bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of the Clock Drawing Test and the Rey–Osterrieth Complex Figure Test-copy with convolutional neural networks to predict cognitive impairment
Authors: Youn Young Chul , Pyun Jung-Min , Ryu Nayoung , Baek Min Jae , Jang Jae-Won , Park Young Ho , Ahn Suk-Won , Shin Hae-Won , Park Kwang-Yeol , Kim Sang Yun
Published: April 2021

Background

The Clock Drawing Test (CDT) and Rey–Osterrieth Complex Figure Test (RCFT) are widely used as a part of neuropsychological test batteries to assess cognitive function. Our objective was to confirm the prediction accuracies of the RCFT-copy and CDT for cognitive impairment (CI) using convolutional neural network algorithms as a screening tool.

Methods

The CDT and RCFT-copy data were obtained from patients aged 60–80 years who had more than 6 years of education. In total, 747 CDT and 980 RCFT-copy figures were utilized. Convolutional neural network algorithms using TensorFlow (ver. 2.3.0) on the Colab cloud platform (www.colab.research.google.com) were used for preprocessing and modeling. We measured the prediction accuracy of each drawing test 10 times using this dataset with the following classes: normal cognition (NC) vs. mildly impaired cognition (MI), NC vs. severely impaired cognition (SI), and NC vs. CI (MI + SI).

Results

The accuracy of the CDT was better for differentiating MI (CDT, 78.04 ± 2.75; RCFT-copy, not being trained) and SI from NC (CDT, 91.45 ± 0.83; RCFT-copy, 90.27 ± 1.52); however, the RCFT-copy was better at predicting CI (CDT, 77.37 ± 1.77; RCFT, 83.52 ± 1.41). The accuracy for a 3-way classification (NC vs. MI vs. SI) was approximately 71% for both tests; no significant difference was found between them.

Conclusions

The two drawing tests showed good performance for predicting severe impairment of cognition; however, a drawing test alone is not enough to predict overall CI. There are some limitations to our study: the sample size was small, all the participants did not perform both the CDT and RCFT-copy, and only the copy condition of the RCFT was used. Algorithms involving memory performance and longitudinal changes are worth future exploration. These results may contribute to improved home-based healthcare delivery.
Mimickers of breast malignancy: imaging findings, pathologic concordance and clinical management
Authors: Guirguis Mary S. , Adrada Beatriz , Santiago Lumarie , Candelaria Rosalind , Arribas Elsa
Published: April 2021

Many benign breast entities have a clinical and imaging presentation that can mimic breast cancer. The purpose of this review is to illustrate the wide spectrum of imaging features that can be associated with benign breast diseases with an emphasis on the suspicious imaging findings associated with these benign conditions that can mimic cancer. As radiologic-pathologic correlation can be particularly challenging in these cases, the radiologist’s familiarity with these benign entities and their imaging features is essential to ensure that a benign pathology result is accepted as concordant when appropriate and that a suitable management plan is formulated.
Efficacy and safety of mesenchymal stem cells co-infusion in allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis
Authors: Li Teng , Luo Chengxin , Zhang Jiasi , Wei Ling , Sun Wei , Xie Qin , Liu Yan , Zhao Yongli , Xu Shuangnian , Wang Lihua
Published: April 2021

Background

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is life-saving for severe hematological conditions. However, its outcomes need further improvement, and co-infusion of mesenchymal stem cells (MSCs) may show promise. A growing body of research on this subject exists, while the results of different trials are conflicting. A systematic review and meta-analysis is needed to appraise the real efficacy and safety of MSC co-transplantation in allo-HSCT.

Methods

Studies comparing MSC co-transplantation in allo-HSCT with allo-HSCT alone were searched in six medical databases from inception to June 10, 2020. The primary outcomes were engraftment and graft-versus-host disease (aGVHD and cGVHD, respectively). Other outcomes included overall survival (OS), relapse rate (RR), non-relapse mortality (NRM), and immune reconstitution. Information was independently extracted by two investigators. Methodological quality was assessed using the Cochrane Collaboration tool. Meta-analysis was performed using RevMan 5.4.

Results

Six randomized controlled trials (RCTs) and 13 non-randomized controlled trials (nRCTs) were included. MSC co-infusion resulted in shorter times to neutrophil engraftment (RCTs: standardized mean difference (SMD) − 1.20, p = 0.04; nRCTs: SMD − 0.54, p = 0.04) and platelet engraftment (RCTs: SMD − 0.60, p = 0.04; nRCTs: SMD − 0.70, p = 0.01), a lower risk of cGVHD (RCTs: risk ratio (RR) 0.53, p = 0.01; nRCTs: RR 0.50, p <  0.01), and a slightly positive trend towards reducing the risk of aGVHD and NRM, without affecting RR and OS. Subgroup analyses revealed that when MSCs were co-transplanted, children and adolescents, and patients receiving human leukocyte antigen (HLA)-nonidentical HSCT showed improvements in engraftment and incidence of GVHD and NRM; adults and patients who received HLA-identical HSCT had lower cGVHD; patients with malignancies exhibited improvements in GVHD and NRM incidence; and patients with non-malignancies experienced accelerated engraftment. Notably, a reduced OS was observed in patients with hematological malignancies undergoing HLA-identical HSCT.

Conclusion

MSC co-infusion generally improved engraftment and reduced cGVHD, without increasing mortality or relapse. Regarding aGVHD and NRM, the effects of MSCs were not quite significant. Specifically, our data support the utilization of MSC co-transplantation in children and young individuals with HLA-nonidentical HSCT, but not in adult patients with hematological malignancies undergoing HLA-identical HSCT.
ABO blood types and sepsis mortality
Authors: Itenov Theis S. , Sessler Daniel I. , Khanna Ashish K. , Ostrowski Sisse R. , Johansson Pär I. , Erikstrup Christian , Pedersen Ole B. , Rygård Sofie L. , Holst Lars B. , Bestle Morten H. , Hein Lars , Lindhardt Anne , Tousi Hami , Andersen Mads H. , Mohr Thomas , Lundgren Jens D. , Jensen Jens-Ulrik
Published: April 2021

Background

We aimed to determine if the ABO blood types carry different risks of 30-day mortality, acute kidney injury (AKI), and endothelial damage in critically ill patients with sepsis. This was a retrospective cohort study of three independent cohorts of critically ill patients from the United States and Scandinavia consisting of adults with septic shock. We compared the 30-day mortality across the blood types within each cohort and pooled the results in a meta-analysis. We also estimated the incidence of AKI and degree of endothelial damage, as measured by blood concentrations of soluble thrombomodulin and syndecan-1.

Results

We included 12,342 patients with severe sepsis. In a pooled analysis blood type B carried a slightly lower risk of 30-day all-cause mortality compared to non-blood type B (adjusted HR 0.88; 95%-CI 0.79–0.98; p = 0.02). There was no difference in the risk of AKI. Soluble thrombomodulin and syndecan-1 concentrations were lower in patients with blood type B and O compared to blood type A, suggesting less endothelial damage.

Conclusion

Septic patients with blood type B had less endothelial damage, and a small reduction in mortality. The exposure is, however, unmodifiable.
Discrete choice experiment to determine preferences of decision-makers in healthcare for different formats of rapid reviews
Authors: Speckemeier Christian , Krabbe Laura , Schwenke Susanne , Wasem Jürgen , Buchberger Barbara , Neusser Silke
Published: April 2021

Background

Time-saving formats of evidence syntheses have been developed to fulfill healthcare policymakers’ demands for timely evidence-based information. A discrete choice experiment (DCE) with decision-makers and people involved in the preparation of evidence syntheses was undertaken to elicit preferences for methodological shortcuts in the conduct of abbreviated reviews.

Methods

D-efficient scenarios, each containing 14 pairwise comparisons, were designed for the DCE: the development of an evidence synthesis in 20 working days (scenario 1) and 12 months (scenario 2), respectively. Six attributes (number of databases, number of reviewers during screening, publication period, number of reviewers during data extraction, full-text analysis, types of HTA domains) with 2 to 3 levels each were defined. These were presented to the target population in an online survey. The relative importance of the individual attributes was determined using logistic regression models.

Results

Scenario 1 was completed by 36 participants and scenario 2 by 26 participants. The linearity assumption was confirmed by the full model. In both scenarios, the linear difference model showed a preference for higher levels for “number of reviewers during data extraction”, followed by “number of reviewers during screening” and “full-text analysis”. Subgroup analyses showed that preferences were influenced by participation in the preparation of evidence syntheses.

Conclusion

The surveyed persons expressed preferences for quality standards in the process of literature screening and data extraction.
Application of triple compound combination anti-synchronization among parallel fractional snap systems & electronic circuit implementation
Authors: Mahmoud Emad E. , Trikha Pushali , Jahanzaib Lone Seth , Higazy M. , Alkinani Monagi H.
Published: April 2021

In this article we examine the dynamical properties of the fractional version of the snap system by means of chaotic attractor, existence, and uniqueness of the solution, symmetry, dissipativity, stagnation point analysis, Lyapunov dynamics, K.Y. dimension, bifurcation diagram, etc. Also, parallel systems to this system are synchronized in presence of uncertainties and external disturbances using triple compound combination anti-synchronization by two ways. Synchronization time is compared with some other works. Also the utilization of achieved synchronization is illustrated in secure transmission. By constructing the snap system’s signal flow graph and its real electronic circuit, some of its additional invariants are investigated.
Individual and community-level determinants of childhood vaccination in Ethiopia
Authors: Fenta Setegn Muche , Fenta Haile Mekonnen
Published: April 2021

Background

Vaccines are one of our most important tools for preventing outbreaks and keeping the world safe. Most unvaccinated children live in the poorest countries including Ethiopia. Therefore, this study aimed to identify the determinants of vaccination coverage among children aged12–23 months in Ethiopia.

Methods

A cross-sectional secondary data were obtained from the 2016 Ethiopian Demographic and Health Survey data (EDHS). A total of 1929 children were included. A Multilevel Proportional Odds Model was used to identify the individual and community-level factors associated with child vaccination.

Result

Among 1, 929 children, only 48.6% (95% CI: 46.3 to 50.8%) were fully vaccinated while 37.8% (95% CI: 35.7 to 40.1%) were partially vaccinated.. The multilevel ordinal logistic regression model reveled that housewife mother (AOR =1.522, 95%CI: 1.139, 2.034), institutional delivery (AOR =2.345, 95%CI: 1.766, 3.114),four or above antenatal care visits (AOR = 2.657; 95% CI: 1.906, 3.704), children of mothers with secondary or higher education (AOR = 2.008; 95% CI: 1.209, 3.334),Children whose fathers primary education (AOR = 1.596; 95% CI: 1.215, 2.096), from the rich households (AOR = 1.679; 95% CI: 1.233, 2.287) were significantly associated with childhood vaccination.

Conclusion

Child vaccination coverage in Ethiopia remains low. Therefore, there is a need to increase child vaccination coverage by promoting institutional delivery and prenatal care visits, as well as maternal tetanus immunization. Besides, public initiatives needed to improve child vaccination coverage, women’s and husband’s education, poor women, and further advancement of health care services for poor women, housewife women, women living in remote areas should be made to maintain further improvements in child vaccination. Furthermore, policies and programs aimed at addressing cluster variations in child vaccination need to be formulated and their implementation must be strongly pursued.
Is telemedicine the answer to rural expansion of medication treatment for opioid use disorder? Early experiences in the feasibility study phase of a National Drug Abuse Treatment Clinical Trials Network Trial
Authors: Hser Yih-Ing , Ober Allison J. , Dopp Alex R. , Lin Chunqing , Osterhage Katie P. , Clingan Sarah E. , Mooney Larissa J. , Curtis Megan E. , Marsch Lisa A. , McLeman Bethany , Hichborn Emily , Lester Laurie S. , Baldwin Laura-Mae , Liu Yanping , Jacobs Petra , Saxon Andrew J.
Published: April 2021

Telemedicine (TM) enabled by digital health technologies to provide medical services has been considered a key solution to increasing health care access in rural communities. With the immediate need for remote care due to the COVID-19 pandemic, many health care systems have rapidly incorporated digital technologies to support the delivery of remote care options, including medication treatment for individuals with opioid use disorder (OUD). In responding to the opioid crisis and the COVID-19 pandemic, public health officials and scientific communities strongly support and advocate for greater use of TM-based medication treatment for opioid use disorder (MOUD) to improve access to care and have suggested that broad use of TM during the pandemic should be sustained. Nevertheless, research on the implementation and effectiveness of TM-based MOUD has been limited. To address this knowledge gap, the National Drug Abuse Treatment Clinical Trials Network (CTN) funded (via the NIH HEAL Initiative) a study on Rural Expansion of Medication Treatment for Opioid Use Disorder (Rural MOUD; CTN-0102) to investigate the implementation and effectiveness of adding TM-based MOUD to rural primary care for expanding access to MOUD. In preparation for this large-scale, randomized controlled trial incorporating TM in rural primary care, a feasibility study is being conducted to develop and pilot test implementation procedures. In this commentary, we share some of our experiences, which include several challenges, during the initial two-month period of the feasibility study phase. While these challenges could be due, at least in part, to adjusting to the COVID-19 pandemic and new workflows to accommodate the study, they are notable and could have a substantial impact on the larger, planned pragmatic trial and on TM-based MOUD more broadly. Challenges include low rates of identification of risk for OUD from screening, low rates of referral to TM, digital device and internet access issues, workflow and capacity barriers, and insurance coverage. These challenges also highlight the lack of empirical guidance for best TM practice and quality remote care models. With TM expanding rapidly, understanding implementation and demonstrating what TM approaches are effective are critical for ensuring the best care for persons with OUD.
Impact of sugar beet pulp and wheat bran on serum biochemical profile, inflammatory responses and gut microbiota in sows during late gestation and lactation
Authors: Shang Qinghui , Liu Sujie , Liu Hansuo , Mahfuz Shad , Piao Xiangshu
Published: April 2021

Background

Sows are frequently subjected to various stresses during late gestation and lactation, which trigger inflammatory response and metabolic disorders. Dietary fiber can influence animal health by modulating gut microbiota and their by-products, with the effects depending upon the source of the dietary fiber. This study aimed to evaluate the impacts of different fiber sources on body condition, serum biochemical parameters, inflammatory responses and fecal microbiota in sows from late gestation to lactation.

Methods

Forty-five multiparous sows (Yorkshire × Landrace; 3–6 parity) were assigned to 1 of 3 dietary treatments from d 85 of gestation to the end of lactation (d 21 post-farrowing): a control diet (CON, a corn-soybean meal diet), a sugar beet pulp diet (SBP, 20% SBP during gestation and 10% SBP during lactation), and a wheat bran diet (WB, 30% WB during gestation and 15% WB during lactation).

Results

Compared with CON, supplementation of SBP decreased (P < 0.05) lactation BW loss, reduced (P < 0.05) serum concentration of total cholesterol, non-esterified fatty acids, interleukin-6 and tumor necrosis factor-α, and increased (P < 0.05) fecal water content on d 110 of gestation and d 21 of lactation, while supplementation of WB reduced (P < 0.05) serum concentration of total cholesterol on d 110 of gestation, increased (P < 0.05) fecal water content and decreased (P < 0.05) serum interleukin-6 concentration on d 110 of gestation and d 21 of lactation. In addition, sows fed SBP had lower (P < 0.01) abundance of Clostridium_sensu_stricto_1 and Terrisporobacter than those fed CON, but had greater (P < 0.05) abundance of Christensenellaceae_R-7_group and Ruminococcaceae_UCG-002 than those fed the other two diets on d 110 of gestation. On d 21 of lactation, supplementation of SBP decreased (P < 0.05) the abundance of Firmicutes and Lactobacillus, but enriched (P < 0.05) the abundance of Christensenellaceae_R-7_group, Prevotellaceae_NK3B31_group, Ruminococcaceae_UCG-002, Prevotellaceae_UCG_001 and unclassified_f__Lachnospiraceae compared with WB. Compared with CON, sows fed SBP had greater (P < 0.05) fecal concentrations of acetate, butyrate and total SCFAs during gestation and lactation, while sows fed WB only had greater (P < 0.05) fecal concentration of butyrate during lactation.

Conclusions

Supplementation of dietary fiber during late gestation and lactation could improve sow metabolism and gut health, and SBP was more effective than WB.
The pregnane X receptor drives sexually dimorphic hepatic changes in lipid and xenobiotic metabolism in response to gut microbiota in mice
Authors: Barretto Sharon Ann , Lasserre Frederic , Huillet Marine , Régnier Marion , Polizzi Arnaud , Lippi Yannick , Fougerat Anne , Person Elodie , Bruel Sandrine , Bétoulières Colette , Naylies Claire , Lukowicz Céline , Smati Sarra , Guzylack Laurence , Olier Maïwenn , Théodorou Vassilia , Mselli-Lakhal Laila , Zalko Daniel , Wahli Walter , Loiseau Nicolas , Gamet-Payrastre Laurence , Guillou Hervé , Ellero-Simatos Sandrine
Published: April 2021

Background

The gut microbiota–intestine–liver relationship is emerging as an important factor in multiple hepatic pathologies, but the hepatic sensors and effectors of microbial signals are not well defined.

Results

By comparing publicly available liver transcriptomics data from conventional vs. germ-free mice, we identified pregnane X receptor (PXR, NR1I2) transcriptional activity as strongly affected by the absence of gut microbes. Microbiota depletion using antibiotics in Pxr+/+vs Pxr-/- C57BL/6J littermate mice followed by hepatic transcriptomics revealed that most microbiota-sensitive genes were PXR-dependent in the liver in males, but not in females. Pathway enrichment analysis suggested that microbiota–PXR interaction controlled fatty acid and xenobiotic metabolism. We confirmed that antibiotic treatment reduced liver triglyceride content and hampered xenobiotic metabolism in the liver from Pxr+/+ but not Pxr-/- male mice.

Conclusions

These findings identify PXR as a hepatic effector of microbiota-derived signals that regulate the host’s sexually dimorphic lipid and xenobiotic metabolisms in the liver. Thus, our results reveal a potential new mechanism for unexpected drug–drug or food–drug interactions.
Novel insights into the m6A-RNA methyltransferase METTL3 in cancer
Authors: Cai Yiqing , Feng Rui , Lu Tiange , Chen Xiaomin , Zhou Xiangxiang , Wang Xin
Published: April 2021

N6-methyladenosine (m6A) is a prevalent internal RNA modification in higher eukaryotic cells. As the pivotal m6A regulator, RNA methyltransferase-like 3 (METTL3) is responsible for methyl group transfer in the progression of m6A modification. This epigenetic regulation contributes to the structure and functional regulation of RNA and further promotes tumorigenesis and tumor progression. Accumulating evidence has illustrated the pivotal roles of METTL3 in a variety of human cancers. Here, we systemically summarize the interaction between METTL3 and RNAs, and illustrate the multiple functions of METTL3 in human cancer. METLL3 is aberrantly expressed in a variety of tumors. Elevation of METTL3 is usually associated with rapid progression and poor prognosis of tumors. On the other hand, METTL3 may also function as a tumor suppressor in several cancers. Based on the tumor-promoting effect of METTL3, the possibility of applying METTL3 inhibitors is further discussed, which is expected to provide novel insights into antitumor therapy.
Economic and fault stability analysis of geothermal field development in direct-use hydrothermal reservoirs
Authors: Zaal Caroline , Daniilidis Alexandros , Vossepoel Femke C.
Published: April 2021

The installed capacity of geothermal systems for direct use of heat is increasing worldwide. As their number and density is increasing, the their interaction with subsurface faults becomes more important as they could lead to safety risks from induced seismicity. Assessment and management of such risks is essential for the further development and extension of geothermal energy for heating. At the same time, the economic output of geothermal systems can be marginal and is hence often supported by subsidy schemes. A combined assessment of fault stability and economic output could help operators to balance economic and safety aspects, but this is currently not common practice. In this study we present a methodology to assess field development plans based on fault stability and Net Present Value (NPV) using reservoir simulations of a fluvial, heterogeneous sandstone representative of the majority of direct-use Dutch geothermal systems. We find that the highest friction coefficient leading to exceedance of the Mohr–Coulomb failure criteria in this sandstone is 0.17; such values could be encountered in clay-rich fault gouges. Similar or lower fault permeability compared to the reservoir results in no changes and an increase respectively of both NPV and fault stability with larger Fault-to-Well Distance (FWD). Fault permeability higher than the reservoir permeability results in a minor increase in NPV with smaller FWD. Our results demonstrate that a combined analysis of thermal, hydraulic, mechanical and economic assessment supports a responsible and viable development of geothermal resources at a large scale. The importance of a high spatial density of supporting stress data will be essential for a better understanding and quantification of economic and fault stability effects of geothermal operations.
Can quasicrystals survive in planetary collisions?
Authors: Stagno Vincenzo , Bindi Luca , Takagi Sota , Kyono Atsushi
Published: April 2021

We investigated the compressional behavior of i-AlCuFe quasicrystal using diamond anvil cell under quasi-hydrostatic conditions by in situ angle-dispersive X-ray powder diffraction measurements (in both compression and decompression) up to 76 GPa at ambient temperature using neon as pressure medium. These data were compared with those collected up to 104 GPa using KCl as pressure medium available in literature. In general, both sets of data indicate that individuald-spacing shows a continuous decrease with pressure with no drastic changes associated to structural phase transformations or amorphization. Thed/d0, whered0is thed-spacing at ambient pressure, showed a general isotropic compression behavior. The zero-pressure bulk modulus and its pressure derivative were calculated fitting the volume data to both the Murnaghan- and Birch-Murnaghan equation of state models. Results from this study extend our knowledge on the stability of icosahedrite at very high pressure and reinforce the evidence that natural quasicrystals formed during a shock event in asteroidal collisions and survived for eons in the history of the Solar System.
NOD1 rs2075820 (p.E266K) polymorphism is associated with gastric cancer among individuals infected with cagPAI-positive H. pylori
Authors: Gonzalez-Hormazabal Patricio , Pelaez Diana , Musleh Maher , Bustamante Marco , Stambuk Juan , Pisano Raul , Valladares Hector , Lanzarini Enrique , Chiong Hector , Suazo Jose , Quiñones Luis A. , Varela Nelson M. , Castro V. Gonzalo , Jara Lilian , Berger Zoltan
Published: April 2021

Background

Helicobacter pylori is detected by pathogen recognition receptors including toll-like receptors (TLR) and nucleotide-binding oligomerization domain (NOD)-like receptors, eliciting an innate immune response against this bacteria. The aim of this study was to assess if polymorphisms of TLR2, TLR4, TLR5, NOD1 and NOD2 genes are associated with gastric cancer, in particular in individuals infected with H. pylori.

Results

A case-control study of 297 gastric cancer patients and 300 controls was performed to assess the association of 17 polymorphisms. Analyses performed under the allele model did not find association with gastric cancer. However, NOD1 rs2075820 (p.E266K) showed association with intestinal-type gastric cancer among H. pylori infected subjects (OR = 2.69, 95% CI 1.41–5.13, p = 0.0026). The association was not statistically significant in diffuse-type gastric cancer cases (OR = 1.26, 95% CI 0.63–2.52, p = 0.51). When the analyses were performed in patients carrying H. pylori strains harboring the cag pathogenicity island (cagPAI), we noticed significant association with NOD1 rs2075820 (OR = 4.90, 95% CI 1.80–3.36, p = 0.0019), in particular for intestinal-type gastric cancer cases (OR = 7.16, 95% CI 2.40–21.33, p = 4.1 × 10− 4) but not among diffuse-type gastric cancer cases (OR = 3.39, 95% CI 1.13–0.10, p = 0.03).

Conclusions

NOD1 rs2075820 increases the risk of intestinal-type gastric cancer among individuals infected with H. pylori, particularly in those harboring the cagPAI.
Study of biaxial mechanical properties of the passive pig heart: material characterisation and categorisation of regional differences
Authors: Nemavhola Fulufhelo
Published: April 2021

Regional mechanics of the heart is vital in the development of accurate computational models for the pursuit of relevant therapies. Challenges related to heart dysfunctioning are the most important sources of mortality in the world. For example, myocardial infarction (MI) is the foremost killer in sub-Saharan African countries. Mechanical characterisation plays an important role in achieving accurate material behaviour. Material behaviour and constitutive modelling are essential for accurate development of computational models. The biaxial test data was utilised to generated Fung constitutive model material parameters of specific region of the pig myocardium. Also, Choi-Vito constitutive model material parameters were also determined in various myocardia regions. In most cases previously, the mechanical properties of the heart myocardium were assumed to be homogeneous. Most of the computational models developed have assumed that the all three heart regions exhibit similar mechanical properties. Hence, the main objective of this paper is to determine the mechanical material properties of healthy porcine myocardium in three regions, namely left ventricle (LV), mid-wall/interventricular septum (MDW) and right ventricle (RV). The biomechanical properties of the pig heart RV, LV and MDW were characterised using biaxial testing. The biaxial tests show the pig heart myocardium behaves non-linearly, heterogeneously and anisotropically. In this study, it was shown that RV, LV and MDW may exhibit slightly different mechanical properties. Material parameters of two selected constitutive models here may be helpful in regional tissue mechanics, especially for the understanding of various heart diseases and development of new therapies.
Influence of calcium ion-modified implant surfaces in protein adsorption and implant integration
Authors: Anitua Eduardo , Cerqueira Andreia , Romero-Gavilán Francisco , García-Arnáez Iñaki , Martinez-Ramos Cristina , Ozturan Seda , Azkargorta Mikel , Elortza Félix , Gurruchaga Mariló , Goñi Isabel , Suay Julio , Tejero Ricardo
Published: April 2021

Background

Calcium (Ca) is a well-known element in bone metabolism and blood coagulation. Here, we investigate the link between the protein adsorption pattern and the in vivo responses of surfaces modified with calcium ions (Ca-ion) as compared to standard titanium implant surfaces (control). We used LC–MS/MS to identify the proteins adhered to the surfaces after incubation with human serum and performed bilateral surgeries in the medial section of the femoral condyles of 18 New Zealand white rabbits to test osseointegration at 2 and 8 weeks post-implantation (n=9).

Results

Ca-ion surfaces adsorbed 181.42 times more FA10 and 3.85 times less FA12 (p<0.001), which are factors of the common and the intrinsic coagulation pathways respectively. We also detected differences in A1AT, PLMN, FA12, KNG1, HEP2, LYSC, PIP, SAMP, VTNC, SAA4, and CFAH (p<0.01). At 2 and 8 weeks post-implantation, the mean bone implant contact (BIC) with Ca-ion surfaces was respectively 1.52 and 1.25 times higher, and the mean bone volume density (BVD) was respectively 1.35 and 1.13 times higher. Differences were statistically significant for BIC at 2 and 8 weeks and for BVD at 2 weeks (p<0.05).

Conclusions

The strong thrombogenic protein adsorption pattern at Ca-ion surfaces correlated with significantly higher levels of implant osseointegration. More effective implant surfaces combined with smaller implants enable less invasive surgeries, shorter healing times, and overall lower intervention costs, especially in cases of low quantity or quality of bone.
A case of contralateral inguinal lymph node metastases from breast cancer
Authors: Kimoto Takeo , Kohno Norio , Okamoto Akiko , Ota Kyosuke , Tani Takafumi , Kondo Takeshi , Nishio Mari
Published: April 2021

Background

Breast cancer is well known to tends to invade through the lymphatic chains mainly to the axillary and subclavian nodes or occasionally to the internal mammary nodes. However, inguinal lymph node metastasis from breast cancer is extremely rare.

Case presentation

We have experienced a case of an 82-year-old woman showing left inguinal lymph node metastases from right breast cancer. Previously, she had received five times abdominal operations and left artificial bone head replacement for metamorphous hip-joint disease. Although the metastases were firstly detected 46 months after the breast surgery, they had already existed at the time of the breast operation, which was retrospectively re-evaluated by CT examination. The progression pattern of inguinal lymph node metastases had much correlated with that of the breast cancer. She underwent inguinal lymph node dissections. Pathological findings revealed them being compatible with breast cancer origin.

Conclusions

This is the sixth case having been reported in English literature. Besides, this is the first case showing the contralateral spread to the primary breast cancer. One of the causes of this complex metastatic pattern is thought be ascribed to the previously performed prolific abdominal operations.
Safety and Effects of Football in Skeletal Metastatic Prostate Cancer: a Subgroup Analysis of the FC Prostate Community Randomised Controlled Trial
Authors: Bjerre Eik Dybboe , Weller Sarah , Poulsen Mads Hvid , Madsen Søren Sørensen , Bjerre Rie Dybboe , Østergren Peter Busch , Borre Michael , Brasso Klaus , Midtgaard Julie
Published: April 2021

Background

Skeletal metastatic disease excludes many cancer patients from participating in exercise and physical activity due to safety concerns. Empirical evidence from high-quality trials is warranted to guide clinicians and patients.

Objective

To evaluate the safety and potential benefits of high-impact aerobic exercise in patients with prostate cancer with skeletal metastases.

Design

Exploratory subgroup analysis of a pragmatic, multicentre, parallel randomised controlled trial.

Setting

The trial recruited 214 patients from five hospital urological departments in Denmark.

Participants

Patients with prostate cancer with skeletal metastases (n = 41).

Intervention

Six months of football training twice weekly at a local club or usual care. Both groups received brief information on physical activity recommendations at the time of randomisation.

Main Outcome(s) and Measure(s)

Safety, defined as falls, fractures and hospital admissions. Effects were evaluated on the primary outcome (prostate cancer-specific quality of life) and secondary outcomes (lean body mass, fat mass, hip and spine bone mineral density, and general physical and mental health).

Results

The original trial comprised 214 participants, 41 of whom had skeletal metastases at enrolment. Of these, 22 were allocated to football and 19 to usual care. The trial retention rate was 95% at 12 weeks and 88% at 6 months. Football participants attended 13 sessions on average at 12 weeks and 23 at 6 months. There were two falls, one in each group after 6 months, and no fractures. There were four unplanned hospital admissions in the study period, all four in the usual care group. Statistically significant between-group difference was observed in the primary outcome change in prostate cancer-specific quality of life at 12 weeks (7.6 points [95% CI 0.5 to 15.0]; P = 0.038). No statistical changes were found in the secondary outcomes.

Conclusion

The analysis showed that football training was safe in patients with skeletal metastatic prostate cancer and significantly improved quality of life. Larger analyses and/or trials are warranted to confirm the safety of exercise more broadly in cancer patients with skeletal metastatic disease.

Trial Registration

ClinicalTrials.gov, NCT02430792. Date of registration 30 April 2015
Azithromycin for uncomplicated severe acute malnutrition: study protocol for a pilot randomized controlled trial
Authors: O’Brien Kieran S. , Sié Ali , Dah Clarisse , Ourohire Millogo , Arzika Ahmed M. , Boudo Valentin , Lebas Elodie , Godwin William W. , Arnold Benjamin F. , Oldenburg Catherine E.
Published: April 2021

Background

Given the high risk of infectious mortality among children with severe acute malnutrition (SAM), the World Health Organization recommends routine administration of a broad-spectrum antibiotic like amoxicillin as part of the management of uncomplicated SAM. However, evidence for the efficacy of amoxicillin to improve nutritional recovery or reduce mortality has been mixed. With a long half-life and evidence of efficacy to reduce mortality in high-risk populations, azithromycin is a potential alternative to amoxicillin in the management of SAM. In this pilot study, we aim to compare the efficacy of azithromycin to amoxicillin to improve nutritional outcomes in children with uncomplicated SAM.

Methods

This pilot randomized controlled trial will enroll 300 children with uncomplicated SAM from 6 Centre de Santé et de Promotion Sociale in the Boromo health district in Burkina Faso. Eligible children are randomized to receive a single directly observed dose of oral azithromycin or a 7-day course of oral amoxicillin in addition to the standard package of care for uncomplicated SAM. Enrolled children are followed weekly until nutritional recovery, and all children return for a final study visit at 8 weeks after enrollment. Anthropometric indicators, vital status, and clinical outcomes are monitored at each visit and compared by arm. Primary feasibility outcomes include enrollment potential, refusals, loss to follow-up, and completeness of data collection. The primary clinical outcome is weight gain (g/kg/day) over the 8-week study period.

Discussion

This pilot trial will establish the feasibility of conducting a full-scale randomized controlled trial to evaluate alternative antibiotics in this setting and provide preliminary evidence for the efficacy of azithromycin compared to amoxicillin to improve outcomes for children with SAM.

Trial registration

This trial was first registered on clinicaltrials.gov on 26 June 2018 (NCT03568643).
Prevention of cervical cancer through two HPV-based screen-and-treat implementation models in Malawi: protocol for a cluster randomized feasibility trial
Authors: Tang Jennifer H. , Smith Jennifer S. , McGue Shannon , Gadama Luis , Mwapasa Victor , Chipeta Effie , Chinkhumba Jobiba , Schouten Erik , Ngwira Bagrey , Barnabas Ruanne , Matoga Mitch , Chagomerana Maganizo , Chinula Lameck
Published: April 2021

Background

Cervical cancer is the leading cause of cancer incidence and mortality among Malawian women, despite being a largely preventable disease. Implementing a cervical cancer screening and preventive treatment (CCSPT) program that utilizes rapid human papillomavirus (HPV) testing on self-collected cervicovaginal samples for screening and thermal ablation for treatment may achieve greater coverage than current programs that use visual inspection with acetic acid (VIA) for screening and cryotherapy for treatment. Furthermore, self-sampling creates the opportunity for community-based screening to increase uptake in populations with low screening rates. Malawi’s public health system utilizes regularly scheduled outreach and village-based clinics to provide routine health services like family planning. Cancer screening is not yet included in these community services. Incorporating self-sampled HPV testing into national policy could address cervical cancer screening barriers in Malawi, though at present the effectiveness, acceptability, appropriateness, feasibility, and cost-effectiveness still need to be demonstrated.

Methods

We designed a cluster randomized feasibility trial to determine the effectiveness, acceptability, appropriateness, feasibility, and budget impact of two models for integrating a HPV-based CCSPT program into family planning (FP) services in Malawi: model 1 involves only clinic-based self-sampled HPV testing, whereas model 2 includes both clinic-based and community-based self-sampled HPV testing. Our algorithm involves self-collection of samples for HPV GeneXpert® testing, visual inspection with acetic acid for HPV-positive women to determine ablative treatment eligibility, and same-day thermal ablation for treatment-eligible women. Interventions will be implemented at 14 selected facilities. Our primary outcome will be the uptake of cervical cancer screening and family planning services during the 18 months of implementation, which will be measured through an Endline Household Survey. We will also conduct mixed methods assessments to understand the acceptability, appropriateness, and feasibility of the interventions, and a cost analysis to assess budget impact.

Discussion

Our trial will provide in-depth information on the implementation of clinic-only and clinic-and-community models for integrating self-sampled HPV testing CCSPT with FP services in Malawi. Findings will provide valuable insight for policymakers and implementers in Malawi and other resource-limited settings with high cervical cancer burden.

Trial registration

ClinicalTrials.gov identifier: NCT04286243. Registered on February 26, 2020.
Hepatoprotective activity against acetaminophen-induced liver dysfunction and GC-MS profiling of a brown algae Sargassum ilicifolium
Authors: Hira Khan , Farhat Hafiza , Sohail Nida , Ansari Madeeha , Ara Jehan , Ehteshamul-Haque Syed
Published: April 2021

Background

Drug-induced hepatotoxicity is one of the most important causes of liver dysfunction. Acetaminophen (paracetamol) an analgesic-antipyretic drug is generally considered safe but its overdose may cause liver toxicity. Marine macro-algae (seaweeds) especially brown seaweeds possess unique biological activities including hepatoprotective potential. The current study focused on the hepatoprotective effect of different solvent fractions of Sargassum ilicifolium and characterization of its n-hexane soluble fraction.

Methods

The ethanol extract (20 g) of S. ilicifolium was mixed with solvents of increasing polarity, starting with n-hexane followed by chloroform and methanol. All three (n-hexane, chloroform and methanol) soluble fractions were administered to the rats at dose of 150 mg/kg, b.w. Intraperitoneal administration of acetaminophen (600 mg/kg b.w.) to rats was used to cause liver injury. The hepatic damage was evaluated by liver markers enzymes; aspartate aminotransferases (AST), alanine aminotransferases (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), bilirubin along with other metabolites i.e., triglycerides, cholesterol, urea, glucose and creatinine. Lipid peroxidation and glutathione and were estimated in liver tissue. n-Hexane fraction was subjected to GC-MS analysis in order to identify potent compounds.

Results

The oral administration of n-hexane and methanol soluble fractions reduced the acetaminophen-augmented liver marker enzymes ALT, AST, ALP, LDH, along with bilirubin, urea, creatinine, glucose and triglycerides. The n-hexane and methanol soluble fractions also improved hepatic antioxidant level via enhancing hepatic glutathione and reversing lipid peroxidation. GC-MS spectroscopy of n-hexane fraction of S. ilicifolium revealed the presence of some new compounds. Among them, fatty acids were found to be in highest concentration followed by halogenated hydrocarbons, benzene derivatives, and sterols. Fatty acid in seaweed may be one of the factors for hepatoprotection from drug-induced hepatotoxicity.

Conclusion

From the results, it is evident that n-hexane and methanol soluble fractions of S. ilicifolium have the ability to protect the liver against toxicity, which is comparable with silymarin used as a standard drug. Sargassum ilicifolium contains bioactive compounds with pharmaceutical importance.
Intravenous lidocaine reduces perioperative opioids without negatively affecting the electrical stapedial reflex threshold in pediatric cochlear implants
Authors: Bakhet W. Z. , El Fiky L. M. , Debis H. A.
Published: April 2021

Background

Total intravenous anesthesia (TIVA) with propofol and remifentanil is frequently used for pediatric cochlear implants (CIs) surgery as it does not suppress the electrical stapedial reflex threshold (ESRT). However, high doses of remifentanil exacerbate postoperative pain and increase opioid consumption. Intravenous lidocaine reduces pain and opioid requirement. This study investigated the effect of intravenous lidocaine on perioperative opioid consumption and ESRT in pediatric CIs.

Results

The mean (95% CI) remifentanil consumption was significantly lower in lidocaine group than in placebo group [0.57 (0.497–0.643) vs 0.69 (0.63–0.75)] μg/kg/min,P= 0.016. The mean (95% CI) propofol consumption was significantly lower in lidocaine group than in placebo group [155.5 (146–165) vs 171 (161–181) μg/kg/min,P= 0.02. MBP and HR were significantly lower after surgical incision, laryngeal mask airway (LMA) removal, and at PACU admission in the lidocaine group compared with the placebo group. The PACU pain score was significantly lower in the lidocaine group compared to the placebo group. The mean (95% CI) pethidine consumption in PACU was significantly lower in the lidocaine group than in the placebo group 7.0 (6.17–7.83) vs. 8.9 (7.84–9.96) mg,P= 0.012. There were no differences between groups regarding ESRT response.

Conclusions

Intravenous lidocaine infusion reduced perioperative opioid requirements without altering the ESRT in pediatric CIs.

Trial registration

Clinical registration number:NCT04194294.
Salmon gut microbiota correlates with disease infection status: potential for monitoring health in farmed animals
Authors: Bozzi Davide , Rasmussen Jacob A. , Carøe Christian , Sveier Harald , Nordøy Kristian , Gilbert M. Thomas P. , Limborg Morten T.
Published: April 2021

Background

Infectious diseases cause significant production losses in aquaculture every year. Since the gut microbiota plays an essential role in regulating the host immune system, health and physiology, altered gut microbiota compositions are often associated with a diseased status. However, few studies have examined the association between disease severity and degree of gut dysbiosis, especially when the gut is not the site of the primary infection. Moreover, there is a lack of knowledge on whether bath treatment with formalin, a disinfectant commonly used in aquaculture to treat external infections, might affect the gut microbiome as a consequence of formalin ingestion. Here we investigate, through 16S rRNA gene metabarcoding, changes in the distal gut microbiota composition of a captive-reared cohort of 80 Atlantic salmon (Salmo salarL.), in consequence of an external bacterial skin infection due to a natural outbreak and subsequent formalin treatment.

Results

We identifiedTenacibaculum dicentrarchias the causative disease pathogen and we show that the distal gut of diseased salmon presented a different composition from that of healthy individuals. A new, yet undescribed,Mycoplasmagenus characterized the gut of healthy salmon, while in the sick fish we observed an increase in terms of relative abundance ofAliivibriosp., a strain regarded as opportunistic. We also noticed a positive correlation between fish weight andMycoplasmasp. relative abundance, potentially indicating a beneficial effect for its host. Moreover, we observed that the gut microbiota of fish treated with formalin was more similar to those of sick fish than healthy ones.

Conclusions

We conclude that externalTenacibaculuminfections have the potential of indirectly affecting the host gut microbiota. As such, treatment optimization procedures should account for that. Formalin treatment is not an optimal solution from a holistic perspective, since we observe an altered gut microbiota in the treated fish. We suggest its coupling with a probiotic treatment aimed at re-establishing a healthy community. Lastly, we have observed a positive correlation ofMycoplasmasp. with salmon health and weight, therefore we encourage further investigations towards its potential utilization as a biomarker for monitoring health in salmon and potentially other farmed fish species.