bluuebunny/crossref_metadata_2025 huggingface dataset:
The oldest millet herbal beer in the Europe? The ninth century BCE bronze luxury bucket from Kladina, Czech Republic
Authors: Jílek Jan , Golec Martin , Bednář Petr , Chytráček Miloslav , Vích David , Zavoral Tomáš , Mírová Zuzana , Petr Libor , Kovárník Jaromír , Milo Peter , Kučera Lukáš
Published: July 2021

In 2017, a luxury bronze bucket was discovered near Kladina village in the Czech Republic. The bucket is dated to the ninth century BCE, and it is a unique artefact, having no parallel in Europe. Stylistically, it is a “transition type” dated between the Late Bronze Age (11th–10th century BCE) and the Hallstatt Period (eighth–sixth century BCE). Detailed palynological analysis of verdigris and soil infill of the bucket identified a wide range of pollen grains belonging mainly to herbs, with bitter‐sour properties, and cereals. Subsequent chemical analysis by gas chromatography/mass spectrometry of soil extracts revealed the presence of the compound miliacin that is a chemical marker of millet. Moreover, a starch analysis reveals the presence of enzymatically modified starch grains. These data, with the help of archaeological knowledge, indicate that the original content may have been millet‐based food/beverage with addition of herbs. We suggest that this luxury vessel, given the contents we have identified, was deposited, in the late spring/summer months of the year.
Effect of relationships among clinical mastitis incidence, reproductive performance, and culling rate on the lifetime of dairy cows at Hiroshima University Farm
Authors: Kurokawa Yuzo , Okita Miki , Kubota Hirokazu , Tsumiyama Yoshimasa , Chikamatsu Ichiro , Tanaka Akiyoshi , Obitsu Taketo , Kawamura Kensuke
Published: July 2021

Farm managers' decision to cull dairy cows is based on the cows' milk production, history of disorder(s), and reproductive performance, each of which affects dairy cows' lifetime (herd life and productive lifespan). We investigated the relationships among the incidence of clinical mastitis (CM), the reproductive performance, and the culling rate. We also assessed the effects of these relationships on the lifetimes of dairy cows, using the records made before and after the introduction of an automatic milking system (AMS) at Hiroshima University Farm. Milk yield, CM incidence density, and culling rate of dairy cows increased after the AMS introduction. The CM incidence was associated with an elongation of the calving interval in cows with the same parity. CM in the 1st parity might have caused the reductions of the cows' lifetime and their parity at culling. A higher age at first calving (AFC) was associated with an increase in culling rate but did not lead to a significant decrease in lifetime. Investigations of the factors mediating CM in the 1st parity or AFC with CM incidence or culling rate in the later stages might contribute to the control of lifetime of dairy cows.
Comparison between physiologically based pharmacokinetic and population pharmacokinetic modelling to select paediatric doses of gepotidacin in plague
Authors: Nguyen Dung , Shaik Jafar Sadik , Tai Guoying , Tiffany Courtney , Perry Caroline , Dumont Etienne , Gardiner David , Barth Aline , Singh Rajendra , Hossain Mohammad
Published: July 2021

Aims

To develop physiologically based pharmacokinetic (PBPK) and population pharmacokinetic (PopPK) models to predict effective doses of gepotidacin in paediatrics for the treatment of pneumonic plague (Yersinia pestis).

Methods

A gepotidacin PBPK model was constructed using a population‐based absorption, distribution, metabolism and excretion simulator, Simcyp®, with physicochemical and in vitro data, optimized with clinical data from a dose‐escalation intravenous (IV) study and a human mass balance study. A PopPK model was developed with pooled PK data from phase 1 studies with IV gepotidacin in healthy adults.

Results

For both the PopPK and PBPK models, body weight was found to be a key covariate affecting gepotidacin clearance. With PBPK, ~90% of the predicted PK for paediatrics fell between the 5th and 95th percentiles of adult values except for subjects weighing ≤5 kg. PopPK‐simulated paediatric means for Cmax and AUC(0‐τ) were similar to adult exposures across various weight brackets. The proposed dosing regimens were weight‐based for subjects ≤40 kg and fixed‐dose for subjects >40 kg. Comparison of observed and predicted exposures in adults indicated that both PBPK and PopPK models achieved similar AUC and Cmax for a given dose, but the Cmax predictions with PopPK were slightly higher than with PBPK. The two models differed on dose predictions in children <3 months old. The PopPK model may be suboptimal for low age groups due to the absence of maturation characterization of drug‐metabolizing enzymes involved with clearance in adults.

Conclusions

Both PBPK and PopPK approaches can reasonably predict gepotidacin exposures in children.
Clinical efficacy of mebeverine for persistent nocturnal enuresis after orthotopic W‐neobladder
Authors: Hashem Abdelwahab , Abdellutif Mohamed M. , Laymon Mahmoud , Abdullateef Muhamad , Abdelhamid Abdalla , Mosbah Ahmed , Abol‐Enein Hassan
Published: July 2021

Objectives

To investigate the efficacy of mebeverine for nocturnal incontinence in male patients with an ileal orthotopic bladder substitute (OBS).

Patients and Methods

A randomised controlled trial was carried out for adult male patients who were nocturnal incontinent. Patients were allocated to receive mebeverine 200 mg or placebo once a day in the evening for 3 months. The primary outcome was to compare the continence status between groups, assessed by the urinary domain of the Bladder Cancer Index (BCI) and pad usage. The secondary outcomes were to assess the safety of mebeverine.

Results

There were 55 patients in the placebo group and 58 in mebeverine group who completed the follow‐up. The median (interquartile range) interval between OBS surgery and starting treatment was 9 (4–13) years in the placebo group and 9 (6–13) years in the mebeverine group. The mean (SD) 3‐month urinary domain score of the BCI was 70.8 (5.6) and 86.4 (14.2) in the placebo and mebeverine groups, respectively (P < 0.001). At 3 months, 54 (98.2%) and 26 (44.8%) patients required the use of a night‐time pad in the placebo and mebeverine groups, respectively. Mebeverine reduced the risk of pad use by 53.4% (95% confidence interval 40.1–66.6; P < 0.001). Constipation occurred in one (2.1%) and three (5.8%) patients in the placebo and mebeverine groups, respectively; abdominal distention occurred in two (3.8%) of the patients in the mebeverine group (P = 0.25).

Conclusion

Mebeverine decreases night‐time pad use and improves the quality of life in male patients with an ileal OBS and is associated with minimal adverse events.
Approved drugs ezetimibe and disulfiram enhance mitochondrial Ca2+ uptake and suppress cardiac arrhythmogenesis
Authors: Sander Paulina , Feng Michael , Schweitzer Maria K. , Wilting Fabiola , Gutenthaler Sophie M. , Arduino Daniela M. , Fischbach Sandra , Dreizehnter Lisa , Moretti Alessandra , Gudermann Thomas , Perocchi Fabiana , Schredelseker Johann
Published: July 2021

Background and Purpose

Treatment of cardiac arrhythmia remains challenging due to severe side effects of common anti‐arrhythmic drugs. We previously demonstrated that mitochondrial Ca2+ uptake in cardiomyocytes represents a promising new candidate structure for safer drug therapy. However, druggable agonists of mitochondrial Ca2+ uptake suitable for preclinical and clinical studies are still missing.

Experimental Approach

Herewe screened 727 compounds with a history of use in human clinical trials in a three‐step screening approach. As a primary screening platform we used a permeabilized HeLa cell‐based mitochondrial Ca2+ uptake assay. Hits were validated in cultured HL‐1 cardiomyocytes and finally tested for anti‐arrhythmic efficacy in three translational models: a Ca2+ overload zebrafish model and cardiomyocytes of both a mouse model for catecholaminergic polymorphic ventricular tachycardia (CPVT) and induced pluripotent stem cell derived cardiomyocytes from a CPVT patient.

Key Results

We identifiedtwo candidate compounds, the clinically approved drugs ezetimibe and disulfiram, which stimulate SR‐mitochondria Ca2+ transfer at nanomolar concentrations. This is significantly lower compared to the previously described mitochondrial Ca2+ uptake enhancers (MiCUps) efsevin, a gating modifier of the voltage‐dependent anion channel 2, and kaempferol, an agonist of the mitochondrial Ca2+ uniporter. Both substances restored rhythmic cardiac contractions in a zebrafish cardiac arrhythmia model and significantly suppressed arrhythmogenesis in freshly isolated ventricular cardiomyocytes from a CPVT mouse model as well as induced pluripotent stem cell derived cardiomyocytes from a CPVT patient.

Conclusion and Implications

Taken together we identified ezetimibe and disulfiram as novel MiCUps and efficient suppressors of arrhythmogenesis and as such as, promising candidates for future preclinical and clinical studies.
Cytokine‐induced apoptosis inhibitor 1 (CIAPIN1) accelerates vascular remodelling via p53 and JAK2‐STAT3 regulation in vascular smooth muscle cells
Authors: Han Joo‐Hui , Heo Kyung‐Sun , Myung Chang‐Seon
Published: July 2021

Background and purpose

Abnormal vascular smooth muscle cell (VSMC) proliferation and migration lead to neointima formation, which eventually results in cardiovascular hyperplastic diseases. The molecular mechanisms underlying these cellular processes have not been fully understood. Cytokine‐induced apoptosis inhibitor 1 (CIAPIN1) has been identified as an anti‐apoptotic molecule, but little is known about its target genes and related pathways in VSMC dysfunction or its clinical implication in neointima formation following vascular injury.

Experimental approach

Determination, using loss/gain‐of‐function approaches by gene delivery, of whether CIAPIN1 modulates VSMC proliferation, migration and neointima formation and the underlying mechanisms was carried out. Balloon injury or ligation and local delivery of lentivirus were performed on rat or mouse carotid arteries. Rat aortic smooth muscle cells, the primary cell, was used as the model to evaluate the effect of CIAPIN1 on proliferation and migration.

Key results

CIAPIN1 was overexpressed in the neointimal region of rat arteries. CIAPIN1 deficiency markedly inhibited injury‐induced or ligation‐induced intimal hyperplasia and suppressed PDGF‐BB‐induced VSMC proliferation, migration and cell cycle progression, while overexpression promoted proliferation, migration and neointima formation. CIAPIN1 negatively regulated Tp53 transcription, which promoted cell cycle progression and migration via cyclin E1‐CDK2/pRb/PCNA and the MMP2 pathway. CIAPIN1 also increased JAK2 expression, enhancing JAK2 and STAT3 phosphorylation by vascular injury, which forced phenotypic switching from contractile to synthetic state in injured arteries.

Conclusions and implications

These findings provide new insights into the mechanism by which CIAPIN1 regulates vascular remodelling and suggest a novel therapeutic target for treating vascular proliferative diseases.
Expanding insect pollinators in the Anthropocene
Authors: Ghisbain Guillaume , Gérard Maxence , Wood Thomas J. , Hines Heather M. , Michez Denis
Published: July 2021

Global changes are severely affecting pollinator insect communities worldwide, resulting in repeated patterns of species extirpations and extinctions. Whilst negative population trends within this functional group have understandably received much attention in recent decades, another facet of global changes has been overshadowed: species undergoing expansion. Here, we review the factors and traits that have allowed a fraction of the pollinating entomofauna to take advantage of global environmental change. Sufficient mobility, high resistance to acute heat stress, and inherent adaptation to warmer climates appear to be key traits that allow pollinators to persist and even expand in the face of climate change. An overall flexibility in dietary and nesting requirements is common in expanding species, although niche specialization can also drive expansion under specific contexts. The numerous consequences of wild and domesticated pollinator expansions, including competition for resources, pathogen spread, and hybridization with native wildlife, are also discussed. Overall, we show that the traits and factors involved in the success stories of expanding pollinators are mostly species specific and context dependent, rendering generalizations of ‘winning traits’ complicated. This work illustrates the increasing need to consider expansion and its numerous consequences as significant facets of global changes and encourages efforts to monitor the impacts of expanding insect pollinators, particularly exotic species, on natural ecosystems.
A comprehensive synthesis unveils the mysteries of phosphate‐solubilizing microbes
Authors: Li Jin‐tian , Lu Jing‐li , Wang Hong‐yu , Fang Zhou , Wang Xiao‐juan , Feng Shi‐wei , Wang Zhang , Yuan Ting , Zhang Sheng‐chang , Ou Shu‐ning , Yang Xiao‐dan , Wu Zhuo‐hui , Du Xiang‐deng , Tang Ling‐yun , Liao Bin , Shu Wen‐sheng , Jia Pu , Liang Jie‐Liang
Published: July 2021

Phosphate‐solubilizing microbes (PSMs) drive the biogeochemical cycling of phosphorus (P) and hold promise for sustainable agriculture. However, their global distribution, overall diversity and application potential remain unknown. Here, we present the first synthesis of their biogeography, diversity and utility, employing data from 399 papers published between 1981 and 2017, the results of a nationwide field survey in China consisting of 367 soil samples, and a genetic analysis of 12986 genome‐sequenced prokaryotic strains. We show that at continental to global scales, the population density of PSMs in environmental samples is correlated with total P rather than pH. Remarkably, positive relationships exist between the population density of soil PSMs and available P, nitrate‐nitrogen and dissolved organic carbon in soil, reflecting functional couplings between PSMs and microbes driving biogeochemical cycles of nitrogen and carbon. More than 2704 strains affiliated with at least nine archaeal, 88 fungal and 336 bacterial species were reported as PSMs. Only 2.59% of these strains have been tested for their efficiencies in improving crop growth or yield under field conditions, providing evidence that PSMs are more likely to exert positive effects on wheat growing in alkaline P‐deficient soils. Our systematic genetic analysis reveals five promising PSM genera deserving much more attention.
Taxonomy of design thinking facilitation
Authors: Starostka Justyna , Evald Majbritt Rostgaard , Clarke Ann Højbjerg , Hansen Per Richard
Published: July 2021

Although the body of research on design thinking (DT) is growing, knowledge regarding DT facilitation in innovation projects is sparse. Through explorative case studies, we explore how facilitators understand and apply DT to innovation projects. Our findings reveal that different DT facilitators take markedly polar different approaches to DT facilitation. We advance the DT literature by establishing links with the group facilitation literature and developing a taxonomy of DT facilitation anchored by two opposite approaches to DT facilitation: a method approach and a cofacilitation approach. Our findings demonstrate that different interpretations of DT can lead to different facilitation practices. This insight is valuable for innovation project owners who hire DT facilitators, the research community and facilitators themselves.
Immunosuppressive activity is attenuated by Astragalus polysaccharides through remodeling the gut microenvironment in melanoma mice
Authors: Ding Guiqing , Gong Qianyi , Ma Jinyun , Liu Xiaojun , Wang Yuanhua , Cheng Xiaodong
Published: July 2021

Astragalus polysaccharides (APS), the main effective component of Astragalus membranaceus, can inhibit tumor growth, but the underlying mechanisms remain unclear. Previous studies have suggested that APS can regulate the gut microenvironment, including the gut microbiota and fecal metabolites. In this work, our results showed that APS could control tumor growth in melanoma‐bearing mice. It could reduce the number of myeloid‐derived suppressor cells (MDSC), as well as the expression of MDSC‐related molecule Arg‐1 and cytokines IL‐10 and TGF‐β, so that CD8+ T cells could kill tumor cells more effectively. However, while APS were administered with an antibiotic cocktail (ABX), MDSC could not be reduced, and the growth rate of tumors was accelerated. Consistent with the changes in MDSC, the serum levels of IL‐6 and IL‐1β were lowest in the APS group. Meanwhile, we found that fecal suspension from mice in the APS group could also reduce the number of MDSC in tumor tissues. These results revealed that APS regulated the immune function in tumor‐bearing mice through remodeling the gut microbiota. Next, we focused on the results of 16S rRNA, which showed that APS significantly regulated most microorganisms, such as Bifidobacterium pseudolongum, Lactobacillus johnsonii and Lactobacillus. According to the Spearman analysis, the changes in abundance of these microorganisms were related to the increase of metabolites like glutamate and creatine, which could control tumor growth. The present study demonstrates that APS attenuate the immunosuppressive activity of MDSC in melanoma‐bearing mice by remodeling the gut microbiota and fecal metabolites. Our findings reveal the therapeutic potential of APS to control tumor growth.
Socioeconomic‐related inequality in dental care utilization among preschool children in China
Authors: Chang Qing , Gao Xiaoli , Xu Mengru , Zhang Chunzi , Du Shuo , Wang Xing , Feng Xiping , Tai Baojun , Hu Deyu , Lin Huancai , Wang Bo , Wang Chunxiao , Zheng Shuguo , Liu Xuenan , Rong Wensheng , Wang Weijian , Xu Tao , Si Yan
Published: July 2021

Objectives

This study aimed to investigate socioeconomic‐related inequality in dental care service utilization in the past 12 months among Chinese preschool children and to explore the contribution of various factors to this inequality.

Method

A total of 40 305 children aged 3‐5 years from 372 kindergartens who participated in the Fourth National Oral Health Survey in China were included in the final analysis. The method of data weighting in complex sampling was adopted to make the samples more representative. Erreygers‐corrected concentration index (EI) was used to measure socioeconomic‐related inequality in dental care service utilization. The horizontal inequality index (HI) was employed to analyse horizontal inequality. Decomposition analyses were conducted to explore the contributions of income level, need variables (dmft, caregiver‐evaluated oral health status and toothache experience) and nonneed variables (caregiver education level, residential location, age, and sex) to the inequality of health service utilization.

Result

The utilization of oral health services within the past 12 months among the high‐, middle‐ and low‐income groups was 17.4% (95% CI: 15.6‐19.3), 13.6% (95% CI: 12.2‐15.1) and 9.4% (95% CI: 8.1‐11.0) respectively. The concentration curve was below the line of equality, and the EI and HI were 0.072 and 0.078, respectively, indicating that dental care utilization in children aged 3‐5 years was concentrated in those who were better off. The contribution of the need variables to socioeconomic‐related inequality in dental services was minimal, and most dental care utilization inequality could be explained by household income, caregiver education attainment and urban‐rural disparities, accounting for 32.0%, 49.4% and 20.4% respectively.

Conclusion

This study reveals the existence of pro‐rich inequality in dental care utilization among preschool children in China. The decomposition analysis suggests that income, caregiver education background and urban‐rural disparities are the main factors contributing to this outcome. Equity‐oriented policies and programmes are needed to achieve equitable dental care utilization.
Bacterial lysate add‐on therapy to reduce exacerbations in severe asthma: A double‐blind placebo‐controlled trial
Authors: de Boer Geertje M. , Braunstahl Gert‐Jan , van der Ploeg Esmee K. , van Zelst Cathelijne M. , van Bruggen Alie , Epping Guido , van Nimwegen Menno , Verhoeven Gert , Birnie Erwin , Boxma‐de Klerk Bianca M. , de Bruijn Marjolein J. W. , Stadhouders Ralph , Hendriks Rudi W. , Tramper‐Stranders Gerdien A.
Published: July 2021

Background

Asthma exacerbations are frequently induced by respiratory tract infections (RTIs). Bacterial lysates have been described to possess immune‐modulatory effects and reduce RTIs as well as asthma symptoms in children. However, whether bacterial lysates have similar effects in adult asthma patients is unknown.

Aims

To reduce asthma exacerbations by add‐on bacterial lysate therapy in adults with severe asthma and to characterize the clinical and immune‐modulatory effects of this treatment.

Methods

Asthma patients (GINA 4) with ≥2 annual exacerbations in the previous year were included. The intervention regimen consisted of OM‐85/placebo for 10 consecutive days per month for 6 months during two winter seasons. Primary end‐point was the number of severe asthma exacerbations within 18 months. The study was approved by the national and local ethical review board and registered in the Dutch Trial Registry (NL5752). All participants provided written informed consent.

Results

Seventy‐five participants were included (38 OM‐85; 37 placebo). Exacerbation frequencies were not different between the groups after 18 months (incidence rate ratio 1.07, 95%CI [0.68–1.69], p = 0.77). With the use of OM‐85, FEV1% increased by 3.81% (p = 0.04) compared with placebo. Nasopharyngeal swabs taken during RTIs detected a virus less frequently in patients using OM‐85 compared to placebo (30.5% vs. 48.0%, p = 0.02).

In subjects with type 2 inflammation adherent to the protocol (22 OM‐85; 20 placebo), a non‐statistically significant decrease in exacerbations in the OM‐85 group was observed (IRR = 0.71, 95%CI [0.39–1.26], p = 0.25). Immune‐modulatory effects included an increase in several plasma cytokines in the OM‐85 group, especially IL‐10 and interferons. Peripheral blood T‐ and B cell subtyping, including regulatory T cells, did not show differences between the groups.

Conclusion

Although OM‐85 may have immune‐modulatory effects, it did not reduce asthma exacerbations in this heterogeneous severe adult asthma group. Post hoc analysis showed a potential clinical benefit in patients with type 2 inflammation.
Differences in cytokine and chemokine profiles in cerebrospinal fluid caused by the etiology of cryptococcal meningitis and tuberculous meningitis in HIV patients
Authors: Xu Lijun , Xu Yufan , Zheng Yanghao , Peng Xiuming , Yang Zongxing , Cao Qing , Xiang Dairong , Zhao Handan
Published: July 2021

The roles of cytokines and chemokines in HIV-associated cryptococcal meningitis (HCM) and HIV-associated tuberculous meningitis (HTBM) are debatable. In sum, 34 HIV-infected patients without meningitis, 44 HCM patients and 27 HTBM patients were enrolled for study. The concentrations of 22 cytokines/chemokines in cerebrospinal fluid (CSF) were assayed at admission. Principal component analysis (PCA), Pearson's and logistic regression analyses were used to assess the role of cytokines/chemokines in HCM and HTBM. We found the levels of T helper (Th)17, Th1 [interleukin (IL)-12p40, interferon (IFN)-γ, tumor necrosis factor (TNF)-α and TNF-β and Th2 (IL-2/4/5/6/10)] cytokines were elevated in patients with meningitis compared with those in HIV-infected patients without central nervous system (CNS) infection. Furthermore, the IL-1Ra, IL-12p40, IL-17α and monocyte chemotactic protein-1 (MCP-1) levels were higher in HCM patients, while the IFN-γ, regulated upon activation, normal T cell expressed and secreted (RANTES) and interferon-inducible protein-10 (IP)-10 levels were higher in HTBM patients. Elevated CSF concentrations of IL-17a, TNF-β, IL-5, IL-12p40 and IL-1Rα were closely related to meningitis, but elevated IP-10, MCP-1, RANTES and IFN-γ levels and CSF white blood cells (WBCs) were protective factors against HCM. Our study suggested that HIV-infected patients with low CSF WBCs have a high risk of HCM. Th1, Th2 and Th17 cytokines/chemokines mediate differences in the pathogenesis of HCM and TBM. Overexpressed proinflammatory MCP-1, RANTES, IFN-γ and IP-10 in CSF are protective factors against HCM but not HTBM.
Long‐term outcomes of open versus closed rectal defect after transanal endoscopic microscopic surgery
Authors: Altaf Kiran , Slawik Simone , Sochorova Dana , Gahunia Sukhpreet , Andrews Timothy , Kehoe Ashley , Ahmed Shakil ,   the Merseyside Early Rectal Cancer Network
Published: July 2021

Aim

Management of the rectal defect after transanal endoscopic microsurgery (TEM) is a matter of debate. Data are lacking on long term outcomes and continence of patients with open or closed rectal defect. We sought to analyse these in a retrospective cohort study.

Methods

Patients undergoing TEM via the Specialist Early Rectal Cancer (SERC) MDT between 2012 and 2019 were included from a prospectively maintained database. These were divided into two groups – open and closed, based on management of rectal defect. Patient demographics and outcomes, including pre‐ and postoperative oncological staging, morbidity, mortality, length of stay and faecal incontinence severity score (FISI) scores were assessed.

Results

A total of 170 matched patients were included (70‐open, 100‐closed rectal defects). Short‐term complications (bleeding, infection, urinary retention and infection, length of stay and pain) were 18.8% with no significant difference between the two groups (22% vs. 16%). Most of the defects were well healed upon endoscopic follow‐up; more unhealed/sinus formation was noticed in the open group (p = 0.01); more strictures were encountered in the closed group (p = 0.04). Comparing the open and closed defect groups, there was no difference in the functional outcome of patients in those who developed sinus (p = 0.87) or stricture (p = 0.79) but a significant difference in post‐TEMS FISI scores in those with healed scar, with those in closed rectal defect group with worsening function (p = 0.02).

Conclusion

There are pros and cons associated with both rectal defect management approaches. Long‐term complications should be expected and actively followed up. Patients should be thoroughly counselled about these and possible deterioration in continence post‐TEM.
Flexible longitudinal and transversal displacement sensors based on a composite of CI Disperse Orange 25 and carbon nanotubes
Authors: Ullah Irfan , Karimov Khasan Sanginovich , Ibrahim Mohd. Adib , Fatima Noshin
Published: July 2021

This paper presents the proposal and characterisation of a flexible, shockproof, vibration‐free, longitudinal and transversal compressive displacement sensor based on a composite of CI Disperse Orange 25 and carbon nanotubes created with an energy‐free, drop‐casting technique. The structural morphology of each layer is studied briefly through X‐ray diffraction. Electric investigations of the sensors in the form of impedance were performed as a function of longitudinal and transversal compressive displacement at three different frequencies. The compressive displacements were measured from 0 to 250 µm at three fixed frequencies (ie, 1, 10 and 200 kHz). The impedance has an inverse relationship with longitudinal compressive displacement but a direct relationship with transversal compressive displacement. The frequency to impedance relationship is inverse with the sensitivity of the impedance as a function of longitudinal displacement. Because of their small size, light weight and simple fabrication technique and design, as well as their low cost and maintenance, these types of devices can be utilised across a wide range of medical applications, such as in rehabilitation centres, for machine status assessment during physiotherapy, and in robotic body parts, as well as for educational purposes in universities.
Long non‐coding RNA colorectal neoplasia differentially expressed correlates negatively with miR‐33a and miR‐495 and positively with inflammatory cytokines in asthmatic children
Authors: Li Weina , Wang Xiaoxue , Sun Shixin , An Hong
Published: July 2021

Objectives

It is reported that long non‐coding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) targets microRNA (miR)‐33a, miR‐181a and miR‐495 to regulate inflammation process, while few studies report their clinical application for paediatric asthma management. Therefore, this study aimed to explore the interaction of lncRNA CRNDE with miR‐33a, miR‐181a and miR‐495, as well as their correlation with inflammation, exacerbation risk and severity in paediatric patients with asthma.

Methods

Asthmatic exacerbation children (N = 65), asthmatic controlled children (N = 65) and controls (N = 65) were recruited. LncRNA CRNDE, miR‐33a, miR‐181a and miR‐495 expressions in peripheral blood mononuclear cells were detected by RT‐qPCR. Besides, serum inflammatory cytokines (including TNF‐α, IL‐1β, IL‐6 and IL‐17) were determined by enzyme‐linked immunosorbent assay (ELISA).

Results

LncRNA CRNDE, miR‐33a and miR‐495 expressions were different, while miR‐181a expression was similar among asthmatic exacerbation children, asthmatic controlled children and controls. Moreover, lncRNA CRNDE negatively correlated with miR‐33a and miR‐495 in asthmatic exacerbation children and asthmatic controlled children, but not in controls. Further analyses showed that lncRNA CRNDE positively correlated with TNF‐α, IL‐1β, IL‐17 and exacerbation severity, while it negatively correlated with FEV1/FVC in asthmatic exacerbation children. Meanwhile, miR‐33a, miR‐181a and miR‐495 all negatively correlated with some individual inflammatory cytokines, while only miR‐33a negatively correlated with exacerbation severity in asthmatic exacerbation children.

Conclusion

LncRNA CRNDE correlates negatively with miR‐33a and miR‐495 and positively with inflammatory cytokines in asthmatic children.
Urban Systems: Understanding and Predicting the Spatial Distribution of China's Population
Authors: Li Pengfei , Lu Ming
Published: July 2021

With urbanization and population migration, some Chinese cities fall into decline whereas others prosper. Using nighttime light data, we redefine the city based on economic function and evaluate the city size distribution in representative countries. The results provide evidence not only for Zipf's law, but also for a distortion in China's current city size distribution. This study proposes a feasible method to predict urban population distribution based on the role of geographical factors in regional development, following the idea of spatial equilibrium. This prediction suggests that the divergence of city size in China tends to be pronounced, with inter‐regional income disparity being narrowed and the city size distribution following Zipf's law. The Chinese government should further relax restrictions on population inflow into large cities and prepare for more migration in the future.
Consumption and Income Poverty in Rural China: 1995–2018
Authors: Chen Yanfeng , Xia Qingjie , Wang Xiaolin
Published: July 2021

This paper studies consumption and income poverty in rural China during the period from 1995 to 2018 using Chinese Household Income Project (CHIP) data. It finds that the wellbeing of Chinese rural residents has improved significantly during this period as part of China's rapid industrialization and economic growth. The incidence of poverty has fallen substantially, either measured in terms of income or consumption. However, consumption poverty is not consistent with income poverty. It was the substantial growth of consumption or income that brought about the sharp fall in poverty, whereas the redistribution of consumption or income in particular during the period from 2002 to 2018 was unfavorable for poverty reduction. A large number of rural household workers moved away from household farming to participate in local or urban non‐farming activities, resulting in a fall in poverty in the households that engaged purely in farming, and economic growth led to a sharp fall in poverty within different rural household groups.
Epidermolysis bullosa dystrophica prätibialis – Klinischer Schnappschuss und Management einer seltenen Erkrankung
Authors: Will Lisa Marlen , Reichrath Jörg , Vogt Thomas
Published: July 2021

Bei Patienten im Kindesalter sollte bei auftretender Blasenbildung auch bei geringer Symptomatik an die Möglichkeit einer hereditären Epidermolysis bullosa gedacht werden. Diagnostisch wegweisend ist neben Klinik und Histologie die molekulargenetische Untersuchung. Therapeutisch stehen aktuell bei lokalisierten Formen symptomatische topische Therapieoptionen weiterhin im Vordergrund. Besonders interessant ist hier die neue Möglichkeit einer topischen Therapie mit Diacerein 1 % Creme. Bei einem ausgeprägten klinischen Bild mit extrakutaner Organbeteiligung ist ein multidisziplinäres Management erforderlich. Zukünftig könnten neue Therapieformen wie die autologe epidermale Stammzelltransplantation und gentherapeutische Verfahren zum Einsatz kommen. Eine humangenetische Beratung ist unerlässlich.
Bekanntes und Neues zum Basalzellkarzinom
Authors: Seidl‐Philipp Magdalena , Frischhut Nina , Höllweger Nicole , Schmuth Matthias , Nguyen Van Anh
Published: July 2021

Das Basalzellkarzinom (BZK) ist der häufigste maligne Tumor bei hellhäutigen Menschen und macht circa 75 % aller Hautkrebsfälle aus. Seit Jahrzehnten werden weltweit steigende Inzidenzraten berichtet. Hauptrisikofaktoren sind UV‐Strahlung, männliches Geschlecht, heller Hauttyp, fortgeschrittenes Alter, langandauernde Immunsuppression, eine positive Familien‐/Eigenanamnese sowie bestimmte Genodermatosen. Das BZK metastasiert selten und die Mortalität ist gering, allerdings kann es zu einer erheblichen Morbidität führen. In der Pathogenese sind genetische Mutationen, welche insbesondere den Hedgehog‐Signalweg betreffen, bedeutsam. In der Diagnostik werden neben der Inspektion mit dem freien Auge und der Dermatoskopie zunehmend auch nichtinvasive Verfahren (optische Kohärenztomographie, konfokale Laserscanmikroskopie) eingesetzt, wobei auf die histologische Diagnosesicherung nur in Ausnahmefällen verzichtet werden kann. Klinisch und histologisch werden zahlreiche Unterformen unterschieden. Die Unterscheidung zwischen BZK mit hohem und niedrigem Rezidivrisiko beeinflusst die Therapieplanung maßgeblich. Die allermeisten BZK können effektiv und sicher mit chirurgischen Standardverfahren beziehungsweise in ausgewählten Fällen mit topischen Therapien behandelt werden. Lokal fortgeschrittene und metastasierte BZK werden einer Radiatio oder Systemtherapie zugeführt. Die Strahlentherapie ist zudem eine Option für ältere Patienten, wenn Kontraindikationen gegen eine Operation bestehen. In der Systemtherapie sind in Europa aktuell die Hedgehog‐Inhibitoren Vismodegib und Sonidegib zugelassen. Eine Zulassung für den PD1‐Inhibitor Cemiplimab in der Zweitlinientherapie ist zu erwarten.
Depth diagnosis of early colorectal cancer: Magnifying chromoendoscopy or image enhanced endoscopy with magnification?
Authors: Ikematsu Hiroaki , Murano Tatsuro , Shinmura Kensuke
Published: July 2021

Depth diagnosis is extremely crucial in making a treatment choice between endoscopic resection and surgery in the early stages of cancers. Among several imaging modalities, we use magnifying endoscopy to diagnose lesions by close observation of the findings at mucosal surface layer. In combination with topical staining, magnifying endoscopy enables us to assess the definite pit structure, which referred to as magnifying chromoendoscopy (MCE). The pit pattern classification by MCE was proposed and is now widely accepted as the standard diagnostic criteria for colorectal lesions. Meanwhile, image enhanced endoscopy (IEE) represented by narrow‐band imaging was developed to improve the visibility of surface and vascular findings without dyeing. Recent collaborative work performed by endoscopic experts in Japan yielded the unified diagnostic criteria, the Japan NBI Expert Team (JNET) classification, based on the findings of IEE with magnification. In this review, focusing on MCE and IEE with magnification, we aimed to give an outline of the pit pattern classification and the JNET classification, and further discuss their accuracy rate of depth diagnosis of early colorectal lesions by performing a review of the related literature. Both modalities have a high accuracy rate of nearly 90% for depth diagnosis. IEE with magnification is an ideal modality because it helps observe lesions without dye spraying; however, lesions with JNET type 2B have an inadequate diagnostic ability, which should be complemented by MCE. We conclude that accurate diagnosis is possible by examining lesions using both modalities properly to overcome the limitations of each modality.
Spin infrequently occurs in abstracts of systematic reviews for the pharmacological treatment of type 2 diabetes mellitus
Authors: Ottwell Ryan , Esmond Lindy , Rea William , Hartwell Micah , Som Mousumi , Harris Rachael , Miao Zhuqi , Zhu Lan , Arthur Wade , Brachtenbach Travis , Wright Drew N. , Vassar Matt
Published: July 2021

Aims

Currently, there is a growing body of research demonstrating that spin—the misinterpretation and distortion of a study's findings—is common in different fields of medicine. To our knowledge, no study has investigated its presence in systematic reviews focused on diabetic therapies.

Methods

We performed a cross‐sectional study by searching MEDLINE and Embase for systematic reviews focused on pharmacologic treatments for type 2 diabetes mellitus. Our search retrieved 26,490 records, from which 199 studies were extracted in a masked, duplicate fashion. Each study was evaluated for the nine most severe types of spin and other study design parameters. Spin was presented as frequencies and odds ratios to identify associations between study characteristics.

Results

Spin was identified in the abstracts of 15 systematic reviews (15/199, 7.5%). Spin type 5 was the most common type identified (7/199, 3.5%). Spin types 1, 2, 4 and 8 were not identified. In the last 5 years (2016–2021), seven systematic reviews contained spin within their abstract. There was no association between the presence of spins and any extracted study characteristic.

Conclusions

Our findings show that spin infrequently occurs in the abstracts of systematic reviews focused on pharmacologic therapies for type 2 diabetes mellitus. However, any amount of spin can lead to the distortion of a reader's interpretation of the study's findings. Thus, we provide recommendations with rationale to prevent spin in future systematic reviews.
What Is Educational about Education? The Distinctiveness of Education
Authors: Norris Trevor
Published: July 2021

This article explores two questions: (1) Is education a unique and distinct discipline? (2) Is education anything other than the achievement of noneducational aims or objectives? In it, Trevor Norris examines how these two questions are interconnected, specifically analyzing how what we think about education as a distinct field of study informs what we ask of it as a practice. When we study education, we should be educational about it, because if we render education as the object of study, it is never endowed with agency or distinctiveness. Norris inquires into the distinctiveness of education as a way of thinking and a way of impacting the world, asking what are the conditions that make it possible for us to identify something as “educational”? To investigate this question, Norris draws from Hannah Arendt's account of politics, and he concludes by describing a case study assignment that requires educational foundations students to draw from philosophy of education in order to show what exactly is educational about education by contrasting education with business and psychology.
Chronic limbic epilepsy models for therapy discovery: Protocols to improve efficiency
Authors: Bertram Edward H. , Edelbroek Peter
Published: July 2021

Objective

There have been recommendations to improve therapy discovery for epilepsy by incorporating chronic epilepsy models into the preclinical process, but unpredictable seizures and difficulties in maintaining drug levels over prolonged periods have been obstacles to using these animals. We report new protocols in which drugs are administered through a new chronic gastric tube to rats with higher seizure frequencies to minimize these obstacles.

Methods

Adult rats with spontaneous limbic seizures following an episode of limbic status epilepticus induced by electrical hippocampal stimulation were monitored with long‐term video– electroencephalography (EEG). Animals with a predetermined baseline seizure frequency received an intragastric tube for drug administration. Carbamazepine, levetiracetam, phenobarbital, and phenytoin were tested with either an acute protocol (an increasing single dose every other day for a maximum of three doses) or with a chronic protocol (multiple administrations of one dose for a week). Drug levels were obtained to correlate the effect with the level.

Results

With the acute protocol, all four drugs induced a clear dose‐related response. Similar dose‐related responses were seen following the week‐long dosing protocol for carbamazepine, phenobarbital, and phenytoin, and these responses were associated with drug levels that were in the human therapeutic range. The response to chronic levetiracetam was much less robust. The gastric tube route of administration was well tolerated over a number of months.

Significance

Using rats with stable, higher seizure frequencies made it possible to identify the potential of a drug to suppress seizures in a realistic model of epilepsy with drug levels that are similar to those of human therapeutic levels. The acute protocol provided a full dose response in 1 week. The chronic administration protocol further differentiated drugs that may be effective long term. The gastric tube facilitates a less stressful, humane, and consistent administration of multiple doses.
Calcium signaling in cancer progression and therapy
Authors: Wu Ling , Lian Weidong , Zhao Liang
Published: July 2021

The old Greek aphorism ‘Panta Rhei’ (‘everything flows’) is true for all living things in general. As a dynamic process, calcium signaling plays fundamental roles in cellular activities under both normal and pathological conditions, with recent researches uncovering its involvement in cell proliferation, migration, survival, gene expression, and more. The major question we address here is how calcium signaling affects cancer progression and whether it could be targeted to combine with classic chemotherapeutics or emerging immunotherapies to improve their efficacy.
The impact of genotype‐by‐environment interaction on the dry matter yield and chemical composition in timothy (Phleum pratense L.) examined by using the additive main effects and multiplicative interaction model
Authors: Bocianowski Jan , Radkowski Adam , Nowosad Kamila , Radkowska Iwona , Zieliński Andrzej
Published: July 2021

Timothy‐grass (Phleum pratense L.) is one of the most valuable pasture grasses in Poland, and the productivity of its genotypes (in the case of outcrossing grass species, the term accession instead of genotype was used in this study) varies depending on environmental conditions. In this study, we aimed to examine the accession‐by‐environment interaction for seven traits in timothy accessions grown in Southern Poland using the additive main effects and multiplicative interaction model. The plant materials used in the study included a total of 11 timothy accessions—six Polish synthetic cultivars (Skald, Egida, Emma, Skala, Skaut and Karta) and five strains (POB‐TT1, POB‐TT2, POB‐TT3, POB‐T‐100 and POB‐T‐107). All these accessions were examined in field trials at three locations, Polanowice, Nieznanice and Palikije, in two growing seasons. The field trials were conducted according to a randomized complete block design with three replicates. The AMMI analyses revealed significant effects of accession and environment as well as the accession‐by‐environment interaction for all the seven analysed traits. The cultivar Skald and the strain POB‐TT3 are recommended for inclusion in future breeding programmes as they exhibit high stability and show good average values for the majority of the examined traits.
Novel insights into immunohistochemical analysis for diagnosing serous neoplasm of the pancreas: aquaporin 1, stereocilin, and transmembrane protein 255B
Authors: Watase Chikashi , Fuse Masanori , Ino Yoshinori , Naito Chie , Hiraoka Nobuyoshi
Published: July 2021

Aims

Serous (cystic) neoplasm (SCN) of the pancreas is generally benign, and surgical treatment is recommended in only a limited number of cases. To avoid unnecessary surgery, an accurate diagnosis of SCN is essential. In the present study, we aimed to identify new immunohistochemical markers with which to distinguish SCN from other tumours.

Methods and results

We compared the comprehensive gene expression profiles of SCN with those of normal pancreas and pancreatic ductal adenocarcinoma (PDAC). We selected the candidate molecules that were up‐regulated in SCN, were minimally expressed or unexpressed in PDAC, and had specific and available antibodies suitable for immunohistochemistry, and then analysed their immunohistochemical expression in various tumours. We selected aquaporin 1 (AQP1), stereocilin (STRC), fibroblast growth factor receptor 3 (FGFR3), and transmembrane protein 255B (TMEM255B), which were diffusely expressed in SCN cells in 79%, 100%, 100% and 100% of SCN cases. AQP1 was not expressed in other tumours, except in 20% of mucinous cystic neoplasms (MCNs) and 19% of PDACs. STRC was rarely expressed in MCNs, neuroendocrine neoplasms (NENs), and PDACs. FGFR3 was expressed in 31% of intraductal papillary mucinous neoplasms (IPMNs), 50% of intraductal oncocytic papillary neoplasms, 40% of NENs, 30% of acinar cell carcinomas, 40% of solid pseudopapillary neoplasms, and 52% of PDACs. TMEM255B was not expressed in the other tumours, except in 50% of MCNs, 80% of gastric‐subtype IPMNs, and 29% of PDACs. All antigens were usually expressed in a small proportion of cells when they were positive in tumours other than SCN.

Conclusions

These findings indicate that AQP1 and STRC, and potentially TMEM255B, may act as SCN markers.
A case of a primary myelofibrosis with progression and related literature review of progression phase genetics
Authors: Chen Dong , Fuda Franklin , Weinberg Olga
Published: July 2021

Philadelphia (BCR‐ABL)‐negative myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). MPN can transform into an accelerated or a blast phase, which is associated with poor response to standard therapy and low overall median survival. We present an interesting case of a patient with a history of PMF and progression and summarize the current studies on genetic features of myeloproliferative neoplasms in blast phase (MPN‐BP) with an emphasis on PMF. Although MPN‐BP show ≥20% blasts in peripheral blood or bone marrow, it is not considered as acute myeloid leukemia (AML) according to the WHO classification. While MPNs‐BP typically lack genetic mutations seen in de novo AML, they commonly harbor IDH1/2, SRSF2, ASXL1, and TP53 mutations, similar to the genetic profiles of acute myeloid leukemia with myelodysplasia‐related changes (AML‐MRC).