bluuebunny/crossref_metadata_2025 huggingface dataset:
LPS-inducible circAtp9b is highly expressed in osteoporosis and promotes the apoptosis of osteoblasts by reducing the formation of mature miR-17-92a
Authors: Feng Yinan , Ding Li , Li Longguang
Published: March 2022

Background

Circular RNA circAtp9b is an enhancer of LPS-induced inflammation, which promotes osteoporosis (OS). This study explored the role of circAtp9b in OS.

Methods

RT-qPCR was performed to detect the expression of circAtp9b and microRNA (miR)-17-92a (both mature and premature) in OS and healthy controls. The subcellular location of circAtp9b was assessed by nuclear fractionation assay. The direct interaction between circAtp9b and premature miR-17-92a was detected by RNA pull-down assay. The role of circAtp9b in regulating the maturation of miR-17-92a in osteoblasts was explored by overexpression assay and RT-qPCR. Cell apoptosis was analyzed by cell apoptosis assay.

Results

OS patients exhibited upregulation of circAtp9b and premature miR-17-92a, but downregulation of mature miR-17-92a. In osteoblasts, circAtp9b suppressed the maturation of miR-17-92a. LPS upregulated circAtp9b and premature miR-17-92a, and downregulated mature miR-17-92a in osteoblasts. CircAtp9b was detected in both nucleus and cytoplasm, and it directly interacted with premature miR-17-92a. Overexpression of circAtp9b reduced the effects of miR-17-92a on the apoptosis of osteoblasts induced by LPS.

Conclusion

CircAtp9b is LPS-inducible and upregulation of circAtp9b in OS promotes the apoptosis of osteoblasts by reducing the formation of mature miR-17-92a.
Long non-coding RNA SNHG5 promotes the osteogenic differentiation of bone marrow mesenchymal stem cells via the miR-212-3p/GDF5/SMAD pathway
Authors: Han Yineng , Yang Qiaolin , Huang Yiping , Jia Lingfei , Zheng Yunfei , Li Weiran
Published: March 2022

Background

The treatment of bone loss has posed a challenge to clinicians for decades. Thus, it is of great significance to identify more effective methods for bone regeneration. However, the role and mechanisms of long non-coding RNA small nucleolar RNA host gene 5 (SNHG5) during osteogenic differentiation remain unclear.

Methods

We investigated the function of SNHG5, Yin Yang 1 (YY1), miR-212-3p and growth differentiation factor 5 (GDF5) in osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) in vitro and in vivo. Molecular mechanisms were clarified by chromatin immunoprecipitation assay and dual luciferase reporter assay.

Results

We found SNHG5 expression was upregulated during osteogenesis of hBMSCs. Knockdown of SNHG5 in hBMSCs inhibited osteogenic differentiation while overexpression of SNHG5 promoted osteogenesis. Moreover, YY1 transcription factor directly bound to the promoter region of SNHG5 and regulated SNHG5 expression to promote osteogenesis. Dual luciferase reporter assay confirmed that SNHG5 acted as a miR-212-3p sponge and miR-212-3p directly targeted GDF5 and further activated Smad1/5/8 phosphorylation. miR-212-3p inhibited osteogenic differentiation, while GDF5 promoted osteogenic differentiation of hBMSCs. In addition, calvarial defect experiments showed knockdown of SNHG5 and GDF5 inhibited new bone formation in vivo.

Conclusion

Our results demonstrated that the novel pathway YY1/SNHG5/miR-212-3p/GDF5/Smad regulates osteogenic differentiation of hBMSCs and may serve as a potential target for the treatment of bone loss.
Impact of resettlement on livestock production and performance among the Maasai pastoralists of RAPland village, Olkaria Kenya
Authors: Gai Abraham Biar , Wahome Raphael Githaiga , Bett Rawlynce Cheruiyot
Published: March 2022

Displacements from developmental-related projects such as dams, conservancies, and geothermals displace 15–20 million people annually, necessitating the relocation of project-affected persons (PAPs). Most resettlement action plans (RAPs) fail in resettling the PAPs fully, causing loss of livelihoods and impoverishment. In 2014, Kenya Electricity Generating Company Limited (KenGen) displaced 155 Maasai pastoral households to create space for the expansion of existing geothermal electricity generation plants at Olkaria. The PAPs were relocated into a newly created area called RAPland village. The study aimed at answering the question: how did displacement and relocation affect livestock production and performance of the resettled pastoralists. Data on livestock population structures and cattle herd structures and performance (age at first calving, calving interval, lactation length, and milk yields) before and after the relocation were collected by a survey of 105 household heads of the intended census of 155. Data collected were summarised using Excel and analysed with Statistical Package for Social Sciences (SPSS). Results showed that daily milk yield per cow decreased from a mean of 3.8 ± 0.19 to 2.38 ± 0.19 l, while total livestock populations reduced from 8383 to 3124 tropical livestock units (TLU) after the relocation. The mean livestock holding per household (TLU) before the relocation was 75.7 ± 8.83, 15.5 ± 1.78, 5.83 ± 0.67, 1.46 ± 0.22, and 0.14 ± 0.02; this decreased after the relocation to 26.4 ± 8.3, 4.62 ± 1.7, 2.5 ± 0.63, 0.34 ± 0.21, and 0.3 ± 0.02 for cattle, sheep, goats, donkeys, and poultry, respectively. Young cattle proportions reduced from 27.6 to 20%, while that of cows increased from 51.7 to 60% after resettlement. Relocation affected livestock production and performances through reduced daily milk yield and livestock populations, thus reducing pastoralists’ resilience for food, nutritional security, and coping with catastrophes. As such, future displacement and resettlement programmes involving pastoral communities should address grazing needs and pastoral resilience to avoid impoverishment.
MIR210HG promotes breast cancer progression by IGF2BP1 mediated m6A modification
Authors: Shi Wenjing , Tang Yongzhe , Lu Jing , Zhuang Yihui , Wang Jie
Published: March 2022

Background

Breast cancer is the most common cancer in women around the world, and the molecular mechanisms of breast cancer progression and metastasis are still unclear. This study aims to clarify the function and N6,2′-O-dimethyladenosine (m6A) regulation of lncRNA MIR210HG in breast cancer.

Results

High expression of MIR210HG was confirmed in breast cancer. MIR210HG promoted breast cancer progression, which was mediated by its encoded miR-210. MIR210HG was regulated by IGF2BP1 mediated m6A modification. IGF2BP1 was confirmed highly expressed in breast cancer and induced both MIR210HG and miR-210 expression, which contributed to breast cancer progression. In addition, MIR210HG transcript was stabilized by IGF2BP1 and co-factor ELAVL1. IGF2BP1 was a direct target of MYCN via E-box binding motif. MYCN induced IGF2BP1 expression in breast cancer cells. MIR210HG and miR-210 expressions were also increased by MYCN.

Conclusions

In breast cancer, MIR210HG functions as an oncogenic lncRNA, which is also mediated by its encoded miR-210. In addition, both IGF2BP1 and ELAVL1 enhance the stability of MIR210HG, which contributes to the progression of breast cancer. Interestingly, IGF2BP1 is directly activated by MYCN, which explains the oncogenic role of MYCN. These findings clarify the m6A regulation related molecular mechanism of breast cancer progression. The MYCN/IGF2BP1/MIR210HG axis may serve as an alternative molecular mechanism of breast cancer progression.
Results of the national biomonitoring program show persistent iodine deficiency in Israel
Authors: Barnett-Itzhaki Zohar , Ehrlich Daniel , Troen Aron M. , Rorman Efrat , Groismann Luda , Blaychfeld-Magnazi Moran , Endevelt Ronit , Berman Tamar
Published: March 2022

Background

Adequate iodine intake is essential for human health, for normal thyroid function, and for attainment of full intellectual potential in children. In light of Israel's lack of a mandatory salt fortification policy, heavy reliance on desalination and low iodine intake from dairy products and seafood, there is concern in Israel that the population is iodine deficient. Indeed, the first Israeli National Iodine Survey in 2016 found a median urinary iodine concentration (UIC) of 83 µg/L among school age children, falling below the WHO’s adequacy range of 100–299 µg/L for children.

Methods

In the framework of the National Human Biomonitoring Program in Israel, spot urine samples and questionnaire data were collected from 166 healthy children aged 4–12 years in 2020–2021. Urinary iodine concentrations were measured at the Ministry of Health National Biomonitoring Laboratory, using mass spectrometry. An international comparison of median urinary iodine concentrations (UIC) was performed taking into consideration the levels of desalinated water per capita, and fortification policies.

Results

The overall median (interquartile range [IQR]) UIC was 80.1 µg/L (44.7–130.8 µg/L) indicating that the population’s iodine status has not improved in the five years that have passed since inadequacy was first identified. When comparing 13 countries with population size above 150,000, whose desalinated water per capita was at least 1 m3, Israel and Lebanon were the only countries with median UIC below the WHO adequacy range.

Conclusions

There is an urgent need for mandatory salt fortification in Israel. Based on our international comparison, we conclude that the potential impact of desalination on iodine intake can be compensated for using the implementation of salt fortification policy. This study highlights the critical need for public health surveillance of nutritional and environmental exposures using human biomonitoring, with emphasis on vulnerable populations such as pregnant women and children.
Metadta: a Stata command for meta-analysis and meta-regression of diagnostic test accuracy data – a tutorial
Authors: Nyaga Victoria Nyawira , Arbyn Marc
Published: March 2022

Background

Although statistical procedures for pooling of several epidemiological metrics are generally available in statistical packages, those for meta-analysis of diagnostic test accuracy studies including options for multivariate regression are lacking. Fitting regression models and the processing of the estimates often entails lengthy and tedious calculations. Therefore, packaging appropriate statistical procedures in a robust and user-friendly program is of great interest to the scientific community.

Methods

metadtais a statistical program for pooling of diagnostic accuracy test data in Stata. It implements both the bivariate random-effects and the fixed-effects model, allows for meta-regression, and presents the results in tables, a forest plot and/or summary receiver operating characteristic (SROC) plot. For a model without covariates, it quantifies the unexplained heterogeneity due to between-study variation using an I2statistic that accounts for the mean-variance relationship and the correlation between sensitivity and specificity. To demonstratemetadta,we applied the program on two published meta-analyses on: 1) the sensitivity and specificity of cytology and other markers including telomerase for primary diagnosis of bladder cancer, and 2) the accuracy of human papillomavirus (HPV) testing on self-collected versus clinician-collected samples to detect cervical precancer.

Results

Without requiring a continuity correction, the pooled sensitivity and specificity generated bymetadtaof telomerase for the diagnosis of primary bladder cancer was 0.77 [95% CI, 0.70, 0.82] and 0.91 [95% CI, 0.75, 0.97] respectively.Metadtaalso allowed to assess the relative accuracy of HPV testing on self- versus clinician-taken specimens using data from comparative studies conducted in different clinical settings. The analysis showed that HPV testing with target-amplification assays on self-samples was as sensitive as on clinician-samples in detecting cervical pre-cancer irrespective of the clinical setting.

Conclusion

Themetadtaprogram implements state of art statistical procedures in an attempt to close the gap between methodological statisticians and systematic reviewers. We expect the program to popularize the use of appropriate statistical methods for diagnostic meta-analysis further.
AQP4 labels a subpopulation of white matter-dependent glial radial cells affected by pediatric hydrocephalus, and its expression increased in glial microvesicles released to the cerebrospinal fluid in obstructive hydrocephalus
Authors: Castañeyra-Ruiz Leandro , González-Marrero Ibrahim , Hernández-Abad Luis G. , Carmona-Calero Emilia M. , Pardo Marta R. , Baz-Davila Rebeca , Lee Seunghyun , Muhonen Michael , Borges Ricardo , Castañeyra-Perdomo Agustín
Published: March 2022

Hydrocephalus is a distension of the ventricular system associated with ventricular zone disruption, reactive astrogliosis, periventricular white matter ischemia, axonal impairment, and corpus callosum alterations. The condition's etiology is typically attributed to a malfunction in classical cerebrospinal fluid (CSF) bulk flow; however, this approach does not consider the unique physiology of CSF in fetal and perinatal patients. The parenchymal fluid contributes to the glymphatic system, and plays a fundamental role in pediatric hydrocephalus, with aquaporin 4 (AQP4) as the primary facilitator of these fluid movements. Despite the importance of AQP4 in the pathophysiology of hydrocephalus, it’s expression in human fetal life is not well-studied. This manuscript systematically defines the brain expression of AQP4 in human brain development under control (n = 13) and hydrocephalic conditions (n = 3). Brains from 8 postconceptional weeks (PCW) onward and perinatal CSF from control (n = 2), obstructive (n = 6) and communicating (n = 6) hydrocephalic samples were analyzed through immunohistochemistry, immunofluorescence, western blot, and flow cytometry. Our results indicate that AQP4 expression is observed first in the archicortex, followed by the ganglionic eminences and then the neocortex. In the neocortex, it is initially at the perisylvian regions, and lastly at the occipital and prefrontal zones. Characteristic astrocyte end-feet labeling surrounding the vascular system was not established until 25 PCW. We also found AQP4 expression in a subpopulation of glial radial cells with processes that do not progress radially but, rather, curve following white matter tracts (corpus callosum and fornix), which were considered as glial stem cells (GSC). Under hydrocephalic conditions, GSC adjacent to characteristic ventricular zone disruption showed signs of early differentiation into astrocytes which may affect normal gliogenesis and contribute to the white matter dysgenesis. Finally, we found that AQP4 is expressed in the microvesicle fraction (p < 0.01) of CSF from patients with obstructive hydrocephalus. These findings suggest the potential use of AQP4 as a diagnostic and prognostic marker of pediatric hydrocephalus and as gliogenesis biomarker.
Integrative Proposals of Sports Monitoring: Subjective Outperforms Objective Monitoring
Authors: Montull Lluc , Slapšinskaitė-Dackevičienė Agne , Kiely John , Hristovski Robert , Balagué Natàlia
Published: March 2022

Current trends in sports monitoring are characterized by the massive collection of tech-based biomechanical, physiological and performance data, integrated through mathematical algorithms. However, the application of algorithms, predicated on mechanistic assumptions of how athletes operate, cannot capture, assess and adequately promote athletes’ health and performance. The objective of this paper is to reorient the current integrative proposals of sports monitoring by re-conceptualizing athletes as complex adaptive systems (CAS). CAS contain higher-order perceptual units that provide continuous and multilevel integrated information about performer–environment interactions. Such integrative properties offer exceptional possibilities of subjective monitoring for outperforming any objective monitoring system. Future research should investigate how to enhance this human potential to contribute further to athletes’ health and performance. This line of argument is not intended to advocate for the elimination of objective assessments, but to highlight the integrative possibilities of subjective monitoring.
Restrictive Fluid Administration vs. Standard of Care in Emergency Department Sepsis Patients (REFACED Sepsis)—protocol for a multicenter, randomized, clinical, proof-of-concept trial
Authors: Jessen Marie Kristine , Andersen Lars Wiuff , Thomsen Marie-Louise Holm , Kristensen Peter , Hayeri Wazhma , Hassel Ranva Espegård , Perner Anders , Petersen Jens Aage Kølsen , Kirkegaard Hans
Published: March 2022

Background

Intravenous fluids are often used in the treatment of sepsis. The better strategy regarding fluid volume is debated, but preliminary data in patients with septic shock or sepsis-related hypotension favor restrictive fluid administration. We describe the protocol and statistical analysis plan for the Restrictive Fluid Administration vs. Standard of Care in Emergency Department Sepsis Patients (REFACED Sepsis)—a multicenter, randomized clinical proof-of-concept trial. The aim of the REFACED Sepsis trial is to test if a restrictive intravenous fluid protocol in emergency department patients with sepsis without shock is feasible and decreases the intravenous fluid volume administered in comparison to standard care.

Methods

This is an investigator-initiated, multicenter, randomized, parallel-group, open-labeled, feasibility trial investigating volumes of crystalloid fluid within 24 h in 124 patients with sepsis without shock enrolled at three emergency departments in the Central Denmark Region. Patients are allocated to two different intravenous fluid regimens: a restrictive approach using four trigger criteria for fluid administration vs. standard care.

The primary, feasibility outcome is total intravenous, crystalloid fluid volume within 24 h, and key secondary outcomes include protocol violations, total fluids (intravenous and oral) within 24 h, and serious adverse reactions and suspected unexpected serious adverse reactions.

Status: The trial started in November 2021, and the last patient is anticipated to be included in January 2022.

Discussion

Sepsis is very common in emergency department patients and fluid administration is very frequently administered in these patients. However, the evidence to guide fluid administration is very sparse. This feasibility trial will be the foundation for a potential future large-scale trial investigating restrictive vs. standard fluid administration in patients with sepsis.

Trial registration

EudraCT number: 2021-000224-35 (date: 2021 May 03), ClinicalTrials.gov number: NCT05076435 (date: 2021 October 13), Committee on Health Research Ethics – Central Denmark Region: 1-10-72-163-21 (date: 2021 June 28).
Understanding the implication of Kawakita model parameters using in-die force-displacement curve analysis for compacted and non-compacted API powders
Authors: Rashid Iyad , Haddadin Rula Raji , Alkafaween Ashaar Abdulsalam , Alkaraki Rawan Nayef , Alkasasbeh Rehan Mohammad
Published: March 2022

The aim of this study was to investigate powder mechanics upon compression using data obtained from force-displacement (F-D) curves. The Kawakita model of powder compression analysis was adopted in order to compare the pressure-volume reduction relationship of the drug powders in relation to the F-D curves. Experiments were carried out on six model drugs (metronidazole, metformin, secnidazole, ciprofloxacin, norfloxacin, and mebeverine). The drugs were compressed at different pressures in the non-processed or processed (using a roller compactor) forms. Results indicate the similarity between the F-D curves and a rearranged form of the Kawakita model. The foregoing enables the calculation of two important powder parameters, “a” (maximum powder volume reduction) and “Pk” (pressure required to achieve half of the maximum volume reduction) from the F-D curves without the need, as in the case of the conventional Kawakita model, to compress powders into tablets at different compression forces.

Graphical abstract
A new concept for the production of 11C-labelled radiotracers
Authors: Wenz Jan , Arndt Felix , Samnick Samuel
Published: March 2022

Background

The GMP-compliant production of radiopharmaceuticals has been performed using disposable units (cassettes) with a dedicated synthesis module. To expand this “plug ‘n’ synthesize” principle to a broader scope of modules we developed a pressure controlled setup that offers an alternative to the usual stepper motor controlled rotary valves. The new concept was successfully applied to the synthesis of N-methyl-[11C]choline, L-S-methyl-[11C]methionine and [11C]acetate.

Results

The target gas purification of cyclotron produced [11C]CO2 and subsequent conversion to [11C]MeI was carried out on a TRACERlab Fx C Pro module. The labelling reactions were controlled with a TRACERlab Fx FE module. With the presented modular principle we were able to produce N-methyl-[11C]choline and L-S-methyl-[11C]methionine by loading a reaction loop with neat N,N'-dimethylaminoethanol (DMAE) or an ethanol/water mixture of NaOH and L-homocysteine (L-HC), respectively and a subsequent reaction with [11C]MeI. After 18 min N-methyl-[11C]choline was isolated with 52% decay corrected yield and a radiochemical purity of > 99%. For L-S-methyl-[11C]methionine the total reaction time was 19 min reaction, yielding 25% of pure product (> 97%). The reactor design was used as an exemplary model for the technically challenging [11C]acetate synthesis. The disposable unit was filled with 1 mL MeMgCl (0.75 M) in tetrahydrofuran (THF) bevore [11C]CO2 was passed through. After complete release of [11C]CO2 the reaction mixture was quenched with water and guided through a series of ion exchangers (H+, Ag+ and OH−). The product was retained on a strong anion exchanger, washed with water and finally extracted with saline. The product mixture was acidified and degassed to separate excess [11C]CO2 before dispensing. Under these conditions the total reaction time was 18 ± 2 min and pure [11C]acetate (n = 10) was isolated with a decay corrected yield of 51 ± 5%.

Conclusion

Herein, we described a novel single use unit for the synthesis of carbon-11 labelled tracers for preclinical and clinical applications of N-methyl-[11C]choline, L-S-methyl-[11C]methionine and [11C]acetate.
Interpolated testing and content pretesting as interventions to reduce task-unrelated thoughts during a video lecture
Authors: Welhaf Matthew S. , Phillips Natalie E. , Smeekens Bridget A. , Miyake Akira , Kane Michael J.
Published: March 2022

Considerable research has examined the prevalence and apparent consequences of task-unrelated thoughts (TUTs) in both laboratory and authentic educational settings. Few studies, however, have explored methods to reduce TUTs during learning; those few studies tested small samples or used unvalidated TUT assessments. The present experimental study attempted to conceptually replicate or extend previous findings of interpolated testing and pretesting effects on TUT and learning. In a study of 195 U.S. undergraduates, we investigated whether interpolated testing (compared to interpolated restudy) and pretesting on lecture-relevant materials (compared to pretesting on conceptually related but lecture-irrelevant materials) would reduce TUTs during a video lecture on introductory statistics. Subjects completed either a content-matched or content-mismatched pretest on statistics concepts and then watched a narrated lecture slideshow. During the lecture, half of the sample completed interpolated tests on the lecture material and half completed interpolated restudy of that material. All subjects responded to unpredictably presented thought probes during the video to assess their immediately preceding thoughts, including TUTs. Following the lecture, students reported on their situational interest elicited by the lecture and then completed a posttest. Interpolated testing significantly reduced TUT rates during the lecture compared to restudying, conceptually replicating previous findings—but with a small effect size and no supporting Bayes-factor evidence. We found statistical evidence for neither an interpolated testing effect on learning, nor an effect of matched-content pretesting on TUT rates or learning. Interpolated testing might have limited utility to support students’ attention, but varying effect sizes across studies warrants further work.
Social networking sites use and college students’ academic performance: testing for an inverted U-shaped relationship using automated mobile app usage data
Authors: Tafesse Wondwesen
Published: March 2022

With the widespread adoption of social networking sites among college students, discerning the relationship between social networking sites use and college students’ academic performance has become a major research endeavor. However, much of the available research in this area rely on student self-reports and findings are notably inconsistent. Further, available studies typically cast the relationship between social networking sites use and college students’ academic performance in linear terms, ignoring the potential moderating role of the intensity of social networking sites use. In this study, we draw on contrasting arguments in the literature predicting positive and negative effects of social networking sites use on college students’ academic performance to propose an inverted U-shaped relationship. We collected data on social networking sites use by having college students install a tracking app on their smartphones for 1 week and data on academic performance from internal college records. Our findings indicate that social networking sites use indeed exhibits an inverted U-shaped relationship with college students’ academic performance. Specifically, we find that spending up to 88.87 min daily on social networking sites is positively associated with academic performance, but beyond that, social networking sites use is negatively associated with academic performance. We discuss the implications of our findings.
Health-related quality of life in patients with COVID-19; international development of a patient-reported outcome measure
Authors: Amdal Cecilie Delphin , Taylor Katherine , Kuliś Dagmara , Falk Ragnhild Sørum , Bottomley Andrew , Arraras Juan Ignacio , Barte James Harold , Darlington Anne Sophie , Hofsø Kristin , Holzner Bernard , Jørgensen Nina Marie Høyning , Mariano Melissa Paulita , Pe Madeline , Piccinin Claire , Riccetti Nicola , Schranz Melanie , Wheelwright Sally , Bjordal Kristin
Published: March 2022

Background

We aimed to create a questionnaire to assess the health-related quality of life including functioning, symptoms, and general health status of adult patients with current or previous COVID-19. Here, we report on Phase I and II of the development.

Methods

Internationally recognized methodology for questionnaire development was followed. In Phase I, a comprehensive literature review was performed to identify relevant COVID-19 issues. Decisions for inclusion, exclusion, and data extraction were completed independently in teams of two and then compared. The resulting issues were discussed with health care professionals (HCPs) and current and former COVID-19 patients. The input of HCPs and patients was carefully considered, and the list of issues updated. In Phase II, this updated list was operationalized into items/questions.

Results

The literature review yielded 3342 publications, 339 of which were selected for full-text review, and 75 issues were identified. Discussions with 44 HCPs from seven countries and 52 patients from six countries showed that psychological symptoms, worries, and reduced functioning lasted the longest for patients, and there were considerable discrepancies between HCPs and patients concerning the importance of some of the symptoms. The final list included 73 issues, which were operationalized into an 80-item questionnaire.

Conclusion

The resulting COVID-19 questionnaire covers health–related quality of life issues relevant to COVID-19 patients and is available in several languages. The next steps include testing of the applicability and patients’ acceptability of the questionnaire (Phase IIIA) and preliminary psychometric testing (Phase IIIB).
The possible ameliorative role of Moringa oleifera seed oil on sofosbuvir-induced nephrotoxicity in albino rats; histopathological, immunohistochemical and biochemical studies
Authors: Mahran Hoda A. , Okdah Yosry A. , Zaky Aisha A. , Arisha Samah M.
Published: March 2022

Background

Hepatitis C is a liver infection caused by the hepatitis C virus (HCV). It can cause both acute and chronic hepatitis. Sofosbuvir (sofo) is a nucleotide analog inhibitor of HCV NS5B polymerase used to treat chronic hepatitis C infection as a component of a combination of antiviral treatment regimen. Many side effects of sofo were reported in different mammalian organs including kidney. Moringa oleifera (MO) is one of the medicinal plants which have many pharmacological activities and nutritional applications due to its rich phytonutrients content. This study aimed to investigate the possible ameliorative effect of MO seed oil against nephrotoxicity induced by sofo in adult male albino rats. The experimental animals were divided equally into four groups. Group I: animals were served as control. Group II: animals were orally given MO oil (2 ml/kg/day). Group III: animals were orally administered with sofo (36 mg/kg/day). Group IV: animals were orally given sofo then after 2 h they were given MO oil (with the same previous doses). All doses were daily given to the animals for eight weeks. At the end of the experiments, animals were sacrificed and sera were collected to determine urea, creatinine and malondialdehyde levels and catalase activity. Kidneys were removed out and prepared for both the histological and immunohistochemical studies.

Results

Sofo-treated animals showed many pathological changes; damaged glomeruli and degenerated renal tubules with vacuolated lining epithelial cells contain pyknotic nuclei. In addition, leukocytic infiltration, congested blood vessels and hemorrhage were seen. Caspase-3 and PCNA were expressed in a large number of cells in the same group. Moreover, a significant increase in urea, creatinine and malondialdehyde levels was recorded as well as a significant decrease in catalase activity. Co-treatment of MO oil with sofo effectively counteracted the observed adverse effects. It attenuated the histological picture of the kidney, significantly ameliorated urea, creatinine and malondialdehyde levels and catalase activity and restored the normal expressions of caspase-3 and PCNA.

Conclusions

Moringa oleifera oil can ameliorate nephrotoxicity induced by sofo via its antioxidant, anti-inflammatory and anti-apoptotic properties.
Evaluating the potential of wild cocoyam (Caladium bicolor) for citric acid production in a submerged culture of Aspergillus niger
Authors: Ezeaa Ifeanyi Boniface , Ezaka Emmanuel
Published: March 2022

Background

Wild cocoyam (Caladium bicolar) is non-edible starchy material which is commonly known as ‘Ede umuagbara’ in the south-east region of Nigeria. Evaluating the potential of wild cocoyam for citric acid production was investigated usingAspergillus nigerin a submerged culture.

Results

This study showed that wild cocoyam flour concentration, pretreatment of wild cocoyam, inoculums size, initial pH of wild cocoyam and incubation temperature of wild cocoyam medium had significant effect on the amount of citric acid produced from wild cocoyam (p < 0.05). Citric acid concentration increased as the concentration wild cocoyam increased up to 15% with the maximum citric acid concentration of 10.0 ± 0.251 g/l after 96 h of fermentation. Also citric acid concentration increased as the pretreatment time of wild cocoyam increased from 5 to 20 min. A 20 min pretreatment time at 121 °C was the optimum with maximum concentration of 14.0 ± 0.325 g/l citric acid after 96 h of fermentation. 15% inoculums was the optimum with the maximum concentration of 16.0 ± 0.431 g/l citric acid. However, the wild cocoyam initial pH value of 5.5 was the optimum for maximum citric acid concentration of 19.0 ± 0.316 after 96 h of fermentation. Moreover, citric acid concentration increased as the incubation temperature of wild cocoyam medium increased from 20 to 30 °C. Incubation of wild cocoyam medium at 30 °C was the optimum with the maximum citric acid concentration of 23.0 ± 0.432 g/l after 96 h of fermentation.

Conclusion

Therefore, the result revealed that wild cocoyam which is found plenty within the south-east region of Nigeria can be converted to citric acid if well harnessed.
Clinical pattern of synthetic cannabinoids users in Upper Egypt: cross-sectional study
Authors: Abdelmoneim Wafaa M. , Ghandour Nagwa M. , Fawzy Mohamed , Mohammed Marwa Kh. , Ramadan Abdelrahman G. , Abdellah Nora Z.
Published: March 2022

Background

There is an expanding use of new psychoactive substances containing synthetic cannabinoids in the last years. This study was conducted to identify the epidemiologic data of acute and chronic toxicity by synthetic cannabinoids in Upper Egypt patients.

Results

All cases included in the presenting study were fifty males. Most users of synthetic cannabinoids were in the adolescence and middle age group (15–< 35) representing 68%. Curiosity was the most common motivator for using synthetic cannabinoids. Alteration of perception was reported in 68% of subjects after synthetic cannabinoids use. Additionally, dizziness, loss of consciousness, convulsion, and panic attacks were also reported. Cardiovascular adverse effects experienced by users were palpitations (76%) and chest pain (12%). Half of included subjects (50%) reported financial problems and about one-third (32%) got involved in domestic violence. Abnormal routine laboratory findings that were found in included cases were in the form of 12% anemia, 10% leukocytosis, and 6% leucopenia. Also, liver and kidney functions were elevated in 8% and 4% of the cases, respectively. While 22% and 4% of cases were positive for hepatitis C and HIV respectively.

Conclusions

This study can be concluded that adolescence are the most common users of SCs; neuro-psychiatric and cardiovascular side effects were the most experienced by subjects. Violence in many forms, especially domestic violence, was associated with synthetic cannabinoids abuse.

Trial registration

Registered in clinical trial under name syntheticcannabinoidsAssiut and ID NCT03866941 and URL.
Health funders’ dissemination and implementation practices: results from a survey of the Ensuring Value in Research (EViR) Funders’ Forum
Authors: van der Linden Barbara , Dunham Kelly M. , Siegel Joanna , Lazowick Emily , Bowdery Michael , Lamont Tara , Ford Alison
Published: March 2022

Background

A significant gap persists between evidence from research and its use in practice. Research funders, important actors in the health research system, can help reduce this gap by initiating dissemination and implementation (D&I) activities. The specific types of D&I activities funders currently lead have not been explored thoroughly. The Ensuring Value in Research (EViR) Funders’ Forum—an international collaboration of health-related research funders—was established in 2017 to address research waste issues and increase the value of research. The Forum surveyed funders to learn about their D&I practices and challenges.

Methods

We distributed a five-item exploratory survey to participating funders in August 2018. The results informed the development of a survey instrument, distributed in June 2019. The survey instrument contained 15 items prompting respondents to categorize and describe their level of effort in six practice areas: release of findings, dissemination, knowledge exchange/partnering, implementation, building capacity, and implementation research. In addition, funders were asked to describe examples of their practices in detail. Thirty-one funders completed the survey instrument, a 58% response rate.

Results

Most funders regard D&I as a high priority, but funders vary in levels of activity per practice area. Over half of respondents reported that they have at least some activity in all D&I practice areas surveyed, with the exception of implementation research. The vast majority indicated some or significant activity in release of findings (97%) and dissemination (87%). Nearly one-fifth of funders (19%) indicated that implementation is outside their remit, and 26% indicated that implementation research is outside their remit. Survey respondents shared a broad range of examples of activities in each practice area. Lack of evidence for successful approaches and measuring impact were named frequently as challenges and as potential areas for collaboration.

Conclusions

Although models of dissemination and implementation vary across organizations, the majority of funders indicated that D&I of research findings is a priority. Funders indicated a need for evidence on effectiveness of various approaches to D&I. Increased collaboration between funders, including sharing good practices, will increase our collective learning and knowledge development.
Quality of life and clinical assessment of joint health in children with hemophilic arthropathy
Authors: Hassab Hoda M. , Saad Hany R. , Abdel Ghany Hayam M.
Published: March 2022

Background

Hemophilic arthropathy results in pain, deformity, and disability with severe impairments, activity limitation, and thus productivity loss. Also patterns of treatment interfere with patients’ life, so the quality of life should be assessed when evaluating treatment. The aim of this work was to assess the quality of life of children with hemophilic arthropathy and its relation to clinical joint health.

Results

The study was carried out on fifty boys with hemophilic arthropathy. All patients were subjected to thorough local clinical assessment of the most affected and/or target joint using Hemophilia Joint Health Score (HJHS 2.1) and assessment of quality of life using Haemo quality of life (Haemo-Qol) questionnaire children and parent versions. Among the fifty hemophilic patients, 36 (72%) patients were hemophilia A and 14 (28 %) patients were hemophilia B. The age at first hemarthrosis ranged from 1 to 8 years with a mean of 2.40±1.78. While the number of joints affected in the studied patients ranged from 2 to 13 joints with a mean of 7±3.25. As regards the severity, 23 patients (46%) had severe, and 27 (54%) had moderate hemophilia. Forty four (88%) patients had different degrees of anemia. There was significant correlation between child Haemo-QoL with degree of anemia (r = 0.291, P = 0.040), mainly with view and school dimensions. There were significant correlations between child and parent Haemo-QoL and HJHS with each of the following: factor activity level, duration of the disease, duration of joint disease, number of bleeding attacks last year, and number of joints affected. Synovectomy was done for 5 (10%) patients. The total child Haemo-QoL score was statistically significantly lower after the intervention (P=0.043), with a significant improvement in physical health, feeling, view, family, school and sports, treatment, and dealing dimensions. In the current study, there were significant positive correlations between child and parent Haemo-QoL and HJHS scores.

Conclusions

The quality of life in patients with hemophilic arthropathy was influenced by the joint health, factor activity level, disease duration, number of bleeding attacks, number of joints affected (during life), duration of joint disease, and presence of hepatitis C virus.
Heterogeneity of pore-throat structures and petrophysical properties of tight sandstone and its influence on seepage: A case study of sandstone in the Yanchang Formation, Ordos Basin, China
Authors: Tang Ying , Bai Jingbiao , Zhang Nan , Lei Jingchao , Wang Ruifei , Tan Shihao , Wang Mingxian , Wang Yuanyi , Chen Kaiyun
Published: March 2022

Tight sandstone reservoirs are characterized by poor petrophysical properties, strong pore-throat structures, and heterogeneous permeability, which prevent oilfield water flooding. We take the tight sandstone reservoir of the Yanchang Formation in Ordos Basin as an example, select samples from the Chang 6 and Chang 8 members in the HX block for constant-rate mercury injection and single-core and combined-core model water-flooding tests, and discuss the effects of heterogeneous pore-throat structures and petrophysical properties on the seepage of the tight sandstone. Constant-rate mercury injection tests found that the permeability of the tight sandstone was controlled by the throats. Compared with the pore structures, the throat structures were more heterogeneous, and the samples with more heterogeneous throats were more permeable. Therefore, in addition to the morphology of the pore-throat structures, the heterogeneity of the throats also was used to evaluate the seepage. When applying the water-flooding tests with the combined-core model, the water absorption capacity of the high-permeability core with a high permeability contrast (7.5) was greater than that of the high-permeability core with a low permeability contrast (3.6). Moreover, by comparing the results from the water-flooding experiment for the same core between a single-core and the combined-core model, the loss of the oil displacement efficiency (70.7%) of the low-permeability core in the combined-core model with a high permeability contrast (7.5) was much higher than that (29.8%) of the low-permeability core in the combined-core model, which had a low permeability contrast (3.6). The water absorption percentage and the recovery of the low-permeability core in the combined-core model with a high permeability contrast were lower, indicating that after water flooding, the remaining oil in the low-permeability reservoir in the area with a strong permeability heterogeneity was enriched. Such enrichment may increase the exploitation potential of tight reservoirs.
Epidermal Growth Factor Receptor Inhibition in Epidermal Growth Factor Receptor–Amplified Gastroesophageal Cancer: Retrospective Global Experience
Authors: Maron Steven B. , Moya Stephanie , Morano Federica , Emmett Matthew J. , Chou Joanne F. , Sabwa Shalom , Walch Henry , Peterson Bryan , Schrock Alexa B. , Zhang Liangliang , Janjigian Yelena Y. , Chalasani Sree , Ku Geoffrey Y. , Disel Umut , Enzinger Peter , Uboha Nataliya , Kato Shumei , Yoshino Takayuki , Shitara Kohei , Nakamura Yoshiaki , Saeed Anwaar , Kasi Pashtoon M. , Chao Joseph , Lee Jeeyun , Capanu Marinela , Wainberg Zev , Petty Russell , Pietrantonio Filippo , Klempner Samuel J. , Catenacci Daniel V.T.
Published: March 2022

PURPOSE

Subset analyses from phase III evaluation of epidermal growth factor receptor inhibition (EGFRi) suggest improved outcomes in patients with EGFR-amplified gastroesophageal adenocarcinoma (GEA), but large-scale analyses are lacking. This multi-institutional analysis sought to determine the role of EGFRi in the largest cohort of patients with EGFR-amplified GEA to date.

PATIENTS AND METHODS

A total of 60 patients from 15 tertiary cancer centers in six countries met the inclusion criteria. These criteria required histologically confirmed GEA in the metastatic or unresectable setting with EGFR amplification identified by using a Clinical Laboratory Improvement Amendments–approved assay, and who received on- or off-protocol EGFRi. Testing could be by tissue next-generation sequencing, plasma circulating tumor DNA next-generation sequencing, and/or fluorescence in situ hybridization performed by a Clinical Laboratory Improvement Amendments approved laboratory. Treatment patterns and outcomes analysis was also performed using a deidentified clinicogenomic database (CGDB).

RESULTS

Sixty patients with EGFR-amplified GEA received EGFRi, including 31 of 60 patients (52%) with concurrent chemotherapy. Across treatment lines, patients achieved a 43% objective response rate with a median progression-free survival of 4.6 months (95% CI, 3.5 to 6.4). Patients receiving EGFRi in first-, second-, and third-line therapy achieved a median overall survival of 20.6 months (95% CI, 13.5 to not reached [NR]), 9 months (95% CI, 7.9 to NR), and 8.4 months (7.6 to NR), respectively. This survival far exceeded the 11.2-month (95% CI, 8.7 to 14.2) median overall survival from first-line initiation of non-EGFRi therapy in patients with EGFR-amplified GEA in the CGDB. Despite this benefit, analysis of the CGDB (January 2011-December 2020) suggests that only 5% of patients with EGFR-amplified GEA received EGFRi.

CONCLUSION

Patients with EGFR-amplified GEA derive significant benefit from EGFRi. Further prospective investigation of EGFRi in a well-selected patient population is ongoing in an upcoming trial of amivantamab in EGFR and/or MET amplified GEA.
Association Between Race and Opioid-Induced Respiratory Depression: An International Post Hoc Analysis of the Prediction of Opioid-induced Respiratory Depression In Patients Monitored by Capnography Trial
Authors: Sim Ming Ann , Seet Edwin , Khanna Ashish K. , Weingarten Toby N. , Liew Lydia , Law Lawrence Siu-Chun , Liu Katherine E. , Di Piazza Fabio , Ti Lian Kah ,   on behalf of the PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) Group Investigators
Published: March 2022

BACKGROUND:

Opioid-induced respiratory depression (OIRD) is common on the medical and surgical wards and is associated with increased morbidity and health care costs. While previous studies have investigated risk factors for OIRD, the role of race remains unclear. We aim to investigate the association between race and OIRD occurrence on the medical/surgical ward.

METHODS:

This is a post hoc analysis of the PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) trial; a prospective multinational observational blinded study of 1335 general ward patients who received parenteral opioids and underwent blinded capnography and oximetry monitoring to identify OIRD episodes. For this study, demographic and perioperative data, including race and comorbidities, were analyzed and assessed for potential associations with OIRD. Univariable χ2 and Mann-Whitney U tests were used. Stepwise selection of all baseline and demographic characteristics was used in the multivariable logistic regression analysis.

RESULTS:

A total of 1253 patients had sufficient racial data (317 Asian, 158 Black, 736 White, and 42 other races) for inclusion. The incidence of OIRD was 60% in Asians (N = 190/317), 25% in Blacks (N = 40/158), 43% in Whites (N = 316/736), and 45% (N = 19/42) in other races. Baseline characteristics varied significantly: Asians were older, more opioid naïve, and had higher opioid requirements, while Blacks had higher incidences of heart failure, obesity, and smoking. Stepwise multivariable logistic regression revealed that Asians had increased risk of OIRD compared to Blacks (odds ratio [OR], 2.49; 95% confidence interval [CI], 1.54–4.04; P = .0002) and Whites (OR, 1.38; 95% CI, 1.01–1.87; P = .0432). Whites had a higher risk of OIRD compared to Blacks (OR, 1.81; 95% CI, 1.18–2.78; P = .0067). The model’s area under the curve was 0.760 (95% CI, 0.733–0.787), with a Hosmer-Lemeshow goodness-of-fit test P value of .23.

CONCLUSIONS:

This post hoc analysis of PRODIGY found a novel association between Asian race and increased OIRD incidence. Further study is required to elucidate its underlying mechanisms and develop targeted care pathways to reduce OIRD in susceptible populations.