bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractN6-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

AbstractThe 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

AbstractWe 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

Abstract
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

AbstractRegional 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractBackgroundTotal 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.ResultsThe 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.ConclusionsIntravenous lidocaine infusion reduced perioperative opioid requirements without altering the ESRT in pediatric CIs.Trial registrationClinical registration number:NCT04194294.