bluuebunny/crossref_metadata_2025 huggingface dataset:
The signaling role of extracellular ATP in co-culture of Shiraia sp. S9 and Pseudomonas fulva SB1 for enhancing hypocrellin A production
Authors: Li Xin Ping , Zhou Lu Lu , Guo Yan Hua , Wang Jian Wen
Published: July 2021

Background

Adenosine 5′-triphosphate (ATP) plays both a central role as an intracellular energy source, and a crucial extracellular signaling role in diverse physiological processes of animals and plants. However, there are less reports concerning the signaling role of microbial extracellular ATP (eATP). Hypocrellins are effective anticancer photodynamic therapy (PDT) agents from bambusicolous Shiraia fungi. The co-culture of Shiraia sp. S9 and a bacterium Pseudomonas fulva SB1 isolated from Shiraia fruiting bodies was established for enhanced hypocrellin A (HA) production. The signaling roles of eATP to mediate hypocrellin biosynthesis were investigated in the co-culture.

Results

The co-culture induced release of eATP at 378 nM to the medium around 4 h. The eATP release was interdependent on cytosolic Ca2+ concentration and reactive oxygen species (ROS) production, respectively. The eATP production could be suppressed by the Ca2+ chelator EGTA or abolished by the channel blocker La3+, ROS scavenger vitamin C and NADPH oxidase inhibitor diphenyleneiodonium chloride (DPI). The bacterium-induced H2O2 production was strongly inhibited by reactive blue (RB), a specific inhibitor of membrane purinoceptors, but dependent on the induced Ca2+ influx in the co-culture. On the other hand, the application of exogenous ATP (exATP) at 10–300 µM to Shiraia cultures also promoted fungal conidiation and HA production, both of which were blocked effectively by the purinoceptor inhibitors pyridoxalphosphate-6-azophenyl-2′, 4′-disulfonic acid (PPADS) and RB, and ATP hydrolase apyrase. Both the induced expression of HA biosynthetic genes and HA accumulation were inhibited significantly under the blocking of the eATP or Ca2+ signaling, and the scavenge of ROS in the co-culture.

Conclusions

Our results indicate that eATP release is an early event during the intimate bacterial–fungal interaction and eATP plays a signaling role in the bacterial elicitation on fungal metabolites. Ca2+ and ROS are closely linked for activation of the induced ATP release and its signal transduction. This is the first report on eATP production in the fungal–bacterial co-culture and its involvement in the induced biosynthesis of fungal metabolites.

Graphic abstract
Using a community-based system dynamics approach for understanding inclusion and wellbeing: a case study of special needs education in an eastern African refugee camp
Authors: Werner Kelsey , St. Arnold Gregory , Crea Thomas M.
Published: July 2021

Background

Children with disabilities face unique challenges in humanitarian aid settings and education may provide protective measures against abuse and exploitation. There are growing calls for inclusive education of children with disabilities in formal education, but little guidance exists on how to enhance inclusion in complex and resource-constrained contexts of humanitarian settings.

Case presentation

This study used a community-based system dynamics approach to understand key stakeholders’ perspectives of the drivers and effects of inclusion and wellbeing for children with disabilities, and to elicit recommendations to enhance educational inclusion in a refugee camp in Eastern Africa. Community-based system dynamics sessions, designed based on group model building scripts and facilitated by a team of four people, took place with organization staff, community leaders, and parents and caregivers of children with disabilities. The process produced a causal loop diagram depicting the stakeholders’ perspectives of how multiple components interact in a system to drive inclusion and wellbeing of children with disabilities over time.

Conclusions

Findings indicate participants have a broad conceptualization of inclusion, highlighting the value of community interaction and importance of meeting basic needs, and also demonstrate that including children in mainstream educational settings in a complex humanitarian context requires a more nuanced approach given the lack of existing resources to support Western models of educational inclusion fully.
The effect of higher versus lower protein delivery in critically ill patients: a systematic review and meta-analysis of randomized controlled trials
Authors: Lee Zheng-Yii , Yap Cindy Sing Ling , Hasan M. Shahnaz , Engkasan Julia Patrick , Barakatun-Nisak Mohd Yusof , Day Andrew G. , Patel Jayshil J. , Heyland Daren K.
Published: July 2021

Background

The optimal protein dose in critical illness is unknown. We aim to conduct a systematic review of randomized controlled trials (RCTs) to compare the effect of higher versus lower protein delivery (with similar energy delivery between groups) on clinical and patient-centered outcomes in critically ill patients.

Methods

We searched MEDLINE, EMBASE, CENTRAL and CINAHL from database inception through April 1, 2021.We included RCTs of (1) adult (age ≥ 18) critically ill patients that (2) compared higher vs lower protein with (3) similar energy intake between groups, and (4) reported clinical and/or patient-centered outcomes. We excluded studies on immunonutrition. Two authors screened and conducted quality assessment independently and in duplicate. Random-effect meta-analyses were conducted to estimate the pooled risk ratio (dichotomized outcomes) or mean difference (continuous outcomes).

Results

Nineteen RCTs were included (n = 1731). Sixteen studies used primarily the enteral route to deliver protein. Intervention was started within 72 h of ICU admission in sixteen studies. The intervention lasted between 3 and 28 days. In 11 studies that reported weight-based nutrition delivery, the pooled mean protein and energy received in higher and lower protein groups were 1.31 ± 0.48 vs 0.90 ± 0.30 g/kg and 19.9 ± 6.9 versus 20.1 ± 7.1 kcal/kg, respectively. Higher vs lower protein did not significantly affect overall mortality [risk ratio 0.91, 95% confidence interval (CI) 0.75–1.10, p = 0.34] or other clinical or patient-centered outcomes. In 5 small studies, higher protein significantly attenuated muscle loss (MD −3.44% per week, 95% CI −4.99 to −1.90; p < 0.0001).

Conclusion

In critically ill patients, a higher daily protein delivery was not associated with any improvement in clinical or patient-centered outcomes. Larger, and more definitive RCTs are needed to confirm the effect of muscle loss attenuation associated with higher protein delivery.

PROSPERO registration number: CRD42021237530
Effects of voluntary pre-contraction of the pelvic floor muscles (the Knack) on female stress urinary incontinence—a study protocol for a RCT
Authors: Fitz Fátima Faní , Gimenez Márcia Maria , de Azevedo Ferreira Letícia , Matias Mayanni Magda Perreira , Bortolini Maria Augusta Tezelli , Castro Rodrigo Aquino
Published: July 2021

Background

Stress urinary incontinence (SUI) is a subtype of urinary incontinence that occurs more commonly amongst women. The pelvic floor muscle training (PFMT) is considered the gold standard for treating SUI. Another technique called the Knack postulated that pre-contraction of the pelvic floor muscles (PFM) during activities of increasing intra-abdominal pressure prevents urinary loss. Currently, there are no studies supporting the Knack for the treatment of SUI. Thus, the aim of this study is to test the hypothesis that voluntary pre-contraction of PFM can treat SUI. For this purpose, the following parameters will be analysed and compared amongst (1) the Knack, (2) PFMT and (3) the Knack + PFMT groups: urine leakage as assessed by the pad test, urinary symptoms, muscle function, quality of life, subjective cure, adherence to exercises in the outpatient setting and at home and perceived self-efficacy of PFM exercises.

Methods

A single-centre, double-blind (investigator and outcome assessor) randomised controlled trial with a 3-month follow-up of supervised treatment and an additional 3 months of follow-up (unsupervised) for a total of 6 months of follow-up. Two hundred ten women with mild to moderate SUI will be included, aged between 18 and 70 years. To compare the primary and secondary outcome measures within and between the groups studied (before and after intervention), the ANOVA statistical test will be used. Primary and secondary outcome measures will be presented as mean, standard deviation, 95% confidence interval and median and minimum and maximum values.

Discussion/significance

This study closes a gap, as voluntary PFM pre-contraction (the Knack) has not yet been included in the physiotherapeutic treatment of SUI, and if shown successful could be implemented in clinical practice.

Trial registration

ClinicalTrials.gov NCT03722719. Registered on October 29, 2018. Study protocol version 1.

Was this trial prospectively registered? Yes

Funded by: The present study did not receive funding.

Anticipated completion date: The anticipated trial commencement and completion dates are October 2018 and October 2021, respectively.

Provenance: Not invited. Peer reviewed.

Human research ethics approval committee: Research Ethical Board of the Universidade Federal de São Paulo (UNIFESP), Brazil.

Human research ethics approval number: 2.517.312.
Active constituents of Zanthoxylum nitidium from Yunnan Province against leukaemia cells in vitro
Authors: Deng Ying , Ding Tongtong , Deng Lulu , Hao Xiaojiang , Mu Shuzhen
Published: July 2021

Zanthoxylum nitidium (Roxb.) DC (Rutaceae) is well known for inhibiting the proliferation of human gastric, liver, kidney and lung cancer cells, though research on its potential use in treating leukaemia is relatively rare. Twenty-six compounds were isolated from the chloroform and petroleum ether extracts of the roots and leaves of Z. nitidium (Zanthoxylum nitidium). They were ( +)-9′-O-transferuloyl-5, 5′-dimethoxylaricriresinol (1), 8-(3′-oxobut-1′-en-1′-yl)-5, 7-dimethoxy-coumarin (2), 5, 7, 8-trimethoxy-coumarin (3), 5-(3′, 3′-dimethyl-2′-butenyloxy)-7, 8-dimethoxy-coumarin (4), 2-(5-methoxy-2-methyl-1H-indol-3-yl) methyl acetate (5), 2′-(5, 6-dihydrochleletrythrine-6-yl) ethyl acetate (6), 6-acetonyldi-hydrochelerythrine (7), 6β-hydroxymethyldihydronitidine (8), bocconoline (9), zanthoxyline (10), O-methylzanthoxyline (11), rhoifoline B (12), N-nornitidine (13), nitidine (14), chelerythrine (15), 4-hydroxyl-7,8-dimethoxy-furoquinoline (16), dictamnine (17), γ-fagarine (18), skimmianine (19), robustine (20), R-( +)-platydesmine (21), 4-methoxyl-1-methyl-2-quinoline (22), 4-methoxy-2-quinolone (23), liriodenine (24), aurantiamide acetate (25), 10-O-demethyl-12-O-methylarnottianamide (26). Four among them, compounds 4 – 6 and 16, were first confirmed in this study by UV, IR, 1D, 2D NMR and HR-ESI–MS spectra. Compounds 1 – 2 and 11 were isolated from Z. nitidium for the first time. Of the assayed compounds, 1, 2, 9, 10, 14, 15 and 24, exhibited good inhibitory activities in the leukaemia cell line HEL, whereas compound 14 (IC50: 3.59 µM) and compound 24 (IC50: 15.95 µM) exhibited potent inhibitory activities. So, to further investigate the possible mechanisms, cell cycle and apoptosis assays were performed, which indicated that compound 14 causes obvious S-phase arrest in HEL cells and induced apoptosis, whereas compound 24 only induced apoptosis. The present results suggested both compounds 14 and 24 are promising potential anti-leukaemia drug candidates.
Enhanced lignin biodegradation by consortium of white rot fungi: microbial synergistic effects and product mapping
Authors: Cui Tangwu , Yuan Bo , Guo Haiwei , Tian Hua , Wang Weimin , Ma Yingqun , Li Changzhi , Fei Qiang
Published: July 2021

Background

As one of the major components of lignocellulosic biomass, lignin has been considered as the most abundant renewable aromatic feedstock in the world. Comparing with thermal or catalytic strategies for lignin degradation, biological conversion is a promising approach featuring with mild conditions and diversity, and has received great attention nowadays.

Results

In this study, a consortium of white rot fungi composed of Lenzites betulina and Trametes versicolor was employed to enhance the ligninolytic enzyme activity of laccase (Lac) and manganese peroxidase (MnP) under microbial synergism. The maximum enzymatic activity of Lac and MnP was individually 18.06 U mL−1 and 13.58 U mL−1 along with a lignin degradation rate of 50% (wt/wt), which were achieved from batch cultivation of the consortium. The activities of Lac and MnP obtained from the consortium were both improved more than 40%, as compared with monocultures of L. betulina or T. versicolor under the same culture condition. The enhanced biodegradation performance was in accordance with the results observed from scanning electron microscope (SEM) of lignin samples before and after biodegradation, and secondary-ion mass spectrometry (SIMS). Finally, the analysis of heteronuclear single quantum coherence (HSQC) NMR and gas chromatography–mass spectrometry (GC–MS) provided a comprehensive product mapping of the lignin biodegradation, suggesting that the lignin has undergone depolymerization of the macromolecules, side-chain cleavage, and aromatic ring-opening reactions.

Conclusions

Our results revealed a considerable escalation on the enzymatic activity obtained in a short period from the cultivation of the L. betulina or T. versicolor due to the enhanced microbial synergistic effects, providing a potential bioconversion route for lignin utilization.
The lungs were on fire: a pilot study of 18F-FDG PET/CT in idiopathic-inflammatory-myopathy-related interstitial lung disease
Authors: Liang Junyu , Cao Heng , Liu Yinuo , Ye Bingjue , Sun Yiduo , Ke Yini , He Ye , Xu Bei , Lin Jin
Published: July 2021

Background

Interstitial lung disease (ILD) and its rapid progression (RP) are the main contributors to unfavourable outcomes of patients with idiopathic inflammatory myopathy (IIM). This study aimed to identify the clinical value of PET/CT scans in IIM-ILD patients and to construct a predictive model for RP-ILD.

Methods

Adult IIM-ILD patients who were hospitalized at four divisions of the First Affiliated Hospital, Zhejiang University School of Medicine (FAHZJU), from 1 January 2017 to 31 December 2020 were reviewed. PET/CT scans and other characteristics of patients who met the inclusion and exclusion criteria were collected and analysed.

Results

A total of 61 IIM-ILD patients were enrolled in this study. Twenty-one patients (34.4%) developed RP-ILD, and 24 patients (39.3%) died during follow-up. After false discovery rate (FDR) correction, the percent-predicted diffusing capacity of the lung for carbon monoxide (DLCO%, P = 0.014), bilateral lung mean standard uptake value (SUVmean, P = 0.014) and abnormal mediastinal lymph node (P = 0.045) were significantly different between the RP-ILD and non-RP-ILD groups. The subsequent univariate and multivariate logistic regression analyses verified our findings. A “DLM” model was established by including the above three values to predict RP-ILD with a cut-off value of ≥ 2 and an area under the curve (AUC) of 0.905. Higher bilateral lung SUVmean (P = 0.019) and spleen SUVmean (P = 0.011) were observed in IIM-ILD patients who died within 3 months, and a moderate correlation was recognized between the two values.

Conclusions

Elevated bilateral lung SUVmean, abnormal mediastinal lymph nodes and decreased DLCO% were significantly associated with RP-ILD in IIM-ILD patients. The “DLM” model was valuable in predicting RP-ILD and requires further validation.
Abrupt-onset, profound erectile dysfunction in a healthy young man after initiating over-the-counter omeprazole: a case report
Authors: Perry Theodore W.
Published: July 2021

Background

Proton pump inhibitors are frequently used (and often overused) medications with adverse effects including vitamin B12 deficiency, Clostridium difficile colitis, and increased risk of chronic kidney disease. Erectile dysfunction is largely unrecognized as an adverse effect of proton pump inhibitors despite increasing evidence that proton pump inhibitors may contribute to impaired nitric oxide generation and endothelial dysfunction.

Case presentation

A 38-year-old Caucasian man with mild hypertension and no other significant medical history developed profound erectile dysfunction within 2 days of initiating over-the-counter omeprazole therapy, with erectile function rapidly normalizing following discontinuation of the drug. At the time of the episode, the patient was on a stable dose of lisinopril and was taking no other medications or supplements. In the 2 years following the episode, the patient has had no further erectile difficulties.

Conclusion

Further study of erectile dysfunction as an adverse effect of proton pump inhibitors is needed. In the meantime, proton pump inhibitors should be considered as a potential cause of erectile dysfunction in healthy young patients and as a cause or contributor to erectile dysfunction in older patients in whom erectile dysfunction is often attributed to age or comorbidities.
Infrasound detection and altitude estimation associated with the December 22, 2020 Yushu fireball
Authors: Cheng Wei , Teng Pengxiao , Lyu Jun , Dai Yijing
Published: July 2021

A large bolide was reported at 23:23:33 UTC on December 22, 2020, at a height of ~ 35.5 km at$$31.9^\circ \mathrm{N}$$31.9∘N,$$96.2^\circ \mathrm{E}$$96.2∘Ein Yushu, Qinghai Province, China. It is the largest fireball observed in China on record with a TNT equivalent of 9.5 kilotons. Infrasound signals were detected by a four-element infrasound array deployed in Yunnan Province, China. The parameters of this event were obtained using the progressive multi-channel correlation method. The altitude of this event was estimated to be$$43.22\pm 15.51\mathrm{ km}$$43.22±15.51kmusing a ray tracing back-projection algorithm.
Rhamnus alaternus aqueous extract enhances the capacity of system redox defence and protects hepatocytes against aluminum chloride toxicity in rats
Authors: Benzaid Chahrazed , Tichati Lazhari , Trea Fouzia , Rouabhia Mahmoud , Ouali Kheireddine
Published: July 2021

Background

This study was designed to evaluate the protective effects of a Rhamnus alaternus aqueous extract (RAAE) on aluminum chloride-induced hepatotoxicity in rats. A preliminary phytochemical study and antioxidant activity tests of the extract were performed.

Methods

A preliminary phytochemical study and antioxidant activity tests of the extract were performed. For the in vivo study, twenty-four male rats were divided into four groups. The control group (C); the RAAE group treated with 250 mg/kg b.w RAAE; the AlCl3 group, which received 50 mg/kg b.w AlCl3; and the AlCl3/RAAE group that was treated with AlCl3 plus RAAE.

Results

The RAAE contains several phenolic compounds. This plant extract showed a high radical scavenging effect and high antioxidant activity. Administration of AlCl3 resulted in a significant increase in the activities of aspartate aminotransferase and alanine aminotransferase (AST, ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) and significant decreases in the plasma concentrations of total proteins and albumin. Moreover, AlCl3 induced a hepatic pro-oxidant effect leading to an increase in malonaldehyde (MDA) and carbonyl protein contents, the depletion of the content of reduced glutathione (GSH) and a decrease in the antioxidant enzymatic activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). However, RAAE supplementation with AlCl3 treatment significantly decreased the levels of MDA and carbonyl proteins and markedly restored the activities of the antioxidant enzymes. These results are supported by the improvement in liver tissue restoration.

Conclusions

The Rhamnus alaternus aqueous extract was shown to have effective antioxidant activity owing to its phenolic compounds protecting against AlCl3-induced liver oxidative damage.
Retractorless brain surgery: technical considerations
Authors: Nazim Wael Mohamed , Elborady Mohamed Abdelrahman
Published: July 2021

Background

Retraction is necessary to access deep areas in the brain and skull base, but prolonged and forceful use of fixed retraction might be injurious. Several techniques were developed, in the concept of minimally invasive neurosurgery, to eliminate or minimize the use of fixed retractors. The authors discuss the technical considerations and limits in applying dynamic retraction in brain surgery for a variety of lesions using different approaches.

Results

We retrospectively collected 123 cases with brain lesions in diverse locations, were dynamic retraction, using the tools in the operator hands and was achieved successfully instead of fixed retraction. Cases with aneurysms were excluded, although retraction was applied during clipping only. Superficial and large masses that do not require fixed retraction as a routine were excluded also. We relied mainly on patient positioning to benefit from the gravity, proper design of the craniotomy, arachnoid dissection, cerebrospinal fluid aspiration, and internal decompression of the mass when possible.

Different approaches for different lesions were utilized in our patients, subfrontal or pterional and their modifications in 45.5% of cases, suboccipital in 21.1%, retrosigmoid in 13%, the interhemispheric approach in 10.5%, transcortical to lateral ventricles in 7.3%, and posterior subtemporal in 2.4%.

Dynamic retraction with the surgical tools was used successfully in all cases except 7 patients (5.6%) where we had to use fixed retraction transiently.

Conclusion

Several considerations are helpful and amenable to achieve successful brain surgery without fixed retraction. Utilizing the gravity, unlocking of the brain, choosing the surgical corridor, cerebrospinal fluid suctioning, and mastering of the microsurgical techniques are the keys.
Graduate- and undergraduate-student perceptions of and preferences for teaching practices in STEM classrooms
Authors: Gonsar Ngawang , Patrick Lorelei , Cotner Sehoya
Published: July 2021

Despite positive evidence for active learning (AL), lecturing dominates science, technology, engineering, and mathematics (STEM) higher education. Though instructors acknowledge AL to be valuable, many resist implementing AL techniques, citing an array of barriers including a perceived lack of student buy-in. However, few studies have explored student perceptions of specific AL teaching practices, particularly the perceptions of graduate students. We explored student-reported instructional strategies and student perceptions of and preferences for a variety of teaching practices in graduate and undergraduate classrooms across three STEM colleges at a large, public, research university. We found that both graduate and undergraduate students desired more time for AL and wanted less lecturing than they were currently experiencing. However, there was no single universally desired or undesired teaching practice, suggesting that a variety of AL teaching practices should be employed in both graduate and undergraduate courses.
Comparison of 99mTc-PSMA SPECT/CT and 68Ga-PSMA PET/CT in patients with prostate cancer: a protocol for systematic review and meta-analysis
Authors: Yunusa Garba Haruna , Kaoje Aminu Umar , Orunmuyi Akintunde Taiwo , More Stuart S. , Jawa Zabah Muhammad , Khalid Abdullahi
Published: July 2021

Background

A wide range of nuclear imaging probes have been developed to address different metabolic processes and cell receptors in prostate cancer patients using positron emission techniques to aid diagnosis, staging, and monitoring for recurrence after treatment. While 68Ga PSMA is a generator-derived PET radiopharmaceutical, SPECT/CT imaging using technetium-99m-labeled PSMA is now available as a suitable alternative. The aim of this study is to compare the pooled sensitivity, specificity, and accuracy of 99mTc-PSMA SPECT/CT and 68Ga-PSMA PET/CT in patients with prostate cancer.

Main body of the abstract

A search strategy was developed using text words, MeSH, and entry terms. The following databases will be searched: PubMed, African Journals Online (AJOL), Embase, Google scholar, ResearchGate, Cochrane Library, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science. Eligibility criteria include (a) all studies that are published or retrievable in English language, (b) observational studies, and (c) histopathology analysis or clinical and imaging follow-up or comparison with reference standards. Exclusion criteria will be interventional studies, editorials, reviews, and commentaries. Quality of the studies will be assessed using QUADAS2 Quality scores and risk of bias for individual studies will be reported. Full text of the studies will be reviewed and snowballed for any relevant literature. Assessment of methodological, clinical, and statistical heterogeneity for all the included studies will be made. Publication bias will be assessed using funnel plots. Statistical analysis and forest plots will be performed using the Open Meta-analyst software. The systematic review and meta-analysis will be reported according to PRISMA 2015 Statement.

Short conclusion

This review will provide data on diagnostic accuracy of 99mTc-PSMA SPECT/CT and 68Ga-PSMA PET/CT in patients with prostate cancer. Results from this study will help nuclear medicine service providers to make better decisions on the appropriate use of 99mTc-PSMA SPECT/CT and 68Ga-PSMA PET/CT especially with regard to the use of 99mTc-PSMA SPECT/CT which is relatively affordable and more readily available in developing countries when compared to 68-Ga PSMA PECT/CT.
Model Development of CDK4/6 Predicted Efficacy in Patients With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced or Metastatic Breast Cancer
Authors: Mason Jeremy , Gong Yutao , Amiri-Kordestani Laleh , Wedam Suparna , Gao Jennifer J. , Prowell Tatiana M. , Singh Harpreet , Amatya Anup , Tang Shenghui , Pazdur Richard , Kuhn Peter , Blumenthal Gideon M. , Beaver Julia A.
Published: July 2021

PURPOSE

Three cyclin-dependent kinase 4/6 inhibitors (CDKIs) are approved by the US Food and Drug Administration for the treatment of patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced or metastatic breast cancer in combination with hormonal therapy (HT). We hypothesized that on an individual basis, efficacy outcomes and adverse event (AE) development can be predicted using baseline patient and tumor characteristics.

METHODS

Individual-level data from seven randomized controlled trials submitted to the US Food and Drug Administration for new or supplemental marketing applications of CDKIs were pooled. Progression-free survival (PFS), overall survival (OS), and AE prediction models were developed for specific treatment regimens (HT v HT plus CDKI). An individual's characteristics were used in all models simultaneously to create a group of predicted outcomes that are comparable across treatment settings.

RESULTS

Accuracy of the PFS and OS prediction models for HT were 66% and 64%, respectively, with the strongest predictors being menopausal status and therapy line. The corresponding AE prediction models resulted in an average area under the curve of 0.613. Accuracy of the PFS and OS prediction models for HT plus CDKI were 62% and 63%, respectively, with the strongest predictors being histologic grade for both. The corresponding AE prediction models resulted in an average area under the curve of 0.639.

CONCLUSION

This exploratory analysis demonstrated that models of efficacy outcomes and AE development can be developed using baseline patient and tumor characteristics. Comparison of paired models can inform treatment selection for individuals on the basis of the patient's personalized goals and concerns. Although use of CDKIs is standard of care in the first- or second-line setting, this model provides prognostic information that may inform individual treatment decisions.
Anisotropy in Faraday instabilities of a shallow conducting fluid
Authors: Tessier J. , Castro-Folker N. , Poulin F. J. , Stastna M.
Published: July 2021

In this work, we study the impact of temporally varying gravity on an idealized shallow conducting fluid with a free surface. We formulate the problem in terms of the shallow magnetohydrodynamic (SMHD) equations which allows the study of the resulting anisotropy in the context of a Faraday instability. We simplify the linear stability problem into a Mathieu equation by assuming gravity is periodic in time. Using the existing theory of Mathieu's equation, we find that anisotropy occurs, with wave vectors parallel to the imposed magnetic field stabilized. We describe the regions of instability in wave number space.
State-Variable Modeling for a Class of Two-Stage Stochastic Optimization Problems
Authors: Doulabi Hossein Hashemi , Ahmed Shabbir , Nemhauser George
Published: July 2021

This paper considers a class of two-stage stochastic mixed-integer optimization problems where, for a given first-stage solution, we can determine the optimal values of recourse variables sequentially. This class of problems arises in a wide variety of applications. In the case of multivariate discrete distributions for uncertain parameters, a standard stochastic programming formulation of these problems involves an exponential number of scenarios, therefore an exponential number of variables and constraints. We propose a new mixed-integer programming modeling approach where the number of variables and constraints is independent of the number of scenarios and scales at most pseudopolynomially with the problem size. The proposed modeling approach relies on state variables that track the system’s state as the uncertainty realizes sequentially. We demonstrate the advantages of the proposed approach in two applications arising in project scheduling and operating room allocation.

Summary of Contribution: This paper proposes a new modeling approach for a class of two-stage stochastic optimization problems that is computationally more efficient than the traditional scenario-based stochastic integer programming models. The proposed modeling approach relies on state variables that track the system's state as the uncertainty realizes sequentially. We demonstrated the efficiency of the proposed approach by computational results on two applications in project scheduling and operating room allocation.
Middle school teacher pedagogic competency map for private vocational school in Wanareja Cilacap
Authors: Basuki Rahmat , Susatya Edhy , Kristiyanto Bambang Noor Achsan
Published: July 2021

This study aims to map the acquisition of teachers’ pedagogical competence at private vocational high schools Wanareja, Cilacap, Central Java. This research used quantitative method. We involved 60 teachers from four private vocational schools as the research subject. We delivered a Likert-scale questionnaire to assess the pedagogical competence. Then, we analyzed the data using non-parametric inferential statistics. The results showed that the pedagogical competence of private vocational school teachers in Wanareja on ten aspects of pedagogical competence had different categories in each aspect. The aspect of mastering the students’ characteristics was very sufficient (55%). The aspect of mastering the learning theory was good (44%) and very sufficient (40%). The aspect of developing a curriculum was good (48%). The aspect of organizing learning was good (63%). The aspect of using ICT in learning was very sufficient (51%). The aspect of developing the students’ potential was good (44%). The aspect of effective communication and politeness was good (63%). The aspect of conducting an assessment was sufficient (53%). The aspect of utilizing the results of the assessment for the benefit of learning was very sufficient (53%). And finally, the aspect of doing reflective action was sufficient (68%). The implementation of the pedagogical competence of private vocational school teachers in Wanareja has not been evenly distributed in all aspects of competencies and efforts to improve teacher pedagogical competence has not been maximized.
Estimation of nominal ocular hazard distance and nominal ocular dazzle
distance for multibeam laser radiation: publisher’s note
Authors: Mlynczak Jaroslaw , Kopczynski Krzysztof , Kaliszewski Miron , Wlodarski Maksymilian
Published: July 2021

This publisher’s note corrects funding information in Appl. Opt.
60, 6414 (2021) APOPAI0003-693510.1364/AO.431490.
Machine learning reveals mesenchymal breast carcinoma cell adaptation in response to matrix stiffness
Authors: Rozova Vlada S. , Anwer Ayad G. , Guller Anna E. , Es Hamidreza Aboulkheyr , Khabir Zahra , Sokolova Anastasiya I. , Gavrilov Maxim U. , Goldys Ewa M. , Warkiani Majid Ebrahimi , Thiery Jean Paul , Zvyagin Andrei V.
Published: July 2021

Epithelial-mesenchymal transition (EMT) and its reverse process, mesenchymal-epithelial transition (MET), are believed to play key roles in facilitating the metastatic cascade. Metastatic lesions often exhibit a similar epithelial-like state to that of the primary tumour, in particular, by forming carcinoma cell clusters via E-cadherin-mediated junctional complexes. However, the factors enabling mesenchymal-like micrometastatic cells to resume growth and reacquire an epithelial phenotype in the target organ microenvironment remain elusive. In this study, we developed a workflow using image-based cell profiling and machine learning to examine morphological, contextual and molecular states of individual breast carcinoma cells (MDA-MB-231). MDA-MB-231 heterogeneous response to the host organ microenvironment was modelled by substrates with controllable stiffness varying from 0.2kPa (soft tissues) to 64kPa (bone tissues). We identified 3 distinct morphological cell types (morphs) varying from compact round-shaped to flattened irregular-shaped cells with lamellipodia, predominantly populating 2-kPa and >16kPa substrates, respectively. These observations were accompanied by significant changes in E-cadherin and vimentin expression. Furthermore, we demonstrate that the bone-mimicking substrate (64kPa) induced multicellular cluster formation accompanied by E-cadherin cell surface localisation. MDA-MB-231 cells responded to different substrate stiffness by morphological adaptation, changes in proliferation rate and cytoskeleton markers, and cluster formation on bone-mimicking substrate. Our results suggest that the stiffest microenvironment can induce MET.
Enrichment of leukocytes in peripheral blood using 3D printed tubes
Authors: Guo Li-fang , Wang Liu , Ren Sai , Su Ning , Wei Kun , Sun Xian-Ge , Ren Xiao-Dong , Huang Qing
Published: July 2021

Leukocytes have an essential role in patient clinical trajectories and progression. Traditional methods of leukocyte enrichment have many significant limitations for current applications. It is demonstrated a novel 3D printing leukocyte sorting accumulator that combines with centrifugation to ensure label-free initial leukocyte enrichment based on cell density and size. The internal structure of leukocyte sorting accumulator (revealed here in a new design, leukocyte sorting accumulator-3, upgraded from earlier models), optimizes localization of the buffy coat fraction and the length of the period allocated for a second centrifugation step to deliver a higher recovery of buffy coats than earlier models. Established methodological parameters were evaluated for reliability by calculating leukocyte recovery rates and erythrocyte depletion rates by both pushing and pulling methods of cell displacement. Results indicate that leukocyte sorting accumulator-3 achieves a mean leukocytes recovery fraction of 96.2 ± 2.38% by the pushing method of layer displacement. By the pulling method, the leukocyte sorting accumulator-3 yield a mean leukocytes recovery fraction of 94.4 ± 0.8%. New procedures for preliminary enrichment of leukocytes from peripheral blood that avoid cellular damage, as well as avert metabolic and phase cycle intervention, are required as the first step in many modern clinical and basic research assays.
Relationships between carotid artery intima-media thickness and echogenicity and body composition using a new magnetic resonance imaging voxel-based technique
Authors: Lind Lars , Kullberg Joel , Ahlström Håkan , Strand Robin
Published: July 2021

Background

We evaluated how carotid artery intima-media thickness (IMT) and the echogenicity of the intima-media (IM-GSM), measured by ultrasound, were related to body composition, evaluated by both traditional imaging techniques, as well as with a new voxel-based “Imiomics” technique.

Methods

In 321 subjects all aged 50 years in the POEM study, IMT and IM-GSM were measured together with a DXA scan for determination of fat and lean mass. Also a whole-body MRI scan was performed and the body volume was divided into >1 million voxels in a standardized fashion. IMT and IM-GSM were related to each of these voxels to create a 3D-view of how these measurements were related to size of each part of the body.

Results

IM-GSM was inversely related to almost all traditional measurements of body composition, like fat and lean mass, liver fat, visceral and subcutaneous fat, but this was not seen for IMT. Using Imiomics, IMT was positively related to the intraabdominal fat volume, as well of the leg skeletal muscle in women. In males, IMT was mainly positively related to the leg skeletal muscle volume. IM-GSM was inversely related to the volume of the SAT in the upper part of the body, leg skeletal muscle, the liver and intraabdominal fat in both men and women.

Conclusion

The voxel-based Imiomics technique provided a detailed view of how the echogenicity of the carotid artery wall was related to body composition, being inversely related to the volume of the major fat depots, as well as leg skeletal muscle.
Water jet as a novel technique for enamel drilling ex vivo
Authors: Liu Chang , Chen Rourong , Han ChengZao , Pi Xiaoqin , Chang Shuli , Jiang Han , Long Xinping , Du Minquan
Published: July 2021

To investigate the usage of a water jet for enamel drilling ex vivo, 210 individual extracted molars without lesions or fillings were collected. Then, the specimens were drilled by a water jet or a high-speed dental drill. The cavities of 50 teeth were reconstructed digitally by micro-computed tomography (micro-CT) to measure the height and width. The cavities of 10 teeth were longitudinally incised and their surfaces were observed by scanning electronic microscopy (SEM). After the cavities were filled, 50 fillings were vertically incised. The bonding interface between tooth and filling was observed by SEM. 50 teeth with fillings were stained in 0.1% rhodamine B solution, and then the dye penetration between tooth and filling was observed under the stereomicroscope and confocal laser scanning microscopy (CLSM). The bonding strength between enamel and filling of 50 teeth was simulated and predicted with finite element analysis (FEA). At 140–150 MPa and for 2–3 s, cavities were made with a depth of approximately 764 μm in each tooth. SEM showed the cavity surface in the water jet group had a more irregular concave and convex structure than that in the high-speed dental drill group. There was a trend that the microleakage and bonding width was smaller in the water jet group than in the high-speed dental drill group. FEA indicated that the stress on the resin surface was greater than on the enamel surface in the water jet group. Compared with the tooth drilled by a high-speed dental drill, the tooth drilled by a water jet gained better retention of the filling material and suffered less bonding strength on the enamel surface. Water jet drilling is effective for enamel drilling.
Commonly available but highly effective protection against SARS-CoV-2 during gastrointestinal endoscopies
Authors: Keil Radan , Hlava Štěpán , Stanovský Petr , Ždímal Vladimír , Šťovíček Jan , Trojánek Milan , Drábek Jiří , Frýbová Barbora , Petráček Vojtěch , Wasserbauer Martin
Published: July 2021

Background and aims

SARS-CoV-2 is a worldwide serious health problem. The aim of this study was to demonstrate the number of potentially infectious particles present during endoscopic procedures and find effective tools to eliminate the risks of SARS-CoV-2 infection while performing them.

Methods

An experimental model which focused on aerosol problematics was made in a specialized laboratory. This model simulated conditions present during endoscopic procedures and monitored the formation of potentially infectious fluid particles from the patient’s body, which pass through the endoscope and are then released into the environment. For this reason, we designed and tested a prototype of a protective cover for the endoscope’s control body to prevent the release and spread of these fluid particles from its working channel. We performed measurements with and without the protective cover of the endoscope’s control body.

Results

It was found that liquid coming through the working channel of the endoscope with forceps or other instruments inside generates droplets with a diameter in the range of 0.1–1.1 mm and an initial velocity of up to 0.9 m/s. The average number of particles per measurement per whole measured area without a protective cover on the endoscope control body was 51.1; with this protective cover on, the measurement was 0.0, p<0.0001.

Conclusions

Our measurements proved that fluid particles are released from the working channel of an endoscope when forceps are inserted. A special protective cover for the endoscope control body, made out of breathable material (surgical cap) and designed by our team, was found to eliminate this release of potentially infectious fluid particles.
Clinical and genetic spectra in patients with dystrophinopathy in Korea: A single-center study
Authors: Yun UnKyu , Lee Seung-Ah , Choi Won Ah , Kang Seong-Woong , Seo Go Hun , Lee Jung Hwan , Park Goeun , Lee Sujee , Choi Young-Chul , Park Hyung Jun
Published: July 2021

Dystrophinopathy is a group of inherited phenotypes arising from pathogenic variants in DMD. We evaluated the clinical and genetic characteristics of Korean patients with genetically confirmed dystrophinopathy. We retrospectively reviewed medical records (January 2004-September 2020) from the myopathy database maintained at the study hospital and found 227 patients from 218 unrelated families with dystrophinopathy. Clinical phenotypes included 120 (53%) Duchenne muscular dystrophy (DMD) cases, 20 (9%) intermediate phenotype muscular dystrophy (IMD) cases, 65 (29%) Becker muscular dystrophy (BMD) cases, 18 (8%) undetermined phenotypes, and 4 (2%) symptomatic carriers. The median ages at symptom onset and diagnosis were 5.0 years (interquartile range [IQR]: 3.8–8.0) and 12.0 years (IQR: 7.0–21.0), respectively. Total manual muscle test (MMT) scores decreased annually in patients with DMD, IMD, and BMD. Overall, when age increased by 1 year, total MMT scores decreased on average by -1.978, -1.681, and -1.303 in patients with DMD (p<0.001), IMD (p<0.001), and BMD (p<0.001), respectively. Exonic deletion and duplication were reported in 147 (67%) and 31 (14%) of the 218 unrelated probands, respectively. A total of 37 different small sequence variants were found in 40 (18%) of the 218 probands. The reading frame rule was applicable to 142 (94%) of the 151 probands. The present results highlight the long-term natural history and genetic spectrum of dystrophinopathy in a large-scale Korean cohort.
Reliability and validity study of the Spanish adaptation of the “Student Satisfaction and Self-Confidence in Learning Scale” (SCLS)
Authors: Farrés-Tarafa Mariona , Bande David , Roldán-Merino Juan , Hurtado-Pardos Barbara , Biurrun-Garrido Ainoa , Molina-Raya Lorena , Raurell-Torredà Marta , Casas Irma , Lorenzo-Seva Urbano
Published: July 2021

The European Higher Education Area (EHEA) recommends the use of new educational methodologies and the evaluation of student satisfaction. Different instruments have been developed in Spain to evaluate different aspects such as clinical decisions and teamwork, however no instruments have been found that specifically evaluate student self-confidence and satisfaction during clinical simulation. The aim was to translate the Student Satisfaction and Self-Confidence in Learning Scale (SCLS) questionnaire into Spanish and analyse its reliability and validity and understand the level of satisfaction and self-confidence of nursing students with respect to learning in clinical simulations. The study was carried out in two phases: (1) adaptation of the questionnaire into Spanish. (2) Cross-sectional study in a sample of 489 nursing students. The reliability and exploratory and confirmatory factorial analyses were performed. To analyse the relationship of the scale scores with the socio-demographic variables, the Fisher Student T-test or the ANOVA was used. The scale demonstrated high internal consistency reliability for the total scale and each of its dimensions. Cronbach’s alpha was 0.88 (0.83 to 0.81) for each of the dimensions. The exploratory and confirmatory factor analysis showed that both the one-dimensional and two-dimensional models were acceptable. The results showed average scores above 4 for both dimensions. The SCLS-Spanish translation demonstrated evidence of its validity and reliability for use to understand the level of satisfaction and self-confidence of nursing students in clinical simulation. Clinical simulations help students to increase their levels of confidence and satisfaction, enabling them to face real scenarios in clinical practice.
Perception of breast cancer risk factors: Dysregulation of TGF-β/miRNA axis in Pakistani females
Authors: Ahmed Fayyaz , Adnan Muhammad , Malik Ayesha , Tariq Somayya , Kamal Farukh , Ijaz Bushra
Published: July 2021

Breast cancer poses a serious health risk for women throughout the world. Among the Asian population, Pakistani women have the highest risk of developing breast cancer. One out of nine women is diagnosed with breast cancer in Pakistan. The etiology and the risk factor leading to breast cancer are largely unknown. In the current study the risk factors that are most pertinent to the Pakistani population, the etiology, molecular mechanisms of tumor progression, and therapeutic targets of breast cancer are studied. A correlative, cross-sectional, descriptive, and questionnaire-based study was designed to predict the risk factors in breast cancer patients. Invasive Ductal Carcinoma (90%) and grade-II tumor (73.2%) formation are more common in our patient’s data set. Clinical parameters such as mean age of 47.5 years (SD ± 11.17), disturbed menstrual cycle (> 2), cousin marriages (repeated), and lactation period (< 0.5 Y) along with stress, dietary and environmental factors have an essential role in the development of breast cancer. In addition to thisin silicoanalysis was performed to screen the miRNA regulating the TGF-beta pathway using TargetScanHuman, and correlation was depicted through Mindjet Manager. The information thus obtained was observed in breast cancer clinical samples both in peripheral blood mononuclear cells, and biopsy through quantitative real-time PCR. There was a significant dysregulation (**P>0.001) of theTGF-β1signaling pathway and the miRNAs (miR-29a, miR-140, and miR-148a) in patients’ biopsy in grade and stage specifically, correlated with expression in blood samples. miRNAs (miR-29a and miR-140, miR-148a) can be an effective diagnostic and prognostic marker as they regulateSMAD4andSMAD2expression respectively in breast cancer blood and biopsy samples. Therefore, proactive therapeutic strategies can be devised considering negatively regulated cascade genes and amalgamated miRNAs to control breast cancer better.