bluuebunny/crossref_metadata_2025 huggingface dataset:
Seedling Growth and Quality of Avicennia marina (Forssk.) Vierh. under Growth Media Composition and Controlled Salinity in an Ex Situ Nursery
Authors: Budiadi Budiadi , Widiyatno Widiyatno , Nurjanto Handojo Hadi , Hasani Habib , Jihad Aqmal Nur
Published: April 2022

Avicennia marina (Forssk.) Vierh. is an important mangrove species that inhabits the outermost zone of mangrove forests, but it has been shown to have a poor ability to regenerate due to its low seedling quality. We conducted a study to evaluate the specific growth requirements of A. marina, i.e., medium and salinity level. Germinated seeds were transplanted to pots filled with media, i.e., silt loam (M1), loam (M2), sandy loam (M3), or sand (M4), with various salinity levels 5 (S1), 5–15 (S2), 15–25 (S3), or 25–35 ppt (S4). Survival rate, growth, biomass partition, and seedling quality were observed for 14 weeks after transplanting the seeds. The highest rate of seedling survival was found in the S2 condition, and higher concentrations of salinity lowered the survival rates. The S1 treatment promoted the initial 8 week growth of the seedlings. Growth medium had no significant effect, except on the survival rates grown in M4. Growth medium composition had no distinct effect on seedling growth. The S2 and S3 treatments induced better growth (in terms of shoot height and root length) and resulted in high-quality (i.e., Dickson quality index) seedlings in any type of medium. The S3 treatment increased the seedling quality in M1 and M4, whereas the S4 treatment only benefited seedlings in the M4 medium. According to the results, a specific range of salinity (5–15 ppt) with circulated water in any type of medium is recommended for the establishment of an ex situ nursery for the propagation of A. marina, in contrast to the general range of salinity (4–35 ppt) stated in previous references.
Estimating Preferences for Wood Furniture in Terms of Sustainable Forest Management
Authors: Sakagami Masaji , Sakaguchi Daishi
Published: April 2022

The world’s forest area decreased to three point nine billion hectares in 2015, a net annual loss of 3.3 million hectares, and large-scale deforestation is occurring in the tropics. Furthermore, greenhouse gas emissions are increasing as forests are converted to other uses such as agricultural land. Against this backdrop, sustainable forest management is becoming increasingly important. This study attempts to quantify people’s general awareness and values concerning for on-line shopping habits (in this study, for wooden furniture) in terms of sustainable forest management in Japan by estimating the acceptable price premium or willingness of consumers to pay for wood-related products made using wood produced under sustainable forest management as the raw material. The study proceeds to quantify the awareness and values of consumers concerning sustainable forest management and conservation of forest environments. Consumers were found to have a certain willingness to pay for wooden furniture made from wood produced through sustainable forest management. As a consequence of this analysis, it was revealed that consumers place a high value on sustainable forest management and environmental conservation, and that they are willing to act on these values when purchasing wood-related products.
Economic Challenges and Behavioral and Mental Health Risks for Overdose during the COVID-19 Pandemic among People Who Inject Drugs
Authors: Williams Leslie D. , Lee Eunhye , Latkin Carl , Mackesy-Amiti Mary Ellen , Kaufmann Maggie , Copulsky Elizabeth , Kaplan Charlie , Boodram Basmattee
Published: April 2022

People who inject drugs (PWID) are a population that disproportionately struggles with economic and mental health challenges. However, despite numerous reports of people globally experiencing new or exacerbated economic and/or mental health challenges during the COVID-19 pandemic, the literature on the effect of the pandemic on PWID and their risk for harm (e.g., overdose) remains sparse. The present study will describe reported changes during the pandemic in risk factors for drug overdose (including changes in mental health symptoms and care access) among PWID in Chicago, and it will examine associations between such risk factor changes and the experience of economic challenges during the pandemic. Participants from an ongoing longitudinal study of young PWID from the Chicago suburbs and their injection risk network members (N = 138; mean age = 28.7 years) were interviewed about changes in their experiences, substance use behavior, and mental health since the start of the COVID-19 pandemic. Bivariate cross tabulations were computed of each “overdose risk factor” with experiences of economic challenges during the pandemic. Fisher’s Exact Tests were used to assess statistical significance. Adjusted logistic regression models were also conducted that controlled for sociodemographic characteristics, for time elapsed since the start of the pandemic, and for pre-pandemic income, homelessness, and injection frequency. Over half of our sample reported using alone more than usual during the pandemic, and over 40% reported using more than usual and/or buying drugs that were of a decreased purity or quality. Additionally, a large proportion of our sample (52.5% of those asked) reported more difficulty than usual accessing mental health care. Experiencing loss of a source of income during the pandemic was associated with using more drugs, using alone more, using a larger amount of drugs while using alone, wanting to stop using but being unable, and difficulty accessing mental health care. The preliminary associations found by the present study suggest that economic challenges or disruptions experienced during the pandemic are likely to increase risk for overdose among PWID experiencing such challenges, via changes in the above behaviors and/or conditions that are associated with risk for overdose. Intervention efforts should therefore be focused not only directly on overdose prevention, but also on assisting PWID with their economic challenges and helping them regain economic stability and access to services that may have been impeded by financial difficulty.
Youth Serial Killers: Psychological and Criminological Profiles
Authors: García-Baamonde María Elena , Blázquez-Alonso Macarena , Moreno-Manso Juan Manuel , Guerrero-Barona Eloísa , Guerrero-Molina Mónica
Published: April 2022

Serial murder is a specific type of violent crime that falls into the crime category of multicide. According to the nomenclature of the Federal Bureau of Investigation’s Violent Crime Classification Manual and Academic Researchers for the Classification of Violent Crimes, most serial killers are adults. However, serial murder is also committed by young people, although to a lesser extent. Young serial killers are a topic of relevance in areas such as psychology, criminology, and the justice system. Given that the study of the variables that could be the basis of such multicide criminality is not conclusive, the need for further research is evident. The homicides perpetrated by children and young people point to a social panorama that is alarming due to their young age. This issue is prevalent enough to conduct a review. The performed review concludes the importance of psychosocial factors to better understand the process by which children and young people commit crimes as serious as serial murders. The scope of the problem of serial murders perpetrated by minors is controversial because it often depends on how the number of real cases is counted. Although official statistics indicate the low prevalence of juvenile serial killers, childhood is a period in which antisocial behaviour can have its beginning. Some authors consider that it is not uncommon for the first murder of this type to occur in adolescence. It is important to consider psychopathy as an influential factor in the various forms of serial criminal conduct committed by children and young people. The research works consulted provide evidence of the special relevance of psychopathy in the generation of serious juvenile delinquency.
Effect of Rural Clinical Placements on Intention to Practice and Employment in Rural Australia: A Systematic Review
Authors: Seaman Claire Ellen , Green Elyce , Freire Kate
Published: April 2022

Background: Supporting the provision of clinical placement (CP) experiences in rural areas is a strategy used worldwide to promote the rural health workforce. While there is international evidence for this intervention in medicine, there is limited understanding of the influence of rural CP for nursing, midwifery, allied health, and dentistry health professions in Australia, which have received substantial federal investment. This review examined the relationship between rural CP and non-medicine health students’ future rural practice intentions and workforce outcomes. Methods: Four databases were systematically searched; papers were screened using defined criteria and appraised using the mixed-methods appraisal tool (MMAT). Findings were synthesized using a critical narrative approach. Results: The methodological quality of the 29 eligible studies (13 quantitative non-randomized, 10 mixed method, 4 qualitative, 2 quantitative description) was appraised. Ten high-quality studies were identified. The review found that positive CP experiences may influence intention to practice rurally amongst undecided students and serve as a reinforcing experience for those students already interested in rural practice. There were mixed findings regarding the influence of CP length. The review also found that there is currently only evidence for the short-term effects of CP on students’ future practice outcomes in rural areas with focus thus far on early practice outcomes. Conclusions: Those looking to use rural CP to promote the rural health workforce should focus on supporting the quality of a large number of CP experiences that are undertaken in rural areas, as there are currently differing findings on the role of rural CP length. Future studies of rural CP should consider greater use of social and educational theories to guide them.
Voices from the Youth in Kenya Addressing Mental Health Gaps and Recommendations
Authors: Memiah Peter , Wagner Fernando A. , Kimathi Robert , Anyango Naomi Idah , Kiogora Samuel , Waruinge Stella , Kiruthi Faith , Mwavua Shillah , Kithinji Celina , Agache Jeremiah Okuto , Mangwana Wincolyne , Merci Niyibeshaho Marie , Ayuma Leonidah , Muhula Samuel , Opanga Yvonne , Nyambura Maureen , Ikahu Annrita , Otiso Lillian
Published: April 2022

Studies including adolescents and young people (AYP) enhance the relevance of research results, benefit stakeholders, and inform future research. There exists a mental health gap in services for AYP living in low and middle-income countries. This study aims to identify mental health challenges faced by adolescents and young people in Kenya, develop practical recommendations to mitigate these issues, and reduce the mental health burden among this population. We convened an AYP-led meeting that involved 41 participants. The meeting objectives were to (1) identify efforts to support existing national and regional strategic priorities and review goals for addressing mental health needs among AYPs, (2) develop immediate action plans for strengthened mental health services, (3) review and strengthen country-level coordination mechanisms, and (4) identify how participating county experiences can inform mental health services in Kenya. Ministry of Health (MoH) officials from national and county levels, academic experts, and implementing partner agencies involved in mental health services participated in the meeting. The team, including AYP representatives, identified various mental health challenges among the AYA and recommended interventions aimed towards improving their mental health situation in the country. The challenges were clustered into three themes and comprehensively reviewed to establish the precipitating factors to mental health outcomes among AYPs in Kenya and provide recommendations. The themes included (1) legislative, (2) service provider/Ministry of Health, and (3) adolescent/individual-level factors. To bridge the mental health gap in the country and scale up mental health outcomes, the stakeholders recommended interventions within the context of the three clusters. The key suggestions included an increase in insurance financing, acceleration of community health interventions, the establishment of adolescent-friendly spaces, the training of adolescent youth champions, interactive service provision models, implementation of the existing mental health policies and structures, the development of comprehensive assessment tools, well equipped mental health departments in health facilities, the enhancement of telehealth services and digital villages, the mobilization of a functional mental health response team, and the development of a mental health database.
The Effects of High-Speed Resistance Training on Health Outcomes in Independent Older Adults: A Systematic Review and Meta-Analysis
Authors: Martins Alexandre Duarte , Fernandes Orlando , Pereira Ana , Oliveira Rafael , Alderete Goñi Franco David , Leite Nilton João Chantre , Brito João Paulo
Published: April 2022

Human ageing involves several physiological impairments—in particular, a decrease in sensorimotor function and changes in the nervous system reduce muscle strength, power, balance, and functional capacity performance. Preventive strategies are essential to ensure the quality of life of the elderly. High-speed resistance training (HSRT) may be an effective approach to muscle power development in this population, with significant short-term effects on neural adaptations and muscle power production. Therefore, the present study intends to analyze and systematize the studies focused on HSRT interventions and their effects on health outcomes in independent older adults. Four electronic databases (PubMed, Web of Science, EBSCO, and Scielo) were used for the purposes of searching randomized controlled trials that measured at least one key outcome measure focusing on velocity-based training and health outcomes in older adults on 7 March 2022 and identified 1950 studies. At the end of the process, fourteen studies were included in this systematic review and ten studies were included in the quantitative analysis. The main results showed that HSRT interventions would improve health measures, mostly cognitive function (large effects, p = 0.001, SMD = 0.94), neuromuscular function (moderate effects, p = 0.003, SMD = 0.70), and physical function (moderate effects, p = 0.04, SMD = 0.55 and p = 0.009, SMD = −0.59). Additionally, the results suggested that interventions with ten weeks or more, performed three times a week, provide significant improvements in neuromuscular function. In this sense, HSRT is effective for improving overall health outcomes in older adults. Future studies should include proper follow-ups (e.g., minimum six months) to assess the durability of HSRT intervention effects on all health-related variables.
ApoA1 Deficiency Reshapes the Phenotypic and Molecular Characteristics of Bone Marrow Adipocytes in Mice
Authors: Kastrenopoulou Afroditi , Kypreos Kyriakos E. , Papachristou Nicholaos I. , Georgopoulos Stavros , Mastora Ioulia , Papadimitriou-Olivgeri Ioanna , Spentzopoulou Argyro , Nikitovic Dragana , Kontogeorgakos Vassilios , Blair Harry C. , Papachristou Dionysios J.
Published: April 2022

In the present study, we studied the effect of apolipoprotein A-1 (APOA1) on the spatial and molecular characteristics of bone marrow adipocytes, using well-characterized ApoA1 knockout mice. APOA1 is a central regulator of high-density lipoprotein cholesterol (HDL-C) metabolism, and thus HDL; our recent work showed that deficiency of APOA1 increases bone marrow adiposity in mice. We found that ApoA1 deficient mice have greatly elevated adipocytes within their bone marrow compared to wild type counterparts. Morphologically, the increased adipocytes were similar to white adipocytes, and displayed proximal tibial-end localization. Marrow adipocytes from wild type mice were significantly fewer and did not display a bone-end distribution pattern. The mRNA levels of the brown/beige adipocyte-specific markers Ucp1, Dio2, Pat2, and Pgc1a; and the expression of leptin were greatly reduced in the ApoA1 knock-out in comparison to the wild-type mice. In the knock-out mice, adiponectin was remarkably elevated. In keeping with the close ties of hematopoietic stem cells and marrow adipocytes, using flow cytometry we found that the elevated adiposity in the ApoA1 knockout mice is associated with a significant reduction in the compartments of hematopoietic stem cells and common myeloid, but not of the common lymphoid, progenitors. Moreover, the ‘beiging’-related marker osteopontin and the angiogenic factor VEGF were also reduced in the ApoA1 knock-out mice, further supporting the notion that APOA1—and most probably HDL-C—regulate bone marrow microenvironment, favoring beige/brown adipocyte characteristics.
Phosphoinositide 3-Kinases as Potential Targets for Thrombosis Prevention
Authors: Setiabakti Natasha M. , Larsson Pia , Hamilton Justin R.
Published: April 2022

As integral parts of pathological arterial thrombi, platelets are the targets of pharmacological regimens designed to treat and prevent thrombosis. A detailed understanding of platelet biology and function is thus key to design treatments that prevent thrombotic cardiovascular disease without significant disruption of the haemostatic balance. Phosphoinositide 3-kinases (PI3Ks) are a group of lipid kinases critical to various aspects of platelet biology. There are eight PI3K isoforms, grouped into three classes. Our understanding of PI3K biology has recently progressed with the targeting of specific isoforms emerging as an attractive therapeutic strategy in various human diseases, including for thrombosis. This review will focus on the role of PI3K subtypes in platelet function and subsequent thrombus formation. Understanding the mechanisms by which platelet function is regulated by the various PI3Ks edges us closer toward targeting specific PI3K isoforms for anti-thrombotic therapy.
Preclinical In Vitro Model to Assess the Changes in Permeability and Cytotoxicity of Polarized Intestinal Epithelial Cells during Exposure Mimicking Oral or Intravenous Routes: An Example of Arsenite Exposure
Authors: Parajuli Pravin , Gokulan Kuppan , Khare Sangeeta
Published: April 2022

The gastrointestinal tract (GIT) is exposed to xenobiotics, including drugs, through both: local (oral) and systemic routes. Despite the advances in drug discovery and in vitro pre-clinical models, there is a lack of appropriate translational models to distinguish the impact of these routes of exposure. Changes in intestinal permeability has been observed in different gastrointestinal and systemic diseases. This study utilized one such xenobiotic, arsenic, to which more than 200 million people around the globe are exposed via their food, drinking water, work environment, soil, and air. The purpose of this study was to establish an in vitro model to mimic gastrointestinal tract exposure to xenobiotics via oral or intravenous routes. To achieve this, we compared the route (mimicking oral and intravenous exposure to GIT and the dose response (using threshold approach) of trivalent and pentavalent inorganic arsenic species on the permeability of in vitro cultured polarized T84 cells, an example of intestinal epithelial cells. Arsenic treatment to polarized T84 cells via the apical and basolateral compartment of the trans-well system reflected oral or intravenous routes of exposure in vivo, respectively. Sodium arsenite, sodium arsenate, dimethyl arsenic acid sodium salt (DMAV), and disodium methyl arsonate hydrate (MMAV) were assessed for their effects on intestinal permeability by measuring the change in trans-epithelial electrical resistance (TEER) of T-84 cells. Polarized T-84 cells exposed to 12.8 µM of sodium arsenite from the basolateral side showed a marked reduction in TEER. Cytotoxicity of sodium arsenite, as measured by release of lactate dehydrogenase (LDH), was increased when cells were exposed via the basolateral side. The mRNA expression of genes related to cell junctions in T-84 cells was analyzed after exposure with sodium arsenite for 72 h. Changes in TEER correlated with mRNA expression of focal-adhesion-, tight-junction- and gap-junction-related genes (upregulation of Jam2, Itgb3 and Notch4 genes and downregulation of Cldn2, Cldn3, Gjb1, and Gjb2). Overall, exposure to sodium arsenite from the basolateral side was found to have a differential effect on monolayer permeability and on cell-junction-related genes as compared to apical exposure. Most importantly, this study established a preclinical human-relevant in vitro translational model to assess the changes in permeability and cytotoxicity during exposure, mimicking oral or intravenous routes.
Vibrational Biospectroscopy: An Alternative Approach to Endometrial Cancer Diagnosis and Screening
Authors: Schiemer Roberta , Furniss David , Phang Sendy , Seddon Angela B. , Atiomo William , Gajjar Ketankumar B.
Published: April 2022

Endometrial cancer (EC) is the sixth most common cancer and the fourth leading cause of death among women worldwide. Early detection and treatment are associated with a favourable prognosis and reduction in mortality. Unlike other common cancers, however, screening strategies lack the required sensitivity, specificity and accuracy to be successfully implemented in clinical practice and current diagnostic approaches are invasive, costly and time consuming. Such limitations highlight the unmet need to develop diagnostic and screening alternatives for EC, which should be accurate, rapid, minimally invasive and cost-effective. Vibrational spectroscopic techniques, Mid-Infrared Absorption Spectroscopy and Raman, exploit the atomic vibrational absorption induced by interaction of light and a biological sample, to generate a unique spectral response: a “biochemical fingerprint”. These are non-destructive techniques and, combined with multivariate statistical analysis, have been shown over the last decade to provide discrimination between cancerous and healthy samples, demonstrating a promising role in both cancer screening and diagnosis. The aim of this review is to collate available evidence, in order to provide insight into the present status of the application of vibrational biospectroscopy in endometrial cancer diagnosis and screening, and to assess future prospects.
The Role of the Microbiota-Gut-Brain Axis in the Development of Alzheimer’s Disease
Authors: Wiatrak Benita , Balon Katarzyna , Jawień Paulina , Bednarz Dominika , Jęśkowiak Izabela , Szeląg Adam
Published: April 2022

Along with the increase in life expectancy in the populations of developed and developing countries resulting from better access and improved health care, the number of patients with dementia, including Alzheimer’s disease (AD), is growing. The disease was first diagnosed and described at the beginning of the 20th century. However, to this day, there is no effective causal therapy, and symptomatic treatment often improves patients’ quality of life only for a short time. The current pharmacological therapies are based mainly on the oldest hypotheses of the disease—cholinergic (drugs affecting the cholinergic system are available), the hypothesis of amyloid-β aggregation (an anti-amyloid drug was conditionally approved by the FDA in 2020), and one drug is an N-methyl-D-aspartate receptor (NMDAR) antagonist (memantine). Hypotheses about AD pathogenesis focus on the nervous system and the brain. As research progresses, it has become known that AD can be caused by diseases that have been experienced over the course of a lifetime, which could also affect other organs. In this review, we focus on the potential association of AD with the digestive system, primarily the gut microbiota. The role of diet quality in preventing and alleviating Alzheimer’s disease is also discussed. The problem of neuroinflammation, which may be the result of microbiota disorders, is also described. An important aspect of the work is the chapter on the treatment strategies for changing the microbiota, potentially protecting against the disease and alleviating its course in the initial stages.
Sink Strength Promoting Remobilization of Non-Structural Carbohydrates by Activating Sugar Signaling in Rice Stem during Grain Filling
Authors: Jiang Zhengrong , Chen Qiuli , Chen Lin , Liu Dun , Yang Hongyi , Xu Congshan , Hong Jinzhi , Li Jiaqi , Ding Yanfeng , Sakr Soulaiman , Liu Zhenghui , Jiang Yu , Li Ganghua
Published: April 2022

The remobilization of non-structural carbohydrates (NSCs) in the stem is essential for rice grain filling so as to improve grain yield. We conducted a two-year field experiment to deeply investigate their relationship. Two large-panicle rice varieties with similar spikelet size, CJ03 and W1844, were used to conduct two treatments (removing-spikelet group and control group). Compared to CJ03, W1844 had higher 1000-grain weight, especially for the grain growth of inferior spikelets (IS) after removing the spikelet. These results were mainly ascribed to the stronger sink strength of W1844 than that of CJ03 contrasting in the same group. The remobilization efficiency of NSC in the stem decreased significantly after removing the spikelet for both CJ03 and W1844, and the level of sugar signaling in the T6P-SnRK1 pathway was also significantly changed. However, W1844 outperformed CJ03 in terms of the efficiency of carbon reserve remobilization under the same treatments. More precisely, there was a significant difference during the early grain-filling stage in terms of the conversion of sucrose and starch. Interestingly, the sugar signaling of the T6P and SnRK1 pathways also represented an obvious change. Hence, sugar signaling may be promoted by sink strength to remobilize the NSCs of the rice stem during grain filling to further advance crop yield.
Effects of Concurrent Exposure to Chronic Restraint-Induced Stress and Total-Body Iron Ion Radiation on Induction of Kidney Injury in Mice
Authors: Xu Duling , Li Hongyan , Katsube Takanori , Huang Guomin , Liu Jiadi , Wang Bing , Zhang Hong
Published: April 2022

Concurrent exposure to ionizing radiation (IR) and psychological stress (PS) may affect the development of adverse health consequences in scenarios such as space missions, radiotherapy and nuclear accidents. IR can induce DNA damage and cell apoptosis in the kidneys, thus potentially leading to renal fibrosis, which is the ultimate outcome of various chronic progressive nephropathies and the morphological manifestation of a continuous coordinated response after renal injury. However, little is known regarding the effects of concurrent IR exposure and PS on renal damage, particularly renal fibrosis. In this study, using a chronic restraint-induced PS (CRIPS) model, we exposed Trp53-heterozygous mice to total body irradiation with 0.1 or 2 Gy 56Fe ions on the eighth day of 28 consecutive days of a restraint regimen. At the end of the restraint period, the kidneys were collected. The histopathological changes and the degree of kidney fibrosis were assessed with H&E and Masson staining, respectively. Fibronectin (FN) and alpha smooth muscle actin (α-SMA), biomarkers of fibrosis, were detected by immunohistochemistry. Analysis of 8-hydroxy-2 deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, was performed with immunofluorescence, and terminal deoxynucleotidyl transferase-mediated nick end labeling assays were used to detect apoptotic cells. Histopathological observations did not indicate significant structural damage induced by IR or CRIPS + IR. Western blotting revealed that the expression of α-SMA was much higher in the CRIPS + IR groups than the CRIPS groups. However, no differences in the average optical density per area were observed for FN, α-SMA and 8-OHdG between the IR and CRIPS + IR groups. No difference in the induction of apoptosis was observed between the IR and CRIPS + IR groups. These results suggested that exposure to IR (0.1 and 2 Gy 56Fe ions), 28 consecutive days of CRIPS or both did not cause renal fibrosis. Thus, CRIPS did not alter the IR-induced effects on renal damage in Trp53-heterozygous mice in our experimental setup.
The Role of Epigenetics in Primary Biliary Cholangitis
Authors: Gerussi Alessio , Paraboschi Elvezia Maria , Cappadona Claudio , Caime Chiara , Binatti Eleonora , Cristoferi Laura , Asselta Rosanna , Invernizzi Pietro
Published: April 2022

Primary Biliary Cholangitis (PBC) is a rare autoimmune disease of the liver, affecting mostly females. There is evidence that epigenetic changes have a pathogenic role in PBC. Epigenetic modifications are related to methylation of CpG DNA islands, post-translational modifications of histone proteins, and non-coding RNAs. In PBC, there are data showing a dysregulation of all these levels, especially in immune cells. In addition, epigenetics seems to be involved in complex phenomena such as X monosomy or abnormalities in the process of X chromosome inactivation, which have been reported in PBC and appear to influence its sex imbalance and pathogenesis. We review here historical data on epigenetic modifications in PBC, present new data, and discuss possible links among X-chromosome abnormalities at a genetic and epigenetic level, PBC pathogenesis, and PBC sex imbalance.
Novel MicroRNA-Regulated Transcript Networks Are Associated with Chemotherapy Response in Ovarian Cancer
Authors: Topouza Danai G. , Choi Jihoon , Nesdoly Sean , Tarnouskaya Anastasiya , Nicol Christopher J. B. , Duan Qing Ling
Published: April 2022

High-grade serous ovarian cancer (HGSOC) is a highly lethal gynecologic cancer, in part due to resistance to platinum-based chemotherapy reported among 20% of patients. This study aims to generate novel hypotheses of the biological mechanisms underlying chemotherapy resistance, which remain poorly understood. Differential expression analyses of mRNA- and microRNA-sequencing data from HGSOC patients of The Cancer Genome Atlas identified 21 microRNAs associated with angiogenesis and 196 mRNAs enriched for adaptive immunity and translation. Coexpression network analysis identified three microRNA networks associated with chemotherapy response enriched for lipoprotein transport and oncogenic pathways, as well as two mRNA networks enriched for ubiquitination and lipid metabolism. These network modules were replicated in two independent ovarian cancer cohorts. Moreover, integrative analyses of the mRNA/microRNA sequencing and single-nucleotide polymorphisms (SNPs) revealed potential regulation of significant mRNA transcripts by microRNAs and SNPs (expression quantitative trait loci). Thus, we report novel transcriptional networks and biological pathways associated with resistance to platinum-based chemotherapy in HGSOC patients. These results expand our understanding of the effector networks and regulators of chemotherapy response, which will help to improve the management of ovarian cancer.
miR-196b-5p and miR-107 Expression Differentiates Ocular Sebaceous Carcinoma from Squamous Cell Carcinoma of the Conjunctiva
Authors: de Keizer Ronald O. B. , Vriends Anne L. M. , Hötte Gijsbert J. , Paridaens Dion A. , Wiemer Erik A. C. , Verdijk Robert M.
Published: April 2022

An Ocular Sebaceous Carcinoma (OSC) is a rare malignant tumor for which initial clinical and pathological diagnosis is often incorrect. OSCs can mimic Squamous Cell Carcinomas of the Conjunctiva (SCCC). The aim of this study was to find microRNA biomarkers to distinguish OSCs and SCCCs from normal tissue and from each other. Clinical OSC and SCCC case files and the corresponding histopathological slides were collected and reviewed. Micro dissected formalin-fixed paraffin-embedded tumor and control tissues were subjected to semi-high throughput microRNA profiling. MicroRNA expression distinguishes OSCs and SCCCs from corresponding control tissues. Selected differentially expressed miRNAs were validated using single RT-PCR assays. No prognostic miRNAs could be identified that reliably predict SCCC metastasis or OSC recurrence. A comparison between OSCs (n = 14) and SCCCs (n = 18) revealed 38 differentially expressed microRNAs (p < 0.05). Differentially expressed miRNAs were selected for validation in the discovery cohort and an independent validation cohort (OSCs, n = 11; SCCCs, n = 12). At least two miRNAs, miR-196b-5p (p ≤ 0.05) and miR-107 (p ≤ 0.001), displayed a statistically significant differential expression between OSCs and SCCCs with miR-196b-5p upregulated in SCCCs and miR-107 upregulated in OSCs. In the validation cohort, microRNA miR-493-3p also showed significant upregulation in SCCCs when compared to OSCs (p ≤ 0.05). ROC analyses indicated that the combined miR-196b-5p and miR-107 expression levels predicted OSCs with 90.0% sensitivity and 83.3% specificity. In conclusion, the combined testing of miR-196b-5p and miR-107, can be of additional use in routine diagnostics to discriminate OSCs from SCCCs.
Candida albicans Potassium Transporters
Authors: Ruiz-Castilla Francisco J. , Ruiz Pérez Francisco S. , Ramos-Moreno Laura , Ramos José
Published: April 2022

Potassium is basic for life. All living organisms require high amounts of intracellular potassium, which fulfils multiple functions. To reach efficient potassium homeostasis, eukaryotic cells have developed a complex and tightly regulated system of transporters present both in the plasma membrane and in the membranes of internal organelles that allow correct intracellular potassium content and distribution. We review the information available on the pathogenic yeast Candida albicans. While some of the plasma membrane potassium transporters are relatively well known and experimental data about their nature, function or regulation have been published, in the case of most of the transporters present in intracellular membranes, their existence and even function have just been deduced because of their homology with those present in other yeasts, such as Saccharomyces cerevisiae. Finally, we analyse the possible links between pathogenicity and potassium homeostasis. We comment on the possibility of using some of these transporters as tentative targets in the search for new antifungal drugs.
Compound-Specific 14N/15N Analysis of Amino Acid Trimethylsilylated Derivatives from Plant Seed Proteins
Authors: Domergue Jean-Baptiste , Lalande Julie , Abadie Cyril , Tcherkez Guillaume
Published: April 2022

Isotopic analyses of plant samples are now of considerable importance for food certification and plant physiology. In fact, the natural nitrogen isotope composition (δ15N) is extremely useful to examine metabolic pathways of N nutrition involving isotope fractionations. However, δ15N analysis of amino acids is not straightforward and involves specific derivatization procedures to yield volatile derivatives that can be analysed by gas chromatography coupled to isotope ratio mass spectrometry (GC-C-IRMS). Derivatizations other than trimethylsilylation are commonly used since they are believed to be more reliable and accurate. Their major drawback is that they are not associated with metabolite databases allowing identification of derivatives and by-products. Here, we revisit the potential of trimethylsilylated derivatives via concurrent analysis of δ15N and exact mass GC-MS of plant seed protein samples, allowing facile identification of derivatives using a database used for metabolomics. When multiple silylated derivatives of several amino acids are accounted for, there is a good agreement between theoretical and observed N mole fractions, and δ15N values are satisfactory, with little fractionation during derivatization. Overall, this technique may be suitable for compound-specific δ15N analysis, with pros and cons.
Positive and Negative Regulators of Sclerostin Expression
Authors: Iwamoto Rina , Koide Masanori , Udagawa Nobuyuki , Kobayashi Yasuhiro
Published: April 2022

Sclerostin is secreted from osteocytes, binds to the Wnt co-receptor Lrp5/6, and affects the interaction between Wnt ligands and Lrp5/6, which inhibits Wnt/β-catenin signals and suppresses bone formation. Sclerostin plays an important role in the preservation of bone mass by functioning as a negative regulator of bone formation. A sclerostin deficiency causes sclerosteosis, which is characterized by an excess bone mass with enhanced bone formation in humans and mice. The expression of sclerostin is positively and negatively regulated by many factors, which also govern bone metabolism. Positive and negative regulators of sclerostin expression and their effects are introduced and discussed herein based on recent and previous findings, including our research.
Direct Injection of Recombinant AAV-Containing Solution into the Oviductal Lumen of Pregnant Mice Caused In Situ Infection of Both Preimplantation Embryos and Oviductal Epithelium
Authors: Sato Masahiro , Sato-Yamamoto Nami , Wakita Ai , Haraguchi Misako , Shimonishi Manabu , Okuno Hiroyuki
Published: April 2022

Adeno-associated virus (AAV) vector is an efficient viral-based gene delivery tool used with many types of cells and tissues, including neuronal cells and muscles. AAV serotype 6 (AAV-6), one of numerous AAV serotypes, was recently found to efficiently transduce mouse preimplantation embryos. Furthermore, through coupling with a clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system—a modern genome editing technology—AAV-6 has been shown to effectively create a mutation at a target locus, which relies on isolation of zygotes, in vitro viral infection, and transplantation of the infected embryos to recipient females. Unfortunately, this procedure, termed “ex vivo handling of embryos”, requires considerable investment of capital, time, and effort. Direct transduction of preimplantation embryos through the introduction of AAV-6 into the oviductal lumen of pregnant females would be an ideal approach. In this study, we injected various types of recombinant AAV vectors (namely, rAAV-CAG-EGFP-1, -2, -5, and -6, each carrying an enhanced green fluorescent protein [EGFP] cDNA whose expression is under the influence of a cytomegalovirus enhancer + chicken β-actin promoter) into the ampulla region of oviducts in pregnant female mice at Day 0.7 of pregnancy (corresponding to the late 1-cell stage), and EGFP-derived green fluorescence was assessed in the respective morulae. The highest levels of fluorescence were observed in rAAV-CAG-EGFP-6. The oviductal epithelium was distinctly fluorescent. The fluorescence in embryos peaked at the morula stage. Our results indicate that intra-oviductal injection of AAV-6 vectors is the most effective method for transducing zona pellucida-enclosed preimplantation embryos in situ. AAV-6 vectors could be a useful tool in the genetic manipulation of early embryos, as well as oviductal epithelial cells.
Role of Presenilin-1 in Aggressive Human Melanoma
Authors: Sidor Julia , Gillette Megan , Dezi Lindsay Ann , Untiveros Gustavo , Strizzi Luigi
Published: April 2022

Presenilin-1 (PS-1), a component of the gamma (γ)-secretase catalytic complex, has been implicated in Alzheimer’s disease (AD) and in tumorigenesis. Interestingly, AD risk is inversely related to melanoma, suggesting that AD-related factors, such as PS-1, may affect melanomagenesis. PS-1 has been shown to reduce Wnt activity by promoting degradation of beta-catenin (β-catenin), an important Wnt signaling partner. Since Wnt is known to enhance progression of different cancers, including melanoma, we hypothesized that PS-1 could affect Wnt-associated melanoma aggressiveness. Western blot results showed that aggressive melanoma cells expressed significantly lower levels of both PS-1 and phosphorylated-β-catenin (P-β-catenin) than nonaggressive melanoma cells. Immunohistochemistry of human melanoma samples showed significantly reduced staining for PS-1 in advanced stage melanoma compared with early stage melanoma. Furthermore, γ-secretase inhibitor (GSI) treatment of aggressive melanoma cells was followed by significant increases in PS-1 and P-β-catenin levels, suggesting impaired Wnt signaling activity as PS-1 expression increased. Finally, a significant reduction in cell migration was associated with the higher levels of PS-1 and P-β-catenin in the GSI-treated aggressive melanoma cells. We demonstrate for the first time that PS-1 levels can be used to assess melanoma aggressiveness and suggest that by enhancing PS-1 expression, Wnt-dependent melanoma progression may be reduced
Risk Management of Startups of Innovative Products
Authors: Bielialov Taliat
Published: April 2022

The activation of the startup movement is one of the fundamental preconditions for the transition from innovation to a startup ecosystem, the development of which is impossible without special innovation structures that help startups promote innovative products on the market. The purpose of this article is to modernize the process of promoting innovative products on the market in the form of startups, taking into account the trends of the innovative development of the modern economy. The following methods are used in the article: situational and design approaches; methods of simulation and structural−functional modeling—to determine the potential market demand for innovative products and plan the process of their promotion to the market; and BPMN notation—to formalize the integration links between actors in the process of promoting innovative products on the market. As a result, a scheme for assessing the economic efficiency of innovative product market promotion process management was developed that sorts out several indicators at each stage of the innovation process, which allows one to increase the clarity and completeness of the promotion process management while reducing costs. The system of risk management of innovative products has been studied using the example of the promotion of the innovative startup Hideez Technology Ltd on the market in Europe and the USA. This has allowed the company to benefit economically from implementing the results, reaching USD 20,000. In conclusion, the sequence of actions for making management decisions during the implementation of the strategy for innovative product promotion process management was defined.
Theoretical Prediction and Experimental Validation of the Glass-Forming Ability and Magnetic Properties of Fe-Si-B Metallic Glasses from Atomic Structures
Authors: Jiang Yuhang , Jia Shangke , Chen Shunwei , Li Xuelian , Wang Li , Han Xiujun
Published: April 2022

Developing new soft magnetic amorphous alloys with a low cost and high saturation magnetization (Bs) in a simple alloy system has attracted substantial attention for industrialization and commercialization. Herein, the glass-forming ability (GFA), thermodynamic properties, soft magnetic properties, and atomic structures of Fe80+xSi5−xB15 (x = 0–4) amorphous soft magnetic alloys were investigated by ab initio molecular dynamics (AIMD) simulations and experiments. The pair distribution function (PDF), Voronoi polyhedron (VP), coordination number (CN), and chemical short- range order (CSRO) were analyzed based on the AIMD simulations for elucidating the correlations between the atomic structures with the glass-forming ability and magnetic properties. For the studied compositions, the Fe82Si3B15 amorphous alloy was found to exhibit the strongest solute–solute avoidance effect, the longest Fe-Fe bond, a relatively high partial CN for the Fe-Fe pair, and the most pronounced tendency to form more stable clusters. The simulation results indicated that Fe82Si3B15 was the optimum composition balancing the saturation magnetization and the GFA. This prediction was confirmed by experimental observations. The presented work provides a reference for synthesizing new Fe-Si-B magnetic amorphous alloys.
High-Temperature Corrosion of Ni-Cr-Mo Cladding Layers with Different Si Contents in NaCl-KCl-Na2SO4-K2SO4 Mixed Salt Medium
Authors: Chen Shanshan , Liu Zongde , Shen Yue , Liu Simin
Published: April 2022

In this work, Ni-Cr-Mo cladding layers with different Si contents were prepared on Q235 steel using laser-cladding technology, and their corrosion characteristics were investigated in NaCl-KCl-Na2SO4-K2SO4 mixed salt at 550 °C. The corrosion resistance of each cladding layer was tested by weight loss method, and the phase compositions and microstructures of the cladding layers and corrosion products were determined by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The results show that Si contributed to the formation of a dense chromium oxide film on the surface, and the addition of Si can significantly improve the corrosion resistance of the cladding layer at high temperature. At 550 °C, the corrosion rate of the cladding layer with 5 wt.% Si was only 38.2% of that of the cladding layer without Si. After 168 h of high-temperature corrosion, no Cr-rich oxide scale was found in the outermost layer of the Ni-Cr-Mo cladding layer without Si. When Si content was 3 wt.% and 5 wt.%, the Cr-rich oxide scale of the cladding layer was denser than that of the coating with 1 wt.% Si content.
Response of Various Yb3+-Doped Oxide Glasses to Different Radiation Treatments
Authors: Hongisto Mikko , Danto Sylvain , Ghena Marian , Iancu Decebal , Ighigeanu Daniel , Mihai Laura , Jubera Véronique , Petit Laeticia
Published: April 2022

The radiation effects of electrons and protons on the spectroscopic and optical properties of oxide glasses doped with Yb3+ in various glass systems were investigated to understand the impact of the glass composition on the glass photo-response. Changes in the optical and emission properties were seen after the radiation treatment, and the magnitude of the changes depended on the irradiation source and dose. For all the investigated materials, the absorption coefficients in the 200–550 nm range increase post-irradiation, revealing the formation of defects in the glasses during the irradiation. While the spectroscopic properties of the tellurite glass remain unchanged, a small reduction in the Yb3+ emission intensity was seen after irradiating the phosphate, borosilicate, and germanate glasses, indicating that a reduction of Yb3+ to Yb2+ might occur in these glasses during the radiation treatment. The changes in the optical and spectroscopic properties after proton irradiation are small as they are localized at the surface of the glasses due to the shallow penetration depth of the proton in the glass. Even though the doses are small, the electron irradiation produces larger changes in the optical and spectroscopic properties since the electrons penetrate the entire volume of the glasses. All the changes in the optical and spectroscopic properties of the glasses were successfully reversed after a short heat treatment revealing the reversible nature of the photo-response of the investigated glasses.