bluuebunny/crossref_metadata_2025_split 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

Abstract
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

Abstract
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

Abstract
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

AbstractMaintenance 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

Abstract
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

Abstract
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

AbstractIn 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

AbstractCOVID-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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.