bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a precision medicine pipeline to identify personalized treatments for colorectal cancer
Authors: Altunel Erdem , Roghani Roham S. , Chen Kai-Yuan , Kim So Young , McCall Shannon , Ware Kathryn E. , Shen Xiling , Somarelli Jason A. , Hsu David S.
Published: June 2020

Background

Metastatic colorectal cancer (CRC) continues to be a major health problem, and current treatments are primarily for disease control and palliation of symptoms. In this study, we developed a precision medicine strategy to discover novel therapeutics for patients with CRC.

Methods

Six matched low-passage cell lines and patient-derived xenografts (PDX) were established from CRC patients undergoing resection of their cancer. High-throughput drug screens using a 119 FDA-approved oncology drug library were performed on these cell lines, which were then validated in vivo in matched PDXs. RNA-Seq analysis was then performed to identify predictors of response.

Results

Our study revealed marked differences in response to standard-of-care agents across patients and pinpointed druggable pathways to treat CRC. Among these pathways co-targeting of fibroblast growth factor receptor (FGFR), SRC, platelet derived growth factor receptor (PDGFR), or vascular endothelial growth factor receptor (VEGFR) signaling was found to be an effective strategy. Molecular analyses revealed potential predictors of response to these druggable pathways.

Conclusions

Our data suggests that the use of matched low-passage cell lines and PDXs is a promising strategy to identify new therapies and pathways to treat metastatic CRC.
The effect of dot size in random-dot stereograms on the results of stereoacuity measurements
Authors: Zhao Lingzhi , Wu Huang
Published: June 2020

Background

This study aimed to evaluate the effect of the size of the dots in random-dot stereograms on the results of stereoacuity measurements.

Methods

A stereopsis measurement system was created using a phoropter and two 4 K smartphones. Three dot sizes, including 1 × 1 pixel, 6 × 6 pixels, and 10 × 10 pixels (equivalent to 0.17 min arc, 1 min arc, and 1.68 min arc, respectively), were used to form random-dot arrays, and each test pattern had one Lea symbol hidden within it. The resulting stereograms were tested on 30 subjects with normal acuity and stereoacuity.

Results

Stereoacuity measured with the 1-pixel dots was significantly worse than that measured with the 6-pixel dots (Wilcoxon signed-rank test, Z = -4.903, P < 0.001) and the 10-pixel dots (Z = -4.941, P < 0.001). No significant difference was found between 6-pixel dot and 10-pixel dot stereograms (Z = -1.000, P = 0.317).

Conclusion

The size of the dots in random-dot stereograms affects the test results significantly when the dots are too small for the eye to resolve.
Prognostic role of the preoperative neutrophil-to-lymphocyte ratio and albumin for 30-day mortality in patients with postoperative acute pulmonary embolism
Authors: Liu Chuan , Zhan Hui-lu , Huang Zhang-Heng , Hu Chuan , Tong Yue-Xin , Fan Zhi-Yi , Zheng Meng-Ying , Zhao Cheng-Liang , Ma Gui-Yun
Published: June 2020

Background

This retrospective study aimed to investigate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and albumin for 30-day mortality in patients with postoperative acute pulmonary embolism (PAPE).

Methods

We retrospectively reviewed the medical records of 101 patients with PAPE admitted from September 1, 2012, to March 31, 2019. The characteristics, surgical information, admission examination data and mortality within 30 days after PAPE were obtained from our electronic medical recording system and follow-up. The associations between the NLR, PLR, and other predictors and 30-day mortality were analyzed with univariate and multivariate analyses. Then, the nomogram including the independent predictors was established and evaluated.

Results

Twenty-four patients died within 30 days, corresponding to a 30-day mortality rate of 23.8%. The results of the multivariate analysis indicated that both the NLR and albumin were independent predictors for 30-day mortality in patients with PAPE. The probability of death increased by approximately 17.1% (OR = 1.171, 95% CI: 1.073–1.277, P = 0.000) with a one-unit increase in the NLR, and the probability of death decreased by approximately 15.4% (OR = 0.846, 95% CI: 0.762c–0.939, P = 0.002) with a one-unit increase in albumin. The area under the curve of the nomogram was 0.888 (95% CI: 0.812–0.964).

Conclusion

Our findings showed that an elevated NLR and decreased albumin were related to poor prognosis in patients with PAPE. The NLR and albumin were independent prognostic factors for PAPE.
LINC01094 triggers radio-resistance in clear cell renal cell carcinoma via miR-577/CHEK2/FOXM1 axis
Authors: Jiang Yufeng , Li Wei , Yan Yang , Yao Xudong , Gu Wenyu , Zhang Haimin
Published: June 2020

Background

Radioresistance is an obstacle to limit efficacy of radiotherapy. Meanwhile, long non-coding RNAs (lncRNAs) have been reported to affect radioresistance. Here, we aimed to investigate lncRNAs involving radioresistance development of clear cell renal cell carcinoma (ccRCC), the most frequent type of renal cell carcinoma (RCC).

Methods

The mRNA and protein expressions of genes were measured via qRT-PCR and western blot. The relationships among genes were verified by RIP and luciferase reporter assay. The radioresistance of ccRCC cells was evaluated through clonogenic survival assay, MTT assay and TUNEL assay.

Results

LINC01094 was over-expressed in ccRCC cell lines. LINC01094 expression was increased along with the radiation exposure time and the final stable level was 8 times of the initial level. Knockdown of LINC01094 resulted in enhanced radiosensitivity of ccRCC cells. Mechanically, LINC01094 was a ceRNA of CHEK2 by sponging miR-577. Also, the enhancement of LINC01094 on ccRCC radioresistance was mediated by CHEK2-stabilized FOXM1 protein.

Conclusion

LINC01094 facilitates ccRCC radioresistance by targeting miR-577/CHEK2/FOXM1 axis, blazing a new trail for overcoming radioresistance in ccRCC.
LncRNA FTX represses the progression of non-alcoholic fatty liver disease to hepatocellular carcinoma via regulating the M1/M2 polarization of Kupffer cells
Authors: Wu Huajun , Zhong Zhiwei , Wang Anji , Yuan Chunhui , Ning Ke , Hu Huanhuan , Wang Chao , Yin Xiangbao
Published: June 2020

Background

The effect of lncRNA FTX on non-alcoholic fatty liver disease (NAFLD) conversion to hepatocellular carcinoma (HCC) is unclear.

Methods

In our study, C57BL/6 mice was fed with high fat diet for obtaining NAFLD mouse model, and diethylnitrosamine induced the formation of HCC tumor. The expression of iNOS and CD206 in tissues were examined using immunohistochemistry. In addition, qRT-PCR was implemented to detect the expression of FTX and mRNAs. The percentage of M1 and M2 Kupffer cells (KCs) were determined using flow cytometry. The pathological change in liver tissues was displayed by H&E staining. Besides, immunofluorescence assay was performed to ensure the primary KCs through labeling F4/80.

Results

Here, we found that the expression of FTX and the ratio of M1/M2 KCs in liver tissues from NAFLD-transformed HCC (NAFLD-HCC) patients lower than in liver tissues from NAFLD patients. Subsequently, we revealed that the expression of FTX and M1/M2 KCs ratio were downregulated during NAFLD conversion to HCC. Importantly, increasing of FTX inhibited HCC tumor growth, improved liver damage and promoted M1 polarization of KCs during NAFLD conversion to HCC, while these effects of FTX were reversed by inactivating of KCs. Finally, in vitro experiments, our data indicated that FTX facilitated the M1 polarization of KCs.

Conclusion

In conclusion, our results demonstrated that upregulation of FTX suppressed NAFLD conversion to HCC though promoting M1 polarization of KCs. Our findings presented a new regulatory mechanism for NAFLD conversion to HCC, and provided a new biomarker for inhibiting this conversion.
Levels of knowledge regarding malaria causes, symptoms, and prevention measures among Malawian women of reproductive age
Authors: Sixpence Alick , Nkoka Owen , Chirwa Gowokani C. , Milanzi Edith B. , Mangani Charles , Mathanga Don P. , Ntenda Peter A. M.
Published: June 2020

Background

Malawi is a malaria-endemic country and approximately 6 million cases are reported annually. Improving knowledge of malaria causes and symptoms, and the overall perception towards malaria and its preventive measures is vital for malaria control. The current study investigated the levels of knowledge of the causes, symptoms and prevention of malaria among Malawian women.

Methods

Data from the 2017 wave of the Malawi Malaria Indicator Survey (MMIS) were analysed. In total, 3422 women of reproductive age (15–49 years) were sampled and analysed. The levels of women’s knowledge about: (1) causes of malaria; (2) symptoms of malaria; and, (3) preventive measures were assessed. The tertiles of the composite score were used as the cut-offs to categorize the levels of knowledge as ‘low’, ‘medium’ and ‘high’. Multinomial logistic regression models were constructed to assess the independent factors while taking into account the complex survey design.

Results

Approximately 50% of all respondents had high levels of knowledge of causes, symptoms and preventive measures. The high level of knowledge was 45% for rural women and 55% for urban dwellers. After adjusting for the a wide range of factors, women of age group 15–19 years adjusted odds ratio ((aOR): 2.58; 95% Confidence Interval (CI) 1.69–3.92), women with no formal education (aOR: 3.73; 95% CI 2.20–6.33), women whose household had no television (aOR: 1.50; 95% CI 1.02–2.22), women who had not seen/heard malaria message (aOR: 1.53; 95% CI 1.20–1.95), women of Yao tribe (aOR: 1.95; 95% CI 1.10–3.46), and women from rural areas had low levels of knowledge about the causes of malaria, symptoms of malaria and preventive measures. Additionally, the results also showed that women aged 15–19 years (beta [β] = − 0.73, standard error [SE] = 0.12); P < .0001, women with no formal education (β = − 1.17, SE = 0.15); P < .0001, women whose household had no radio (β = − 0.15, SE = 0.0816); P = 0.0715 and women who had not seen or heard malaria message (β = − 0.41, SE = 0.07); P < .0001 were likely to have a lower knowledge score.

Conclusions

The levels of malaria knowledge were reported to be unsatisfactory among adult women, underscoring the need to scale up efforts on malaria education. Beside insecticide-treated bed nets (ITNs) and prompt diagnosis, malaria can be best managed in Malawi by increasing knowledge of malaria causes, and symptoms especially for younger women, women with no formal education, women whose households have no media, women from Yao tribes, and rural dwellers.
Sustainable and acceptable school meals through optimization analysis: an intervention study
Authors: Eustachio Colombo Patricia , Patterson Emma , Lindroos Anna Karin , Parlesak Alexandr , Elinder Liselotte Schäfer
Published: June 2020

Background

School meals hold considerable potential to shape children’s diets and reduce food-related greenhouse gas emissions (GHGE)—in the short and long term. This study applied linear optimization to develop a GHGE-reduced, nutritionally adequate, and affordable school lunch menu. The effects on food waste, consumption and pupils’ satisfaction with the meals were evaluated.

Methods

A pre-post design was employed to assess the effects of implementing an optimized lunch menu on daily food waste, consumption, and pupils’ school meal satisfaction in three schools (grades 0–9) from one Swedish municipality. A food list containing amounts, prices, nutrient content, and GHGE-values of all foods used for a previously served (baseline) four-week lunch menu was created. Using linear programming, this food list was optimized for minimum deviation and constrained to ensure nutritional adequacy and a reduced climate impact. The optimized food list was developed into a new (intervention) four-week lunch menu by a professional meal planner, following the baseline menu as closely as possible. The baseline and intervention menus were served for four weeks, respectively, with a two week break in between. Prepared, wasted and leftover food were weighed daily by the school kitchen staff during both periods. Interrupted time series analysis assessed mean and slope differences in daily food waste and consumption between the two periods. School lunch satisfaction was assessed with an online questionnaire at baseline and during the intervention.

Results

Optimization resulted in a food list that was 40% lower in GHGE, met all nutrient recommendations for school meals, and cost 11% less compared to baseline. The intervention menu was served as planned, with only minor changes required (for practical reasons). Plate waste, serving waste, consumption and school lunch satisfaction did not differ significantly from baseline, in any of the schools.

Conclusions

The findings demonstrate that school meals can successfully be improved regarding health and environmental sustainability using linear optimization, without negative effects on food waste, consumption or cost. This approach offers the necessary flexibility to tailor menus towards different priorities and could therefore be transferred to other types of meal services.

Trial registration

The trial is registered at clinicaltrials.gov (NCT04168632 Fostering Healthy and Sustainable Diets Through School Meals (OPTIMAT).
Correction to: When is an abscess more than an abscess? Syringe services programs and the harm reduction safety-net: a case report
Authors: Castillo Marcus , Ginoza Margaret E. C. , Bartholomew Tyler S. , Forrest David W. , Greven Costaki , Serota David P. , Tookes Hansel E.
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
A fast, simple, and cost-effective method of expanding patient-derived xenograft mouse models of pancreatic ductal adenocarcinoma
Authors: Liu Zhenyang , Ahn Michael Ho-Young , Kurokawa Tomohiro , Ly Amy , Zhang Gong , Wang Fuyou , Yamada Teppei , Sadagopan Ananthan , Cheng Jane , Ferrone Cristina R. , Liss Andrew S. , Honselmann Kim C. , Wojtkiewicz Gregory R. , Ferrone Soldano , Wang Xinhui
Published: June 2020

Background

Patient-derived xenograft (PDX) mouse models of cancer have been recognized as better mouse models that recapitulate the characteristics of original malignancies including preserved tumor heterogeneity, lineage hierarchy, and tumor microenvironment. However, common challenges of PDX models are the significant time required for tumor expansion, reduced tumor take rates, and higher costs. Here, we describe a fast, simple, and cost-effective method of expanding PDX of pancreatic ductal adenocarcinoma (PDAC) in mice.

Methods

We used two established frozen PDAC PDX tissues (derived from two different patients) and implanted them subcutaneously into SCID mice. After tissues reached 10–20 mm in diameter, we performed survival surgery on each mouse to harvest 90–95% of subcutaneous PDX (incomplete resection), allowing the remaining 5–10% of PDX to continue growing in the same mouse.

Results

We expanded three consecutive passages (P1, P2, and P3) of PDX in the same mouse. Comparing the times required for in vivo expansion, P2 and P3 (expanded through incomplete resection) grew 26-60% faster than P1. Moreover, such expanded PDX tissues were successfully implanted orthotopically into mouse pancreases. Within 20 weeks using only 14 mice, we generated sufficient PDX tissue for future implantation of 200 mice. Our histology study confirmed that the morphologies of cancer cells and stromal structures were similar across all three passages of subcutaneous PDX and the orthotopic PDX and were reflective of the original patient tumors.

Conclusions

Taking advantage of incomplete resection of tumors associated with high local recurrence, we established a fast method of PDAC PDX expansion in mice.
Evaluating blood–brain barrier permeability in a rat model of type 2 diabetes
Authors: Qiao Ju , Lawson Christopher M. , Rentrup Kilian F. G. , Kulkarni Praveen , Ferris Craig F.
Published: June 2020

Background

This is an exploratory study using a novel imaging modality, quantitative ultrashort time-to-echo, contrast enhanced (QUTE-CE) magnetic resonance imaging to evaluate the permeability of the blood–brain barrier in a rat model of type 2 diabetes with the presumption that small vessel disease is a contributing factor to neuropathology in diabetes.

Methods

The BBZDR/Wor rat, a model of type 2 diabetes, and age-matched controls were studied for changes in blood–brain barrier permeability. QUTE-CE, a quantitative vascular biomarker, generated angiographic images with over 500,000 voxels that were registered to a 3D MRI rat brain atlas providing site-specific information on blood–brain barrier permeability in 173 different brain areas.

Results

In this model of diabetes, without the support of insulin treatment, there was global capillary pathology with over 84% of the brain showing a significant increase in blood–brain barrier permeability over wild-type controls. Areas of the cerebellum and midbrain dopaminergic system were not significantly affected.

Conclusion

Small vessel disease as assessed by permeability in the blood–brain barrier in type 2 diabetes is pervasive and includes much of the brain. The increase in blood–brain barrier permeability is a likely contributing factor to diabetic encephalopathy and dementia.
Artificial intelligence in health care: laying the Foundation for Responsible, sustainable, and inclusive innovation in low- and middle-income countries
Authors: Alami Hassane , Rivard Lysanne , Lehoux Pascale , Hoffman Steven J. , Cadeddu Stéphanie Bernadette Mafalda , Savoldelli Mathilde , Samri Mamane Abdoulaye , Ag Ahmed Mohamed Ali , Fleet Richard , Fortin Jean-Paul
Published: June 2020

The World Health Organization and other institutions are considering Artificial Intelligence (AI) as a technology that can potentially address some health system gaps, especially the reduction of global health inequalities in low- and middle-income countries (LMICs). However, because most AI-based health applications are developed and implemented in high-income countries, their use in LMICs contexts is recent and there is a lack of robust local evaluations to guide decision-making in low-resource settings. After discussing the potential benefits as well as the risks and challenges raised by AI-based health care, we propose five building blocks to guide the development and implementation of more responsible, sustainable, and inclusive AI health care technologies in LMICs.
Three years of growth hormone treatment in young adults with Prader-Willi syndrome: sustained positive effects on body composition
Authors: Damen Layla , Donze Stephany H. , Kuppens Renske J. , Bakker Nienke E. , de Graaff Laura C. G. , van der Velden Janielle A. E. M. , Hokken-Koelega Anita C. S.
Published: June 2020

Background

In children with Prader-Willi syndrome (PWS), the benefits of growth hormone treatment are well established. Several one-year studies have shown that growth hormone is also beneficial for adults with PWS, improving body composition. However, little is known about the longer-term effects.

This study investigated the effects on body composition in adult patients with PWS during 3 years of growth hormone therapy in a dose of 0.33 mg/m2/day.

Methods

Open-label, prospective study in 43 young adults with PWS with a median (IQR) age of 19.0 (17.5 to 20.7) years. Fat mass percentage SDS and lean body mass SDS were measured annually by DXA.

Results

Estimated mean (95% CI) fat mass percentage SDS decreased during the three-year study from 2.1 (1.9 to 2.3) SDS at start to 1.9 (1.8 to 2.1) SDS,p = 0.012, while lean body mass SDS remained stable at − 2.1 (− 2.4 to − 1.8) SDS at start to − 1.9 (− 2.3 to − 1.6) after 3 years,p = 0.15. Fasting glucose and insulin remained similar during the three-year study, glucose being 4.6 (4.4 to 4.8) mmol/l at start and 4.6 (4.5 to 4.7) mmol/l after 3 years of growth hormone,p = 0.93 and insulin being 59.5 (42.2 to 81.5) pmol/l and 55.0 (42.4 to 69.2) pmol/l, resp.,p = 0.54. There were no growth hormone-related adverse events during the study.

Conclusions

Three years of growth hormone treatment in young adults with PWS maintains the positive effects on body composition attained during childhood. Thus, adults with PWS benefit from longer-term growth hormone treatment.

Trial registration

EudraCT, EudraCT number2011-001313-14. Registered 17 October 2012.
Shenhuang granule in the treatment of severe coronavirus disease 2019 (COVID-19): study protocol for an open-label randomized controlled clinical trial
Authors: Fang Bangjiang , Zhang Wen , Wu Xinxin , Huang Tingrong , Li Huacheng , Zheng You , Che Jinhua , Sun Shuting , Jiang Chao , Zhou Shuang , Feng Jun
Published: June 2020

Background

Currently, coronavirus disease 2019 (COVID-19) is continuously and rapidly circulating, causing heavy damage on public health. No effective antiviral treatment has been proved thus far. Traditional Chinese medicine (TCM) has been widely applied in the treatment of a variety of infection diseases in China, hoping to produce clinical effects and reduce the use of antibiotics and glucocorticoid. The aim of this study is to evaluate the efficacy and safety of Shenhuang granule in treatment of severe COVID-19.

Methods/design

This multicenter, open-label randomized controlled trial is conducted in 160 participants with severe COVID-19. The participants will be randomly (1:1) divided into treatment group or control group. All participants are given standard therapy at the same time. The experiment will receive Shenhuang granule treatment twice a day for 14 days. The clinical indicators of patients will be assessed at baseline and at 3, 5, 7, and 14 days after treatment initiation. The primary outcome is 14-day clinical outcome. Adverse events will be monitored throughout the trial.

Discussion

This will be the first randomized controlled trial, which evaluate the effect of Shenhuang granule in patients with severe COVID-19 in China. The results of this trial may not only provide evidence-based recommendations to clinicians to treat severe COVID-19, but also enrich the theory and practice of TCM in treating infectious diseases.

Trial registration

Chinese Clinical Trial Registry, ChiCTR2000029777. Registered on 13 February 2020.
Development of optimal steam explosion pretreatment and highly effective cell factory for bioconversion of grain vinegar residue to butanol
Authors: Xia Menglei , Peng Mingmeng , Xue Danni , Cheng Yang , Li Caixia , Wang Di , Lu Kai , Zheng Yu , Xia Ting , song Jia , Wang Min
Published: June 2020

Background

The industrial vinegar residue (VR) from solid-state fermentation, mainly cereals and their bran, will be a potential feedstock for future biofuels because of their low cost and easy availability. However, utilization of VR for butanol production has not been as much optimized as other sources of lignocellulose, which mainly stem from two key elements: (i) high biomass recalcitrance to enzymatic sugar release; (ii) lacking of suitable industrial biobutanol production strain. Though steam explosion has been proved effective for bio-refinery, few studies report SE for VR pretreatment. Much of the relevant knowledge remains unknown. Meanwhile, recent efforts on rational metabolic engineering approaches to increase butanol production inClostridiumstrain are quite limited. In this study, we assessed the impact of SE pretreatment, enzymatic hydrolysis kinetics, overall sugar recovery and applied atmospheric and room temperature plasma (ARTP) mutant method for theClostridiumstrain development to solve the long-standing problem.

Results

SE pretreatment was first performed. At the optimal condition, 29.47% of glucan, 71.62% of xylan and 22.21% of arabinan were depolymerized and obtained in the water extraction. In the sequential enzymatic hydrolysis process, enzymatic hydrolysis rate was increased by 13-fold compared to the VR without pretreatment and 19.60 g glucose, 15.21 g xylose and 5.63 g arabinose can be obtained after the two-step treatment from 100 g VR. Porous properties analysis indicated that steam explosion can effectively generate holes with diameter within 10–20 nm. Statistical analysis proved that enzymatic hydrolysis rate of VR followed the Pseudop-second-order kinetics equation and the relationship between SE severity and enzymatic hydrolysis rate can be well revealed by Boltzmann model. Finally, a superior inhibitor-tolerant strain,Clostridium acetobutylicumTust-001, was generated with ARTP treatment. The water extraction and enzymolysis liquid gathered were successfully fermented, resulting in butanol titer of 7.98 g/L and 12.59 g/L of ABE.

Conclusions

SE proved to be quite effective for VR due to high fermentable sugar recovery and enzymatic hydrolysate fermentability. Inverse strategy employing ARTP and repetitive domestication for strain breeding is quite feasible, providing us with a new tool for solving the problem in the biofuel fields.
The increased sensitivity of qPCR in comparison to Kato-Katz is required for the accurate assessment of the prevalence of soil-transmitted helminth infection in settings that have received multiple rounds of mass drug administration
Authors: Dunn Julia C. , Papaiakovou Marina , Han Kay Thwe , Chooneea Darren , Bettis Alison A. , Wyine Nay Yee , Lwin Aye Moe Moe , Maung Nay Soe , Misra Raju , Littlewood D. T. J. , Anderson Roy M.
Published: June 2020

Background

The most commonly used diagnostic tool for soil-transmitted helminths (STH) is the Kato-Katz (KK) thick smear technique. However, numerous studies have suggested that the sensitivity of KK can be problematic, especially in low prevalence and low intensity settings. An emerging alternative is quantitative polymerase chain reaction (qPCR).

Methods

In this study, both KK and qPCR were conducted on stool samples from 648 participants in an STH epidemiology study conducted in the delta region of Myanmar in June 2016.

Results

Prevalence of any STH was 20.68% by KK and 45.06% by qPCR. Prevalence of each individual STH was also higher by qPCR than KK, the biggest difference was for hookworm with an approximately 4-fold increase between the two diagnostic techniques. Prevalence of Ancylostoma ceylanicum, a parasite predominately found in dogs, was 4.63%, indicating that there is the possibility of zoonotic transmission in the study setting. In individuals with moderate to high intensity infections there is evidence for a linear relationship between eggs per gram (EPG) of faeces, derived from KK, and DNA copy number, derived from qPCR which is particularly strong for Ascaris lumbricoides.

Conclusions

The use of qPCR in low prevalence settings is important to accurately assess the epidemiological situation and plan control strategies for the ‘end game’. However, more work is required to accurately assess STH intensity from qPCR results and to reduce the cost of qPCR so that is widely accessible in STH endemic countries.
Discovery of CD80 and CD86 as recent activation markers on regulatory T cells by protein-RNA single-cell analysis
Authors: Trzupek Dominik , Dunstan Melanie , Cutler Antony J. , Lee Mercede , Godfrey Leila , Jarvis Lorna , Rainbow Daniel B. , Aschenbrenner Dominik , Jones Joanne L. , Uhlig Holm H. , Wicker Linda S. , Todd John A. , Ferreira Ricardo C.
Published: June 2020

Background

Traditionally, the transcriptomic and proteomic characterisation of CD4+T cells at the single-cell level has been performed by two largely exclusive types of technologies: single-cell RNA sequencing (scRNA-seq) and antibody-based cytometry. Here, we present a multi-omics approach allowing the simultaneous targeted quantification of mRNA and protein expression in single cells and investigate its performance to dissect the heterogeneity of human immune cell populations.

Methods

We have quantified the single-cell expression of 397 genes at the mRNA level and up to 68 proteins using oligo-conjugated antibodies (AbSeq) in 43,656 primary CD4+T cells isolated from the blood and 31,907 CD45+cells isolated from the blood and matched duodenal biopsies. We explored the sensitivity of this targeted scRNA-seq approach to dissect the heterogeneity of human immune cell populations and identify trajectories of functional T cell differentiation.

Results

We provide a high-resolution map of human primary CD4+T cells and identify precise trajectories of Th1, Th17 and regulatory T cell (Treg) differentiation in the blood and tissue. The sensitivity provided by this multi-omics approach identified the expression of the B7 molecules CD80 and CD86 on the surface of CD4+Tregs, and we further demonstrated that B7 expression has the potential to identify recently activated T cells in circulation. Moreover, we identified a rare subset of CCR9+T cells in the blood with tissue-homing properties and expression of several immune checkpoint molecules, suggestive of a regulatory function.

Conclusions

The transcriptomic and proteomic hybrid technology described in this study provides a cost-effective solution to dissect the heterogeneity of immune cell populations at extremely high resolution. Unexpectedly, CD80 and CD86, normally expressed on antigen-presenting cells, were detected on a subset of activated Tregs, indicating a role for these co-stimulatory molecules in regulating the dynamics of CD4+T cell responses.
Post-developmental extracellular proteoglycan maintenance in attractin-deficient mice
Authors: Azouz Abdallah , Duke-Cohan Jonathan S.
Published: June 2020

Objective

Neurodegeneration and hair pigmentation alterations in mice occur consequent to aberrations at the Atrn locus coding for the transmembrane form of attractin. Earlier results pointed to a possible involvement in intracellular trafficking/export of secretory vesicles containing proteoglycan. Here we examined kidney and liver, both heavily dependent upon proteoglycan, of attractin-deficient mice to determine whether abnormalities were observed in these tissues.

Results

Histological and histochemical analysis to detect glycosylated protein identified a severe loss in attractin-deficient mice of extracellular proteoglycan between kidney tubules in addition to a loss of glycosylated material within the intratubular brush border. In the liver, extracellular matrix material was significantly depleted between hepatocytes together with swollen sinuses and aberrations in the proteoglycan-dependent space of Disse. These results are consistent with a generalized defect in extracellular proteoglycan deposition in Atrn-mutant mice and support previous reports suggesting a role for attractin in the secretory vesicle pathway.
Modelling and simulation of flame cutting for steel plates with solid phases and melting
Authors: Arenas Manuel J. , Hömberg Dietmar , Lasarzik Robert , Mikkonen Pertti , Petzold Thomas
Published: June 2020

The goal of this work is to describe in detail a quasi-stationary state model which can be used to deeply understand the distribution of the heat in a steel plate and the changes in the solid phases of the steel and into liquid phase during the flame cutting process. We use a 3D-model similar to previous works from Thiébaud (J. Mater. Process. Technol. 214(2):304–310, 2014) and expand it to consider phases changes, in particular, austenite formation and melting of material. Experimental data is used to validate the model and study its capabilities. Parameters defining the shape of the volumetric heat source and the power density are calibrated to achieve good agreement with temperature measurements. Similarities and differences with other models from literature are discussed.
From public vs. private to public/private mix in healthcare: lessons from the Israeli and the Spanish cases
Authors: Filc Dani , Rasooly Alon , Davidovitch Nadav
Published: June 2020

Background

Different forms of public/private mix have become a central mode of the privatization of healthcare, in both financing and provision. The present article compares the processes of these public/private amalgams in healthcare in Spain and Israel in order to better understand current developments in the privatization of healthcare.

Main text

While in both Spain and Israel combinations between the public and the private sectors have become the main forms of privatization, the concrete institutional forms differ. In Spain, these institutional forms maintain relatively clear boundaries between the private and the public sectors. In Israel, the main forms of public/private mix have blurred such boundaries: nonprofit health funds sell private insurance; public nonprofit health funds own private for-profit hospitals; and public hospitals sell private services.

Conclusions

Comparison of the processes of privatization of healthcare in Spain and Israel shows their variegated characters. It reveals the active role played by national and regional state apparatuses as initiators and supporters of healthcare reforms that have adopted different forms of public/private mix. While in Israel, until recently, these processes have been perceived as mainly technical, in Spain they have created deep political rifts within both the medical community and the public. The present article contains lessons each country can learn from the other, to be adapted in each one’s local context: The failure of the Alzira model in Spain warns us of the problems of for-profit HMOs and the Israeli private private/public mix shows the risk of eroding trust in the public system, thus reinforcing market failures and inefficient medical systems.
Effects of dietary Hermetia illucens meal inclusion on cecal microbiota and small intestinal mucin dynamics and infiltration with immune cells of weaned piglets
Authors: Biasato Ilaria , Ferrocino Ilario , Colombino Elena , Gai Francesco , Schiavone Achille , Cocolin Luca , Vincenti Valeria , Capucchio Maria Teresa , Gasco Laura
Published: June 2020

Background

The constant interaction between diet and intestinal barrier has a crucial role in determining gut health in pigs. Hermetia illucens (HI) meal (that represents a promising, alternative feed ingredient for production animals) has recently been demonstrated to influence colonic microbiota, bacterial metabolite profile and mucosal immune status of pigs, but no data about modulation of gut mucin dynamics are currently available. The present study evaluated the effects of dietary HI meal inclusion on the small intestinal mucin composition of piglets, as well as providing insights into the cecal microbiota and the mucosal infiltration with immune cells.

Results

A total of 48 weaned piglets were randomly allotted to 3 dietary treatments (control diet [C] and 5% or 10% HI meal inclusion [HI5 and HI10], with 4 replicate boxes/treatment and 4 animals/box) and slaughtered after 61 days of trial (3 animals/box, 12 piglets/diet). The cecal microbiota assessment by 16S rRNA amplicon based sequencing showed higher beta diversity in the piglets fed the HI-based diets than the C (P <  0.001). Furthermore, the HI-fed animals showed increased abundance of Blautia, Chlamydia, Coprococcus, Eubacterium, Prevotella, Roseburia, unclassified members of Ruminococcaceae, Ruminococcus and Staphylococcus when compared to the C group (FDR <  0.05). The gut of the piglets fed the HI-based diets showed greater neutral mucin percentage than the C (P <  0.05), with the intestinal neutral mucins of the HI-fed animals being also higher than the sialomucins and the sulfomucins found in the gut of the C group (P <  0.05). Furthermore, the piglets fed the HI-based diets displayed lower histological scores in the jejunum than the other gut segments (ileum [HI5] or ileum and duodenum [HI10], P <  0.05).

Conclusions

Dietary HI meal utilization positively influenced the cecal microbiota and the small intestinal mucin dynamics of the piglets in terms of selection of potentially beneficial bacteria and preservation of mature mucin secretory architecture, without determining the development of gut inflammation. These findings further confirm the suitability of including insect meal in swine diets.
Ultrastructural and dynamic studies of the endosomal compartment in Down syndrome
Authors: Botté Alexandra , Lainé Jeanne , Xicota Laura , Heiligenstein Xavier , Fontaine Gaëlle , Kasri Amal , Rivals Isabelle , Goh Pollyanna , Faklaris Orestis , Cossec Jack-Christophe , Morel Etienne , Rebillat Anne-Sophie , Nizetic Dean , Raposo Graça , Potier Marie-Claude
Published: June 2020

Enlarged early endosomes have been visualized in Alzheimer’s disease (AD) and Down syndrome (DS) using conventional confocal microscopy at a resolution corresponding to endosomal size (hundreds of nm). In order to overtake the diffraction limit, we used super-resolution structured illumination microscopy (SR-SIM) and transmission electron microscopies (TEM) to analyze the early endosomal compartment in DS.

By immunofluorescence and confocal microscopy, we confirmed that the volume of Early Endosome Antigen 1 (EEA1)-positive puncta was 13–19% larger in fibroblasts and iPSC-derived neurons from individuals with DS, and in basal forebrain cholinergic neurons (BFCN) of the Ts65Dn mice modelling DS. However, EEA1-positive structures imaged by TEM or SR-SIM after chemical fixation had a normal size but appeared clustered. In order to disentangle these discrepancies, we imaged optimally preserved High Pressure Freezing (HPF)-vitrified DS fibroblasts by TEM and found that early endosomes were 75% denser but remained normal-sized.

RNA sequencing of DS and euploid fibroblasts revealed a subgroup of differentially-expressed genes related to cargo sorting at multivesicular bodies (MVBs). We thus studied the dynamics of endocytosis, recycling and MVB-dependent degradation in DS fibroblasts. We found no change in endocytosis, increased recycling and delayed degradation, suggesting a “traffic jam” in the endosomal compartment.

Finally, we show that the phosphoinositide PI (3) P, involved in early endosome fusion, is decreased in DS fibroblasts, unveiling a new mechanism for endosomal dysfunctions in DS and a target for pharmacotherapy.
Correction to: Loss of homeostatic microglial phenotype in CSF1R-related Leukoencephalopathy
Authors: Kempthorne Liam , Yoon Hyejin , Madore Charlotte , Smith Scott , Wszolek Zbigniew K. , Rademakers Rosa , Kim Jungsu , Butovsky Oleg , Dickson Dennis W.
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
Looking for paint mixtures to glimpse pictorial techniques: a micro-stratigraphic physicochemical approach to the rock art from the Oyola’s Caves (Argentina)
Authors: Gheco Lucas , Tascon Marcos , Ahets Etcheberry Eugenia , Quesada Marcos , Marte Fernando
Published: June 2020

Could not be possible that rock paintings with similar hues and morphologies were the result of different paint preparations inside a cave but distanced in time? Is there any archaeometric approach that allow us to evidence these subtle differences? Aiming to address these inquires, in this work are presented the potentials of new physicochemical lines of evidence for characterization and differentiation of paint mixtures. This will improve the understanding of the technical heterogeneity and temporal complexity of painting sets executed in a particular archaeological site. In order to explore these points, the results obtained in the micro-stratigraphic studies of samples taken from the painted walls of Oyola, an archaeological site located in the northwest of Argentina, are presented. These samples have been analyzed by micro-Raman spectroscopy (mRS) and scanning electron microscopy with energy dispersive X-ray (SEM–EDS). The differences found by cross-section chemical studies could be explained as a consequence of two situations: 1-differences in the painting’s chemical components, either in the pigments involved or additives used; and, 2-differences in the physical properties of the mixtures such as stratum thickness and/or particle size. Also, in this article are explained each of the hypothesis, presenting the limits of these interpretations and pointing out future research challenges. As we discussed, it could be possible that the chemical and physical differences found between paint mixtures were the material expression of varied types of pictorial techniques.
A feasibility investigation of mindfulness-based cognitive therapy for people with Huntington’s disease
Authors: Eccles Fiona J. R. , Craufurd David , Smith Alistair , Davies Rhys , Glenny Kristian , Homberger Max , Peeren Siofra , Rogers Dawn , Rose Leona , Skitt Zara , Theed Rachael , Simpson Jane
Published: June 2020

Background

Huntington’s disease (HD) is an inherited neurodegenerative condition which affects movement, coordination and cognitive functioning. Psychological difficulties are commonly experienced; however, psychological interventions have been little researched with this population. We investigated the feasibility of conducting a randomised controlled trial (RCT) of mindfulness-based cognitive therapy (MBCT) with people with the HD genetic mutation, either pre-manifest (before onset of movement symptoms) or at an early disease stage. Specifically, we evaluated the willingness of participants to be recruited into and complete the intervention; the acceptability of the study measures in relation to completion; the feasibility of offering the standard MBCT course to people with HD; the acceptability of the intervention and the estimated effect sizes.

Methods

Participants were recruited from two UK HD centres and took part in an 8-week course of MBCT, with three reunions throughout the following year. Stress, depression, anxiety, and mindfulness were measured pre-, mid-, and post-course, at 3 months and at 1 year. Sleep, quality of life, positive affect and coping were measured pre- and post-course, at 3 months and at 1 year. Descriptive data and approximate effect sizes were calculated. Interviews were conducted post-course and at 1 year and data pertaining to the acceptability of the course were extracted.

Results

Twelve participants took part in two groups; all were pre-manifest. Levels of depression and anxiety were low pre-course leaving little room for improvement. Changes in stress and in some aspects of mindfulness were medium to large. The qualitative data suggested participants rated the course highly and found it helpful and no changes to the standard course were needed. Recruitment levels were below those anticipated. Most measures were found to be acceptable.

Conclusions

Although the course was acceptable to those who took part, given the difficulties in recruiting and the rarity of HD, conducting an RCT of MBCT teaching groups in person does not seem feasible. However, alternative modes of course delivery (e.g. online) would allow the recruitment of people from a greater geographical area and may make an RCT feasible; this revised focus would be suitable for future feasibility studies.

Trial registration

ClinicalTrials.govidentifierNCT02464293, registered 8 June 2015.
Facial fractures and associated injuries in high- versus low-energy trauma: all are not created equal
Authors: Hilaire Cameron St. , Johnson Arianne , Loseth Caitlin , Alipour Hamid , Faunce Nick , Kaminski Stephen , Sharma Rohit
Published: June 2020

Introduction

Facial fractures (FFs) occur after high- and low-energy trauma; differences in associated injuries and outcomes have not been well articulated.

Objective

To compare the epidemiology, management, and outcomes of patients suffering FFs from high-energy and low-energy mechanisms.

Methods

We conducted a 6-year retrospective local trauma registry analysis of adults aged 18–55 years old that suffered a FF treated at the Santa Barbara Cottage Hospital. Fracture patterns, concomitant injuries, procedures, and outcomes were compared between patients that suffered a high-energy mechanism (HEM: motor vehicle crash, bicycle crash, auto versus pedestrian, falls from height > 20 feet) and those that suffered a low-energy mechanism (LEM: assault, ground-level falls) of injury.

Results

FFs occurred in 123 patients, 25 from an HEM and 98 from an LEM. Rates of Le Fort (HEM 12% vs. LEM 3%, P = 0.10), mandible (HEM 20% vs. LEM 38%, P = 0.11), midface (HEM 84% vs. LEM 67%, P = 0.14), and upper face (HEM 24% vs. LEM 13%, P = 0.217) fractures did not significantly differ between the HEM and LEM groups, nor did facial operative rates (HEM 28% vs. LEM 40%, P = 0.36). FFs after an HEM event were associated with increased Injury Severity Scores (HEM 16.8 vs. LEM 7.5, P <0.001), ICU admittance (HEM 60% vs. LEM 13.3%, P <0.001), intracranial hemorrhage (ICH) (HEM 52% vs. LEM 15%, P <0.001), cervical spine fractures (HEM 12% vs. LEM 0%, P = 0.008), truncal/lower extremity injuries (HEM 60% vs. LEM 6%, P <0.001), neurosurgical procedures for the management of ICH (HEM 54% vs. LEM 36%, P = 0.003), and decreased Glasgow Coma Score on arrival (HEM 11.7 vs. LEM 14.2, P <0.001).

Conclusion

FFs after HEM events were associated with severe and multifocal injuries. FFs after LEM events were associated with ICH, concussions, and cervical spine fractures. Mechanism-based screening strategies will allow for the appropriate detection and management of injuries that occur concomitant to FFs.

Type of study

Retrospective cohort study.

Level of evidence

Level III.
A Japanese man with malaria tests negative for fever after spending 6 months in rural Kenya
Authors: Sugimoto Takashi , Takahashi Kensuke , Matsui Kosuke , Asada Masahito , Kaneko Osamu , Ariyoshi Koya
Published: June 2020

A previously healthy Japanese man in his fifties was admitted to our hospital because of a recurrent fever after returning from Kenya and Madagascar. He was ambulant with a body temperature of 36.6 °C. His physical examination revealed normal except for tender hepatomegaly. The blood test results showed no apparent abnormality except thrombocytopenia and mild liver dysfunction. The rapid diagnostic test and Giemsa-stained blood film were repeatedly negative for malaria. Computed tomography scans of the chest, abdomen, and pelvis revealed no significantly abnormal findings.
Executive function in obsessive compulsive disorder at Zagazig University Hospitals: a case-control study
Authors: Youssef Amira Mohamed , AbouHendy Wa-il , Elshabrawy Amany , Amin Shimaa Ibrahim
Published: June 2020

Background

Executive function (EF) domain deficits which most reported include in particular set shifting and inhibition, which are considered main deficits in obsessive-compulsive disorder (OCD). So, this research aimed to assess EF in patients with a primary diagnosis of OCD in comparison to a healthy control group; in order to understand the impaction of this disorder on the patient’s neuropsychological status.

Results

There was no significant difference between OCD patients and controls regarding demographic characteristics. Average duration of illness in OCD group was 3.97 ± 5.08 years. Forty patients (60.6%) had OCD medication prior to the study. Depression was the most prevalent comorbidity among OCD group (36.4%) then anxiety (12.1%) and social anxiety (3%). Regarding WCST indices, a significant difference (P < 0.05) was found between both groups in total number of correct answers, total number of errors, mean of errors, total number of perseverative errors, mean of perseverative errors, total number of non-perseverative errors, mean of non-perseverative errors, and conceptual level responses without significant difference (P ≥ 0.05) in the remaining indices. In ToL indices, there was highly significant difference (P < 0.001) between both groups regarding total time, but not regarding total moves (P ≥ 0.05). The defect in EF was positively correlated to the severity of symptoms of OCD. There was no significant difference between patients who had been receiving medical treatment and those who had not, also between patients who had comorbidities accompanying OCD and those who had not regarding EF as evident by both WCST measured parameters and TOL parameters.

Conclusions

OCD patients appear to have EF deficits in the fields of set-shifting, inhibitory control, working memory, and planning ability.