bluuebunny/crossref_metadata_2025 huggingface dataset:
Intrapulmonary airway smooth muscle is hyperreactive with a distinct proteome in asthma
Authors: Ijpma Gijs , Kachmar Linda , Panariti Alice , Matusovsky Oleg S. , Torgerson Dara , Benedetti Andrea , Lauzon Anne-Marie
Published: April 2020

Constriction of airways during asthmatic exacerbation is the result of airway smooth muscle (ASM) contraction. Although it is generally accepted that ASM is hypercontractile in asthma, this has not been unambiguously demonstrated. Whether airway hyperresponsiveness (AHR) is the result of increased ASM mass alone or also increased contractile force generation per unit of muscle directly determines the potential avenues for treatment.

To assess whether ASM is hypercontractile we performed a series of mechanics measurements on isolated ASM from intrapulmonary airways and trachealis from human lungs. We analysed the ASM and whole airway proteomes to verify if proteomic shifts contribute to changes in ASM properties.

We report an increase in isolated ASM contractile stress and stiffness specific to asthmatic human intrapulmonary bronchi, the site of increased airway resistance in asthma. Other contractile parameters were not altered. Principal component analysis (PCA) of unbiased mass spectrometry data showed clear clustering of asthmatic subjects with respect to ASM specific proteins. The whole airway proteome showed upregulation of structural proteins. We did not find any evidence for a difference in the regulation of myosin activity in the asthmatic ASM.

In conclusion, we showed that ASM is indeed hyperreactive at the level of intrapulmonary airways in asthma. We identified several proteins that are upregulated in asthma that could contribute to hyperreactivity. Our data also suggest enhanced force transmission associated with enrichment of structural proteins in the whole airway. These findings may lead to novel directions for treatment development in asthma.
Genetically modified Caenorhabditis elegans may lead to inaccurate toxicity evaluation of mixtures
Authors: Huang Peng , Li Kai , Xu Ya-Qian , Wang Ze-Jun , Liu Shu-Shen
Published: April 2020

Background

One of the major challenges in environmental science is how to assess the toxicity and risk of complex pollutant mixtures. However, only a few studies have pointed out that there is a significant difference between the toxicities of chemicals on genetically modified strains and wild-type organisms and there are few reports of the differences in the toxicity of chemical mixtures. Therefore, six chemicals, two substituted phenols (4-chlorophenol and 4-nitrophenol), two pesticides (dichlorvos and glyphosate) and two ionic liquids (1-butylpyridinium chloride and 1-butylpyridinium bromide), were selected to construct a six-component mixture system, the lethality of various mixtures on the genetically modified Caenorhabditis elegans strain mtl-2::GFP (MTL-2) at 12 and 24 h were determined, and differences in toxicity to other strains were compared.

Results

Although the toxicity of 4-chlorophenol on MTL-2 was not significantly different from that on N2 wild-type Caenorhabditis elegans (N2), the toxicities of the other five chemicals on MTL-2 were greater than those on N2. The toxicities of six single chemicals and nine mixture rays on MTL-2 increased with time, which is consistent with the effect on N2 and on the genetically modified strain sod-3::GFP Caenorhabditis elegans (SOD-3). The toxicological interactions of various mixtures in MTL-2 at 12 h were half antagonistic (ANT) and half additive (ADD), while at 24 h, they were mainly synergistic (SYN). The toxicological interactions of various mixtures in MTL-2 change from ANT/ADD to primarily SYN with time, which is different from the change from ANT to ADD in SOD-3 and from SYN to ADD in N2.

Conclusions

The toxicity and toxicity interactions of chemical mixtures on different Caenorhabditis elegans strains are different. Therefore, it is necessary to examine the effect of genetic factors on the toxicological interaction of mixtures to avoid underestimating or overestimating the mixture risk.
EphB4/ TNFR2/ERK/MAPK signaling pathway comprises a signaling axis to mediate the positive effect of TNF-α on osteogenic differentiation
Authors: Zhang Yu , Yang Chengzhe , Ge Shaohua , Wang Limei , Zhang Jin , Yang Pishan
Published: April 2020

Background

Low concentrations of tumor necrosis factor-alpha (TNF-α) and its receptor TNFR2 are both reported to promote osteogenic differentiation of osteoblast precursor cells. Moreover, low concentrations of TNF-α up-regulate the expression of EphB4. However, the molecular mechanisms underlying TNF-α-induced osteogenic differentiation and the roles of TNFR2 and EphB4 have not been fully elucidated.

Results

The ALP activity, as well as the mRNA and protein levels of RUNX2, BSP, EphB4 and TNFR2, was significantly elevated in MC3T3-E1 murine osteoblast precursor cells when stimulated with 0.5 ng/ml TNF-α. After TNFR2 was inhibited by gene knockdown with lentivirus-mediated shRNA interference or by a neutralizing antibody against TNFR2, the pro-osteogenic effect of TNF-α was partly reversed, while the up-regulation of EphB4 by TNF-α remained unchanged. With EphB4 forward signaling suppressed by a potent inhibitor of EphB4 auto-phosphorylation, NVP-BHG712, TNF-α-enhanced expressions of TNFR2, BSP and Runx2 were significantly decreased. Further investigation into the signaling pathways revealed that TNF-α significantly increased levels of p-JNK, p-ERK and p-p38. However, only the p-ERK level was significantly inhibited in TNFR2-knockdown cells. In addition, the ERK pathway inhibitor, U0126 (10 μM), significantly reversed the positive effect of TNF-α on the protein levels of RUNX2 and BSP.

Conclusions

The EphB4, TNFR2 and ERK/MAPK signaling pathway comprises a signaling axis to mediate the positive effect of TNF-α on osteogenic differentiation.
Forcing external constraints on tree inference using ASTRAL
Authors: Rabiee Maryam , Mirarab Siavash
Published: April 2020

Background

To account for genome-wide discordance among gene trees, several widely-used methods seek to find a species tree with the minimum distance to input gene trees. To efficiently explore the large space of species trees, some of these methods, including ASTRAL, use dynamic programming (DP). The DP paradigm can restrict the search space, and thus, ASTRAL and similar methods use heuristic methods to define a restricted search space. However, arbitrary constraints provided by the user on the output tree cannot be trivially incorporated into such restrictions. The ability to infer trees that honor user-defined constraints is needed for many phylogenetic analyses, but no solution currently exists for constraining the output of ASTRAL.

Results

We introduce methods that enable the ASTRAL dynamic programming to infer constrained trees in an effective and scalable manner. To do so, we adopt a recently developed tree completion algorithm and extend it to allow multifurcating input and output trees. In simulation studies, we show that the approach for honoring constraints is both effective and fast. On real data, we show that constrained searches can help interrogate branches not recovered in the optimal ASTRAL tree to reveal support for alternative hypotheses.

Conclusions

The new algorithm is added ASTRAL to all user-provided constraints on the species tree.
Protocol of a multicentric prospective cohort study for the VALIDation of the IBD-disk instrument for assessing disability in inflammatory bowel diseases: the VALIDate study
Authors: Le Berre C. , Bourreille A. , Flamant M. , Bouguen G. , Siproudhis L. , Dewitte M. , Dib N. , Cesbron-Metivier E. , Goronflot T. , Hanf M. , Gourraud P.-A. , Kerdreux E. , Poinas A. , Trang-Poisson C.
Published: April 2020

Background

Inflammatory Bowel Diseases (IBD) affect psychological, family, social and professional dimensions of patients’ life, leading to disability which is essential to quantify as part of Patient-Reported Outcomes (PROs) newly included in the targets to reach in IBD patients. Up to now, the IBD-Disability Index (IBD-DI) was the only validated tool to assess disability, but it is not appropriate for use in clinical practice. The IBD Disk was developed, a shortened and self-administered tool, adapted from the IBD-DI, in order to give immediate representation of patient-reported disability. However, the IBD Disk has not been validated yet in clinical practice. The aims of the VALIDate study are to validate this tool in a large population of IBD patients and to compare it to the already validated IBD-DI.

Methods

The VALIDate study is an ongoing multicentric prospective cohort study launched in April 2018 in 3 French University Hospitals (Nantes, Rennes, Angers), with an objective to reach a sample of 400 patients over a period inclusion of 6 months. Each patient will fill in the two questionnaires IBD Disk and IBD-DI at baseline, then between 3 and 12 months later, during a follow-up visit. Clinical and socio-demographic data will also be collected. During these two consultations, gastroenterologists and patients will evaluate disease activity thanks to a semi-quantitative 4-grade scale, named respectively PGA (Physician Global Assessment) and PtGA (Patient Global Assessment). This cohort will allow to evaluate the validity of the IBD Disk with respect to the IBD-DI in order to generalize its use for clinical practice. Other psychometric criteria of the IBD Disk will also be analysed as its reliability or its discriminant capacity. Close attention will nonetheless be needed to minimize the number of lost to follow-up patients between baseline and follow-up.

Discussion

The VALIDate study is the study designed to validate the IBD Disk, a visual tool easily useable in daily practice to assess disability in IBD patients. The results of this trial should enable the diffusion of this tool.

Trial registration

The trial is registered in ClinicalTrials.Gov with registration number NCT03590639. First posted: July 18, 2018.
A comparative analysis on human resources among the specialized ophthalmic medical institutions in China
Authors: Zhan Leilei , Safaya Neha , Erkou Hana , An Lei , Wang Zhifeng , Feng Jingjing , Xu Xiao
Published: April 2020

Background

This study compares perspectives on specialized ophthalmic medical institutions, identifies the gaps in property and geographic offerings, and explores the ways that ophthalmic medical institutions can better allocate resources. The results of this research will increase patient’s access to equitable and high-quality ophthalmic care in China.

Methods

The data for this research was gathered from the Survey of China National Eye Care Capacity and Resource for the year 2015. The paper specified the number, professional level of expertise, and educational background of ophthalmic health personnel. The authors of the paper analyzed and compared the differences in ophthalmic care in public vs. private and urban vs. rural regions in China. Descriptive statistics were used.

Results

Of the 395 specialized ophthalmic hospitals surveyed, 332 were private medical institutions (84%), and 63 were public (16%). Of the 26 607 ophthalmic personnel surveyed, working in specialized ophthalmic hospitals, 17 561 were in private hospitals (66%) and 9 046 were in public ones (34%). Furthermore, 22 578 of those personnel worked in urban ophthalmic institutions (85%) and 4 029 worked in rural ones (15%). As for regional differences, 14 090 personnel were located in eastern China (53%), 8 828 in central regions (33%), and 3 689 in the western regions (14%).

Conclusions

Public ophthalmic medical institutions still face challenges in providing equitable and widespread care. The availability of well-staffed health centers varies significantly by region. These variations impact resource allocation and directly lead to inequalities and inaccessibility of health services in certain regions of China.
Intracranial pressure elevation alters CSF clearance pathways
Authors: Vinje Vegard , Eklund Anders , Mardal Kent-Andre , Rognes Marie E. , Støverud Karen-Helene
Published: April 2020

Background

Infusion testing is a common procedure to determine whether shunting will be beneficial in patients with normal pressure hydrocephalus. The method has a well-developed theoretical foundation and corresponding mathematical models that describe the CSF circulation from the choroid plexus to the arachnoid granulations. Here, we investigate to what extent the proposed glymphatic or paravascular pathway (or similar pathways) modifies the results of the traditional mathematical models.

Methods

We used a compartment model to estimate pressure in the subarachnoid space and the paravascular spaces. For the arachnoid granulations, the cribriform plate and the glymphatic circulation, resistances were calculated and used to estimate pressure and flow before and during an infusion test. Finally, different variations to the model were tested to evaluate the sensitivity of selected parameters.

Results

At baseline intracranial pressure (ICP), we found a very small paravascular flow directed into the subarachnoid space, while 60% of the fluid left through the arachnoid granulations and 40% left through the cribriform plate. However, during the infusion, 80% of the fluid left through the arachnoid granulations, 20% through the cribriform plate and flow in the PVS was stagnant. Resistance through the glymphatic system was computed to be 2.73 mmHg/(mL/min), considerably lower than other fluid pathways, giving non-realistic ICP during infusion if combined with a lymphatic drainage route.

Conclusions

The relative distribution of CSF flow to different clearance pathways depends on ICP, with the arachnoid granulations as the main contributor to outflow. As such, ICP increase is an important factor that should be addressed when determining the pathways of injected substances in the subarachnoid space. Our results suggest that the glymphatic resistance is too high to allow for pressure driven flow by arterial pulsations and at the same time too small to allow for a direct drainage route from PVS to cervical lymphatics.
The value of moderate dose escalation for re-irradiation of recurrent or second primary head-and-neck cancer
Authors: Rühle Alexander , Sprave Tanja , Kalckreuth Tobias , Stoian Raluca , Haehl Erik , Zamboglou Constantinos , Laszig Roland , Knopf Andreas , Grosu Anca-Ligia , Nicolay Nils H.
Published: April 2020

Background

Treatment for local and locoregional recurrence or second head-and-neck (H&N) cancers after previous radiotherapy is challenging, and re-irradiation carries a significantly increased risk for radiotherapy-related normal tissue toxicities and treatment failure due to a radioresistant tumor phenotype. Here, we analyzed re-irradiation management and outcomes in patients with recurrent or second primary H&N carcinoma using state-of-the-art diagnostic procedures and radiotherapy techniques.

Methods

Between 2010 and 2019, 48 patients with recurrent or second primary H&N carcinoma received re-radiotherapy at the University of Freiburg Medical Center and were included in this study. Overall survival (OS) and progression-free survival (PFS) were calculated with the Kaplan-Meier method, and univariate Cox-regression analyses were performed to assess the effects of clinico-pathological factors on treatment outcomes. Acute and chronic treatment-related toxicities were quantified using the Common Terminology Criteria for Adverse Events (CTCAE v4.03).

Results

Thirty-one patients (64.6%) received definitive and 17 (35.4%) adjuvant radiotherapy. Simultaneous chemotherapy was administered in 28 patients (58.3%) with cetuximab as the most commonly used systemic agent (n = 17, 60.7%). After a median time of 17 months (range 4 months to 176 months) between first and second radiotherapy, patients were re-irradiated with a median of 58.4 Gy and a treatment completion rate of 87.5% (n = 42). Median OS was 25 months with a 1-year OS amounting to 62.4%, and median PFS was 9 months with a 1-year PFS of 37.6%. Univariate analyses demonstrated that both a lower rT-status and a radiotherapy boost were associated with improved OS (p < 0.05). There was a trend towards superior OS for patients who received > 50 Gy (p = 0.091) and who completed the prescribed radiotherapy (p = 0.055). Five patients (10.4%) suffered from at least one grade 3 toxicities, while 9 patients (27.3%) experienced chronic higher-grade toxicities (≥ grade 3) with one (3.0%) grade 4 carotid blowout and one (3.0%) grade 4 osteoradionecrosis.

Conclusion

Re-irradiation of recurrent or second primary H&N cancer with modern radiation techniques such as intensity-modulated radiotherapy resulted in promising survival rates with acceptable toxicities compared to historical cohorts. Increased re-irradiation doses, utilization of a radiotherapy boost and completion of the re-irradiation treatment were found to result in improved survival.
The effectiveness of a self-made modular elastic compression device for patients with a fracture of the tibia and fibula
Authors: Zeng Lingyuan , Wang Yongrong , He Dongdong , He Yao , Wang Yuze , Wei Xiaochun
Published: April 2020

Background

To evaluate the effectiveness of a self-made modular elastic compression device for patients with a fracture of the tibia and fibula.

Methods

Fifty-nine healthy adult patients with a unilateral fracture of the tibia and fibula were randomly divided into an experimental group and a control group. The experimental group was given the self-made combined elastic compression device for the compression treatment of the affected limbs after the operation. The main endpoints included the convenience, safety, and effectiveness of the self-made modular elastic compression device for patients with a fracture of the tibia and fibula.

Results

There were 29 cases in the experimental group and 30 cases in the control group. There were no significant differences between the two groups in the general data: age, gender, fracture site, and cause of injury. The preoperative swelling elimination time was 3.3 ± 1.2 days, and the postoperative swelling elimination time was 3.1 ± 1.4 days in the experimental group; the preoperative swelling elimination time was 6.3 ± 1.2 days, and the postoperative swelling elimination time was 7.3 ± 1.2 days in the control group. The preoperative and postoperative swelling degree in the experimental group was shorter than those in the control group. The difference in the postoperative detumescence time between the experimental group (3.1 ± 1.4 days) and the control group (7.3 ± 1.2 days) was significant, and the total hospital stay was 8.1 ± 1.5 days in the experimental group and 13 ± 2.5 days in the control group with a statistical significance of P < 0.05. The change of discharge hemoglobin volume (11.2 ± 6.5 g/L) of the experimental group was lower than that of the control group (3.5 ± 1.2 days), the total drainage volume was 260 ± 50 ml, and the change of admission and discharge hemoglobin volume was 30.3 ± 10.4 g/L. Specifically, although the difference in the average hospital stay between the two groups was statistically significant, the difference was only 1 day, and the clinical difference was not significant. However, in the change of the cumulative drainage volume and hemoglobin volume, the experimental group that was given compression therapy was significantly lower than the control group with a statistical significance (P < 0.05). The pressure injury (4 cases) in the experimental group was significantly lower than that in the control group (8 cases) (P < 0.05).

Conclusion

A modular combined elastic compression device in patients with a tibial and fibular fracture can significantly accelerate a patient’s rehabilitation, shorten the hospital stay, reduce blood loss, relieve the patient’s pain, and relieve the patient’s social-economic burden during recovery.
Evidence for ligninolytic activity of the ascomycete fungus Podospora anserina
Authors: van Erven Gijs , Kleijn Anne F. , Patyshakuliyeva Aleksandrina , Di Falco Marcos , Tsang Adrian , de Vries Ronald P. , van Berkel Willem J. H. , Kabel Mirjam A.
Published: April 2020

Background

The ascomycete fungus Podospora anserina has been appreciated for its targeted carbohydrate-active enzymatic arsenal. As a late colonizer of herbivorous dung, the fungus acts specifically on the more recalcitrant fraction of lignocellulose and this lignin-rich biotope might have resulted in the evolution of ligninolytic activities. However, the lignin-degrading abilities of the fungus have not been demonstrated by chemical analyses at the molecular level and are, thus far, solely based on genome and secretome predictions. To evaluate whether P. anserina might provide a novel source of lignin-active enzymes to tap into for potential biotechnological applications, we comprehensively mapped wheat straw lignin during fungal growth and characterized the fungal secretome.

Results

Quantitative 13C lignin internal standard py-GC–MS analysis showed substantial lignin removal during the 7 days of fungal growth (24% w/w), though carbohydrates were preferably targeted (58% w/w removal). Structural characterization of residual lignin by using py-GC–MS and HSQC NMR analyses demonstrated that Cα-oxidized substructures significantly increased through fungal action, while intact β-O-4′ aryl ether linkages, p-coumarate and ferulate moieties decreased, albeit to lesser extents than observed for the action of basidiomycetes. Proteomic analysis indicated that the presence of lignin induced considerable changes in the secretome of P. anserina. This was particularly reflected in a strong reduction of cellulases and galactomannanases, while H2O2-producing enzymes clearly increased. The latter enzymes, together with laccases, were likely involved in the observed ligninolysis.

Conclusions

For the first time, we provide unambiguous evidence for the ligninolytic activity of the ascomycete fungus P. anserina and expand the view on its enzymatic repertoire beyond carbohydrate degradation. Our results can be of significance for the development of biological lignin conversion technologies by contributing to the quest for novel lignin-active enzymes and organisms.
Characterisation of extraembryonic endoderm-like cells from mouse embryonic fibroblasts induced using chemicals alone
Authors: He Xia , Chi Guangfan , Li Meiying , Xu Jinying , Zhang Lihong , Song Yaolin , Wang Lina , Li Yulin
Published: April 2020

Background

The development of somatic reprogramming, especially purely chemical reprogramming, has significantly advanced biological research. And chemical-induced extraembryonic endoderm-like (ciXEN) cells have been confirmed to be an indispensable intermediate stage of chemical reprogramming. They resemble extraembryonic endoderm (XEN) cells in terms of transcriptome, reprogramming potential, and developmental ability in vivo. However, the other characteristics of ciXEN cells and the effects of chemicals and bFGF on the in vitro culture of ciXEN cells have not been systematically reported.

Methods

Chemicals and bFGF in combination with Matrigel were used to induce the generation of ciXEN cells derived from mouse embryonic fibroblasts (MEFs). RNA sequencing was utilised to examine the transcriptome of ciXEN cells, and PCR/qPCR assays were performed to evaluate the mRNA levels of the genes involved in this study. Hepatic functions were investigated by periodic acid-Schiff staining and indocyanine green assay. Lactate production, ATP detection, and extracellular metabolic flux analysis were used to analyse the energy metabolism of ciXEN cells.

Results

ciXEN cells expressed XEN-related genes, exhibited high proliferative capacity, had the ability to differentiate into visceral endoderm in vitro, and possessed the plasticity allowing for their differentiation into induced hepatocytes (iHeps). Additionally, the upregulated biological processes of ciXEN cells compared to those in MEFs focused on metabolism, but their energy production was independent of glycolysis. Furthermore, without the cocktail of chemicals and bFGF, which are indispensable for the generation of ciXEN cells, induced XEN (iXEN) cells remained the expression of XEN markers, the high proliferative capacity, and the plasticity to differentiate into iHeps in vitro.

Conclusions

ciXEN cells had high plasticity, and energy metabolism was reconstructed during chemical reprogramming, but it did not change from aerobic oxidation to glycolysis. And the cocktail of chemicals and bFGF were non-essential for the in vitro culture of ciXEN cells.
Enhancing the therapeutic effects of in vitro targeted radionuclide therapy of 3D multicellular tumor spheroids using the novel stapled MDM2/X-p53 antagonist PM2
Authors: Mortensen Anja C. L. , Morin Eric , Brown Christopher J. , Lane David P. , Nestor Marika
Published: April 2020

Background

Precision therapeutics continuously make advances in cancer therapy, and a field of growing interest is the combination of targeted radionuclide therapy (TRNT) with potential radiosensitizing agents. This study evaluated whether the effects of in vitro TRNT, using the 177Lu-labeled anti-CD44v6 antibody AbN44v6, were potentiated by the novel stapled MDM2/X-p53 antagonist PM2.

Materials and methods

Two wt p53 cell lines, HCT116 (colorectal carcinoma) and UM-SCC-74B (head and neck squamous cell carcinoma), expressing different levels of the target antigen, CD44v6, were used. Antigen-specific binding of 177Lu-AbN44v6 was initially verified in a 2D cell assay, after which the potential effects of unlabeled AbN44v6 on downstream phosphorylation of Erk1/2 were evaluated by western blotting. Further, the therapeutic effects of unlabeled AbN44v6, 177Lu-AbN44v6, PM2, or a combination (labeled/unlabeled AbN44v6 +/− PM2) were assessed in 3D multicellular tumor spheroid assays.

Results

Radiolabeled antibody bound specifically to CD44v6 on both cell lines. Unlabeled AbN44v6 binding did not induce downstream phosphorylation of Erk1/2 at any of the concentrations tested, and repeated treatments with the unlabeled antibody did not result in any spheroid growth inhibition. 177Lu-AbN44v6 impaired spheroid growth in a dose-dependent and antigen-dependent manner. A single modality treatment with 20 μM of PM2 significantly impaired spheroid growth in both spheroid models. Furthermore, the combination of TRNT and PM2-based therapy proved significantly more potent than either monotherapy. In HCT116 spheroids, this resulted in a two- and threefold spheroid growth rate decrease for the combination of PM2 and 100 kBq 177Lu-AbN44v6 compared to monotherapies 14-day post treatment. In UM-SCC-74B spheroids, the combination therapy resulted in a reduction in spheroid size compared to the initial spheroid size 10-day post treatment.

Conclusion

TRNT using 177Lu-AbN44v6 proved efficient in stalling spheroid growth in a dose-dependent and antigen-dependent manner, and PM2 treatment demonstrated a growth inhibitory effect as a monotherapy. Moreover, by combining TRNT with PM2-based therapy, therapeutic effects of TRNT were potentiated in a 3D multicellular tumor spheroid model. This proof-of-concept study exemplifies the strength and possibility of combining TRNT targeting CD44v6 with PM2-based therapy.
Effect of Aso limonite on anaerobic digestion of waste sewage sludge
Authors: Mustapha Nurul Asyifah , Toya Shotaro , Maeda Toshinari
Published: April 2020

The effect of Aso volcanic limonite was explored in anaerobic digestion using waste sewage sludge (WSS). In this study, methane and hydrogen sulfide were remarkably inhibited when Aso limonite was mixed with WSS as well as a significant reduction of ammonia. Although pH was lowered after adding Aso limonite, methane was still inhibited in neutralized pH condition at 7.0. Hydrolysis stage was not influenced by Aso limonite as supported by the result that a high protease activity was still detected in the presence of the material. However, acidogenesis stage was affected by Aso limonite as indicated by the different productions of organic acids. Acetic acid, was accumulated in the presence of Aso limonite due to the inhibition of methane production, except in the highest concentration of Aso limonite which the production of acetate may be inhibited. Besides, the production of propionate and butyrate reduced in accordance to the increased concentration of Aso limonite. In addition, Archaeal activity (methanogens) in WSS with Aso limonite was low in agreement with the low methane production. Thus, these results indicate that Aso limonite influences the acidogenesis and methanogenesis processes, by which the productions of methane and ammonia were inhibited. On the other hand, in the contactless of Aso limonite during the anaerobic digestion of WSS (Aso limonite was placed in the area of headspace in the vial), Aso limonite had the adsorptive ability for hydrogen sulfide from WSS, but not for methane. This contactless system of Aso limonite may be a practical means to remove hydrogen sulfide without inhibiting methane production as an important bioenergy source.
SEA-MAKE score as a tool for predicting major adverse kidney events in critically ill patients with acute kidney injury: results from the SEA-AKI study
Authors: Sukmark Theerapon , Lumlertgul Nuttha , Praditpornsilpa Kearkiat , Tungsanga Kriang , Eiam-Ong Somchai , Srisawat Nattachai
Published: April 2020

Background

Acute kidney injury (AKI) is a common problem in critically ill patients and associated with high rates of morbidity and mortality. Recently, Major Adverse Kidney Events (MAKE) were introduced as important kidney endpoints. If these endpoints can be predicted, then it may help the physicians to identify high-risk patients and provide the opportunity to have targeted preventive therapy. The objective of this study was to create a simplified scoring system to predict MAKE within 28 days among AKI patients in ICU.

Methods

This is a prospective web-based multicenter cohort study that was conducted in adults who were admitted to the ICU in 17 centers across Thailand from 2013 to 2015. A predicting score was derived from the regression equation with Receiver Operating Characteristic (ROC) analysis to evaluate the diagnostic test and produce predictive models. Internal validation was obtained using the bootstrapping method.

Results

From 5071 cases, 2856 (56%) had AKI. Among those with AKI, 1749 (61%) had MAKE. Among those that have MAKE, there were 1175 (41.4%) deaths, 414 (14.4%) were on dialysis and 1154 (40.7%) had non-recovery renal function. The simplified score points of low Glasgow coma scale was 3, tachypnea was 1, vasopressor use was 1, on mechanical ventilation was 2, oliguria was 2, serum creatinine rising ≥ 3 times was 5, high blood urea nitrogen was 3, low hematocrit was 2, and thrombocytopenia was 1. The area under ROC curve for optimism corrected performance was 0.80 (0.78, 0.81). When the cut-off value was 7, the sensitivity, specificity, positive likelihood ratio, and positive predictive values were 0.75, 0.76, 3.10, and 0.84, respectively. When the scoring system was calibrated, the α intercept and β slope were 1.001 and 0, respectively.

Conclusions

SEA-MAKE scoring system is a new simplified clinical tool that can be used to predict major adverse kidney events in AKI patients. The simplicity of the scoring system is highly likely to be used in resource-limited settings. However, external validation is necessary before widespread use.
Effectiveness and cost-effectiveness of telehealth in rural and remote emergency departments: a systematic review protocol
Authors: Tsou Christina , Robinson Suzanne , Boyd James , Jamieson Andrew , Blakeman Robert , Bosich Kylie , Yeung Justin , Waters Stephanie , Hendrie Delia
Published: April 2020

Background

Emergency telehealth has been used to improve accessibility of rural and remote patients to specialist care. Evidence to date has demonstrated effectiveness and cost-effectiveness of telehealth in rural and remote emergency departments within a variety of contexts. However, systematic reviews to date have not focused on the rural and remote emergency departments. The purpose of this study is to review the outcome measures used in evaluations of emergency telehealth in rural and remote settings and assess evidence relating to their effectiveness and cost-effectiveness.

Methods

Randomised controlled trials, non-randomised controlled trials, and full and partial economic evaluations (e.g. cost-effectiveness, cost-benefit, and cost-utility analyses) of telehealth in rural and remote emergency departments will be included. Comprehensive literature searches will be conducted in multiple electronic databases (from 1990 onwards): MEDLINE (Ovid), Cochrane Library, Scopus, CINAHL, ProQuest, EconLit, CRD databases (e.g. NHS Economic Evaluation database), and Tufts Cost-Effectiveness Registry. Two authors will independently screen all citations, full-text articles, and abstract data. The methodological quality (or risk of bias) of individual studies will be appraised using an appropriate tool. A systematic narrative synthesis will be provided with information presented in the text and tables to summarise and explain the characteristics and findings of the studies. If feasible, we will conduct random effects meta-analysis.

Discussion

This review will identify gaps in the current body of evidence relating to the effectiveness and cost-effectiveness of rural and remote emergency telehealth services. By confining to articles written in the English language, this analysis may be subjected to publication bias and results need to be interpreted accordingly. We believe the results of this review could be valuable for the design of future economic evaluations of emergency telehealth services implemented in the rural and remote context.

Systematic review registration

PROSPERO CRD42019145903
Arithmetic properties derived from coefficients of certain eta quotients
Authors: Hwang Jihyun , Li Yan , Kim Daeyeoul
Published: April 2020

For a positive integer k, let $$ F (q)^{k}:= \prod_{n \geq 1} \frac{(1-q^{n})^{4k}}{(1+q^{2n})^{2k}} = \sum_{n\geq 0} \frak{a}_{k} (n)q^{n} $$F(q)k:=∏n≥1(1−qn)4k(1+q2n)2k=∑n≥0ak(n)qn be the eta quotients. The coefficients $\frak{a}_{1} (n)$a1(n) can be interpreted as a certain kind of restricted divisor sums. In this paper, we give the signs and modulo values for $\frak{a}_{1} (n)$a1(n) and $\frak{a}_{2} (m)$a2(m) and calculate several convolution sums involving $\frak{a}_{k} (n)$ak(n).
Linkages, fields of influence and key sectors
Authors: ten Raa Thijs
Published: April 2020

Linkages, fields of influence and key sectors are troublesome concepts.
Innovations in maternal and child health: case studies from Uganda
Authors: Awor Phyllis , Nabiryo Maxencia , Manderson Lenore
Published: April 2020

Background

Nearly 300 children and 20 mothers die from preventable causes daily, in Uganda. Communities often identify and introduce pragmatic and lasting solutions to such challenging health problems. However, little is known of these solutions beyond their immediate surroundings. If local and pragmatic innovations were scaled-up, they could contribute to better health outcomes for larger populations. In 2017 an open call was made for local examples of community-based solutions that contribute to improving maternal and child health in Uganda. In this article, we describe three top innovative community-based solutions and their contributions to maternal health.

Main text

In this study, all innovations were implemented by non-government entities. Two case studies highlight the importance of bringing reproductive health and maternal delivery services closer to populations, through providing accessible shelters and maternity waiting homes in isolated areas. The third case study focuses on bringing obstetric imaging services to lower level rural health facilities, which usually do not provide this service, through task-shifting certain sonography services to midwives. Various health system and policy relevant lessons are highlighted.

Conclusions

The described case studies show how delays in access to health care by pregnant women in rural communities can be systematically removed, to improve pregnancy and delivery outcomes. Emphasis should be put on identification, capacity building and research to support the scale up of these community-based health solutions.
Validation of the English version of the Mood Rhythm Instrument
Authors: Oliveira Melissa A. B. , Epifano Kristina , Mathur Salina , Carvalho Felipe Gutiérrez , Scop Marina , Carissimi Alicia , Francisco Ana Paula , Garay Luciene L. S. , Adan Ana , Hidalgo Maria Paz , Frey Benicio N.
Published: April 2020

Background

Disruption of biological rhythms has been linked to the pathophysiology of mental disorders. However, little is known regarding the rhythmicity of mood symptoms due to the lack of validated clinical questionnaires. A better understanding of the rhythmicity of mood symptoms can help identifying individuals whose severity of mood symptoms follows an altered circadian rhythm. The objective of this study was to validate the English version of the Mood Rhythm Instrument (MRhI), a self-reported measure of self-perceived rhythmicity of mood symptoms and behaviours, in a sample of the general population from Canada.

Methods

After the translation process, the final English version of the Mood Rhythm Instrument (MRhI-English) was applied on participants recruited at McMaster University and St. Joseph’s Healthcare Hamilton campuses. Individuals were also asked to answer the Reduced Morningness-Eveningness Questionnaire (rMEQ).

Results

Four hundred one individuals completed the English version of the MRhI and the rMEQ. The MRhI-English presented a Cronbach’s alpha of 0.75. The factorial analysis grouped the MRhI-15 items in 3 factors (cognitive, affective and somatic), with affective items having a lower frequency of self-reported 24-h peaks. Comparison between sexes showed that women reported a higher frequency of daily peaks in irritability, anxiety, sadness and talking to friends, while men exhibited peaks more frequently in problem-solving, sexual arousal and motivation to exercise.

Conclusions

Our findings suggest that the English version of the MRhI displayed good internal consistency. Future directions will include the use of the MRhI instrument in individuals with mood disorders, aiming to provide a better understanding of the relationship between daily patterns of mood variability and mental health outcomes.
TBL1XR1 mutation predicts poor outcome in primary testicular diffuse large B-cell lymphoma patients
Authors: Wang Xinfeng , Xu Xiaoyu , Cai Wenzhi , Bao Haiyan , Huang Hongming , Liu Yifei , Yang Xi , Ruan Changgeng , Wu Depei , Shen Hongjie , Chen Suning
Published: April 2020

Primary testicular lymphoma (PTL), often appearing as focal masses in the scrotum and epididymides, is the most frequent testicular tumor in aged men. Although MYD88 and CD79B mutations were the most common genetic alterations observed, the gene mutation landscape of PTL remains poorly defined. In this study, we identified 1326 mutations involving 311 genes or regions in 90 PTL patients through next-generation sequencing (NGS). PTL patients with the TBL1XR1 mutation, irrespective of treatment therapy, had an inferior overall survival (OS) than TBL1XR1 WT (wild type) patients (p = 0.045). Moreover, patients with this mutation, treated with a CHOP regimen (CTX 750 mg/m2 iv, d1,8 ADM 50 mg/m2 iv, d1 VCR 1.4 mg/m2 iv, d1 PDN 100 mg/m2 po d1–5), had a poorer OS (p = 0.019). In addition, such patients were prone to have a more intensive infiltration of tumors (p = 0.025, x2 = 4.890). Thus, we speculated that patients with a TBL1XR1 mutation have poorer prognosis, partly due to greater invasion and infiltration of tumors. Our results suggest that the TBL1XR1 mutation can be used as an indicator to predict the prognosis of PTL and can be employed as a promising new target for treatment of PTL in the future.
Mitochondrial respiratory chain deficiency correlates with the severity of neuropathology in sporadic Creutzfeldt-Jakob disease
Authors: Flønes Irene H. , Ricken Gerda , Klotz Sigrid , Lang Alexandra , Ströbel Thomas , Dölle Christian , Kovacs Gabor G. , Tzoulis Charalampos
Published: April 2020

Mitochondrial dysfunction has been implicated in multiple neurodegenerative diseases but remains largely unexplored in Creutzfeldt-Jakob disease. Here, we characterize the mitochondrial respiratory chain at the individual neuron level in the MM1 and VV2 common molecular subtypes of sporadic Creutzfeldt-Jakob disease. Moreover, we investigate the associations between the mitochondrial respiratory chain and neuropathological markers of the disease.

Brain tissue from individuals with sporadic Creutzfeldt-Jakob disease and age-matched controls were obtained from the brain collection of the Austrian Creutzfeldt-Jakob Surveillance. The mitochondrial respiratory chain was studied through a dichotomous approach of immunoreactivities in the temporal cortex and the hippocampal subregions of CA4 and CA3.

We show that profound deficiency of all mitochondrial respiratory complexes (I-V) occurs in neurons of the severely affected temporal cortex of patients with Creutzfeldt-Jakob disease. This deficiency correlates strongly with the severity of neuropathological changes, including vacuolation of the neuropil, gliosis and disease associated prion protein load. Respiratory chain deficiency is less pronounced in hippocampal CA4 and CA3 regions compared to the temporal cortex. In both areas respiratory chain deficiency shows a predilection for the MM1 molecular subtype of Creutzfeldt-Jakob disease.

Our findings indicate that aberrant mitochondrial respiration could be involved early in the pathogenesis of sporadic Creutzfeldt-Jakob disease and contributes to neuronal death, most likely via ATP depletion. Based on these results, we propose that the restricted MRI diffusion profile seen in the brain of patients with sporadic Creutzfeldt-Jakob disease might reflect cytotoxic changes due to neuronal respiratory chain failure and ATP loss.
Increasing high school teachers self-efficacy for integrated STEM instruction through a collaborative community of practice
Authors: Kelley Todd R. , Knowles J. Geoffery , Holland Jeffrey D. , Han Jung
Published: April 2020

Background

Teachers can have a significant impact on student interest and learning in science, technology, engineering, and math (STEM) subjects and careers. Teacher self-efficacy can also significantly affect student learning. Researchers investigated the effects of teacher professional development and integrated STEM curriculum development on teacher self-efficacy. Participants in the study included high school science and engineering technology teachers enrolled in a National Science Foundation–ITEST project called Teachers and Researchers Advancing Integrated Lessons in STEM (TRAILS). The TRAILS program sought to prepare teachers to integrate STEM content using engineering design, biomimicry, science inquiry, and 3D printing as pedagogical approaches. Teachers learned within a community of practice working alongside industry partners and college faculty. The purpose of the study was to investigate the impact of the 70 h of professional development to train three cohorts of teachers over 3 years on teacher self-efficacy. The research design utilized a quasi-experimental nonequivalent control group approach, including an experimental group and an untreated control group.

Results

Measurements on beliefs about teacher self-efficacy were collected on pretest, posttest, and delayed posttest survey assessments. Researchers analyzed the T-STEM survey results for teaching self-efficacy using the Wilcoxson signed-rank test for detecting significant differences. Science teachers showed a significant increase in teacher self-efficacy comparing the pretest and delayed posttest scores after TRAILS professional development and STEM lesson implementation (p=.001, effect size = .95). Additionally, significant differences between groups (science experimental vs science control group teachers) using the Wilcoxon rank-sum test were detected from pretest to posttest (p= .033, effect size = .46), posttest to delayed posttest (p= .029, effect size = .47), and pretest to delayed posttest (p= .005, effect size = .64). There were no significant differences detected in the control group. Engineering technology teachers showed no significant differences between the pretest, posttest, and delayed posttest self-efficacy scores.

Conclusions

The results indicate the science teachers’ self-efficacy increased after professional development and after lesson implementation. Potential implications from this research suggest that the science teacher participants benefited greatly from learning within a community of practice, engaging in science practices, and using science knowledge to solve a real-world problem (engineering design).
Liver resection for a congenital intrahepatic portosystemic shunt in a child with hyperammonemia and hypermanganesemia: a case report
Authors: Takama Yuichi , Nakamura Tetsuro , Santo Kenji , Yoneda Akihiro
Published: April 2020

Background

Congenital portosystemic shunt (CPSS) is a rare malformation that leads to hyperammonemia, hypermanganesemia, and various symptoms. CPSSs are divided into intrahepatic and extrahepatic shunts. In patients with persistent CPSS including an intrahepatic portosystemic shunt (IPSS), early intervention to occlude the shunt reverses the associated complications.

Case presentation

The patient was a 1-year-and-7-month-old girl. She presented with hypergalactosemia and elevation of blood ammonia level (75 μg/dL) and total bile acid levels (68.2 μmol/L) during the neonatal period. Two IPSSs were detected using ultrasound and enhanced computerized tomography. Magnetic resonance imaging (MRI) at 1 year and 3 months of age showed abnormally high signal intensity in the pallidum of her brain. Spontaneous closure was not observed. We performed a right hepatectomy at 1 year and 7 months of age. The portal vein pressure was 16 mmHg after temporary occlusion of the right portal vein. Blood ammonia and serum manganese levels decreased immediately after the operation. The abnormal signal on brain MRI disappeared. She had a favorable course with no sign of recurrence of IPSS 5 years postoperatively.

Conclusion

Liver resection for an IPSS to control the symptoms of a portosystemic shunt is reasonable in a child for whom interventional radiological treatment is not indicated.