bluuebunny/crossref_metadata_2025 huggingface dataset:
Do we always need to treat patients with spinal muscular atrophy? A personal view and experience
Authors: Agosto Caterina , Salamon Eleonora , Divisic Antuan , Benedetti Francesca , Giacomelli Luca , Shah Aashni , Perilongo Giorgio , Benini Franca
Published: February 2021

Background

We report the clinical outcomes observed in our patients with SMA type 1 or 2 receiving nusinersen, and we comment on the ethical implications of this treatment, in line with our results and those reported by Audic et al. in their analysis published in the Orphanet Journal of Rare Diseases.

Methods

We analyzed records of all children with a genetically diagnosed SMA and clinically confirmed diagnosis of SMA Type 1 or 2 to whom nusinersen was offered. Follow-up lasted 30 months.

Results

Among the 17 children with SMA type 1, 6 interrupted treatment with nusinersen due to adverse events or lack of efficacy. Of the remaining 11 patients, 9 are responding to therapy, though multidisciplinary complex care is still required. All those children started nusinersen at a very early age.

Eighteen patients with SMA type 2 received nusinersen; five required treatment interruption. The other 13 patients are still on nusinersen therapy, and 6 are responders. Among the seven non-responders, only two met the inclusion criteria of the pivotal trial.

Conclusions

Our analysis further supports the findings reported in the study by Audic et al. We believe that a wider use of nusinersen in clinical practice would require a comprehensive assessment of its actual benefits weighed against the discomfort caused to patients, as well as the identification of the patients who may obtain the best benefits from this treatment.
Airway Pseudomonas aeruginosa density in mechanically ventilated patients: clinical impact and relation to therapeutic efficacy of antibiotics
Authors: Migiyama Yohei , Sakata Shinya , Iyama Shinji , Tokunaga Kentaro , Saruwatari Koichi , Tomita Yusuke , Saeki Sho , Okamoto Shinichiro , Ichiyasu Hidenori , Sakagami Takuro
Published: February 2021

Background

The bacterial density of Pseudomonas aeruginosa is closely related to its pathogenicity. We evaluated the effect of airway P. aeruginosa density on the clinical course of mechanically ventilated patients and the therapeutic efficacy of antibiotics.

Methods

We retrospectively analyzed data of mechanically ventilated ICU patients with P. aeruginosa isolated from endotracheal aspirates. Patients were divided into three groups according to the peak P. aeruginosa density during ICU stay: low (≤ 104 cfu/mL), moderate (105‒106 cfu/mL), and high (≥ 107 cfu/mL) peak density groups. The relationship between peak P. aeruginosa density and weaning from mechanical ventilation, risk factors for isolation of high peak density of P. aeruginosa, and antibiotic efficacy were investigated using multivariate and propensity score-matched analyses.

Results

Four-hundred-and-sixty-one patients were enrolled. Patients with high peak density of P. aeruginosa had higher inflammation and developed more severe respiratory infections. High peak density of P. aeruginosa was independently associated with few ventilator-free days on day 28 (P < 0.01) and increased ICU mortality (P = 0.047). Risk factors for high peak density of P. aeruginosa were prolonged mechanical ventilation (odd ratio [OR] 3.07 95% confidence interval [CI] 1.35‒6.97), non-antipseudomonal cephalosporins (OR 2.17, 95% CI 1.35‒3.49), hyperglycemia (OR 2.01, 95% CI 1.26‒3.22) during ICU stay, and respiratory diseases (OR 1.9, 95% CI 1.12‒3.23). Isolation of commensal colonizer was associated with lower risks of high peak density of P. aeruginosa (OR 0.43, 95% CI 0.26‒0.73). Propensity score-matched analysis revealed that antibiotic therapy for patients with ventilator-associated tracheobronchitis improved weaning from mechanical ventilation only in the high peak P. aeruginosa group.

Conclusions

Patients with high peak density of P. aeruginosa had worse ventilator outcome and ICU mortality. In patients with ventilator-associated tracheobronchitis, antibiotic therapy was associated with favorable ventilator weaning only in the high peak P. aeruginosa density group, and bacterial density could be a good therapeutic indicator for ventilator-associated tracheobronchitis due to P. aeruginosa.
Circulating cell-free nucleosomes as biomarker for kidney transplant rejection: a pilot study
Authors: Verhoeven Jeroen G. H. P. , Baan Carla C. , Peeters Annemiek M. A. , Clahsen-van Groningen Marian C. , Nieboer Daan , Herzog Mariëlle , Eccleston Marc , Hesselink Dennis A. , Boer Karin
Published: February 2021

Background

There is an unmet need for noninvasive markers specific for kidney transplant rejection. Such a marker may eventually overcome the need for a transplant biopsy. In this pilot study, the potential of circulating cell-free nucleosomes (CCFN) to serve as a biomarker for kidney transplant rejection was evaluated.

Methods

Forty de novo kidney transplant recipients were prospectively followed as part of a randomized, controlled clinical trial. Total CCFN (H3) and CCFN with the histone modifications H3K36me3 and H3 citrulline were measured in patients at four fixed time points: before transplantation and on days 3–6, 30 and 180 after kidney transplantation. In addition, serum collected at times of transplant rejection (n = 14) was analyzed. CCFN were measured with a Nu.Q™ Assay kit (VolitionRx), an ELISA-based assay using antibodies directed against nucleosomes.

Results

For total CCFN (H3), H3K36me3, and H3 citrulline, the same pattern was seen over time: Concentrations were elevated shortly after transplantation (day 3–6) followed by a decline reaching baseline (pre-transplantation) values at days 30 and 180. At times of acute rejection, the median concentration of total CCFN (H3) was significantly higher compared to the stable situation (day 30): 4309 (3435–5285) versus 2885 (1668–3923) ng/mL, p < 0.05, respectively. Total CCFN (H3) had an acceptable ability to discriminate rejection from no rejection (AUC-ROC = 0.73) with a negative predictive value of 92.9%. For both histone modifications (H3K36me3 and H3 citrulline), there was no significant difference between episodes of acute rejection and the stable situation (day 30).

Conclusion

In this pilot study, total CCFN (H3) concentrations are increased at times of acute kidney transplant rejection. The high negative predictive value implies that whenever a patient experiences loss of renal transplant function and the total CCFN (H3) is not increased, causes other than acute rejection should be considered. Clinical implementation of total CCFN (H3) measurement may avoid unnecessary and potentially harmful kidney transplant biopsies.
Strategy required: “Maintenance of certification for European radiologists”
Authors: Karantanas Apostolos H. , Maas Mario
Published: February 2021

Maintenance of certification (MOC) is thought to be an important tool in assessing and controlling quality of medical professionals. Considerations on the heterogeneity of implementation throughout various National Radiology Associations are described. Testocracy is warned for. The urge for defining strategical steps from a central institute is discussed.
Iodine-124 PET quantification of organ-specific delivery and expression of NIS-encoding RNA
Authors: Miederer Matthias , Pektor Stefanie , Miederer Isabelle , Bausbacher Nicole , Keil Isabell Sofia , Hefesha Hossam , Haas Heinrich , Sahin Ugur , Diken Mustafa
Published: February 2021

Background

RNA-based vaccination strategies tailoring immune response to specific reactions have become an important pillar for a broad range of applications. Recently, the use of lipid-based nanoparticles opened the possibility to deliver RNA to specific sites within the body, overcoming the limitation of rapid degradation in the bloodstream. Here, we have investigated whether small animal PET/MRI can be employed to image the biodistribution of RNA-encoded protein.
For this purpose, a reporter RNA coding for the sodium-iodide-symporter (NIS) was in vitro transcribed in cell lines and evaluated for expression. RNA-lipoplex nanoparticles were then assembled by complexing RNA with liposomes at different charge ratios, and functional NIS protein translation was imaged and quantified in vivo and ex vivo by Iodine-124 PET upon intravenous administration in mice.

Results

NIS expression was detected on the membrane of two cell lines as early as 6 h after transfection and gradually decreased over 48 h. In vivo and ex vivo PET/MRI of anionic spleen-targeting or cationic lung-targeting NIS-RNA lipoplexes revealed a visually detectable rapid increase of Iodine-124 uptake in the spleen or lung compared to control-RNA-lipoplexes, respectively, with minimal background in other organs except from thyroid, stomach and salivary gland.

Conclusions

The strong organ selectivity and high target-to-background acquisition of NIS-RNA lipoplexes indicate the feasibility of small animal PET/MRI to quantify organ-specific delivery of RNA.
Comparative evaluation of methods for isolating small extracellular vesicles derived from pancreatic cancer cells
Authors: Wang Jie-Min , Li Yong-Jiang , Wu Jun-Yong , Cai Jia-Xin , Wen Jing , Xiang Da-Xiong , Hu Xiong-Bin , Li Wen-Qun
Published: February 2021

Background

Small extracellular vesicles (sEVs) are nanosized vesicles involved in cell-to-cell communication. sEVs have been widely studied for clinical applications such as early detection of diseases and as therapeutics. Various methods for sEVs isolation are been using, but different methods may result in different qualities of sEVs and impact downstream analysis and applications. Here, we compared current isolation methods and performed a comparative analysis of sEVs from supernatant of cultured pancreatic cancer cells.

Methods

Ultracentrifugation, ultrafiltration and co-precipitation as concentration methods were firstly evaluated for yield, size, morphology and protein level of pellets. Then, isolate sEVs obtained by four different purification methods: size exclusion chromatography, density gradient ultracentrifugation, ultracentrifugation, and immunoaffinity capturing, were analysed and compared.

Results

For the concentration process, ultracentrifugation method obtained high quality and high concentration of pellets. For the purification process, immunoaffinity capturing method obtained the purest sEVs with less contaminants, while density gradient ultracentrifugation-based method obtained sEVs with the smallest size. Proteomic analysis revealed distinct protein contents of purified sEVs from different methods.

Conclusions

For isolating sEVs derived from supernatant of cultured pancreatic cancer cell line, ultracentrifugation-based method is recommended for concentration of sEVs, density gradient ultracentrifugation-based method may be applied for obtaining purified sEVs with controlled size, immunoaffinity capturing may be suitable for studies requiring sEVs with high purity but may loss subtypes of sEVs without specific protein marker.
Weighted Hermite–Hadamard type inclusions for products of co-ordinated convex interval-valued functions
Authors: Kara Hasan , Budak Hüseyin , Ali Muhammad Aamir , Sarikaya Mehmet Zeki , Chu Yu-Ming
Published: February 2021

In this paper, we establish some Hermite–Hadamard–Fejér type inclusions for the product of two co-ordinated convex interval-valued functions. These inclusions are generalizations of some results given in earlier works.
A fractional order mathematical model for COVID-19 dynamics with quarantine, isolation, and environmental viral load
Authors: Aba Oud Mohammed A. , Ali Aatif , Alrabaiah Hussam , Ullah Saif , Khan Muhammad Altaf , Islam Saeed
Published: February 2021

COVID-19 or coronavirus is a newly emerged infectious disease that started in Wuhan, China, in December 2019 and spread worldwide very quickly. Although the recovery rate is greater than the death rate, the COVID-19 infection is becoming very harmful for the human community and causing financial loses to their economy. No proper vaccine for this infection has been introduced in the market in order to treat the infected people. Various approaches have been implemented recently to study the dynamics of this novel infection. Mathematical models are one of the effective tools in this regard to understand the transmission patterns of COVID-19. In the present paper, we formulate a fractional epidemic model in the Caputo sense with the consideration of quarantine, isolation, and environmental impacts to examine the dynamics of the COVID-19 outbreak. The fractional models are quite useful for understanding better the disease epidemics as well as capture the memory and nonlocality effects. First, we construct the model in ordinary differential equations and further consider the Caputo operator to formulate its fractional derivative. We present some of the necessary mathematical analysis for the fractional model. Furthermore, the model is fitted to the reported cases in Pakistan, one of the epicenters of COVID-19 in Asia. The estimated value of the important threshold parameter of the model, known as the basic reproduction number, is evaluated theoretically and numerically. Based on the real fitted parameters, we obtained $\mathcal{R}_{0} \approx 1.50$

R
0

≈
1.50
. Finally, an efficient numerical scheme of Adams–Moulton type is used in order to simulate the fractional model. The impact of some of the key model parameters on the disease dynamics and its elimination are shown graphically for various values of noninteger order of the Caputo derivative. We conclude that the use of fractional epidemic model provides a better understanding and biologically more insights about the disease dynamics.
Linkage between the intestinal microbiota and residual feed intake in broiler chickens
Authors: Liu Jing , Stewart Sydney N. , Robinson Kelsy , Yang Qing , Lyu Wentao , Whitmore Melanie A. , Zhang Guolong
Published: February 2021

Background

Intestinal microbiota plays a key role in nutrient digestion and utilization with a profound impact on feed efficiency of livestock animals. However, the intestinal microbes that are critically involved in feed efficiency remain elusive.

Methods

To identify intestinal bacteria associated with residual feed intake (RFI) in chickens, male Cobb broiler chicks were individually housed from day 14 to day 35. Individual RFI values were calculated for 56 chickens. Luminal contents were collected from the ileum, cecum, and cloaca of each animal on day 35. Bacterial DNA was isolated and subjected to 16S rRNA gene sequencing. Intestinal microbiota was classified to the feature level using Deblur and QIIME 2. High and low RFI groups were formed by selecting 15 and 17 chickens with the most extreme RFI values for subsequent LEfSe comparison of the difference in the microbiota. Spearman correlation analysis was further performed to identify correlations between the intestinal microbiota composition and RFI.

Results

No significant difference in evenness, richness, and overall diversity of the microbiota in the ileum, cecum, or cloaca was observed between high and low RFI chickens. However, LEfSe analysis revealed a number of bacterial features being differentially enriched in either high or low RFI chickens. Spearman correlation analysis further identified many differentially enriched bacterial features to be significantly correlated with RFI (P < 0.05). Importantly, not all short-chain fatty acid (SCFA) producers showed a positive association with RFI. While two novel members of Oscillibacter and Butyricicoccus were more abundant in low-RFI, high-efficiency chickens, several other SCFA producers such as Subdoligranulum variabile and two related Peptostreptococcaceae members were negatively associated with feed efficiency. Moreover, a few closely-related Lachnospiraceae family members showed a positive correlation with feed efficiency, while others of the same family displayed an opposite relationship.

Conclusions

Our results highlight the complexity of the intestinal microbiota and a need to differentiate the bacteria to the species, subspecies, and even strain levels in order to reveal their true association with feed efficiency. Identification of RFI-associated bacteria provides important leads to manipulate the intestinal microbiota for improving production efficiency, profitability, and sustainability of poultry production.
Repeatability and reproducibility assessment in a large-scale population-based microbiota study: case study on human milk microbiota
Authors: Moossavi Shirin , Fehr Kelsey , Khafipour Ehsan , Azad Meghan B.
Published: February 2021

Background

Quality control including assessment of batch variabilities and confirmation of repeatability and reproducibility are integral component of high throughput omics studies including microbiome research. Batch effects can mask true biological results and/or result in irreproducible conclusions and interpretations. Low biomass samples in microbiome research are prone to reagent contamination; yet, quality control procedures for low biomass samples in large-scale microbiome studies are not well established.

Results

In this study, we have proposed a framework for an in-depth step-by-step approach to address this gap. The framework consists of three independent stages: (1) verification of sequencing accuracy by assessing technical repeatability and reproducibility of the results using mock communities and biological controls; (2) contaminant removal and batch variability correction by applying a two-tier strategy using statistical algorithms (e.g. decontam) followed by comparison of the data structure between batches; and (3) corroborating the repeatability and reproducibility of microbiome composition and downstream statistical analysis. Using this approach on the milk microbiota data from the CHILD Cohort generated in two batches (extracted and sequenced in 2016 and 2019), we were able to identify potential reagent contaminants that were missed with standard algorithms and substantially reduce contaminant-induced batch variability. Additionally, we confirmed the repeatability and reproducibility of our results in each batch before merging them for downstream analysis.

Conclusion

This study provides important insight to advance quality control efforts in low biomass microbiome research. Within-study quality control that takes advantage of the data structure (i.e. differential prevalence of contaminants between batches) would enhance the overall reliability and reproducibility of research in this field.
Influence of thermal stratification and storms on acoustic telemetry detection efficiency: a year-long test in the US Southern Mid-Atlantic Bight
Authors: O’Brien Michael H. P. , Secor David H.
Published: February 2021

Background

The detection efficiency of ultrasonic transmitters is seasonally variable, requiring long-term studies to evaluate key environmental features that mask, alter speed, bend, or reflect transmissions. The US Southern Mid-Atlantic Bight shelf is characterized by a strong summer thermocline capping remnant winter water, known as the Cold Pool, and a well-mixed water column in other seasons. To investigate the effects of interactions between temperature stratification and storm-induced noise on transmission detectability, we conducted a year-long range test of 69-kHz acoustic transmitters in the bottom waters of the US Southern Mid-Atlantic Bight. We used generalized additive models and cross-validation to develop and evaluate a predictive model of detection efficiency and visualize variability in detection distance throughout the year of deployment.

Results

The most-predictive model contained the effects of temperature stratification and ambient noise, predicting that stratification results in a 33% increase in detectability and 56% increase in detection distance. The model had an overall error rate of 17.1% and an 18.7% error at a distance of 800 m, predicting 17% detectability at median ambient noise when the water column was not stratified and > 50% when the difference between surface and bottom temperatures was greater than 4.2 °C. The distance at 50% detectability increased with the formation of the Cold Pool during spring, increasing by nearly 300 m over 3 days. All seasons were associated with storm-induced reductions in overall detectability and distance at 50% detectability.

Conclusion

Thermal stratification within the Southern Mid-Atlantic Bight increases bottom water ultrasonic transmitter detection distance and reduces the impact of surface noise. This effect leads to a seasonal increase in detection distance from the late-spring through the summer. To our knowledge, this study is the first to report and quantify an increase in detection range as a result of temperature stratification, likely due to placing transmitters and receivers on the same side of a strong thermocline.
Eating disorder symptoms and foraging for food related items
Authors: Kristjánsson Árni , Helgadóttir Auður , Kristjánsson Tómas
Published: February 2021

Background

Foraging tasks have recently been increasingly used to investigate visual attention. Visual attention can be biased when certain stimuli capture our attention, especially threatening or anxiety-provoking stimuli, but such effects have not been addressed in foraging studies.

Methods

We measured potential attentional bias associated with eating disorder symptoms to food related stimuli with our previously developed iPad foraging task. Forty-four participants performed a foraging task where they were instructed to tap predesignated food related targets (healthy and unhealthy) and other non-food objects and completed four self-report questionnaires measuring symptoms of eating disorders. Participants were split into two groups based on their questionnaire scores, a symptom group and no symptom group.

Results

The foraging results suggest that there are differences between the groups on switch costs and target selection times (intertarget times) but they were only statistically significant when extreme-group analyses (EGA) were used. There were also notable food versus non-food category effects in the foraging patterns.

Conclusions

The results suggest that foraging tasks of this sort can be used to assess attentional biases and we also speculate that they may eventually be used to treat them through attention bias modification. Additionally, the category effects that we see between food items and other items are highly interesting and encouraging. At the same time, task sensitivity will need to be improved. Finally, future tests of clinical samples could provide a clearer picture of the effects of eating disorder symptoms on foraging for food.
Treatment of Clostridium difficile infection in community teaching hospital: a retrospective study
Authors: Elbeddini Ali , Gerochi Rachel
Published: February 2021

Objectives

Clostridium difficile infection (CDI) is responsible for 15–25% cases of health-care-associated diarrhea. The CDI treatment algorithm used at our hospital is adapted from the Infectious Diseases Society of America 2010 C. difficile guideline. The primary objective of this study was to assess the treatment adherence to our algorithm; this was defined as therapy consisting of the appropriate antibiotic, dose, route, interval, and duration indicated based on the disease severity and episode within 24 h of diagnosis. Furthermore, our study also described the population and their risk factors for CDI at our hospital.

Methods

This was a single-centre, retrospective cohort chart review of CDI cases that were diagnosed at admission or during hospitalization from June 1st, 2017 to June 30th, 2018. Cases were identified by a positive stool test along with watery diarrhea or by colonoscopy.

Results

Sixty cases were included, of which adherence to our algorithm was 50%. Overall, severe CDI had the highest treatment non-adherence (83%), and the biggest contributing factor was prescribing the wrong antibiotic (72%). In severe CDI, which warrants vancomycin monotherapy, wrong antibiotic consisted of metronidazole monotherapy (55%) or dual therapy with metronidazole and vancomycin (45%). Patients were mostly older, females being treated for an initial episode of mild-to-moderate CDI. Common risk factors identified were age over 65 years (80%), use of antibiotics (83%) and proton pump inhibitors (PPI) (68%) within the previous 3 months. The use of a PPI in this study, a modifiable risk factor without a clear indication, was 35%.

Conclusion

An area for antimicrobial stewardship intervention in CDI treatment at our hospital is prescribing the right antibiotic based on the CDI indication. In severe CDI, an emphasis should be on prescribing vancomycin monotherapy as the drug of choice. PPI use should be reassessed for tapering when appropriate.
Hydrogen production from water electrolysis: role of catalysts
Authors: Wang Shan , Lu Aolin , Zhong Chuan-Jian
Published: February 2021

As a promising substitute for fossil fuels, hydrogen has emerged as a clean and renewable energy. A key challenge is the efficient production of hydrogen to meet the commercial-scale demand of hydrogen. Water splitting electrolysis is a promising pathway to achieve the efficient hydrogen production in terms of energy conversion and storage in which catalysis or electrocatalysis plays a critical role. The development of active, stable, and low-cost catalysts or electrocatalysts is an essential prerequisite for achieving the desired electrocatalytic hydrogen production from water splitting for practical use, which constitutes the central focus of this review. It will start with an introduction of the water splitting performance evaluation of various electrocatalysts in terms of activity, stability, and efficiency. This will be followed by outlining current knowledge on the two half-cell reactions, hydrogen evolution reaction (HER) and oxygen evolution reaction (OER), in terms of reaction mechanisms in alkaline and acidic media. Recent advances in the design and preparation of nanostructured noble-metal and non-noble metal-based electrocatalysts will be discussed. New strategies and insights in exploring the synergistic structure, morphology, composition, and active sites of the nanostructured electrocatalysts for increasing the electrocatalytic activity and stability in HER and OER will be highlighted. Finally, future challenges and perspectives in the design of active and robust electrocatalysts for HER and OER towards efficient production of hydrogen from water splitting electrolysis will also be outlined.
The BGS candidate models for IGRF-13 with a retrospective analysis of IGRF-12 secular variation forecasts
Authors: Brown William J. , Beggan Ciarán D. , Cox Grace A. , Macmillan Susan
Published: February 2021

The three candidate models submitted by the British Geological Survey for the 13th generation International Geomagnetic Reference Field are described. These DGRF and IGRF models are derived from vector and scalar magnetic field data from the European Space Agency Swarm satellites and ground observatories, covering the period 2013.9 to 2019.7. The internal field model has time dependence for degrees 1 to 15, represented by order 6 B-splines with knots at six monthly intervals. We also solve for a degree 1 external field time dependence describing annual and semi-annual signals with additional dependence on a bespoke Vector Magnetic Disturbance index. Satellite data are weighted by spatial density, along-track standard deviations, and a larger-scale noise estimator defined in terms of a measure of Local Area Vector Activity at the geographically closest magnetic observatories to the sampled datum. Forecasting of the magnetic field secular variation for 2020–2025 is by advection of the main field using steady core surface flows with steady acceleration applied. We also investigate the performance of the previous generation of candidate secular variation models, for IGRF-12, analysing the agreement of the candidates between 2015 and 2020 with the retrospective IGRF-13. We find that there is no clear distinction between the performance of mathematically and physically extrapolated forecasts in the period 2015–2020. We confirm that the methodology for the BGS IGRF-12 predictions performed well, despite observed secular accelerations that are highlighted by our analysis, and thus justify the methodology used for our IGRF-13 SV candidate.
A secular variation candidate model for IGRF-13 based on Swarm data and ensemble inverse geodynamo modelling
Authors: Fournier Alexandre , Aubert Julien , Lesur Vincent , Ropp Guillaume
Published: February 2021

This paper describes the design of a candidate secular variation model for the 13th generation of the International Geomagnetic Reference Field. This candidate is based upon the integration of an ensemble of 100 numerical models of the geodynamo between epochs 2019.0 and 2025.0. The only difference between each ensemble member lies in the initial condition that is used for the numerical integration, all other control parameters being fixed. An initial condition is defined as follows: an estimate of the magnetic field and its rate-of-change at the core surface for 2019.0 is obtained from a year (2018.5–2019.5) of vector Swarm data. This estimate (common to all ensemble members) is subject to prior constraints: the statistical properties of the numerical dynamo model for the main geomagnetic field and its secular variation, and prescribed covariances for the other sources. One next considers 100 three-dimensional core states (in terms of flow, buoyancy and magnetic fields) extracted at different discrete times from a dynamo simulation that is not constrained by observations, with the time distance between each state exceeding the dynamo decorrelation time. Each state is adjusted (in three dimensions) in order to take the estimate of the geomagnetic field and its rate-of-change for 2019.0 into account. This methodology provides 100 different initial conditions for subsequent numerical integration of the dynamo model up to epoch 2025.0. Focussing on the 2020.0–2025.0 time window, we use the median average rate-of-change of each Gauss coefficient of the ensemble and its statistics to define the geomagnetic secular variation over that time frame and its uncertainties.
IZMIRAN candidate field model for IGRF-13
Authors: Petrov Valeriy G. , Bondar Tatyana N.
Published: February 2021

The International Geomagnetic Reference Field (IGRF) model is a combination of the several models developed by independent groups of scientists using different approaches for the selection of input data and methods for calculating harmonic coefficients. This approach allows for mutual comparison of individual models and for their combination to obtain the most reliable values of the harmonic coefficients. This letter provides a brief description of methods for building the IZMIRAN Earth’s main magnetic field model, submitted to the IAGA Working Group V-MOD for creating IGRF-13. Special efforts were made to obtain as uniform coverage of the entire Earth’s surface as possible with observations. The surface was divided into a grid of approximately equal cells. Then the data for geomagnetically quiet intervals were placed in the corresponding cells and a median filter was applied to select the data in each cell. Spherical harmonic coefficients up to degree 13 were calculated for the interval 2014-Jan to 2019-Aug with a time step of 10 days and extrapolated to 01.01.2010.
Panel of significant risk factors predicts early stage gastric cancer and indication of poor prognostic association with pathogens and microsatellite stability
Authors: Chakraborty Payel , Ghatak Souvik , Chenkual Saia , Pachuau Lalawmpuii , Zohmingthanga John , Bawihtlung Zothankima , Khenglawt Lalfakzuala , Pautu Jeremy L. , Maitra Arindam , Chhakchhuak Lalchhandama , Kumar Nachimuthu Senthil
Published: February 2021

Background

There are very few studies covering the epidemiological risk factors associated with Epstein Barr Virus (EBV) and Microsatellite stability for Gastric Cancer (GC) cases. Early diagnosis of GC through epidemiological risk factors is very necessary for the clinical assessment of GC. The aim of this study was to find out the major risk factors to predict GC in early stage and the impact of pathogen infection and MSI on survival rate of patients. GC samples were screened for Helicobacter pylori, Epstein Barr Virus, and Mismatch repair (MMR) gene status (microsatellite stable or instable). Chi-square and logistic regression analysis of Odd ratio and 95% confidence interval (OR, 95% CI) were performed to find out the association between epidemiological factors and the risk of gastric cancer. The pathogen and MMR gene status were analysed to predict their effect on overall survival and the risk score and hazard ratio was calculated for prognostic assessment.

Results

Excess body weight, consumption of extra salt, smoked food, alcohol, and smoking were the major risk factors for GC development. This study achieved a high area under the curve (AUC 0.94) for the probable GC patients in early-stage using the five-panel epidemiological risk factors. H. pylori infected cases were significant with smoked food, while EBV was found to be associated with tuibur intake and smoked food. In overall survival analysis EBV infected and microsatellite stable (HR: 1.32 and 1.34 respectively) GC cases were showing poor prognosis.

Conclusion

This study might provide new opportunities for personalized treatment options using this epidemiological factor risk score and clinicopathological factors assessment for early detection and prognosis in high-risk GC populations.
Gemini surfactant assisted synthesis of mesoporous Mn/Mg bimetal doped TiO2 nanomaterial: characterization and photocatalytic activity studies under visible light irradiation
Authors: Miditana Sankara Rao , Tirukkovalluri Siva Rao , Raju Imandi Manga , Alim Shaik Abdul , Jaishree Genji , Chippada M. L. V. Prasanna
Published: February 2021

The present work mainly aimed to synthesize different weight percentages (0.25–1.00 wt%) of Manganese (Mn2+) and Magnesium (Mg2+) bimetal ions doped TiO2 nanomaterial assisted with different weight percentages (5–15 wt%) of Gemini surfactant (GS) using sol-gel method. The bimetal doped and undoped TiO2 photocatalysts were characterized by X-ray Diffraction, Scanning Electron Microscopy, Energy Dispersive X-ray Spectroscopy, Fourier Transform Infrared Spectroscopy (FT-IR), UV-Visible Diffused Reflectance Spectroscopy, Transmission Electron Microscopy, Brunauer-Emmett-Teller surface area analyzer, and Photoluminescence Spectroscopy. Characterization results revealed that mesoporous multi-particle anatase TiO2 nanoparticles with a narrowed band gap, small particle size, and high surface area were formed due to the combined effect of Mn2+/Mg2+ bimetal ions doping and effective encapsulation of GS over the initially formed TiO2 nanoparticles. The surface elemental composition of the 0.25 wt% Mn2+ and 1.00 wt% Mg2+ bimetal doped TiO2 in the presence of 10 wt% of GS (after calcination) revealed the presence of both the metal dopants Mn2+ and Mg2+ along with the Ti and O and their chemical interactions were further confirmed by FT-IR results. The photocatalytic activity of these catalysts was assessed by the degradation of Methyl Red using visible light irradiation. To understand the effect of different reaction parameters on the photocatalytic activity of the nanocatalysts such as the dopant concentration, surfactant concentration, catalyst dosage, solution pH, and initial dye concentration were investigated and optimized to achieve the best performance. The photoluminescence results conclude that OH radicals are the crucial reactive species responsible for oxidative photocatalytic degradation of Methyl Red.
Electron generation in water induced by magnetic effect and its impact on dissolved oxygen concentration
Authors: Yap Augustine Chung Wei , Lee Hwang Sheng , Loo Joo Ling , Mohd Nuruol Syuhadaa
Published: February 2021

pH, oxidation-reduction potential (ORP) and dissolved oxygen (DO) concentration are important parameters in water quality surveillance and treatment. The changes of these parameters are associated with electron density in water. Several techniques including electrolysis and catalysis which require redox reactions and electron exchange are employed to improve these parameters. In recent years, studies reported that magnetic effects can impart considerable changes on the pH, ORP and DO concentration of water. However, the correlation between electron density and magnetic effects on these parameters has yet to be disclosed despite the fact that increased electron density in water could improve water’s reductive properties, heat capacity and hydrogen bonding characteristics. In this study, the magnetic effects on pH, ORP and DO concentration were investigated using different magnets arrangements and water flow rates based on reversed electric motor principle. Results showed that the improvement of pH, ORP and DO concentration from 5.40–5.42 to 5.58–5.62 (+ 3.5%), 392 to 365 mV (− 6.9%), and 7.30 to 7.71 mg L− 1(+ 5.6%), respectively were achieved using combined variables of non-reversed polarity magnet arrangement (1000–1500 G magnetic strength) and water flow rate of 0.1–0.5 mL s− 1. Such decrement in ORP value also corresponded to 8.0 × 1013number of electron generation in water. Furthermore, Raman analysis revealed that magnetic effect could strengthen the intermolecular hydrogen bonding of water molecules and favor formation of smaller water clusters. The findings of this study could contribute to potential applications in aquaculture, water quality control and treatment of cancer attributed to free radical induced-oxidative stress.
Developmental anomalies and associated impairments in Saudi children with cerebral palsy: a registry-based, multicenter study
Authors: Al-Garni Saeed , Derbala Shereen , Saad Hatem , Maaty Ahmed I.
Published: February 2021

Background

There are few epidemiological data to support rehabilitation programs for cerebral palsy (CP). Scarce international studies described the developmental anomalies (DAs) among children with CP. To our knowledge, the Arab countries did not publish data regarding this topic. This study aimed to describe the percentage of DAs among children with CP and detect the association between clinical subtypes and impairment severity in children with various DAs. We collected registry data of 679 children with cerebral palsy, between 2014 and 2019, from Armed Forces Hospitals, Taif, Kingdom of Saudi Arabia (KSA). We recorded demographic, perinatal, postnatal, developmental anomalies, subtypes, and impairment characteristics. We utilized the chi-square test to calculate the differences between groups.

Results

We reported significant differences between the children with and without anomalies regarding the percentages of consanguinity, preterm labor, low birth weight, and neonatal intensive care unit admission (P = 0.001, 0.002, 0.003, 0.005, respectively). Congenital dysplasia of the hip and hydrocephalus was the most frequent skeletal and nervous anomalies among children with DAs (19.1% and 12.8%, respectively). The spastic bilateral pattern was significantly higher among children with skeletal anomalies than the central nervous system/other groups (P < 0.001). The nervous anomalies group had higher frequencies of severe intellectual, motor, speech, and visual disabilities and a higher percentage of seizures than all other groups.

Conclusions

The frequency of children with anomalies in this study was comparable to previous studies. Children with CP and nervous system anomalies had more severe motor disabilities and associated impairments.
FrenchFISH: Poisson Models for Quantifying DNA Copy Number From Fluorescence In Situ Hybridization of Tissue Sections
Authors: Macintyre Geoff , Piskorz Anna M. , Berman Adam , Ross Edith , Morse David B. , Yuan Ke , Ennis Darren , Pike Jeremy A. , Goranova Teodora , McNeish Iain A. , Brenton James D. , Markowetz Florian
Published: February 2021

PURPOSE

Chromosomal aberration and DNA copy number change are robust hallmarks of cancer. The gold standard for detecting copy number changes in tumor cells is fluorescence in situ hybridization (FISH) using locus-specific probes that are imaged as fluorescent spots. However, spot counting often does not perform well on solid tumor tissue sections due to partially represented or overlapping nuclei.

MATERIALS AND METHODS

To overcome these challenges, we have developed a computational approach called FrenchFISH, which comprises a nuclear volume correction method coupled with two types of Poisson models: either a Poisson model for improved manual spot counting without the need for control probes or a homogeneous Poisson point process model for automated spot counting.

RESULTS

We benchmarked the performance of FrenchFISH against previous approaches using a controlled simulation scenario and tested it experimentally in 12 ovarian carcinoma FFPE-tissue sections for copy number alterations at three loci (c-Myc, hTERC, and SE7). FrenchFISH outperformed standard spot counting with 74% of the automated counts having < 1 copy number difference from the manual counts and 17% having < 2 copy number differences, while taking less than one third of the time of manual counting.

CONCLUSION

FrenchFISH is a general approach that can be used to enhance clinical diagnosis on sections of any tissue by both speeding up and improving the accuracy of spot count estimates.
Frameworks for Radiation Oncology Global Health Initiatives in US Residency Programs
Authors: Li Benjamin C. , Chew Jessica , Wakefield Daniel V. , Agarwal Ankit , Jhingran Anuja
Published: February 2021

PURPOSE

To understand trends, pathways, and experiences and to establish a framework for radiation oncology (RO) programs interested in developing global health (GH) initiatives.

METHODS

An in-depth interview was conducted of all US RO programs with established GH initiatives. Programs were identified by reviewing results of the 2018 Association of Residents in Radiation Oncology Global Health Resident Survey and individualized outreach to screen for additional programs meeting the following criteria: (1) active resident involvement in RO-specific GH opportunities, (2) active faculty involvement in these initiatives, and (3) department chair or program director awareness and support for ongoing opportunities. Among 88 residency programs, 11 were identified. Standardized questions explored the type of initiative, planning, staff and resident involvement, challenges, components to success, and history of programs through December 2018.

RESULTS

Between 2010 and 2018, 11 programs started initiatives. Total resident participants ranged from one to 13 (median = 3) in each program's history. Initiatives spanned education (n = 9 [82%]), clinical mentorship (73%), innovative technology (55%), bilateral hosting programs (45%), clinical development and equipment (45%), promotion of local research (36%), clinical care (36%), industry partnerships (27%), and remote tumor board (18%). Faculty involvement included radiation oncologists (91%), medical physicists (55%), and non-RO department faculty (27%). Six programs (55%) had faculty with prior GH experience. Four (36%) programs reported medical student involvement in projects. Barriers included international communication (36%), time for faculty (18%), funding (9%), and legal (9%) concerns. Commonest components of success included fostering relationships with international sites and identifying needs before solutions.

CONCLUSION

RO GH initiatives were reported as positive, educational, and feasible across 11 US residency programs. Growth is expected, representing opportunities for innovation and service among US programs.
Novel Clinician-Lead Intervention to Address Fear of Cancer Recurrence in Breast Cancer Survivors
Authors: Liu Jia , Butow Phyllis , Bui Kim T. , Serafimovska Anastasia , Costa Daniel S. J. , Kiely Belinda E. , Hui Mun N. , Goodwin Annabel , McNeil Catriona M. , Beith Jane M.
Published: February 2021

PURPOSE:

Fear of cancer recurrence (FCR) affects 50%-70% of cancer survivors. This multicenter, single-arm study sought to determine the participant-rated usefulness of an oncologist-delivered FCR intervention.

METHODS:

Women who completed treatment for early breast cancer (could be receiving endocrine therapy) with baseline FCR > 0 were invited to participate. FCR was measured using a validated 42-item FCR Inventory. The brief oncologist-delivered intervention entailed (1) FCR normalization; (2) provision of personalized prognostic information; (3) recurrence symptoms education, (4) advice on managing worry, and (5) referral to psycho-oncologist if FCR was high. FCR, depression, and anxiety were assessed preintervention (T0), at 1 week (T1), and 3 months (T2) postintervention. The primary outcome was participant-rated usefulness. Secondary outcomes included feasibility and efficacy.

RESULTS:

Five oncologists delivered the intervention to 61/255 women invited. Mean age was 58 ± 12 years. Mean time since breast cancer diagnosis was 2.5 ± 1.3 years. Forty-three women (71%) were on adjuvant endocrine therapy. Of 58 women who completed T1 assessment, 56 (97%) found the intervention to be useful. FCR severity decreased significantly at T1 (F = 18.5, effect size = 0.39, P < .0001) and T2 (F = 24, effect size = 0.68, P < .0001) compared with baseline. There were no changes in unmet need or depression or anxiety. Mean consultation length was 22 minutes (range, 7-47 minutes), and mean intervention length was 8 minutes (range, 2-20 minutes). The intervention was perceived as useful and feasible by oncologists.

CONCLUSION:

A brief oncologist-delivered intervention to address FCR is useful and feasible, and has preliminary efficacy in reducing FCR. Plans for a cluster randomized trial are underway.
DPP4 Activity, Hyperinsulinemia, and Atherosclerosis
Authors: Love Kaitlin M , Liu Zhenqi
Published: February 2021

Context

Obesity and type 2 diabetes are associated with chronic hyperinsulinemia, elevated plasma levels of dipeptidyl peptidase-4 (DPP4), and a pro-atherosclerotic milieu.

Evidence Acquisition

PubMed search of the term “insulin and atherosclerosis,” “hyperinsulinemia,” “atherosclerosis,” or “cardiovascular outcomes” cross-referenced with “DPP4.” Relevant research and review articles were reviewed.

Evidence Synthesis

Hyperinsulinemia in the setting of insulin resistance promotes vascular inflammation, vascular smooth muscle cell growth, pathological cholesterol profile, hypertension, and recruitment of immune cells to the endothelium, all contributing to atherosclerosis. DPP4 has pleiotropic functions and its activity is elevated in obese humans. DPP4 mirrors hyperinsulinemia’s atherogenic actions in the insulin resistant state, and genetic deletion of DPP4 protects rodents from developing insulin resistance and improves cardiovascular outcomes. DPP4 inhibition in pro-atherosclerotic preclinical models results in reduced inflammation and oxidative stress, improved endothelial function, and decreased atherosclerosis. Increased incretin levels may have contributed to but do not completely account for these benefits. Small clinical studies with DPP4 inhibitors demonstrate reduced carotid intimal thickening, improved endothelial function, and reduced arterial stiffness. To date, this has not been translated to cardiovascular risk reduction for individuals with type 2 diabetes with prior or exaggerated risk of cardiovascular disease.

Conclusion

DPP4 may represent a key link between central obesity, insulin resistance, and atherosclerosis. The gaps in knowledge in DPP4 function and discrepancy in cardiovascular outcomes observed in preclinical and large-scale randomized controlled studies with DPP4 inhibitors warrant additional research.