of the curvicollide family in T. brucei.
Lysosomal Exocytosis of Olivacine on the Way to Explain Drug Resistance in Cancer Cells
Authors: Wiatrak Benita , Gębarowski Tomasz , Czwojdziński Eddie , Gąsiorowski Kazimierz , Tylińska Beata
Published: May 2022

Ellipticine is an indole alkaloid with proven antitumor activity against various tumors in vitro and a diverse mechanism of action, which includes topoisomerase II inhibition, intercalation, and cell cycle impact. Olivacine—ellipticine’s isomer—shows similar properties. The objectives of this work were as follows: (a) to find a new path of olivacine synthesis, (b) to study the cytotoxic properties of olivacine and ellipticine in comparison to doxorubicin as well as their impact on the cell cycle, and (c) to investigate the cellular pharmacokinetics of the tested compounds to understand drug resistance in cancer cells better. SRB and MTT assays were used to study the anticancer activity of olivacine and ellipticine in vitro. Both compounds showed a cytotoxic effect on various cell lines, most notably on the doxorubicin-resistant LoVo/DX model, with olivacine’s cytotoxicity approximately three times higher than doxorubicin. Olivacine proved to be less effective against cancer cells and less cytotoxic to normal cells than ellipticine. Olivacine proved to have fluorescent properties. Microscopic observation of cells treated with olivacine showed the difference in sensitivity depending on the cell line, with A549 cells visibly affected by a much lower concentration of olivacine than normal NHDF cells. An increased percentage of cells in G0/G1 was observed after treatment with olivacine and ellipticine, suggesting an impact on cell cycle progression, potentially via higher p53 protein expression, which blocks the transition from G0/G1 to the S phase. Ellipticine induced apoptosis at a concentration as low as 1 μM. It has been proved that the tested compounds (ellipticine and olivacine) undergo lysosomal exocytosis. Reducing exocytosis is possible through the use of compounds that inhibit the activity of the proton pump. Olivacine and ellipticine exhibited diverse cytotoxicity against a panel of cancer cells. Analysis of the lysosomal exocytosis of olivacine and ellipticine shows the need to look for derivatives with comparable anticancer activity but reduced weak base character.
EpCAM- and EGFR-Specific Antibody Drug Conjugates for Triple-Negative Breast Cancer Treatment
Authors: Zhang Chaoyu , Sheng Wenjie , Al-Rawe Marwah , Mohiuddin T. M. , Niebert Marcus , Zeppernick Felix , Meihold-Heerlein Ivo , Hussain Ahmad Fawzi
Published: May 2022

Triple-negative breast cancer (TNBC) is a group of heterogeneous and refractory breast cancers with the absence of estrogen receptor (ER), progesterone receptor (PgR) and epidermal growth factor receptor 2 (HER2). Over the past decade, antibody drug conjugates (ADCs) have ushered in a new era of targeting therapy. Since the epidermal growth factor receptor (EGFR) and epithelial cell adhesion molecule (EpCAM) are over expressed on triple-negative breast cancer, we developed novel ADCs by conjugating benzylguanine (BG)-modified monomethyl auristatin E (MMAE) to EpCAM- and EGFR-specific SNAP-tagged single chain antibody fragments (scFvs). Rapid and efficient conjugation was achieved by SNAP-tag technology. The binding and internalization properties of scFv-SNAP fusion proteins were confirmed by flow cytometry and fluorescence microscopy. The dose-dependent cytotoxicity was evaluated in cell lines expressing different levels of EGFR and EpCAM. Both ADCs showed specific cytotoxicity to EGFR or EpCAM positive cell lines via inducing apoptosis at a nanomolar concentration. Our study demonstrated that EGFR specific scFv-425-SNAP-BG-MMAE and EpCAM-specific scFv-EpCAM-SNAP-BG-MMAE could be promising ADCs for the treatment of TNBC.
Redox Homeostasis in Thyroid Cancer: Implications in Na+/I− Symporter (NIS) Regulation
Authors: Cazarin Juliana , Dupuy Corinne , Pires de Carvalho Denise
Published: May 2022

Radioiodine therapy (RAI) is a standard and effective therapeutic approach for differentiated thyroid cancers (DTCs) based on the unique capacity for iodide uptake and accumulation of the thyroid gland through the Na+/I− symporter (NIS). However, around 5–15% of DTC patients may become refractory to radioiodine, which is associated with a worse prognosis. The loss of RAI avidity due to thyroid cancers is attributed to cell dedifferentiation, resulting in NIS repression by transcriptional and post-transcriptional mechanisms. Targeting the signaling pathways potentially involved in this process to induce de novo iodide uptake in refractory tumors is the rationale of “redifferentiation strategies”. Oxidative stress (OS) results from the imbalance between ROS production and depuration that favors a pro-oxidative environment, resulting from increased ROS production, decreased antioxidant defenses, or both. NIS expression and function are regulated by the cellular redox state in cancer and non-cancer contexts. In addition, OS has been implicated in thyroid tumorigenesis and thyroid cancer cell dedifferentiation. Here, we review the main aspects of redox homeostasis in thyrocytes and discuss potential ROS-dependent mechanisms involved in NIS repression in thyroid cancer.
Age-Related Changes in the Fibroblastic Differon of the Dermis: Role in Skin Aging
Authors: Zorina Alla , Zorin Vadim , Kudlay Dmitry , Kopnin Pavel
Published: May 2022

Skin aging is a multi-factorial process that affects nearly every aspect of skin biology and function. The processes developing in the skin during aging are based on fundamental molecular mechanisms associated with fibroblasts, the main cellular population of the dermis. It has been revealed that the amount of fibroblasts decreases markedly with age and their functional activity is also reduced. This inevitably leads to a decrease in the regenerative abilities of the skin and the progression of its aging. In this review we consider the mechanisms underlying these processes, mainly the changes observed with age in the stem/progenitor cells that constitute the fibroblastic differon of the dermis and form their microenvironment (niches). These changes lead to the depletion of stem cells, which, in turn, leads to a decrease in the number of differentiated (mature) dermal fibroblasts responsible for the production of the dermal extracellular matrix and its remodeling. We also describe in detail DNA damages, their cellular and systemic consequences, molecular mechanisms of DNA damage response, and also the role of fibroblast senescence in skin aging.
Role of the Microbiota in Lung Cancer: Insights on Prevention and Treatment
Authors: Pizzo Federica , Maroccia Zaira , Hammarberg Ferri Ivano , Fiorentini Carla
Published: May 2022

The microbiota is increasingly recognized as a critical player in cancer onset and progression and response to cancer chemotherapy treatment. In recent years, several preclinical and clinical studies have evidenced the involvement of microbiota in lung cancer, one of the world’s deadliest cancers. However, the mechanisms by which the microbiota can impact this type of cancer and patient survival and response to treatments remain poorly investigated. In this review, the peculiarities of the gut and lung microbial ecosystems have been highlighted, and recent findings illustrating the possible mechanisms underlying the microbiota–lung cancer interaction and the host immune response have been discussed. In addition, the mucosal immune system has been identified as a crucial communication frame to ease interactive dynamics between the immune system and the microbiota. Finally, the use of specific next-generation intestinal probiotic strains in counteracting airway diseases has been evaluated. We believe that restoring homeostasis and the balance of bacterial microflora should become part of the routine of integrated cancer interventions, using probiotics, prebiotics, and postbiotics, and promoting a healthy diet and lifestyle.
Concurrent Infection with SARS-CoV-2 and Pneumocystis jirovecii in Immunocompromised and Immunocompetent Individuals
Authors: Gioia Francesca , Albasata Hanan , Hosseini-Moghaddam Seyed M.
Published: May 2022

Coronavirus disease 2019 (COVID-19) may occur with concurrent infections caused by bacterial and fungal microorganisms. This systematic review evaluated studies reporting concomitant COVID-19 and Pneumocystis jirovecii pneumonia (PJP). We found 39 patients (74% male, median age: 56.8 (range: 11–83) years), including 66% immunosuppressed individuals (23% HIV-infected and 41% on long-term corticosteroid therapy). Patients were characteristically severely ill (mechanical ventilation: 70%), associated with 41% mortality. The median lymphocyte count was 527 cells/mm3 (range: 110–2200), and the median CD4+ T cell count was 206 cells/mm3 (range: 8–1021). We identified three patterns of concurrent COVID-19 and P. jirovecii infection. The first pattern (airway colonization with a low burden of P. jirovecii) does not seem to modify the COVID-19 course of illness. However, P. jirovecii superinfection, typically occurring weeks after COVID-19 diagnosis as a biphasic illness, and P. jirovecii coinfection characteristically results in progressive multilobar pneumonia, which is associated with poor outcomes. To support this categorization, we reported three patients with concurrent PJP and COVID-19 identified in our institution, presenting these clinical scenarios. The diagnosis of PJP requires a high index of suspicion, since clinical and radiological characteristics overlap with COVID-19. Observational studies are necessary to determine the PJP burden in patients with COVID-19 requiring hospitalization.
Epidemiology of Clinical Sporotrichosis in the Americas in the Last Ten Years
Authors: Hernández-Castro Rigoberto , Pinto-Almazán Rodolfo , Arenas Roberto , Sánchez-Cárdenas Carlos Daniel , Espinosa-Hernández Víctor Manuel , Sierra-Maeda Karla Yaeko , Conde-Cuevas Esther , Juárez-Durán Eder R. , Xicohtencatl-Cortes Juan , Carrillo-Casas Erika Margarita , Steven-Velásquez Jimmy , Martínez-Herrera Erick , Rodríguez-Cerdeira Carmen
Published: May 2022

Background: Sporotrichosis is a fungal infection caused by species of the Sporothrix genus. Presently, the prevalence of sporotrichosis in the Americas is unknown, so this study aims to analyze the cases reported in the past 10 years. Methods: An advanced search was conducted from 2012 to 2022 in English and Spanish in PUBMED, SciELO, and Cochrane, with the terms: “sporotrichosis”, “lymphocutaneous sporotrichosis”, “fixed sporotrichosis”, “mycosis”, “Sporothrix spp.”, “Sporothrix complex”, “S. schenckii sensu stricto”, “S. schenckii sensu lato”, “S. globose”, “S. brasiliensis”, “S. luriei”. Sporotrichosis is a fungal infection caused by species of the Sporothrix genus associated with “pathogenicity” or “epidemiology”. Results: A total of 124 articles were found in the Americas, corresponding to 12,568 patients. Of these, 87.38% of cases were reported in South America, 11.62% in North America, and 1.00% in Central America and the Caribbean. Brazil, Peru, and Mexico had the highest number of cases. The most prevalent etiological agents were S. schenckii complex/Sporothrix spp. (52.91%), S. schenckii (42.38%), others (4.68%), and Not Determined (ND) (0.03%). The most frequent form of the disease was lymphocutaneous infection; however, the infection type was not determined in 5639 cases. Among the diagnostic methods, culture was the most used. Conclusions: There is a high occurrence of cases reported in the literature. South America is the region with the highest number of reports because of its environment (climate, inhalation of spores, etc.), zoonotic transmission (scratches and sneezes from contaminated animals), and possible traumatic inoculation due to outdoor activities (agriculture, gardening, and related occupations). Molecular diagnosis has not been sufficiently developed due to its high cost.
Grain Size Effects on Mechanical Properties of Nanocrystalline Cu6Sn5 Investigated Using Molecular Dynamics Simulation
Authors: Huang Wei , Pan Kailin , Wang Bo , Gong Yubing
Published: May 2022

Intermetallic compounds (IMCs) are inevitable byproducts during the soldering of electronics. Cu6Sn5 is one of the main components of IMCs, and its mechanical properties considerably influence the reliability of solder joints. In this study, the effects of grain size (8–20 nm) on the mechanical properties (Young’s modulus, yield stress, ultimate tensile strength (UTS), and strain rate sensitivity) of polycrystalline Cu6Sn5 were investigated using molecular dynamics simulations at 300 K and at a strain rate of 0.0001–10 ps−1. The results showed that at high strain rates, grain size only slightly influenced the mechanical properties. However, at low strain rates, Young’s modulus, yield stress, and UTS all increased with increasing grain size, which is the trend of an inverse Hall–Petch curve. This is largely attributed to the sliding and rotation of grain boundaries during the nanoscale stretching process, which weakens the interaction between grains. Strain rate sensitivity increased with a decrease in grain size.
Fucoxanthin Is a Potential Therapeutic Agent for the Treatment of Breast Cancer
Authors: Lau Tsz-Ying , Kwan Hiu-Yee
Published: May 2022

Breast cancer (BC) is one of the most common cancers diagnosed and the leading cause of cancer-related death in women. Although there are first-line treatments for BC, drug resistances and adverse events have been reported. Given the incidence of BC keeps increasing, seeking novel therapeutics is urgently needed. Fucoxanthin (Fx) is a dietary carotenoid commonly found in seaweeds and diatoms. Both in vitro and in vivo studies show that Fx and its deacetylated metabolite fucoxanthinol (Fxol) inhibit and prevent BC growth. The NF-κB signaling pathway is considered the major pathway contributing to the anti-proliferation, anti-angiogenesis and pro-apoptotic effects of Fx and Fxol. Other signaling molecules such as MAPK, MMP2/9, CYP and ROS are also involved in the anti-cancer effects by regulating the tumor microenvironment, cancer metastasis, carcinogen metabolism and oxidation. Besides, Fx also possesses anti-obesity effects by regulating UCP1 levels and lipid metabolism, which may help to reduce BC risk. More importantly, mounting evidence demonstrates that Fx overcomes drug resistance. This review aims to give an updated summary of the anti-cancer effects of Fx and summarize the underlying mechanisms of action, which will provide novel strategies for the development of Fx as an anti-cancer therapeutic agent.
The Mode of Activity of Cervical Extensors and Flexors in Healthy Adults: A Cross-Sectional Study
Authors: Yajima Hiroyoshi , Nobe Ruka , Takayama Miho , Takakura Nobuari
Published: May 2022

Background and Objectives: The purpose of this study was to investigate the activity of bilateral cervical extensors and flexors on the sagittal, frontal, and horizontal planes of healthy adults during motions of the neck in a sitting position, which has not been satisfactorily investigated by surface electromyogram (sEMG). Materialand Methods: We recruited 35 healthy participants (mean ± standard deviation of age, 20.3 ± 2.4). sEMG recordings of the cervical extensors and flexors were performed for a total of nine seconds in three phases: Phase I involved the motion of the neck from the neutral position to the maximum range of motion; Phase II involved maintaining the neck at the maximum range of motion; and Phase III involved the motion of the neck from the maximum range of motion to the neutral position during neck flexion, extension, right and left lateral flexion, right and left rotation, and maintaining the neck in the neutral position. Muscle activities in each motion were normalized as a percentage of maximal voluntary contraction (%MVC) so that the muscles could be compared. Results: The %MVC of the extensors was significantly larger than that of the flexors in the neutral position (p < 0.001). In addition, the %MVCs of the following were significantly larger than the %MVC in the neutral position: the extensors in flexion (p = 0.014) and extension (p = 0.020), the ipsilateral extensors (p = 0.006) and flexors (p < 0.001) in lateral flexion in Phase I; the flexors in flexion (p < 0.001), the extensors in extension (p = 0.010), and the ipsilateral extensors and flexors in lateral flexion (p < 0.001) in Phase II; the extensors and flexors in flexion (p < 0.001), the flexors in extension (p < 0.001), the ipsilateral flexors (p < 0.001), the contralateral flexors (p = 0.004) and the contralateral extensors (p = 0.018) in lateral flexion in Phase III; and the bilateral extensors and contralateral flexors during rotation in all three phases (p < 0.001). Conclusion: The typical sEMG activities of the extensors and flexors during motion of the neck in healthy adults were identified in this study; this information can be used to understand the pathophysiology of non-specific neck pain and to provide an index for evaluating the effect of treatment.
Caesarean Scar Pregnancy: A Case Report and a Literature Review
Authors: Valasoulis George , Magaliou Ioulia , Koufidis Dimitrios , Garas Antonios , Daponte Alexandros
Published: May 2022

Background and Objectives: Caesarean scar pregnancy (CSP) refers to placental implantation on or in the scar of a previous caesarean section and represents a potentially life-threatening condition. CSP is considered a diagnostic challenge in obstetrics, with the diagnosis relying mainly on transvaginal ultrasound (TVS) and the management depending upon case presentation and available healthcare infrastructures. Case Presentation: We present a case of 34-year-old G3P2 with a history of two-previous caesarean sections referred to the outpatient gynaecology clinic of our Department at the 7th week (7/40) of gestation with abnormal early pregnancy TVS findings, illustrating the gestational sac attached to the caesarean scar and a foetal pole with evidence of foetal cardiac activity. We discuss the outcome of an alternative combined medical and surgical approach we followed as well as an updated review of the current literature. Conclusions: The ideal management of CSP requires tertiary centers, equipment availability and experienced healthcare professionals capable of dealing with any possible complication, as well as individualized treatment based on each case presentation.
Membrane Photobioreactor Applied for Municipal Wastewater Treatment at a High Solids Retention Time: Effects of Microalgae Decay on Treatment Performance and Biomass Properties
Authors: Zou Hui , Rutta Neema Christopher , Chen Shilei , Zhang Meijia , Lin Hongjun , Liao Baoqiang
Published: May 2022

Membrane photobioreactor (MPBR) technology is a microalgae-based system that can simultaneously realize nutrient recovery and microalgae cultivation in a single step. Current research is mainly focused on the operation of MPBR at a medium SRT. The operation of MPBR at a high SRT is rarely reported in MPBR studies. Therefore, this study conducted a submerged MPBR to treat synthetic municipal wastewater at a long solids retention time of 50 d. It was found that serious microalgae decay occurred on day 23. A series of characterizations, including the biomass concentration, chlorophyll-a content, nutrients removal, and physical-chemical properties of the microalgae, were conducted to evaluate how microalgae decay affects the treatment performance and biomass properties. The results showed that the biomass concentration and chlorophyll-a/MLSS dropped rapidly from 3.48 to 1.94 g/L and 34.56 to 10.71 mg/g, respectively, after the occurrence of decay. The effluent quality significantly deteriorated, corresponding to the total effluent nitrogen and total phosphorus concentration sharply rising and exceeding that of the feed. In addition, the particle became larger, the content of the extracellular polymeric substances (EPSs) decreased, and the soluble microbial products (SMPs) increased instantaneously. However, the filtration resistance had no significant increase because of the comprehensive interactions of the floc size, EPSs, and SMPs. The above results suggest that the MPBR system cannot maintain long-term operation under a high SRT for municipal wastewater treatment. In addition, the biological treatment performance of the MPBR deteriorated while the antifouling performance of the microalgae flocs improved after the occurrence of decay. The occurrence of microalgae decay was attributed to the double stresses from the light shading and intraspecific competition under high biomass concentration. Therefore, to avoid microalgae decay, periodic biomass removal is required to control the environmental stress within the tolerance range of the microalgae. Further studies are required to explore the underlying mechanism of the occurrence of decay.
Effect of Melissa officinalis L. Essential Oil Nanoemulsions on Structure and Properties of Carboxymethyl Chitosan/Locust Bean Gum Composite Films
Authors: Yu Huijie , Zhang Chi , Xie Yao , Mei Jun , Xie Jing
Published: May 2022

This study aimed to develop active films based on carboxymethyl chitosan (CMCS)/locust bean gum (LBG) films containing Melissa officinalis L. essential oil (MOEO) nanoemulsions. The results showed that the active films incorporated with MOEO nanoemulsion resulted in an increase in the elongation of break, water resistance and improved the film hydrophilicity. Elongation of break increased from 18.49% to 27.97% with the addition of 4% MOEO nanoemulsion. Water resistance was decreased from 56.32% to 25.43%, and water contact angle was increased from 75.13 to 83.86 with the addition of 4% MOEO nanoemulsion. However, the water vapor barrier properties and tensile strength decreased with the addition of MOEO nanoemulsions. The scanning electron microscopic images and Fourier transform infrared spectroscopy results showed that the MOEO was very compatible with the film materials and dispersed evenly in the films. At the same time, the addition of MOEO nanoemulsion significantly enhanced antioxidant and antibacterial activities of C/L-MOEO films. The antioxidant and antimicrobial activities of C/L-MOEO films were increased from 7.16% to 33.81% and 3.52% to 54.50%, respectively. In general, C/L-MOEO film has great application prospects.
Memory-Efficient Searching of Gas-Chromatography Mass Spectra Accelerated by Prescreening
Authors: Smirnov Aleksandr , Liao Yunfei , Du Xiuxia
Published: May 2022

The number of metabolomics studies and spectral libraries for compound annotation (i.e., assigning possible compound identities to a fragmentation spectrum) has been growing steadily in recent years. Accompanying this growth is the number of mass spectra available for searching through those libraries. As the size of spectral libraries grows, accurate and fast compound annotation becomes more challenging. We herein report a prescreening algorithm that was developed to address the speed of spectral search under the constraint of low memory requirements. This prescreening has been incorporated into the Automated Data Analysis Pipeline Spectral Knowledgebase (ADAP-KDB) and can be applied to compound annotation by searching other spectral libraries as well. Performance of the prescreening algorithm was evaluated for different sets of parameters and compared to the original ADAP-KDB spectral search and the MSSearch software. The comparison has demonstrated that the new algorithm is about four-times faster than the original when searching for low-resolution mass spectra, and about as fast as the original when searching for high-resolution mass spectra. However, the new algorithm is still slower than MSSearch due to the relational database design of the former. The new search workflow can be tried out at the ADAP-KDB web portal.
Discovery of Synergistic Drug Combinations for Colorectal Cancer Driven by Tumor Barcode Derived from Metabolomics “Big Data”
Authors: Lv Bo , Xu Ruijie , Xing Xinrui , Liao Chuyao , Zhang Zunjian , Zhang Pei , Xu Fengguo
Published: May 2022

The accumulation of cancer metabolomics data in the past decade provides exceptional opportunities for deeper investigations into cancer metabolism. However, integrating a large amount of heterogeneous metabolomics data to draw a full picture of the metabolic reprogramming and to discover oncometabolites of certain cancers remains challenging. In this study, a tumor barcode constructed based upon existing metabolomics “big data” using the Bayesian vote-counting method is proposed to identify oncometabolites in colorectal cancer (CRC). Specifically, a panel of oncometabolites of CRC was generated from 39 clinical studies with 3202 blood samples (1332 CRC vs. 1870 controls) and 990 tissue samples (495 CRC vs. 495 controls). Next, an oncometabolite-protein network was constructed by combining the tumor barcode and its involved proteins/enzymes. The effect of anti-cancer drugs or drug combinations was then mapped into this network by the random walk with restart process. Utilizing this network, potential Irinotecan (CPT-11)-sensitizing agents for CRC treatment were discovered by random forest and Xgboost. Finally, a compound named MK-2206 was highlighted and its synergy with CPT-11 was validated on two CRC cell lines. To summarize, we demonstrate in the present study that the metabolomics “big data”-based tumor barcodes and the subsequent network analyses are potentially useful for drug combination discovery or drug repositioning.
Ratios of Acetaminophen Metabolites Identify New Loci of Pharmacogenetic Relevance in a Genome-Wide Association Study
Authors: Thareja Gaurav , Evans Anne M. , Wood Spencer D. , Stephan Nisha , Zaghlool Shaza , Halama Anna , Kastenmüller Gabi , Belkadi Aziz , Albagha Omar M. E. ,   The Qatar Genome Program Research Consortium, Suhre Karsten
Published: May 2022

Genome-wide association studies (GWAS) with non-targeted metabolomics have identified many genetic loci of biomedical interest. However, metabolites with a high degree of missingness, such as drug metabolites and xenobiotics, are often excluded from such studies due to a lack of statistical power and higher uncertainty in their quantification. Here we propose ratios between related drug metabolites as GWAS phenotypes that can drastically increase power to detect genetic associations between pairs of biochemically related molecules. As a proof-of-concept we conducted a GWAS with 520 individuals from the Qatar Biobank for who at least five of the nine available acetaminophen metabolites have been detected. We identified compelling evidence for genetic variance in acetaminophen glucuronidation and methylation by UGT2A15 and COMT, respectively. Based on the metabolite ratio association profiles of these two loci we hypothesized the chemical structure of one of their products or substrates as being 3-methoxyacetaminophen, which we then confirmed experimentally. Taken together, our study suggests a novel approach to analyze metabolites with a high degree of missingness in a GWAS setting with ratios, and it also demonstrates how pharmacological pathways can be mapped out using non-targeted metabolomics measurements in large population-based studies.
Reduction in RF Loss Based on AlGaN Back-Barrier Structure Changes
Authors: Fang Yi , Chen Ling , Liu Yuqi , Wang Hong
Published: May 2022

We designed a high electron mobility transistor (HEMT) epitaxial structure based on an AlGaN/GaN heterojunction, utilizing Silvaco TCAD, and selected AlGaN with an aluminum composition of 0.1 as the back-barrier of the AlGaN/GaN heterojunction. We enhanced the confinement of the two-dimensional electron gas (2DEG) by optimizing the structural parameters of the back barrier, so that the leakage current of the buffer layer is reduced. Through these optimization methods, a lower drain leakage current and a good radio frequency performance were obtained. The device has a cut-off frequency of 48.9 GHz, a maximum oscillation frequency of 73.20 GHz, and a radio frequency loss of 0.239 dB/mm (at 6 GHz). This work provides a basis for the preparation of radio frequency devices with excellent frequency characteristics and low RF loss.
A THz Waveguide Bandpass Filter Design Using an Artificial Neural Network
Authors: Lin Chu-Hsuan , Cheng Yu-Hsiang
Published: May 2022

This paper presents a 300 GHz waveguide bandpass filter based on asymmetric inductive irises. The coupling matrix synthesis technique is used to design a 6-pole Chebyshev filter. In addition, an artificial neural network is applied to provide the filter geometries using the desired frequency response. The optimized filter is fabricated by the computer numeric controlled milling process. The measurement results show that the insertion loss is less than 3 dB and the return loss is better than 17 dB in the range 276–310 GHz.
Development of a Hybrid Intelligent Process Model for Micro-Electro Discharge Machining Using the TTM-MDS and Gaussian Process Regression
Authors: Chen Yanyan , Guo Xudong , Zhang Guojun , Cao Yang , Shen Dili , Li Xiaoke , Zhang Shengfei , Ming Wuyi
Published: May 2022

This paper proposed a hybrid intelligent process model, based on a hybrid model combining the two-temperature model (TTM) and molecular dynamics simulation (MDS) (TTM-MDS). Combined atomistic-continuum modeling of short-pulse laser melting and disintegration of metal films [Physical Review B, 68, (064114):1–22.], and Gaussian process regression (GPR), for micro-electrical discharge machining (micro-EDM) were also used. A model of single-spark micro-EDM process has been constructed based on TTM-MDS model to predict the removed depth (RD) and material removal rate (MRR). Then, a GPR model was proposed to establish the relationship between input process parameters (energy area density and pulse-on duration) and the process responses (RD and MRR) for micro-EDM machining. The GPR model was trained, tested, and tuned using the data generated from the numerical simulations. Through the GPR model, it was found that micro-EDM process responses can be accurately predicted for the chosen process conditions. Therefore, the hybrid intelligent model proposed in this paper can be used for a micro-EDM process to predict the performance.
Self-Attention-Augmented Generative Adversarial Networks for Data-Driven Modeling of Nanoscale Coating Manufacturing
Authors: Ji Shanling , Zhu Jianxiong , Yang Yuan , Zhang Hui , Zhang Zhihao , Xia Zhijie , Zhang Zhisheng
Published: May 2022

Nanoscale coating manufacturing (NCM) process modeling is an important way to monitor and modulate coating quality. The multivariable prediction of coated film and the data augmentation of the NCM process are two common issues in smart factories. However, there has not been an artificial intelligence model to solve these two problems simultaneously. Focusing on the two problems, a novel auxiliary regression using a self-attention-augmented generative adversarial network (AR-SAGAN) is proposed in this paper. This model deals with the problem of NCM process modeling with three steps. First, the AR-SAGAN structure was established and composed of a generator, feature extractor, discriminator, and regressor. Second, the nanoscale coating quality was estimated by putting online control parameters into the feature extractor and regressor. Third, the control parameters in the recipes were generated using preset parameters and target quality. Finally, the proposed method was verified by the experiments of a solar cell antireflection coating dataset, the results of which showed that our method performs excellently for both multivariable quality prediction and data augmentation. The mean squared error of the predicted thickness was about 1.6~2.1 nm, which is lower than other traditional methods.
Influence of Surface Cleaning on Quantum Efficiency, Lifetime and Surface Morphology of p-GaN:Cs Photocathodes
Authors: Schaber Jana , Xiang Rong , Teichert Jochen , Arnold André , Murcek Petr , Zwartek Paul , Ryzhov Anton , Ma Shuai , Gatzmaga Stefan , Michel Peter , Gaponik Nikolai
Published: May 2022

Accelerator scientists have high demands on photocathodes possessing high quantum efficiency (QE) and long operational lifetime. p-GaN, as a new photocathode type, has recently gained more and more interest because of its ability to form a negative electron affinity (NEA) surface. Being activated with a thin layer of cesium, p-GaN:Cs photocathodes promise higher QE and better stability than the known photocathodes. In our study, p-GaN samples grown on sapphire or silicon were wet chemically cleaned and transferred into an ultra-high vacuum (UHV) chamber, where they underwent a subsequent thermal cleaning. The cleaned p-GaN samples were activated with cesium to obtain p-GaN:Cs photocathodes, and their performance was monitored with respect to their quality, especially their QE and storage lifetime. The surface topography and morphology were examined by atomic force microscopy (AFM) and scanning electron microscopy (SEM) in combination with energy dispersive X-ray (EDX) spectroscopy. We have shown that p-GaN could be efficiently reactivated with cesium several times. This paper systematically compares the influence of wet chemical cleaning as well as thermal cleaning at various temperatures on the QE, storage lifetime and surface morphology of p-GaN. As expected, the cleaning strongly influences the cathodes’ quality. We show that high QE and long storage lifetime are achievable at lower cleaning temperatures in our UHV chamber.
Research on Locally Resonant Characteristics of Pipelines with Periodic Structure
Authors: Lao Xingsheng , Yu Yonghua , Zhang Fan , Ye Jinxiao , Xu Xiangxi , Xia Zhaowang
Published: May 2022

In this paper, the propagation characteristics of vibration waves in periodic pipelines were studied based on the band theory of phononic crystals, and we analyzed the influence of the geometrical structure parameters on the band gap characteristics of pipelines. The results show that, by increasing the number of layers of local resonant structure, both the initial frequency and the cutoff frequency of the band gap moved towards the lower frequency, while the width of the system band gap increased by 35 Hz, and the damping effect increased by 18.3 dB. By changing the thickness of the wall of the pipeline system, the width of the system band gap increased by 20 Hz, and the damping effect increased by 9.1 dB. The maximum vibration isolation of the offshore platform truss based on the periodic structure can be up to 7.93 dB. Therefore, it is feasible to apply the local resonant periodic structure to the vibration control of a practical offshore platform.