bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutation analysis of the ATP7B gene and genotype–phenotype correlation in Chinese patients with Wilson disease
Authors: Li Mingming , Ma Jing , Wang Wenlong , Yang Xu , Luo Kaizhong
Published: September 2021

Aim

To discover the novel ATP7B mutations in 103 southern Chinese patients with Wilson disease (WD), and to determine the spectrum and frequency of mutations in the ATP7B gene and genotype–phenotype correlation in a large-scale sample of Chinese WD patients.

Methods

One hundred three WD patients from 101 unrelated families in southern China were enrolled in this study. Genomic DNA was extracted from the peripheral blood. Direct sequencing of all 21 exons within ATP7B was performed. Subsequently, an extensive study of the overall spectrum and frequency of ATP7B mutations and genotype–phenotype correlation was performed in all Chinese patients eligible from the literature, combined with the current southern group.

Results

In 103 patients with WD, we identified 48 different mutations (42 missense mutations, 4 nonsense mutations and 2 frameshifts). Of these, 3 mutations had not been previously reported: c.1510_1511insA, c.2233C>A (p.Leu745Met) and c.3824T>C (p.Leu1275Ser). The c.2333G>T (p.Arg778 Leu) at exon 8, was the most common mutation with an allelic frequency of 18.8%, followed by c.2975C>T (p.Pro992Leu) at exon 13, with an allelic frequency of 13.4%. In the comprehensive study, 233 distinct mutations were identified, including 154 missense mutations, 23 nonsense mutations and 56 frameshifts. Eighty-five variants were identified as novel mutations. The c.2333G>T (p.Arg778 Leu) and c.2975C>T (p.Pro992Leu) were the most common mutations, with allelic frequencies of 28.6% and 13.0%, respectively. Exons 8, 12, 13, 16 and 18 were recognised as hotspot exons. Phenotype–genotype correlation analysis suggested that c.2333G>T (p.Arg778 Leu) was significantly associated with lower levels of serum ceruloplasmin (P = 0.034). c.2975C>T (p.Pro992Leu) was correlated with earlier age of disease onset (P = 0.002). Additionally, we found that the c.3809A>G (p.Asn1270Ser) mutation significantly indicated younger onset age (P = 0.012), and the c.3884C>T (p.Ala1295Val) mutation at exon 18 was significantly associated with hepatic presentation (P = 0.048). Moreover, the patients with mixed presentation displayed the initial WD features at an older onset age than the groups with either liver disease or neurological presentation (P = 0.039, P = 0.015, respectively). No significant difference was observed in the presence of KF rings among the three groups with different clinical manifestations.

Conclusion

In this study, we identified three novel mutations in 103 WD patients from the southern part of China, which could enrich the previously established mutational spectrum of the ATP7B gene. Moreover, we tapped into a large-scale study of a Chinese WD cohort to characterise the overall phenotypic and genotypic spectra and assess the association between genotype and phenotype, which enhances the current knowledge about the population genetics of WD in China.
How are we evaluating the cost-effectiveness of companion biomarkers for targeted cancer therapies? A systematic review
Authors: Seo Mikyung Kelly , Cairns John
Published: September 2021

Background

Despite the increasing economic assessment of biomarker-guided therapies, no clear agreement exists whether existing methods are sufficient or whether different methods might produce different cost-effectiveness results. This study aims to examine current practices of modeling companion biomarkers when assessing the cost-effectiveness of targeted cancer therapies. It investigates the current methods in modeling the characteristics of companion diagnostics based on existing economic evaluations of biomarker-guided therapies in cancer.

Methods

A literature search was performed using Medline, Embase, EconLit, Cochrane library for economic evaluations of biomarker-guided therapies with companion diagnostics in cancer. Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Studies were selected using pre-specified eligibility criteria based on the PICO framework. To make the included studies more comparable, we qualitatively synthesized the data under nine domains of methods where consensus was deemed lacking.

Results

Only four of the twenty-two studies included in this review were found to be of good quality with respect to incorporating the characteristics of companion biomarkers in economic evaluations. However, many evaluations focused on a pre-selected patient group rather than including all patients regardless of their biomarker status. Companion biomarker characteristics captured in evaluations were often limited to the cost or the accuracy of the test. Often, only the costs of biomarker testing were modelled. Clinical outcomes and health state utilities were often not included due to the limited data generated by clinical trials. Methods of economic evaluation were not applied consistently in assessments of companion cancer biomarkers for targeted therapies. It was also shown that conflicting cost-effectiveness results were likely depending on what comparator arm was chosen and what comparison structure was designed in the model.

Conclusion

We found no consistent approach applied in assessing the value of companion biomarker tests and including the characteristics of biomarkers in an economic evaluation of targeted oncology therapies. Currently, many economic evaluations fail to capture the full value of companion biomarkers beyond sensitivity/specificity and cost related to biomarker testing.
COVID-19 pandemic spread against countries’ non-pharmaceutical interventions responses: a data-mining driven comparative study
Authors: Xylogiannopoulos Konstantinos F. , Karampelas Panagiotis , Alhajj Reda
Published: September 2021

Background

The first half of 2020 has been marked as the era of COVID-19 pandemic which affected the world globally in almost every aspect of the daily life from societal to economical. To prevent the spread of COVID-19, countries have implemented diverse policies regarding Non-Pharmaceutical Intervention (NPI) measures. This is because in the first stage countries had limited knowledge about the virus and its contagiousness. Also, there was no effective medication or vaccines. This paper studies the effectiveness of the implemented policies and measures against the deaths attributed to the virus between January and May 2020.

Methods

Data from the European Centre for Disease Prevention and Control regarding the identified cases and deaths of COVID-19 from 48 countries have been used. Additionally, data concerning the NPI measures related policies implemented by the 48 countries and the capacity of their health care systems was collected manually from their national gazettes and official institutes. Data mining, time series analysis, pattern detection, machine learning, clustering methods and visual analytics techniques have been applied to analyze the collected data and discover possible relationships between the implemented NPIs and COVID-19 spread and mortality. Further, we recorded and analyzed the responses of the countries against COVID-19 pandemic, mainly in urban areas which are over-populated and accordingly COVID-19 has the potential to spread easier among humans.

Results

The data mining and clustering analysis of the collected data showed that the implementation of the NPI measures before the first death case seems to be very effective in controlling the spread of the disease. In other words, delaying the implementation of the NPI measures to after the first death case has practically little effect on limiting the spread of the disease. The success of implementing the NPI measures further depends on the way each government monitored their application. Countries with stricter policing of the measures seems to be more effective in controlling the transmission of the disease.

Conclusions

The conducted comparative data mining study provides insights regarding the correlation between the early implementation of the NPI measures and controlling COVID-19 contagiousness and mortality. We reported a number of useful observations that could be very helpful to the decision makers or epidemiologists regarding the rapid implementation and monitoring of the NPI measures in case of a future wave of COVID-19 or to deal with other unknown infectious pandemics. Regardless, after the first wave of COVID-19, most countries have decided to lift the restrictions and return to normal. This has resulted in a severe second wave in some countries, a situation which requires re-evaluating the whole process and inspiring lessons for the future.
The protective effect of crocin on cisplatin-induced testicular impairment in rats
Authors: Mesbahzadeh Behzad , Hassanzadeh-Taheri Mohammadmehdi , Aliparast Mohadese-sadat , Baniasadi Pardis , Hosseini Mehran
Published: September 2021

Background

Side effects of cisplatin (CIS) such as testicular toxicity restrict its clinical use. Instead, evidence indicates that crocin (CR) has synergistic anti-cancer potential with CIS and exhibited beneficial effects on CIS-induced hepatorenal damage. The aim of this study was to investigate the protective potential of CR against CIS-induced testicular toxicity in rats.

Methods

Fifty adult male Wistar rats randomly assigned to five equal groups including control, CIS, and CIS plus CR at doses of 6.25 mg/kg (CIS + CR6.25), 25 mg/kg (CIS + CR25), and 100 mg/kg (CIS + CR100). CIS and CIS + CR groups received a single intraperitoneally (i.p.) injection of CIS (7 mg/kg). CR (6.25–100 mg/kg i.p.) injections were started three days before the CIS injection and continued once a day for up to 13 days. On the 14th day, all animals were sacrificed and their blood samples and testes were removed for biochemical and histological analyses.

Results

Compared to the control group, CIS significantly decreased relative testis weight (0.28 vs. 0.39,p < 0.001), testosterone level (0.3 vs. 2.31 ng/mL,p < 0.001), germinal layer area (25,886 vs. 35,320 µm2,p < 0.001), superoxide dismutase (SOD) (0.9 vs.1.73 U/mg,p < 0.001) and increased testicular lipid peroxidation (3.05 vs. 15.35 nmol/mg,p < 0.001). CR at 25 mg/kg ameliorated testicular lipid peroxidation and enhanced SOD activity compared to CIS group (p < 0.05). Besides, CR treatment at the maximum dose (100 mg/kg) resulted in reversing CIS effects on testis weight, testosterone level, SOD, lipid peroxidation, and germinal layer area.

Conclusions

These findings demonstrated that CR co-treatment could prevent CIS-induced testicular toxicity in rats.
Predictors and reasons for inappropriate hospitalization days for surgical patients in a tertiary hospital in Wuhan, China: a retrospective study
Authors: Li Hao , Tao Hongbing , Li Gang
Published: September 2021

Background

Inappropriate hospitalization day (IHD) is recognized as an important indication of the excessive demand for health-care services, especially for surgical patients. We aim to examine the degree of IHDs, predictors associated with higher incidences of IHDs, and reasons for each IHD in different periods of hospitalization.

Methods

A total of 4586 hospital days from 408 cases were evaluated by a cross-sectional and retrospective audit program carried out in a tertiary hospital with 5613 beds and 9623 faculty in Wuhan, China. This study used the revised Chinese version of the Appropriateness Evaluation Protocol (C-AEP) to assess IHDs, and the Delay Tool to ascertain each reason for IHDs. A binary logistic regression model was performed to examine the predictors of higher incidences of IHDs.

Results

The average frequency of IHDs was 23.24 %, and a total of 322 cases (78.92 %) were reported to have experienced at least one IHD. The multivariate analysis showed that patients at the age of 60–69 with respect to under 50, and with overlength of stay were predictors of higher incidences of preoperative IHDs, while admission from outpatient, multiple diagnosis, higher surgical incision level, and overlength of stay were predictors of higher incidence of postoperative IHDs. The most frequent reasons related to health providers for IHDs were doctor’s conservative views of patient management and delays in inspection, prescription, appointment, or result report. Patient factors gave rise to nearly a quarter of postoperative IHDs.

Conclusions

Findings from this study indicate that measures including paying more attention to the construction of MDT for diagnosis and treatment in general surgery, reducing laboratory turnaround time, dispelling distrust among health-care providers and patients, setting stricter discharge standards and, providing integrated out-of-hospital services could be adopted accordingly to improve the inappropriateness of hospital stays.
Prevalence and associated factors of hypertension among veterans of the Indian Gorkha regiments living in Pokhara Metropolitan City, Nepal
Authors: Sapkota Abhishek , Neupane Dinesh , Shrestha Aamod Dhoj , Adhikari Tara Ballav , McLachlan Craig Steven , Shrestha Naveen
Published: September 2021

Background

Hypertension is a major preventable risk factor for cardiovascular disease. Occupational factors such as having served or serving in armed forces may be associated with hypertension. This study aimed to assess the prevalence and factors associated with hypertension among veterans of the Indian Gorkha army living in western Nepal.

Methods

A community-based cross-sectional study was conducted among the veterans living in the Pokhara metropolitan city. Data on blood pressure (BP), anthropometric measurements, and behavioral factors were collected by face-to-face interviews using the World Health Organization's non-communicable disease risk factor surveillance (STEPS) tool. Hypertension was defined as systolic blood pressure (BP) ≥ 140 mm Hg and/or diastolic BP of ≥ 90 mm Hg or currently on antihypertensive medication.

Results

The age-adjusted prevalence of hypertension was 66.2 % among the study participants (317). Mean systolic and diastolic blood pressure was 144.5 mmHg (± 18.3) and 89.3mmHg (± 16.0), respectively. Among the hypertensive participants, 67 % were aware of their disease, 90 % of them were under treatment, and 14 % of the individuals who received treatment had their hypertension under control. The proportion of smokers was 12.9 % and alcohol drinker was 86.1 %. One-fourth (25.9 %) of the participants had a family history of hypertension. Veterans aged 55-64 years had higher odds (AOR: 5.3; 95 % CI: 1.8–15.9; p = 0.003) of being associated with hypertension as compared to 35–44 years. Being a current alcohol drinker (AOR: 2.5; 95 % CI: 1.4–4.5; p = 0.003), overweight (AOR: 1.9; 95 % CI: 1.0-3.5; p = 0.04), obese (AOR: 3.1; 95 % CI: 1.1–8.3; p = 0.03) and family history of hypertension (AOR: 2.9; 95 % CI: 1.5–5.8; p = 0.002) were independently associated with hypertension.

Conclusions

Hypertension was prevalent in retired Nepal veterans. Hypertension was associated with a number of modifiable lifestyle and behavioral factors. Our findings suggest the need for screening, education and management of Nepal veterans for hypertension.
How accurate is frozen section pathology compared to permanent pathology in detecting involved margins and lymph nodes in breast cancer?
Authors: Namdar Zahra Mehdipour , Omidifar Navid , Arasteh Peyman , Akrami Majid , Tahmasebi Sedigheh , Nobandegani Aida Salehi , Sedighi Sogol , Zangouri Vahid , Talei Abdolrasoul
Published: September 2021

Background

Frozen section (FS) pathology has multiple limitations, and different institutions report variable experiences with the use of FS for diagnosis of tumor involvement. We aimed to compare the FS accuracy with that of permanent pathology (gold standard) regarding marginal involvement and lymph node status using data from the largest breast cancer registry in Iran.

Methods

In this retrospective study, women who had both FS and permanent pathology reports were included. The two pathology reports were cross compared with regard to the involvement of tumor margins and sentinel lymph nodes.

Results

Overall, 2786 patients entered the study. Mean age of patients was 48.96±11.44 years. A total of 1742 margins were analyzed. Accordingly, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FS pathology for detection of involvement of involved margins were 78.49%, 97.63%, 65.1%, and 98.7%, respectively. The accuracy and area under the curve (AUC) for FS pathology were 96.61% and 0.73 (95% CI: 0.64–0.831), respectively.

A total of 1702 sentinel lymph node biopsies were assessed. Sensitivity, specificity, PPV, and NPV, of FS pathology for detection of lymph node involvement, were 87.1%, 98%, 95.5%, and 93.3%, respectively. Accuracy and AUC of FS for diagnosis of involved lymph nodes were 94.1% and 0.926 (95% CI: 0.909–0.942), respectively.

Conclusion

Frozen pathology is a suitable method for identifying involved sentinel lymph nodes in patients with breast cancer, but this method has a less than optimum efficacy for detecting and confirming marginal involvement.
AMULET: a novel read count-based method for effective multiplet detection from single nucleus ATAC-seq data
Authors: Thibodeau Asa , Eroglu Alper , McGinnis Christopher S. , Lawlor Nathan , Nehar-Belaid Djamel , Kursawe Romy , Marches Radu , Conrad Daniel N. , Kuchel George A. , Gartner Zev J. , Banchereau Jacques , Stitzel Michael L. , Cicek A. Ercument , Ucar Duygu
Published: September 2021

Detecting multiplets in single nucleus (sn)ATAC-seq data is challenging due to data sparsity and limited dynamic range. AMULET (ATAC-seq MULtiplet Estimation Tool) enumerates regions with greater than two uniquely aligned reads across the genome to effectively detect multiplets. We evaluate the method by generating snATAC-seq data in the human blood and pancreatic islet samples. AMULET has high precision, estimated via donor-based multiplexing, and high recall, estimated via simulated multiplets, compared to alternatives and identifies multiplets most effectively when a certain read depth of 25K median valid reads per nucleus is achieved.
H2A ubiquitination is essential for Polycomb Repressive Complex 1-mediated gene regulation in Marchantia polymorpha
Authors: Liu Shujing , Trejo-Arellano Minerva S. , Qiu Yichun , Eklund D. Magnus , Köhler Claudia , Hennig Lars
Published: September 2021

Background

Polycomb repressive complex 1 (PRC1) and PRC2 are chromatin regulators maintaining transcriptional repression. The deposition of H3 lysine 27 tri-methylation (H3K27me3) by PRC2 is known to be required for transcriptional repression, whereas the contribution of H2A ubiquitination (H2Aub) in the Polycomb repressive system remains unclear in plants.

Results

We directly test the requirement of H2Aub for gene regulation in Marchantia polymorpha by generating point mutations in H2A that prevent ubiquitination by PRC1. These mutants show reduced H3K27me3 levels on the same target sites as mutants defective in PRC1 subunits MpBMI1 and the homolog MpBMI1L, revealing that PRC1-catalyzed H2Aub is essential for Polycomb system function. Furthermore, by comparing transcriptome data between mutants in MpH2A and MpBMI1/1L, we demonstrate that H2Aub contributes to the PRC1-mediated transcriptional level of genes and transposable elements.

Conclusion

Together, our data demonstrates that H2Aub plays a direct role in H3K27me3 deposition and is required for PRC1-mediated transcriptional changes in both genes and transposable elements in Marchantia.
Intrathecal baclofen therapy for severe spasticity in an adult with tethered cord syndrome: a case report
Authors: Takagi Yasutaka , Yamada Hiroshi , Ebara Hidehumi , Hayashi Hiroyuki , Kidani Satoshi , Toyooka Kazu , Ishino Yuji , Kitano Yoshiyuki , Nakanami Aki , Kagechika Kenji , Yahata Tetsutaro , Tsuchiya Hiroyuki
Published: September 2021

Background

Patients with tethered cord syndrome often suffer severe spasticity. To the best of our knowledge, intrathecal baclofen (ITB) therapy in a patient with tethered cord syndrome has not been reported previously. We describe a case in which ITB therapy was useful for treating severe spasticity in an adult with tethered cord syndrome.

Case presentation

We present the case of a 50-year-old Japanese woman with tethered cord syndrome and related conditions suffering from severe spasticity and pain in the lower limbs. She was born with a lumbosacral myelomeningocele, which was closed in the neonatal period. For 4–5 years before this presentation, spasticity in the lower limbs had been exacerbated without any obvious cause. She received rehabilitation and pharmacotherapy from a local doctor, but symptoms were unimproved, and her previous doctor referred her to this department. A test with 50 μg of intrathecally delivered baclofen showed total relief of spasticity and pain, so a pump was implanted for continuous baclofen delivery. During 24 months of follow-up, spasticity has remained under excellent control with baclofen at 38.5–41.0 μg/day.

Conclusions

ITB therapy proved extremely effective in this adult with severe spasticity from tethered code syndrome.
Transcriptome-wide m6A methylome during osteogenic differentiation of human adipose-derived stem cells
Authors: Sun Wentian , Song Yidan , Xia Kai , Yu Liyuan , Huang Xinqi , Zhao Zhihe , Liu Jun
Published: September 2021

Objectives

Adipose-derived stem cells are frequently used for bone regeneration both in vitro and in vivo. N6-methyladenosine (m6A) is the most abundant post-transcriptional modification on eukaryotic RNAs and plays multifaceted roles in development and diseases. However, the regulatory mechanisms of m6A in osteogenic differentiation of human adipose-derived stem cells (hASCs) remain elusive. The present study aimed to build the transcriptome-wide m6A methylome during the osteogenic differentiation of hASCs.

Materials and methods

hASCs were harvested after being cultured in a basic or osteogenic medium for 7 days, and the osteogenic differentiation was validated by alkaline phosphatase (ALP) and Alizarin Red S staining, ALP activity assay, and qRT-PCR analysis of ALP, RUNX2, BGLAP, SPP1, SP7, and COL1A1 genes. The m6A level was colorimetrically measured, and the expression of m6A regulators was confirmed by qRT-PCR and western blot. Moreover, m6A MeRIP-seq and RNA-seq were performed to build the transcriptome and m6A methylome. Furthermore, bioinformatic analyses including volcano plots, Venn plots, clustering analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, gene sets enrichment analysis, and protein-protein interaction analysis were conducted.

Results

In total, 1145 differentially methylated peaks, 2261 differentially expressed genes, and 671 differentially methylated and expressed genes (DMEGs) were identified. GO and KEGG pathway analyses conducted for these DMEGs revealed extensive and osteogenic biological functions. The “PI3K-Akt signaling pathway”; “MAPK signaling pathway”; “parathyroid hormone synthesis, secretion, and action”; and “p53 signaling pathway” were significantly enriched, and the DMEGs in these pathways were identified as m6A-specific key genes. A protein-protein interaction network based on DMEGs was built, and VEGFA, CD44, MMP2, HGF, and SPARC were speculated as the hub DMEGs.

Conclusions

The total m6A level was reduced with osteogenic differentiation of hASCs. The transcriptome-wide m6A methylome built in the present study indicated quite a few signaling pathways, and hub genes were influenced by m6A modification. Future studies based on these epigenetic clues could promote understanding of the mechanisms of osteogenic differentiation of hASCs.
Paleoceanography and dinoflagellate cyst stratigraphy across the Lower–Middle Pleistocene Subseries (Calabrian–Chibanian Stage) boundary at the Chiba composite section, Japan
Authors: Balota Eseroghene J. , Head Martin J. , Okada Makoto , Suganuma Yusuke , Haneda Yuki
Published: September 2021

A dinoflagellate cyst record from the highly resolved Chiba composite section in Japan has been used to reconstruct sea-surface paleoceanographic changes across the Lower–Middle Pleistocene Subseries (Calabrian–Chibanian Stage) boundary at the global stratotype, constituting the first detailed study of this microfossil group from the Pleistocene of the Japanese Pacific margin. Cold, subarctic water masses from 794.2 ka gave way to warming and rapid retreat of the Subpolar Front at 789.3 ka, ~ 2000 years before the end of Marine Isotope Stage (MIS) 20. Throughout the fully interglacial conditions of MIS 19c, assemblages are consistent with warm sea surface temperatures but also reveal instability and latitudinal shifts in the Kuroshio Extension system. The abrupt dominance ofProtoceratium reticulatumcysts between 772.9 and 770.4 ka (MIS 19b) registers the influence of cooler, mixed, nutrient-rich waters of the Kuroshio–Oyashio Interfrontal Zone resulting from a southward shift of the Kuroshio Extension. Its onset at 772.9 ka serves as a local ecostratigraphic marker for the Chibanian Stage Global Boundary Stratotype Section and Point (GSSP) which occurs just 1.15 m (= 1300 years) below it. An interval from 770.1 ka to the top of the examined succession at 765.8 ka (MIS 19a) represents warm, presumably stratified but still nutrient-elevated surface waters, indicating a northward shift of the Kuroshio Extension ~ 5 kyrs after the termination of full interglacial conditions on land.
Sedimentary facies analysis of the fluvial environment in the Siwalik Group of eastern Nepal: deciphering its relation to contemporary Himalayan tectonics, climate and sea-level change
Authors: Rai Lalit Kumar , Yoshida Kohki
Published: September 2021

The Siwalik Group, ranging from the Early Miocene to Pleistocene, is believed to be deposited in the fluvial environment and controlled by contemporary Himalayan tectonics and climate. In this study, we established the fluvial environment and its controlling factors responsible for the deposition of the Siwalik succession along the Muksar Khola section in the eastern Nepal Himalaya. Five sedimentary facies associations are identified; these are interpreted as the deposits of flood plain-dominated fine-grained meandering river (FA1), flood-dominated overbank environment (FA2), sandy meandering river (FA3), anastomosing river (FA4), and debris flow-dominated gravelly braided river (FA5). These changes in the fluvial system occurred around 10.5 Ma, 10.0 Ma, 5.9 Ma and 3.5 Ma, defined by existing magnetostratigraphy constraints, due to the effects of hinterland tectonics, climate and sea-level change and continuous drifting of the foreland basin towards the hinterland concerning depositional age. The thick succession of an intraformational conglomerate reveals intensification of the monsoon started around 10.5 Ma in the eastern Nepal Himalaya. The present study also shows asynchronous exhumation of the Himalaya from east to west brought a significant difference in the fluvial environment of the Neogene foreland basin.
Impact of Althaea Officinalis extract in patients with atopic eczema: a double-blind randomized controlled trial
Authors: Khalighi Negar , Jabbari-Azad Farahzad , Barzegar-Amini Maral , Tavakkol-Afshari Jalil , Layegh Pouran , Salari Roshanak
Published: September 2021

Background

Althaea Officinalis introduced as an emerging anti-inflammatory agent with immunomodulatory effects that may suppress the symptoms of atopic eczema. In this study, we aimed to investigate the impact of liposomal formulation of Althaea Officinalis flower extract compared with steroids for atopic eczema treatment.

Methods

In this randomized, double-blind controlled trial phase II, forty patients with moderate to severe allergic atopic eczema confirmed by skin prick test were enrolled in the study from October 2018 to January 2019. Steroids on the lesions of the left side of the body and topical Althaea Officinalis extract (intervention) or eucerin as a topical placebo on the lesions of the right side of the body were tested. SCORAD (SCORing Atopic Dermatitis) was assessed at the baseline, and two, and four weeks after completing the trial. Data were analyzed by SPSS version 22.

Results

In the active treatment group, after two weeks, the SCORAD was significantly lower in the left side (recovery with steroid treatment) (p < 0.001), and after 4 weeks the SCORAD was lower on both sides, and there were no significant differences between two sides (similarity between Althaea Officinalis and steroid effects). In the control group, the SCORAD score was significantly lower on the left side (steroid) after two and four weeks (p < 0.001). There was no side effect and reaction to drugs.

Conclusions

Considering the potential side effects of steroids, and the similar efficacy of Althaea Officinalis flower extract, using this component may be accompanied by higher benefits in patients with atopic eczema.

Trial registration

IRCT2016102323235N5.
Exploring critical factors of the perceived usefulness of a learning analytics dashboard for distance university students
Authors: Rets Irina , Herodotou Christothea , Bayer Vaclav , Hlosta Martin , Rienties Bart
Published: September 2021

Learning analytics dashboards (LADs) can provide learners with insights about their study progress through visualisations of the learner and learning data. Despite their potential usefulness to support learning, very few studies on LADs have considered learners’ needs and have engaged learners in the process of design and evaluation. Aligning with that, there is a limited understanding of what specific student cohorts, in particular distance and online learners, may seek from LADs to effectively support their studies. In this study, we present findings from 21 interviews with undergraduate distance learners, mainly high performers, that aimed to capture student perceptions about the usefulness of specific LAD features and the factors that explain these perceptions. Our findings revealed that amongst the LAD features favoured by students was the potential to receive study recommendations, whereas comparison with peers was amongst the least favoured elements, unless informed by qualitative information. Factors including information trust, attitudes, age, performance and academic self-confidence were found to explain these perceptions.
Metabolic Dysfunction-associated Fatty Liver Disease and Mortality Among Chinese Adults: a Prospective Cohort Study
Authors: Wang Xiaomo , Wu Shouling , Yuan Xiaojie , Chen Shuohua , Fu Qingjiang , Sun Yuanyuan , Lan Yanqi , Hu Shiqi , Wang Yanhong , Lu Ying , Qu Shunxi , Wang Li
Published: September 2021

Context

Nonalcoholic fatty liver disease (NAFLD) was renamed metabolic dysfunction associated with fatty liver disease (MAFLD) recently.

Objective

We aimed to explore the risk of all-cause deaths in MAFLD participants and compare it with NAFLD in Chinese adults.

Methods

We enrolled 152 139 participants with abdominal ultrasonography in the Kailuan Cohort from 2006 to 2012. We categorized the participants into MAFLD and non-MAFLD, NAFLD and non-NAFLD, and 4 groups of Neither FLD, MAFLD only, NAFLD only, and MAFLD-NAFLD, respectively. We used Cox regression models to estimate the hazard ratios (HRs) and 95% CI of death.

Results

The prevalence of MAFLD and NAFLD was 31.5% and 27.3%, respectively. After a median follow-up of 12.7 years, MAFLD and NAFLD both were associated with increased mortality, especially in men younger than 40 years, with HR (95% CI) of 1.51 (1.19-1.93) and 1.37 (1.06-1.78), respectively. The MAFLD-only group had higher mortality than the NAFLD-only in males 60 years or older (adjusted HR = 1.43; 95% CI, 1.00-2.03) and lower risk in males aged 40 to 59 years (adjusted HR = 0.65; 95% CI, 0.48-0.90). MAFLD with overweight/obesity-only decreased, but those with diabetes and/or metabolic dysregulation increased the risk of death. MAFLD with positive hepatitis B surface antigen and/or excessive alcohol consumption further increased the risk of death, especially in men younger than 40 years (HR = 9.86; 95% CI, 2.44-39.98).

Conclusion

MAFLD was associated with increased all-cause mortality among the Chinese population, which was different according to the status of overweight/obesity, diabetes, other metabolic indicators, and second causes. MAFLD patients should be managed by metabolic indicators and second causes to fulfill precise treatment and management.
Parasitic Infections of the Nervous System
Authors: Garcia Hector H.
Published: September 2021

PURPOSE OF REVIEW

This article reviews how parasites affect the human nervous system, with a focus on four parasitic infections of major public health importance worldwide, two caused by protozoa (malaria and toxoplasmosis) and two by helminths (neurocysticercosis and schistosomiasis).

RECENT FINDINGS

Parasitic infections in humans are common, and many can affect the central nervous system where they may survive unnoticed or may cause significant pathology that can even lead to the death of the host. Neuroparasitoses should be considered in the differential diagnosis of neurologic lesions, particularly in individuals from endemic regions or those with a history of travel to endemic regions.

Cerebral malaria is a significant cause of mortality, particularly in African children, in whom infected red blood cells affect the cerebral vessels, causing severe encephalopathy. Neurocysticercosis is the most common cause of acquired epilepsy worldwide and has varied clinical presentations, depending on the number, size, and location of the parasites in the nervous system as well as on the host’s inflammatory response. Toxoplasmosis is distributed worldwide, affecting a significant proportion of the population, and may reactivate in patients who are immunosuppressed, causing encephalitis and focal abscesses. Schistosomiasis causes granulomatous lesions in the brain or the spinal cord.
Congenital Infections of the Nervous System
Authors: Patel Payal
Published: September 2021

PURPOSE OF REVIEW

This article provides an overview of congenital infections affecting the central nervous system (CNS), discussing the epidemiology, clinical features, diagnostic tools, and preventive and treatment measures for a variety of pathogens with the potential to infect the developing fetal brain.

RECENT FINDINGS

Contrary to popular belief, many congenital CNS infections are preventable and treatable. Treatment options exist for congenital cytomegalovirus, human immunodeficiency virus (HIV), herpes simplex virus, toxoplasmosis, and syphilis, although the efficacy of these treatments and the populations that may benefit from treatment are variable. Zika virus has recently emerged as a pathogen affecting the fetal brain, and new data suggest that the pathogenesis of Zika virus involves direct infection of neuronal progenitor cells leading to destruction of CNS tissue. The incidence of congenital syphilis has been increasing in the United States over the past decade as a direct result of new syphilis cases among adults and poor access to adequate maternal health care.

Congenital CNS infections often result in significant neurologic morbidity in pediatric patients. Therefore, early identification of maternal illness and implementation of preventive measures are important in improving developmental outcomes and quality of life.
Neurologic Complications of Tuberculosis
Authors: Saylor Deanna
Published: September 2021

PURPOSE OF REVIEW

This article describes the current epidemiology, common clinical characteristics, and up-to-date evidence-based approaches to the diagnosis and management of the most common neurologic complications of tuberculosis (TB): tuberculous meningitis, intracranial tuberculoma, and spinal TB.

RECENT FINDINGS

Central nervous system (CNS) TB remains common and associated with significant mortality and neurologic sequelae worldwide. Human immunodeficiency virus (HIV) co-infection is strongly associated with both the development of and mortality due to CNS TB. Strongyloides co-infection is associated with reduced CNS inflammation and improved outcomes in the setting of tuberculous meningitis. Stroke remains a common complication of tuberculous meningitis, and emerging evidence suggests aspirin may be used in this context. Although a recent nucleic acid amplification test has demonstrated suboptimal sensitivity in the diagnosis of CNS TB, emerging diagnostic techniques include cell-free DNA, peripheral blood microRNA, metagenomic next-generation sequencing, and advanced imaging techniques, but these are not yet well validated. CNS TB is associated with high mortality even with current treatment regimens, although novel, promising strategies for treatment are under investigation, including a combination of IV isoniazid and ethambutol and high-dose rifampicin.

TB can affect the nervous system in various ways and is associated with high mortality. Diagnosis remains challenging in endemic settings, with empiric treatment often initiated without a definitive diagnosis. Furthermore, optimal treatment regimens remain uncertain because current treatment for all forms of CNS TB is extrapolated from trials of tuberculous meningitis whereas the role of steroids in people with HIV and tuberculous meningitis remains controversial.
Infections of the Spine and Spinal Cord
Authors: Bhattacharyya Shamik , Bradshaw Michael J.
Published: September 2021

PURPOSE OF REVIEW

Infections of the spine and spinal cord are associated with a high risk of morbidity and mortality and, therefore, require prompt clinical recognition, efficient diagnostic evaluation, and interdisciplinary treatment. This article reviews the pathophysiology, epidemiology, clinical manifestations, diagnosis, and treatment of infections of the spine and spinal cord to help practicing clinicians recognize, evaluate, and manage patients with such infections.

RECENT FINDINGS

Aging of the population, increasing use of immunosuppressive medications, and other factors have contributed to increasing rates of spinal infections. Although the most common agents responsible for spinal infections remain bacteria and viruses, fungal infections occur in individuals who are immunocompromised, and parasitic infections are common in endemic regions, but patterns are in evolution with migration and climate change. Recent outbreaks of acute flaccid myelitis in children have been associated with enteroviruses A71 and D68.

Infections of the spine and spinal cord can be challenging to diagnose, requiring a thorough history and neurologic examination, laboratory studies of serum and CSF, neuroimaging (particularly MRI), and, in some instances, biopsy, to establish a diagnosis and treatment regimen. Interdisciplinary management including collaboration with experts in internal medicine, infectious disease, and neurosurgery is important to improve clinical outcomes.
Between Scylla and Charybdis?
Authors: Ferradou Mathieu
Published: September 2021

In 1792 foreigners flocked to France to participate in the new republican regime, redefining the nation as the conduct of popular sovereignty. A number of American, British, and Irish foreigners formed a club in Paris, the Society of the Friends of the Rights of Man (Société des Amis des Droits de l'Homme), among whom Irish republicans were a key component. Eager to “revolutionize” Britain and Ireland, they contributed to the rise in tensions and, ultimately, to the outbreak of war between France and Britain. The author argues that these Irish, because of their colonial experience, were a crucial factor in the redefinition of and opposition between British imperial and French republican models of nation and citizenship. Their defense of a cosmopolitan citizenship ideal was violently rejected in Britain and was severely tested by the “Terror” in France.

En 1792, de nombreux étrangers vinrent en France pour participer à l’élaboration du nouveau régime républicain, redéfinissant la nation comme le vecteur de la souveraineté populaire. Plusieurs Américains, Anglais, Irlandais et Ecossais formèrent un club à Paris, la Société des amis des droits de l'homme (SADH), parmi lesquels les Irlandais furent une composante clé. Désireux de « révolutionner » la Grande-Bretagne et l'Irlande, ils contribuèrent à la montée des tensions et à l’éclatement du conflit entre la France et la Grande-Bretagne. Cet article cherche à démontrer que ces Irlandais, du fait de leur expérience coloniale, jouèrent un rôle central dans la redéfinition et l'opposition entre le modèle impérial britannique et le modèle français républicain de la nation et de la citoyenneté. Leur défense d'un idéal cosmopolite de citoyenneté suscita un violent rejet en Grande-Bretagne et fut mise à rude épreuve pendant la « Terreur » en France.
Barriers and facilitators to health insurance enrolment among people working in the informal sector in Morogoro, Tanzania
Authors: Abraham Elisante , Gray Cindy , Fagbamigbe Adeniyi F. , Tediosi Fabrizio , Otesinky Brianna , Haafkens Joke , Mhalu Grace , Mtenga Sally
Published: September 2021

Background: Health insurance is a crucial pathway towards the achievement of universal health coverage. In Tanzania, health-financing reforms are underway to speed up universal health coverage in the informal sector. Despite improved Community Health Fund (iCHF) rollout, iCHF enrolment remains a challenge in the informal sector. This study aimed to explore the perspectives of local women food vendors (LWFV) and Bodaboda (motorcycle taxi) drivers on factors that challenge and facilitate their enrolment in iCHF.

Methods: A qualitative study was conducted in Morogoro Municipality through in-depth interviews with LWFV (n=24) and Bodaboda drivers (n=26), and two focus group discussions with LWFV (n=8) and Bodaboda drivers (n=8). Theory of planned behaviour (TPB) constructs (attitude, subjective norms, and perceived control) provided a framework for the study and informed a thematic analysis focusing on the barriers and facilitators of iCHF enrolment.

Results: The views of LWFV and Bodaboda drivers on factors that influence iCHF enrolment converged. Three main barriers emerged: lack of knowledge about the iCHF (attitude); negative views from friends and families (subjective norms); and inability to overcome challenges, such as the quality and range of health services available to iCHF members and iCHF not being accepted at non-government facilities (perceived control). A number of facilitators were identified, including opinions that enrolling to iCHF made good financial sense (attitude), encouragement from already-enrolled friends and relatives (subjective norms) and the belief that enrolment payment is affordable (perceived control).

Conclusions: Results suggest that positive attitudes supported by perceived control and encouragement from significant others could potentially motivate LWFV and Bodaboda drivers to enroll in iCHF. However, more targeted information about the scheme is needed for individuals in the informal sector. There is also a need to ensure that quality health services are available, including coverage for non-communicable diseases (NCDs), and that non-government facilities accept iCHF.
Alteration in surface roughness of reciprocating endodontic instruments
Authors: Pham Khoa Van
Published: September 2021

Background: Surface roughness is one of the most important characteristics of endodontic instruments, correlating to instrument fracture. The purpose of this study was to measure the surface roughness values of these instruments before and after resin root canal preparation without previous glide path preparation, with the new method. Data was obtained from field emission scanning electron microscopes (FE-SEM) combined with independent ImageJ software (NIH, Bethesda, MD, USA).

Methods: A total of 20 simulated J-shape resin blocks with a radius of 4.5 mm, length of 16 mm, and angle of inflection of 600 were chosen and distributed into two equal groups. Each group was prepared by the WaveOne Gold Primary (Dentsply Sirona, Maillefer, Ballaigues, Switzerland) or the Reciproc Blue R25 (VDW, Munich, Germany) instruments, without glide path preparation. Special molds were used to confirm the same areas on the cutting blade at 3 mm and the instruments’ tips were scanned by FE-SEM, at different observed times. The parameters of Ra, Rq, and Rz in each sample were collected using the ImageJ software for analyses. The data was processed using the paired t-test with a significance level of 0.05.

Results: Right after the first resin canal instrumentation, the surface roughness parameters of the two reciprocating investigated instruments were decreased.

Conclusions: The FE-SEM images processed using the ImageJ software offered a trustworthy and suitable method for assessment of the NiTi endodontic file surface roughness.
Harmonising the human biobanking consent process: an Irish experience
Authors: O'Sullivan Lydia , Carroll Tomás , Cooper Sarah , Cullen Ann , Gorman Laura , McCann Billy , Mee Blánaid , Miller Nicola , Murphy Verena , Murray Máiréad , O'Leary Jackie , O'Toole Sharon , Snapes Emma , Bracken Suzanne
Published: September 2021

Biobanks are repositories of human biological samples and data. They are an important component of clinical research in many disease areas and often represent the first step toward innovative treatments. For biobanks to operate, researchers need human participants to give their samples and associated health data. In Ireland, research participants must provide their freely given informed consent for their samples and data to be taken and used for research purposes. Biobank staff are responsible for communicating the relevant information to participants prior to obtaining their consent, and this communication process is supported by documentation in the form of Participant Information Leaflets and Informed Consent Forms (PILs/ICFs). PILs/ICFs should be concise, intelligible, and contain relevant information. While not a substitute for layperson and research staff discussions, PILs and ICFs ensure that a layperson has enough information to make an informed choice to participate or not. However, PILs/ICFs are often lengthy, contain technical language and can be complicated and onerous for a layperson to read. The introduction of the General Data Protection Regulation (GDPR) and the related Irish Health Research Regulation (HRR) presented additional challenges to the Irish biobank community. In May 2019, the National Biobanking Working Group (NBWG) was established in Ireland. It consists of members from diverse research backgrounds located in universities, hospitals and research centres across Ireland and a public/patient partner. The NBWG aimed to develop a suite of resources for health research biobanks via robust and meaningful patient engagement, which are accessible, GDPR/HRR-compliant and could be used nationally, including a PIL/ICF template. This open letter describes the process whereby this national biobank PIL/ICF template was produced. The development of this template included review by the Patient Voice in Cancer Research, led by Professor Amanda McCann at University College Dublin and the Health Research Data Protection Network.