bluuebunny/crossref_metadata_2025 huggingface dataset:
Lactate-induced MRP1 expression contributes to metabolism-based etoposide resistance in non-small cell lung cancer cells
Authors: Dong Qi , Zhou Chenkang , Ren Haodong , Zhang Zhijian , Cheng Feng , Xiong Zhenkai , Chen Chuantao , Yang Jianke , Gao Jiguang , Zhang Yao , Xu Lei , Fang Jian , Cao Yuxiang , Wei Huijun , Wu Zhihao
Published: October 2020

Background

Metabolic reprogramming contributes significantly to tumor development and is tightly linked to drug resistance. The chemotherapeutic agent etoposide (VP-16) has been used clinically in the treatment of lung cancer but possess different sensitivity and efficacy towards SCLC and NSCLC. Here, we assessed the impact of etoposide on glycolytic metabolism in SCLC and NSCLC cell lines and investigated the role of metabolic rewiring in mediating etoposide resistance.

Methods

glycolytic differences of drug-treated cancer cells were determined by extracellular acidification rate (ECAR), glucose consumption, lactate production and western blot. DNA damage was evaluated by the comet assay and western blot. Chemoresistant cancer cells were analyzed by viability, apoptosis and western blot. Chromatin immunoprecipitation (ChIP) was used for analysis of DNA-protein interaction.

Results

Here we showed that exposure to chemotherapeutic drug etoposide induces an exacerbation of ROS production which activates HIF-1α-mediated the metabolic reprogramming toward increased glycolysis and lactate production in non-small cell lung cancer (NSCLC). We identified lactic acidosis as the key that confers multidrug resistance through upregulation of multidrug resistance-associated protein 1 (MRP1, encoded by ABCC1), a member of ATP-binding cassette (ABC) transporter family. Mechanistically, lactic acid coordinates TGF-β1/Snail and TAZ/AP-1 pathway to induce formation of Snail/TAZ/AP-1 complex at the MRP1/ABCC1 promoter. Induction of MRP1 expression inhibits genotoxic and apoptotic effects of chemotherapeutic drugs by increasing drug efflux. Furthermore, titration of lactic acid with NaHCO3 was sufficient to overcome resistance.

Conclusions

The chemotherapeutic drug etoposide induces the shift toward aerobic glycolysis in the NSCLC rather than SCLC cell lines. The increased lactic acid in extracellular environment plays important role in etoposide resistance through upregulation of MRP expression. These data provide first evidence for the increased lactate production, upon drug treatment, contributes to adaptive resistance in NSCLC and reveal potential vulnerabilities of lactate metabolism and/or pathway suitable for therapeutic targeting.

Graphical abstract
Bacillus coagulans GBI-30, 6086 improves amino acid absorption from milk protein
Authors: Stecker Richard A. , Moon Jessica M. , Russo Travis J. , Ratliff Kayla M. , Mumford Petey W. , Jäger Ralf , Purpura Martin , Kerksick Chad M.
Published: October 2020

Background

Probiotic Bacillus coagulans GBI-30, 6086 (BC30) has been shown to increase protein digestion in an in vitro model of the stomach and small intestine. Once active in the small intestine after germination, BC30 aids the digestion of carbohydrates and proteins. The extent to which BC30 administration may impact protein digestion and amino acid appearance in humans after protein ingestion is currently unknown. This study examined the impact of adding BC30 to a 25-g dose of milk protein concentrate on post-prandial changes in blood amino acids concentrations.

Methods

14 males and 16 females (n = 30, 26.4 ± 6.5 years; 172.3 ± 10.8 cm; 78.2 ± 14.8 kg; 22.6 ± 7.2% fat) completed two supplementation protocols that each spanned two weeks separated by a washout period that lasted three weeks. Participants were instructed to track their dietary intake and ingest a daily 25-g dose of milk protein concentrate with (MPCBC30) or without (MPC) the addition of BC30. Body composition and demographics were assessed upon arrival to the laboratory. Upon ingestion of their final assigned supplemental dose, blood samples were taken at 0 (baseline), 30, 60, 90, 120, 180, and 240 min post-consumption and analyzed for amino acid concentrations.

Results

Arginine (p = 0.03) and Isoleucine (p = 0.05) revealed greater area-under-the curve (AUC) in MPCBC30 group compared to MPC. In addition, Arginine (p = 0.02), Serine (p = 0.01), Ornithine (p = 0.02), Methionine (p = 0.04), Glutamic Acid (p = 0.01), Phenylalanine (p = 0.05), Isoleucine (p = 0.04), Tyrosine (p = 0.02), Essential Amino Acids (p = 0.02), and Total Amino Acids (p < 0.01) all revealed significantly greater concentration maximum (CMax) in MPCBC30 compared to MPC. Finally, time to reach CMax (TMax) was significantly faster for Glutamine (p < 0.01), Citrulline (p < 0.01), Threonine (p = 0.04), Alanine (p = 0.02) in MPCBC30 when compared to MPC. Greater mean differences between groups for AUC and CMax in women when compared to the mean differences in men were found for several amino acids.

Conclusion

In concert with previous in vitro evidence of improved protein digestion and amino acid appearance, these results reveal that adding BC30 to protein sources such as milk protein concentrate can improve AUC, CMax, and faster TMax. Follow-up research should examine differences between gender and explore how aging can impact these outcomes. Retrospectively registered on June 11, 2020 at ClinicalTrials.gov as NCT04427020.
Isolation of antimicrobial peptides from different plant sources: Does a general extraction method exist?
Authors: Barashkova Anna S. , Rogozhin Eugene A.
Published: October 2020

Plants are good sources of biologically active compounds with antimicrobial activity, including polypeptides. Antimicrobial peptides (AMPs) represent one of the main barriers of plant innate immunity to environmental stress factors and are attracting much research interest. There are some extraction methods for isolation of AMPs from plant organs based on the type of extractant and initial fractionation stages. But most methods are directed to obtain some specific structural types of AMPs and do not allow to understand the molecular diversity of AMP inside a whole plant. In this mini-review, we suggest an optimized scheme of AMP isolation from plants followed by obtaining a set of peptides belonging to various structural families. This approach can be performed for large-scale screening of plants to identify some novel or homologous AMPs for fundamental and applied studies.
Serum IgE in the clinical features and disease outcomes of IgG4-related disease: a large retrospective cohort study
Authors: Zhou Jiaxin , Peng Yu , Peng Linyi , Wu Di , Li Jing , Jiang Nan , Li Jieqiong , Lu Hui , Liu Zheng , Luo Xuan , Teng Fei , Fei Yunyun , Zhang Wen , Zhao Yan , Zeng Xiaofeng
Published: October 2020

Objective

The aim of this study was to investigate the role of serum IgE levels in the clinical features and outcomes of IgG4-related disease (IgG4-RD).

Methods

We retrospectively enrolled 459 newly diagnosed IgG4-RD patients with serum IgE examined at baseline from 2012 to 2019 and compared the clinical features between group A (serum IgE level ≤ 60 KU/L) and group B (serum IgE level > 60 KU/L). Subsequently, 312 patients who had been followed up for ≥ 1 year were further selected to evaluate the correlation between serum IgE level and disease outcome.

Results

At baseline, the serum IgE level was positively correlated with the serum IgG4 level (r = 0.1779, P = 0.0001), eosinophil count (r = 0.3004, P < 0.0001), and serum IgG level (r = 0.2189, P < 0.0001) in IgG4-RD patients. Compared with group A, group B had more patients with allergic diseases (P = 0.004), more organ involvement (P = 0.003), and higher IgG4-RD responder index scores (P = 0.002). During follow-up, group A patients had a higher remission induction rate than group B patients (88.4% vs. 73.6%, P = 0.035), while group B patients had a higher relapse rate than group A patients (29.0% vs. 16.2%, P = 0.039). Multivariate analysis found that a serum IgE level > 125 KU/L at baseline was a risk factor for disease relapse (hazard ratio [HR], 1.894 [95% confidence interval (CI) 1.022–3.508]; P = 0.042). Cox regression analysis showed that elevation of the eosinophil count was a risk factor for relapse in both group A and group B patients (HR, 8.504 [95% CI 1.071–42.511]; P = 0.009; and HR, 2.078 [95% CI 1.277–3.380]; P = 0.003, respectively), and the involvement of the lacrimal gland (HR, 1.756 [95% CI 1.108–2.782]; P = 0.017), submandibular gland (HR, 1.654 [95% CI 1.037–2.639]; P = 0.035), and kidney (HR, 3.413 [95% CI 1.076–10.831]; P = 0.037) were also risk factors for relapse in group B patients.

Conclusion

IgG4-RD patients with high serum IgE levels at baseline were more likely to have higher disease activity, and baseline high IgE levels were associated with disease relapse.
Effects of maximal strength training on bone mineral density in people living with HIV and receiving anti-retroviral therapy: a pilot study
Authors: Chisati Enock M. , Constantinou Demitri , Lampiao Fanuel
Published: October 2020

Background

Anti-retroviral therapy (ART) is associated with low bone mineral density (BMD) among people living with HIV (PLWHIV). Although physical activity is recommended for improving bone health in patients with reduced BMD, data on effects of strength exercises on low BMD among PLWHIV is scarce. This study therefore aimed to determine the effects of a 12 weeks maximal strength training (MST) on BMD among PLWHIV in Blantyre, Malawi.

Methods

Twenty-six PLWHIV with reduced BMD were randomised into a training group (TG, n = 15) and control group (CG, n = 11). The TG underwent 12 weeks of MST consisting of 4 sets of 3 to 5 repetitions at 85–90% of one repetition maximum (1RM) 3 times per week. The CG was advised to maintain their usual lifestyle. Measurements of BMD using dual-energy X-ray absorptiometry, 1RM using a squat machine, heart rate using a heart rate monitor, weight, height and body mass index were obtained before and after the intervention in the TG and CG. Descriptive statistics and student’s t - tests were used to analyse data.

Results

The study was conducted for 12 weeks. Data of 24 participants [14 (TG) and 10 (CG)] were analysed. At base line, there were no significant differences in age (p = 0.34), height (p = 0.91), weight (p = 0.43) and body mass index (p = 0.34) between participants in the TG and the CG. After the intervention, there were significant improvements in lumbar BMD (p < 0.001) and resting heart rate (p = 0.03) in the TG compared to the CG. There were significant improvements in muscle strength (1 RM) in both the TG (p < 0.001) and the CG (p = 0.01).

Conclusions

MST improves lumbar BMD and strength in PLWHIV receiving ART in Blantyre, Malawi. MST with a shorter exercise duration of 12 weeks seem to have the potential in treating reduced BMD in PLWHIV.

Trial registration

PACTR201712002889203. Registered with the Pan African Clinical Trial Registry on 22nd December, 2017 at www. pactr.org
Identification of AAV serotypes for lung gene therapy in human embryonic stem cell-derived lung organoids
Authors: Meyer-Berg Helena , Zhou Yang Lucia , Pilar de Lucas María , Zambrano Alberto , Hyde Stephen C. , Gill Deborah R.
Published: October 2020

Gene therapy is being investigated for a range of serious lung diseases, such as cystic fibrosis and emphysema. Recombinant adeno-associated virus (rAAV) is a well-established, safe, viral vector for gene delivery with multiple naturally occurring and artificial serotypes available displaying alternate cell, tissue, and species-specific tropisms. Efficient AAV serotypes for the transduction of the conducting airways have been identified for several species; however, efficient serotypes for human lung parenchyma have not yet been identified. Here, we screened the ability of multiple AAV serotypes to transduce lung bud organoids (LBOs)—a model of human lung parenchyma generated from human embryonic stem cells. Microinjection of LBOs allowed us to model transduction from the luminal surface, similar to dosing via vector inhalation. We identified the naturally occurring rAAV2 and rAAV6 serotypes, along with synthetic rAAV6 variants, as having tropism for the human lung parenchyma. Positive staining of LBOs for surfactant proteins B and C confirmed distal lung identity and suggested the suitability of these vectors for the transduction of alveolar type II cells. Our findings establish LBOs as a new model for pulmonary gene therapy and stress the relevance of LBOs as a viral infection model of the lung parenchyma as relevant in SARS-CoV-2 research.
Further results on existence of positive solutions of generalized fractional boundary value problems
Authors: Afshari Hojjat , Abdo Mohammed S. , Alzabut Jehad
Published: October 2020

This paper studies two classes of boundary value problems within the generalized Caputo fractional operators. By applying the fixed point result ofα-ϕ-Geraghty contractive type mappings, we derive new results on the existence and uniqueness of the proposed problems. Illustrative examples are constructed to demonstrate the advantage of our results. The theorems reported not only provide a new approach but also generalize existing results in the literature.
Associations between adolescents’ physical activity behavior and their perceptions of parental, peer and teacher support
Authors: Pluta Beata , Korcz Agata , Krzysztoszek Jana , Bronikowski Michał , Bronikowska Małgorzata
Published: October 2020

Background

The aim of this study was to examine adolescents’ perceptions of parental, teacher, and peer support for physical activity, and to examine the associations between these perceptions and physical activity behavior.

Methods

The study included 902 secondary school students, who completed the Short Scale of Youth’s Social Support Assessment (SSYSS). The level of physical activity – more specifically, moderate to vigorous physical activity – was measured using a Physical Activity Screening Measure. The associations were examined by a five-step hierarchical regression. Body mass index (BMI) was defined using the LMS method, which summarizes the distribution of BMI by age and gender in terms of three curves, L (lambda), M (mu), and S (sigma), and was based on a nationally representative sample of Polish children and adolescents.

Results

The study indicated a positive correlation between MVPA (moderate to vigorous physical activity) and three sources of social support; however, in the regression model, this explained only part of the variance. In the hierarchical multiple regression analysis, MVPA level was predicted by five variables involvement in sports training, teachers support, parents support, gender and BMI. The direct effects for teachers and parents support were similar. This demonstrates that both teachers’ and parents’ social support exert influence on adolescent MVPA.

Conclusions

The findings from this research suggest that school-based interventions for adolescents should specifically take into consideration family, teachers, and peers as important sources of social support for general physical activity promotion that aims to increase its levels.
Long interspersed nuclear element 1 hypomethylation has novel prognostic value and potential utility in liquid biopsy for oral cavity cancer
Authors: Misawa Kiyoshi , Yamada Satoshi , Mima Masato , Nakagawa Takuya , Kurokawa Tomoya , Imai Atsushi , Mochizuki Daiki , Shinmura Daichi , Yamada Taiki , Kita Junya , Ishikawa Ryuji , Yamaguchi Yuki , Misawa Yuki , Kanazawa Takeharu , Kawasaki Hideya , Mineta Hiroyuki
Published: October 2020

Background

New biomarkers are urgently needed to improve personalized treatment approaches for head and neck squamous cell carcinoma (HNSCC). Global DNA hypomethylation has wide-ranging functions in multistep carcinogenesis, and the hypomethylation of long interspersed nucleotide element-1 (LINE-1) is related to increased retrotransposon activity and induced genome instability. However, little information is available regarding LINE-1 hypomethylation and its prognostic implications in HNSCC.

Methods

In this study, we analyzed LINE-1 hypomethylation levels in a well-characterized dataset of 317 primary HNSCC tissues and 225 matched pairs of normal mucosa tissues, along with five oral cavity cancer (OCC) circulating tumor DNA (ctDNA) samples using quantitative real-time methylation and unmethylation PCR. The analysis was performed according to various clinical characteristics and prognostic implications.

Results

The results demonstrated that LINE-1 hypomethylation levels were significantly higher in the HNSCC tissues than in corresponding normal tissues from the same individuals (P < 0.001). Univariate analysis revealed that high levels of LINE-1 hypomethylation were correlated with poor disease-free survival (DFS; log-rank test, P = 0.038), whereas multivariate analysis demonstrated that they were significant independent prognostic factor for DFS (hazard ratio: 2.10, 95% confidence interval: 1.02–4.36; P = 0.045). Moreover, samples with high LINE-1 hypomethylation levels exhibited the greatest decrease in 5-hydroxymethylcytosine (5-hmC) levels and increase in tumor-suppressor gene methylation index (P = 0.006 and P < 0.001, respectively). Further, ctDNA studies also showed that LINE-1 hypomethylation had high predictive ability in OCC.

Conclusions

LINE-1 hypomethylation is associated with a higher risk of early OCC relapse, and is hence, a potential predictive biomarker for OCC. Furthermore, 5-hmC levels also exhibited predictive potential in OCC, based on their inverse correlation with LINE-1 hypomethylation levels. LINE-1 hypomethylation analysis, therefore, has applications in determining patient prognosis and real-time surveillance of disease recurrence, and could serve as an alternative method for OCC screening.
Anatomy of active volcanic edifice at the Kusatsu–Shirane volcano, Japan, by magnetotellurics: hydrothermal implications for volcanic unrests
Authors: Tseng Kuo Hsuan , Ogawa Yasuo , Nurhasan  , Tank Sabri Bülent , Ujihara Naoto , Honkura Yoshimori , Terada Akihiko , Usui Yoshiya , Kanda Wataru
Published: October 2020

We aimed to perform three-dimensional imaging of the underlying geothermal system to a depth of 2 km using magnetotellurics (MT) at around the Yugama crater, the Kusatsu–Shirane Volcano, Japan, which is known to have frequent phreatic eruptions. We deployed 91 MT sites focusing around the peak area of 2 km × 2 km with typical spacings of 200 m. The full tensor impedances and the magnetic transfer functions were inverted, using an unstructured tetrahedral finite element code to include the topographic effect. The final model showed (1) low-permeability bell-shaped clay cap (C1) as the near-surface conductor, (2) brine reservoir as a deep conductor (C3) at a depth of 1.5 km from the surface, and (3) a vertical conductor (C2) connecting the deep conductor to the clay cap which implies an established fluid path. The columnar high-seismicity distribution to the east of the C2 conductor implies that the flushed vapor and magmatic gas was released from the brine reservoir by breaking the silica cap at the brittle–ductile transition. The past magnetization/demagnetization sources and the inflation source of the 2014 unrest are located just below the clay cap, consistent with the clay capped geothermal model underlain by brine reservoir. The resistivity model showed the architecture of the magmatic–hydrothermal system, which can explain the episodic volcanic unrest.
Neuromuscular blocking agents in acute respiratory distress syndrome: updated systematic review and meta-analysis of randomized trials
Authors: Tarazan Nehal , Alshehri Moayad , Sharif Sameer , Al Duhailib Zainab , Møller Morten Hylander , Belley-Cote Emilie , Alshahrani Mohammed , Centofanti John , McIntyre Lauralyn , Baw Bandar , Meade Maureen , Alhazzani Waleed ,   for the GUIDE Group
Published: October 2020

Purpose

Existing clinical practice guidelines support the use of neuromuscular blocking agents (NMBA) in acute respiratory distress syndrome (ARDS); however, a recent large randomized clinical trial (RCT) has questioned this practice. Therefore, we updated a previous systematic review to determine the efficacy and safety of NMBAs in ARDS.

Methods

We searched MEDLINE, EMBASE (October 2012 to July 2019), the Cochrane (Central) database, and clinical trial registries (ClinicalTrials.gov, ISRCTN Register, and WHO ICTRP) for RCTs comparing the effects of NMBA as a continuous infusion versus placebo or no NMBA infusion (but allowing intermittent NMBA boluses) on patient-important outcomes for adults with ARDS. Two independent reviewers assessed the methodologic quality of the primary studies and abstracted data.

Results

Seven RCTs, including four new RCTs, met eligibility criteria for this review. These trials enrolled 1598 patients with moderate to severe ARDS at centers in the USA, France, and China. All trials assessed short-term continuous infusions of cisatracurium or vecuronium. The pooled estimate for mortality outcomes showed significant statistical heterogeneity, which was only explained by a subgroup analysis by depth of sedation in the control arm. A continuous NMBA infusion did not improve mortality when compared to a light sedation strategy with no NMBA infusion (relative risk [RR] 0.99; 95% CI 0.86–1.15; moderate certainty; P = 0.93). On the other hand, continuous NMBA infusion reduced mortality when compared to deep sedation with as needed NMBA boluses (RR 0.71; 95% CI 0.57–0.89; low certainty; P = 0.003). Continuous NMBA infusion reduced the rate of barotrauma (RR 0.55; 95% CI 0.35–0.85, moderate certainty; P = 0.008) across eligible trials, but the effect on ventilator-free days, duration of mechanical ventilation, and ICU-acquired weakness was uncertain.

Conclusions

Inconsistency in study methods and findings precluded the pooling of all trials for mortality. In a pre-planned sensitivity analysis, the impact of NMBA infusion on mortality depends on the strategy used in the control arm, showing reduced mortality when compared to deep sedation, but no effect on mortality when compared to lighter sedation. In both situations, a continuous NMBA infusion may reduce the risk of barotrauma, but the effects on other patient-important outcomes remain unclear. Future research, including an individual patient data meta-analysis, could help clarify some of the observed findings in this updated systematic review.
The dangers of mass drug administration of albendazole in Nepal, a Neurocysticercosis-endemic region
Authors: Nepal Gaurav , Kharel Ghanshyam , Shing Yow Ka , Ojha Rajeev , Jamarkattel Sujan , Yadav Jayant Kumar , Vyas Himani , Poudyal Dhiraj , Sah Ranjit
Published: October 2020

The majority of cases of Neurocysticercosis (NCC) are asymptomatic. Injudicious use of antihelmintics like albendazole (ALB) can cause cyst degeneration and perilesional inflammation, thus rendering asymptomatic individuals symptomatic with seizures, headache, vascular events, or cerebral edema. Mass drug administration (MDA) using ALB is a very common practice in developing countries like Nepal to contain transmission of soil-transmitted helminths (STH) and lymphatic filariasis (LF). Although the benefits of ALB-based MDA in the general population cannot be undermined, there can be severe consequences in certain groups, especially those with latent NCC. In this commentary, we discuss the effect it may have on such patients, and suggest potential solutions.
Discontinuation of implants use and associated factors among women attending health facility clinics in Hawassa City, Southern Ethiopia, 2019; cross sectional study
Authors: Amare Abebe Belay , Reda Terefe Mulu
Published: October 2020

Background

Despite improving the availability and use of Implants, discontinuation is becoming a public health concern. A significant proportion of women discontinuing the service before its due date, which is of concern in the health system and its consequence may lead to a program failure. This might have also social and economic consequences for users. Only 8% of married women in Ethiopia use implants. Apart from its low utilization, premature removal is common for unknown reasons. However, there is paucity of information on discontinuation of implants use and associated factors in the study area.

Objective

The study was aimed to assess discontinuation of implants use and associated factors among women attending health facility clinics in Hawassa city, southern Ethiopia, from March, 01-April, 01/2019.

Methods

Facility based cross sectional study design was used. Out of 16 health facilities, 9 of them were selected for this study using simple random sampling. Total sample size of this study was determined to be 351. Data were collected from study subjects using pretested, structured questionnaire through a face-to-face interview. Data was analyzed using descriptive statistics and logistic regression. The result is presented using the Crude Odds ratio as well as Adjusted Odds Ratio with the corresponding 95% confidence level.

Result

Out of 351 study participants, the overall proportion of implants discontinuation was 49.3%(95% CI: 44.2–55.0). Lack of counseling about side effects (AOR = 2.394; 95% CI: 1.422–4.030), developing side effects (AOR = 6.325; 95% CI: 3.719–10.757) and lack of post insertion follow-up (AOR = 2.241; 95% CI: 1.186–4.234) the major factors associated with discontinuation of Implants.

Conclusion and recommendation

In this study, the overall proportion of discontinuation of Implants among women who were using Implants was high. Health professionals could give pre-insertion counseling about side effects and post insertion dates for follow-up to improve of utilization of implants.
The development of body and organ shape
Authors: Cobham Ansa E. , Mirth Christen K.
Published: October 2020

Background

Organisms show an incredibly diverse array of body and organ shapes that are both unique to their taxon and important for adapting to their environment. Achieving these specific shapes involves coordinating the many processes that transform single cells into complex organs, and regulating their growth so that they can function within a fully-formed body.

Main text

Conceptually, body and organ shape can be separated in two categories, although in practice these categories need not be mutually exclusive. Body shape results from the extent to which organs, or parts of organs, grow relative to each other. The patterns of relative organ size are characterized using allometry. Organ shape, on the other hand, is defined as the geometric features of an organ’s component parts excluding its size. Characterization of organ shape is frequently described by the relative position of homologous features, known as landmarks, distributed throughout the organ. These descriptions fall into the domain of geometric morphometrics.

Conclusion

In this review, we discuss the methods of characterizing body and organ shape, the developmental programs thought to underlie each, highlight when and how the mechanisms regulating body and organ shape might overlap, and provide our perspective on future avenues of research.
The effect of individual factors on user behaviour and the moderating role of trust: an empirical investigation of consumers’ acceptance of electronic banking in the Kurdistan Region of Iraq
Authors: M. Hamakhan Yadgar Taha
Published: October 2020

The popularity of self-service technologies, particularly in the banking industry, more precisely with electronic banking channel services, has undergone a major change as individuals' lifestyles develop. This change has affected individuals’ decisions about accepting any new Information Technology, and Information Communications Technology services that are electronically mediated, for example, E-Banking channel services. This study investigates the effect of Individual Factors on User Behaviour, and the moderating role of Trust in the relationship between Individual Factors, and User Behaviour based on the Unified Theory of Acceptance and Use of Technology. This research proposes a model, with a second-order components research framework. It improves current explanations of the acceptance of electronic banking channel services. Furthermore, this study highlights the role of trust on the acceptance of electronic banking channel services, which is the most crucial consideration in customers’ decisions to accept electronic banking channels services. Thus, trust is the spine of the system in the Kurdistan Region of Iraq. Data were collected using an online questionnaire that received 476 valid responses from academic staff who work at the University of Sulaimani. The model tested data using the Partial Least Squares-Structural Equation Modelling approach. The results show that Individual Factors have a positive effect on User Behaviour. Besides, results show that trust moderates the relationship between Individual Factors and User Behaviour.
UV irradiation-promoting effect on the antibacterial activity of cyanobacterial extracts against plant pathogens: a first record
Authors: Aldayel Munirah , El Semary Nermin
Published: October 2020

Background

Cyanobacteria possess a wide array of bioactive compounds including those with antimicrobial activities. The target was to investigate the UV effect on antimicrobial activity of cyanobacterial extracts. Several cyanobacterial strains were isolated from Eastern region of KSA as well as three plant pathogenic bacterial strains. Four cyanobacterial strains were used. Two strains were isolated from Al Uquair region, Arabian Gulf, and identified as Synechococcus sp. and Oscillatoria sp. The two other strains were collected from brackish stream of underground water and were characterized as Synechocystis sp. and Phormidium sp. The antimicrobial bioassay was then performed using cyanobacterial aqueous extracts. The antimicrobial effect was estimated by measuring the inhibition zone compared to that of control. The extract was divided into 2 parts: part was not exposed to UV and the other was exposed to UV-B irradiation for 10 min. The antimicrobial bioassay was performed for both parts of the extract, using plant pathogenic bacteria, namely, Erwinia sp., Pseudomonas sp., and Bacillus sp.

Main body

The antimicrobial profile was examined and results showed that the extracts showed non-antimicrobial effect before UV irradiation, and antimicrobial effect after UV exposure. Also, those that were active against pathogenic bacteria were more active after UV exposure. This is mostly attributed to a high optical energy of UV irradiation that subsequently had a significant impact on the electron transitions in the molecules of the extract rendering some of them more effective in their antibacterial action.

Conclusion

This short communication was the first report where the UV can alter the antimicrobial profile of cyanobacterial extracts. This is a novel approach in enhancing antibacterial activity. Future molecular investigations will be conducted to further characterize the isolate whose extract showed the highest response to UV treatment.
Nutritional quality of formulated complementary diet from defatted almond seed, yellow maize and quality protein maize flours
Authors: Adesanmi Ade Raymond , Malomo Sunday Abiodun , Fagbemi Tayo Nathaniel
Published: October 2020

Traditional complementary foods are mainly starchy foods with limiting nutrient quality and can be fortified using protein rich crops like almond seed. This research thus aimed at investigating the nutritional quality of the formulated complementary diet from locally available almond seeds (Prunus amygdalus), high quality protein (QPM) and yellow maize after blending into flours. The proximate and amino acid compositions, in vitro protein qualities and functional properties of the blended flours were determined using standard methods. The in vivo studies involved feeding the weanling Wister albino rats with blended flours and commercial Cerelac (control), followed by hematological and histopathological determinations, while sensory attributes were evaluated by the semi-trained panelists. The protein contents of the flour blends (24–28%) were significantly (p < 0.05) better with adequate indispensable amino acids and improved functionalities than commercial cerelac (23%). Comparatively, the dried germinated QPM (DGQPM) has significant (p < 0.05) higher biological value (~ 37%) than fermented high QPM (FHQPM) (~ 30%), thereby indicating that the germination process improved protein quality of the diets. Besides, the in vivo data showed a positive effect of germination process as the rats fed with DGQPM has low white blood cells (30 × 102) compared to FHQPM (42 × 102) and cerelac (51 × 102). However, the fermentation process improved the packed cell volume of rats fed with FHQPM (49%) when compared to DGQPM and cerelac (47%). The formulated diets have no negative effects on the protein content (45.19–51.88 mg N/g) and weight (0.25–1.36 g) of the internal organs (liver, kidney and tissue) of the animals when compared to cerelac (53.72–55.04 mg N/g; 0.25–1.98 g), respectively. The panelists generally accepted all the formulated diets, hence encouraging their utilization in the global preparation of complimentary foods for young children to meet their nutritional needs and adding value to the locally produced underutilized almond seeds.
PET/CT and contrast-enhanced CT: making a difference in assessment and staging of patients with lymphoma
Authors: Zytoon Ashraf Anas , Mohamed Hala Hafez , Mostafa Basma Adel Abd Elaziz , Houseni Mohamed Mohamed
Published: October 2020

Background

The aim of this study is to evaluate the diagnostic performance of contrast-enhanced computed tomography (CECT) and 2-[Fluorine-18] fluoro-2-deoxy-d-glucose positron emission tomography combined to computed tomography (18 F-FDG PET/CT) in assessment of lymphoma.

Methods

Hundred patients, pathologically proven as lymphoma, were evaluated by CECT and 18F-FDG PET/CT for initial assessment and staging of the disease. The number of lesions and the disease stage detected by each modality was calculated and further analyzed to be compared.

Results

18F-FDG PET/CT diagnosed a total number of 545 lymphoma involved regions with sensitivity 96.6%, specificity 98.8%, and accuracy 99% that was higher than CECT which diagnosed a total number of 439 lymphomatous regions with sensitivity 87.5%, specificity 85.7%, and accuracy 88%. Discordant staging by both modalities was found in 23% of the patients. Lymphoma was upstaged by PET/CT in 17% of the patients; with major changes in 12% of them and downstaged in 6% of the patients.

Conclusion

18F-FDG PET/CT scan has a better diagnostic performance, represented by sensitivity, specificity, and accuracy, than CECT scan in the initial assessment of lymphoma regarding its nodal and extra-nodal lesions that could lead to alteration of disease staging which in turn markedly affecting the decision of treatment regimens.
Heterotopic pregnancy: a case report
Authors: Ali Tamer , Tawab Mohamed A. , ElHariri Mona Abdel Ghaffar , Ayad Alaa A.
Published: October 2020

Background

Heterotopic pregnancy describes the occurrence of two pregnancies in different implantation sites simultaneously, which is rare, yet it is a challenge to diagnose such a problem due to complex clinical and laboratory findings. In the current study, we present a case of first trimester heterotopic pregnancy diagnosed by ultrasound (US) and magnetic resonance imaging (MRI) and was managed successfully.

Case presentation

A 22-year-old primigravida lady with spontaneous pregnancy was presented by increasing lower abdominal pain for 5 days with brownish vaginal discharge, nausea, and vomiting episodes. Trans-abdominal and endovaginal ultrasound was performed and revealed a viable intrauterine pregnancy of 8 weeks and 1 day, associated with a heterogeneous complex right adnexal mass. MR imaging revealed a right adnexal mass intimately anterior to the normal right ovary. Laparascopy was done; it revealed a distended right fallopian tube with pregnancy while the right ovary was not seen (impeded in the pouch of Douglas), and right salpingectomy was done. The specimen was sent for histopathology. The patient tolerated the procedure well and was then taken to the recovery room in stable condition. The histopathological report confirmed the diagnosis of ectopic pregnancy.

Conclusion

However, heterotopic is a rare condition, any pregnant woman presenting with alarming abdominal pain and adnexal abnormality; heterotopic pregnancy should be among the differential diagnosis possibilities. The patient should be thoroughly investigated using ultrasound and MRI if needed, to exclude this rare diagnosis and allow on-time proper management.
Development of a tool for identifying and addressing prioritised determinants of quality improvement initiatives led by healthcare professionals: a mixed-methods study
Authors: van Tuijl Anne A. C. , Wollersheim Hub C. , Fluit Cornelia R. M. G. , van Gurp Petra J. , Calsbeek Hiske
Published: October 2020

Background

Several frameworks have been developed to identify essential determinants for healthcare improvement. These frameworks aim to be comprehensive, leading to the creation of long lists of determinants that are not prioritised based on being experienced as most important. Furthermore, most existing frameworks do not describe the methods or actions used to identify and address the determinants, limiting their practical value. The aim of this study is to describe the development of a tool with prioritised facilitators and barriers supplemented with methods to identify and address each determinant. The tool can be used by those performing quality improvement initiatives in healthcare practice.

Methods

A mixed-methods study design was used to develop the tool. First, an online survey was used to ask healthcare professionals about the determinants they experienced as most facilitating and most hindering during the performance of their quality improvement initiative. A priority score was calculated for every named determinant, and those with a priority score ≥ 20 were incorporated into the tool. Semi-structured interviews with implementation experts were performed to gain insight on how to analyse and address the determinants in our tool.

Results

The 25 healthcare professionals in this study experienced 64 facilitators and 66 barriers when performing their improvement initiatives. Of these, 12 facilitators and nine barriers were incorporated into the tool. Sufficient support from management of the department was identified as the most important facilitator, while having limited time to perform the initiative was considered the most important barrier. The interviews with 16 experts in implementation science led to various inputs for identifying and addressing each determinant. Important themes included maintaining adequate communication with stakeholders, keeping the initiative at a manageable size, learning by doing and being able to influence determinants.

Conclusions

This paper describes the development of a tool with prioritised determinants for performing quality improvement initiatives with suggestions for analysing and addressing these determinants. The tool is developed for those engaged in quality improvement initiatives in practice, so in this way it helps in bridging the research to practice gap of determinants frameworks. More research is needed to validate and develop the tool further.
The Non-hormonal Male Contraceptive Adjudin Exerts its Effects via MAPs and Signaling Proteins mTORC1/rpS6 and FAK-Y407
Authors: Wang Lingling , Yan Ming , Li Huitao , Wu Siwen , Ge Renshan , Wong Chris K C , Silvestrini Bruno , Sun Fei , Cheng C Yan
Published: October 2020

Adjudin, 1-(2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide (formerly called AF-2364), is a nonhormonal male contraceptive, since it effectively induces reversible male infertility without perturbing the serum concentrations of follicle stimulating hormone (FSH), testosterone, and inhibin B based on studies in rats and rabbits. Adjudin was shown to exert its effects preferentially by perturbing the testis-specific actin-rich adherens junction (AJ) at the Sertoli–spermatid interface known as apical ectoplasmic specialization (apical ES), thereby effectively inducing spermatid exfoliation. Adjudin did not perturb germ cell development nor germ cell function. Also, it had no effects on Sertoli cell–cell AJ called basal ectoplasmic specialization (basal ES), which, together with tight junction constitute the blood-testis barrier (BTB), unless an acute dose of adjudin was used. Adjudin also did not perturb the population of spermatogonial stem cells nor Sertoli cells in the testis. However, the downstream signaling protein(s) utilized by adjudin to induce transient male infertility remains unexplored. Herein, using adult rats treated with adjudin and monitored changes in the phenotypes across the seminiferous epithelium between 6 and 96 h in parallel with the steady-state protein levels of an array of signaling and cytoskeletal regulatory proteins, recently shown to be involved in apical ES, basal ES and BTB function. It was shown that adjudin exerts its contraceptive effects through changes in microtubule associated proteins (MAPs) and signaling proteins mTORC1/rpS6 and p-FAK-Y407. These findings are important to not only study adjudin-mediated male infertility but also the biology of spermatogenesis.
Congenital Adrenal Hyperplasia Causing Poor Response to Androgen Deprivation Therapy in Prostate Cancer
Authors: Kinaan Mustafa , Hamidi Oksana , Yau Hanford , Courtney Kevin D , Eraslan Akin , Simon Kenneth
Published: October 2020

Androgen deprivation therapy (ADT) is recommended for the treatment of advanced prostate cancer. Inadequate suppression of testosterone while on ADT poses a clinical challenge and requires evaluation of multiple potential causes, including adrenal virilizing disorders. We present 2 cases of elderly patients with prostate cancer who had undiagnosed congenital adrenal hyperplasia (CAH) driving persistent testosterone elevation during ADT. The first patient is a 73-year-old man who underwent radical prostatectomy on initial diagnosis and was later started on ADT with leuprolide following tumor recurrence. He had a testosterone level of 294.4 ng/dL and prostate-specific antigen (PSA) level of 17.7 ng/mL despite leuprolide use. Additional workup revealed adrenal nodular hyperplasia, elevated 17-hydroxyprogesterone (19 910 ng/dL) and dehydroepiandrosterone sulfate (378 mcg/dL), and 2 mutations of the CYP21A2 gene consistent with simple virilizing CAH. The second patient is an 82-year-old man who received stereotactic radiation therapy at time of diagnosis. He had insufficient suppression of testosterone with evidence of metastatic disease despite treatment with leuprolide and subsequently degarelix. Laboratory workup revealed elevated 17-hydroxyprogesterone (4910 ng/dL) and dehydroepiandrosterone sulfate (312 mcg/dL). Based on clinical, radiographic and biochemical findings, the patient was diagnosed with nonclassic CAH. The first patient initiated glucocorticoid therapy, and the second patient was treated with the CYP17 inhibitor abiraterone in combination with glucocorticoids. Both patients experienced rapid decline in testosterone and PSA levels. Inadequate testosterone suppression during ADT should trigger evaluation for causes of persistent hyperandrogenemia. CAH can lead to hyperandrogenemia and pose challenges when treating patients with prostate cancer.
Shifting away from the business-as-usual approach to research conferences
Authors: Counsell Chelsie W. W. , Elmer Franziska , Lang Judith C.
Published: October 2020

To combat the climate crisis, we need rapid, unprecedented social change. Scientists can play a lead role by signaling to society that we recognize the critical importance of redesigning our business-as-usual approach to research conferences. Traditional research conferences have high CO2 emissions as well as significant financial and travel time costs for participants. Using available technology, early career scientists Chelsie Counsell and Franziska Elmer created a global, virtual, coral reef research conference with live talks, recorded contributions, and networking events. Funding from The Company of Biologists allowed this event to be free, supporting attendance of 2700 subscribers and content contributions from 165 participants from diverse backgrounds and career stages. We provide metrics on content viewership and participation in networking activities, note the success of incorporating regionally focused sub-events, and discuss the emergence of a collaborative research project. We highlight the broad accessibility of virtual conferences as well as their increased flexibility in programming, health benefits, and cost savings. Our approach to organizing and hosting a global, low-carbon emission research conference is documented. Finally, we propose a hybrid approach to future conferences with virtually connected remote (sub-regional or local) hubs.
Insulin/IGF signaling and TORC1 promote vitellogenesis via inducing juvenile hormone biosynthesis in the American cockroach
Authors: Zhu Shiming , Liu Fangfang , Zeng Huanchao , Li Na , Ren Chonghua , Su Yunlin , Zhou Shutang , Wang Guirong , Palli Subba Reddy , Wang Jian , Qin Yiru , Li Sheng
Published: October 2020

Vitellogenesis, including vitellogenin (Vg) production in the fat body and Vg uptake by maturing oocytes, is of great importance for the successful reproduction of adult females. The endocrinal and nutritional regulation of vitellogenesis differs distinctly in insects. Here, the complex crosstalk between juvenile hormone (JH) and the two nutrient sensors insulin/IGF signaling (IIS) and target of rapamycin complex1 (TORC1), was investigated to elucidate the molecular mechanisms of vitellogenesis regulation in the American cockroach, Periplaneta americana. Our data showed that a block of JH biosynthesis or JH action arrested vitellogenesis, in part by inhibiting the expression of doublesex (Dsx), a key transcription factor gene involved in the sex determination cascade. Depletion of IIS or TORC1 blocked both JH biosynthesis and vitellogenesis. Importantly, the JH analog methoprene, but not bovine insulin (to restore IIS) and amino acids (to restore TORC1 activity), restored vitellogenesis in the neck-ligated (IIS-, TORC1- and JH-deficient) and rapamycin-treated (TORC1- and JH-deficient) cockroaches. Combining classic physiology with modern molecular techniques, we have demonstrated that IIS and TORC1 promote vitellogenesis, mainly via inducing JH biosynthesis in the American cockroach.
Mitochondrial dysfunction triggers a catabolic response in chondrocytes via ROS-mediated activation of the JNK/AP1 pathway
Authors: Ansari Mohammad Y. , Ahmad Nashrah , Voleti Sriharsha , Wase Saima J. , Novak Kimberly , Haqqi Tariq M.
Published: October 2020

Mitochondrial function is impaired in osteoarthritis (OA) but its impact on cartilage catabolism is not fully understood. Here, we investigated the molecular mechanism of mitochondrial dysfunction-induced activation of the catabolic response in chondrocytes. Using cartilage slices from normal and OA cartilage, we showed that mitochondrial membrane potential was lower in OA cartilage, and that this was associated with increased production of mitochondrial superoxide and catabolic genes [interleukin 6 (IL-6), COX-2 (also known as PTGS2), MMP-3, -9, -13 and ADAMTS5]. Pharmacological induction of mitochondrial dysfunction in chondrocytes and cartilage explants using carbonyl cyanide 3-chlorophenylhydrazone increased mitochondrial superoxide production and the expression of IL-6, COX-2, MMP-3, -9, -13 and ADAMTS5, and cartilage matrix degradation. Mitochondrial dysfunction-induced expression of catabolic genes was dependent on the JNK (herein referring to the JNK family)/activator protein 1 (AP1) pathway but not the NFκB pathway. Scavenging of mitochondrial superoxide with MitoTEMPO, or pharmacological inhibition of JNK or cFos and cJun, blocked the mitochondrial dysfunction-induced expression of the catabolic genes in chondrocytes. We demonstrate here that mitochondrial dysfunction contributes to OA pathogenesis via JNK/AP1-mediated expression of catabolic genes. Our data shows that AP1 could be used as a therapeutic target for OA management.

This article has an associated First Person interview with the first author of the paper.