bluuebunny/crossref_metadata_2025_split huggingface dataset:
Idiopathic Interstitial Pneumonias: A Review of the Past and Emerging Therapies
Authors: Sagardia Lisa M. , Taylor Bethany E. , Mehta Ishan 
Published: October 2021

Purpose This article is an in-depth review of the complex classification, diagnosis, and treatment of idiopathic interstitial pneumonias (IIP), as well as emergence of new treatment options. Summary: Idiopathic interstitial pneumonias consist of various subgroup classifications that require expert analysis of imaging and histology to accurately diagnose this broad group of patients. Timely and accurate assessment of these patients is key in developing an appropriate pharmacological plan. The pathophysiology of IIP is not well understood but has been linked to an immune response resulting in inflammation, fibrosis, or proliferation of lung tissue which reduces lung function. Lung transplantation is currently the only curative option for treatment, but many new antiproliferative and immunosuppressive agents are being used to effectively slow the progression of lung dysfunction. Conclusion: An often mixed radiological and histological pattern along with the invasive nature of biopsy for gold standard diagnosis create a challenge for the accurate identification of IIP. Further understanding of these idiopathic interstitial pneumonias will pave the way forward to the emergence of new treatment options and updates to standards of care.
On the subsonic and low transonic aerodynamic performance of the land speed record car, Bloodhound LSR
Authors: Evans Ben , Townsend Jack , Hassan Oubay , Morgan Kenneth , Ayers Ron , Chapman Mark , Green Andy 
Published: October 2021

The land speed record vehicle, Bloodhound, undertook testing at subsonic and low transonic speeds (up to Mach 0.8) at Hakskeen Pan, South Africa, during October and November of 2019. A decade of CFD-led aerodynamic design had been undertaken to produce a vehicle with the aim of minimised Mach number aerodynamic dependencies and minimised overall drag. This paper sets out and explains the measured pressure distributions with a focus on the highest speed run of Bloodhound up to a peak speed of 628 mile/h. It compares the measured aerodynamic performance with the various CFD model predictions used throughout the design process showing that, whilst localised discrepancies between CFD model and real behaviour exist, overall the Reynolds-averaged Navier–Stokes (RANS)-based CFD tools used to design the car did result in sufficiently accurate aerodynamic data to predict the overall vehicle performance to a high degree of accuracy. The work outlined in this paper, and the conclusions and recommendations drawn, form the basis for a future record attempt and the understanding of what will be required in principle to extend the World Land Speed Record to 1000 mile/h. It also provides guidance on how to effectively make use of RANS-based CFD modelling predictions for other complex, ground-interacting high-speed applications.
Preparation and characterization of pH-responsive ionic crosslinked microparticles of mercaptopurine to target ulcerative colitis
Authors: Hameed Huma , Rehman Khurram , Hameed Anam , Qayuum Abdul 
Published: October 2021

The objective of this study was the preparation of ionically crosslinked 6-mercaptopurine (6-MP) monohydrate microparticles through preparing polyelectrolyte complexes of drug and polymers. Polymers such as chitosan, casein, and carrageenan were used to prepare crosslinked microparticles, and sodium tripolyphosphate was used as crosslinker. Microparticles were characterized for their flow behavior, compressibility, percentage yield, micromeritic, and entrapment efficiency. Scanning electron microscopy was conducted to understand the surface morphology of the microparticles, and the result was correlated with the swelling index and percentage drug release. Mathematical modeling of drug release in order to determine the drug release kinetics was also determined to understand the mechanism involving the release of 6-mercaptopurine from the microparticles. The ionic crosslinked microparticles were in the range of 664 μm–798 μm particle size having good flow and compressibility properties with percentage yield were found to be from 77.5% to 87.5% in range. The entrapment efficiency for the formulations were found to be from 63.5% to 83.5%, with MCP-5 gave maximum entrapment efficiency of 83.5%. In vitro swelling and drug release studies were in accordance with the polymer properties following zero-order model with super-case transport II.
Degradation and inactivation efficacy of ozone water for antineoplastic drugs in hospital settings
Authors: Kato Ginjiro , Mitome Hidemichi , Shigematsu Saki , Utsunomiya Aya , Shimasaki Miho , Sasaki Yuta , Maki Tsuneo , Yamamoto Hiroshi , Tanabe Tomotaka , Funahashi Tatsuya , Hatae Noriyuki , Hidaka Noriaki , Tanaka Mamoru , Akira Kazuki 
Published: October 2021

Purpose Occupational exposure to antineoplastic drugs in hospital settings is recognized to be hazardous, and as such environmental decontamination including degradation and inactivation of such drugs is recommended. To data, although various agents such as oxidants have been reported to be useful for decontamination, simpler, safer, and more convenient methods are required. In this study, the degradation and inactivation efficacy of ozone water, which has newly been introduced for decontamination of antineoplastic drugs in spills, was investigated for formulations of gemcitabine, irinotecan, and paclitaxel. Methods Antineoplastic formulations (medicinal ingredient: ∼1.5 μmol) were mixed with 50 mL of ozone water (>4 mg/L). The reactions were monitored by high-performance liquid chromatography, and the degradation mixtures were analyzed by 1H nuclear magnetic resonance spectroscopy in order to obtain the structural information of the degradation products. The formulations of gemcitabine and irinotecan and those degradation mixtures were evaluated for their mutagenicity using the Ames test and cytotoxicity against human cancer cells. Results Gemcitabine and irinotecan were found to be readily degraded by the ozone treatment, and their active sites were suggested to be degraded. In contrast, paclitaxel was hard to be decomposed, possibly owing to the consumption of ozone by the polyoxyethylene castor oil added as a pharmaceutical additive of the formulation. No significant mutagenic changes of Salmonella typhimurium strains used for the Ames test were observed for the samples within the concentration ranges examined. The ozone treatment showed obvious increases in cell viability for gemcitabine formulation, and mild increases for irinotecan formulation. Conclusions Ozone water was shown to be effective as a decomposition agent for the antineoplastic drug formulations examined, although the efficacy depends on the chemical structures of the drugs and the pharmaceutical additives. It was also suggested that ozone treatment has a tendency to decrease the toxicity of the antineoplastic drug formulations. As such, further studies are required in order to clarify the effects and application limitations of ozone water.
A higher burden of multiple sclerosis genetic risk confers an earlier onset
Authors: Misicka Elina , Davis Mary F , Kim Woori , Brugger Steven W , Beales Jeremy , Loomis Stephanie , Bronson Paola G , Briggs Farren BS 
Published: October 2021

Background: Age at onset of multiple sclerosis (MS) is an objective, influential predictor of the evolution of MS independent of disease duration. Objectives: Determine the influence of MS genetic predisposition on age of onset. Methods: We conducted a comprehensive investigation of MS risk variants and age at onset in 3495 non-Latinx white individuals, including for combinations of HLA-DRB1*15:01 alleles and quintiles of an unweighted genetic risk score (GRS) for 198 of 200 autosomal MS risk variants that reside outside the major histocompatibility complex. Results: The mean age at onset was 32 years, 29% were male, and 46% were HLA-DRB1*15:01 carriers. For those with the greatest genetic risk burden (the highest GRS quintile with two HLA-DRB1*15:01 alleles) were on average 5 years younger at onset ( p = 0.002) than those with the lowest genetic risk burden (the lowest GRS quintile with no HLA-DRB1*15:01 alleles). There was a strong inverse relationship between the MS genetic risk burden and age at onset of MS ( p < 5 × 10−8). Conclusion: We demonstrate a significant gradient between elevated MS genetic risk burden and an earlier onset of MS, suggesting that a higher MS genetic risk burden accelerates onset of the disease.
Risk factors of recurrence after endovascular embolization of posterior communicating artery aneurysms
Authors: Wu Degang , Sheng Bin , Fang Xinggen , Li Zhenbao 
Published: October 2021

Background and objective To determine the risk factors for recurrence after endovascular embolization of posterior communicating artery aneurysms (PcomA). Methods We retrospectively analyzed a cohort of 163 patients harboring 172 PocmAs who were treated with endovascular embolization from January 2019 to December 2020. The patients were divided into recurrence and stable groups depending on outcome. Univariate and logistic regression analyses were performed to determine the potential risk factors of recurrence during follow-up. Results Of the total 163 patients harboring 172 aneurysms, 107 were treated with simple coil occlusion and 65 were treated with stent-assisted coil embolization. There were significant differences in aneurysm sizes and use of non-stent-assisted coil embolizations between the groups (P < 0.05). The incidence of saccular aneurysm and Raymond grade were significantly higher in the recurrent group than in the stable group (P < 0.01). After variable selection, Raymond grade, aneurysm size, saccular aneurysm and non-stent-assisted coil embolization were included in further analysis. Binary logistic regression analysis revealed significant associations with non-stent-assisted coil embolization (P = 0.007), packing density (P < 0.001) and Raymond grades II (P < 0.001) and III (P = 0.002). Conclusion Non-stent-assisted coil embolization, as well as packing density and Raymond grades II grade III are associated with recurrence after endovascular treatment of PcomA.
An exploratory study of undergraduate healthcare student perspectives regarding human papillomavirus and vaccine intent in India
Authors: Shetty Seemitha , Shetty Veena , Badiger Sanjeev , Shetty Avinash K 
Published: October 2021

Objective: Safe and effective human papillomavirus vaccines are available against cervical cancer and other human papillomavirus–associated diseases. Vaccine uptake is low in India given lack of universal vaccination programme. This exploratory study describes the medical, dental and nursing undergraduate student perspectives about human papillomavirus and intentions to receive the vaccine. Methods: Using a cross-sectional, explorative study design, we conducted two focus group discussions among a convenience sample of male (n = 11) and female (n = 9) student group aged ⩾18 years, respectively, at a medical college in South India. The focus group discussion sessions were recorded, transcribed and analysed using thematic content analysis. Results: Over half of the students showed adequate knowledge of cervical cancer and human papillomavirus. Medical students had much in-depth knowledge of cervical cancer, vaccine cost and its side effects compared to dental and nursing students. Human papillomavirus vaccine knowledge was relatively less among males compared to females; most male participants were unaware of the availability of the human papillomavirus vaccine. Intention to receive the vaccine was higher among females than males. All the participants had positive attitude in creating awareness in the community and making the vaccine cost-effective. Cultural concerns and high vaccine cost were cited major barriers for vaccine uptake. Suggestion of physician recommendation in promotion of human papillomavirus vaccine uptake was an emerging theme. Conclusion: Educating male students and those enrolled in dental and nursing courses about human papillomavirus vaccine, addressing cultural concerns and advocating provider recommendation for promoting vaccine uptake are potential strategies to improve future human papillomavirus vaccine intent among students and recommendations to patients in their role as future healthcare provider.
Baseline IL-6 is a biomarker for unfavourable tuberculosis treatment outcomes: a multisite discovery and validation study
Authors: Gupte Akshay N. , Kumar Pavan , Araújo-Pereira Mariana , Kulkarni Vandana , Paradkar Mandar , Pradhan Neeta , Menon Pradeep , Padmapriyadarsini Chandrasekaran , Hanna Luke-Elizabeth , Yogendra Shivakumar Shri Vijay Bala , Rockwood Neesha , Du Bruyn Elsa , Karyakarte Rajesh , Gaikwad Sanjay , Bollinger Robert , Golub Jonathan , Gupte Nikhil , Viswanathan Vijay , Wilkinson Robert J. , Mave Vidya , Babu Subash , Kornfeld Hardy , Andrade Bruno B. , Gupta Amita 
Published: October 2021

BackgroundBiomarkers of unfavourable tuberculosis (TB) treatment outcomes are needed to accelerate new drug and regimen development. Whether plasma cytokine levels can predict unfavourable TB treatment outcomes is unclear.MethodsWe identified and internally validated the association between 20a prioriselected plasma inflammatory markers and unfavourable treatment outcomes of failure, recurrence and all-cause mortality among adults with drug-sensitive pulmonary TB in India. We externally validated these findings in two independent cohorts of predominantly diabetic and HIV co-infected TB patients in India and South Africa, respectively.ResultsPre-treatment interferon-γ, interleukin (IL)-13 and IL-6 were associated with treatment failure in the discovery analysis. Internal validation confirmed higher pre-treatment IL-6 concentrations among failure cases compared with controls. External validation among predominantly diabetic TB patients found an association between pre-treatment IL-6 concentrations and subsequent recurrence and death. Similarly, external validation among predominantly HIV co-infected TB patients found an association between pre-treatment IL-6 concentrations and subsequent treatment failure and death. In a pooled analysis of 363 TB cases from the Indian and South African validation cohorts, high pre-treatment IL-6 concentrations were associated with higher risk of failure (adjusted OR (aOR) 2.16, 95% CI 1.08–4.33; p=0.02), recurrence (aOR 5.36, 95% CI 2.48–11.57; p<0.001) and death (aOR 4.62, 95% CI 1.95–10.95; p<0.001). Adding baseline IL-6 to a risk prediction model comprised of low body mass index, high smear grade and cavitation improved model performance by 15% (C-statistic 0.66versus0.76; p=0.02).ConclusionsPre-treatment IL-6 is a biomarker for unfavourable TB treatment outcomes. Future studies should identify optimal IL-6 concentrations for point-of-care risk prediction.
The Frail’BESTest: an adaptation of the “balance evaluation system test” for frail older adults; Concurrent validity, responsiveness, validity for fall prediction and detection of slower walkers
Authors: Kubicki A. , Laroche D. , Coquisart L. , Basile G. , Brika M. , Mourey F. 
Published: October 2021

Abstract
Background
The Frail’BESTest was developed in order to include frail older adults when they are using the BESTest. Recently, psychometrics properties (internal coherence, systems usefulness, complementarity and inter-rater reliability) of the Frail’BESTest were tested. To complete these analyses, this study will aim the assessment of its concurrent validity, responsiveness, predictive validity on falls occurrence, and slower walkers detection.

Methods
The correlation between the Frail’BESTest and the Gait Speed Test permitted to assess concurrent validity. The variation between the initial test score and the score obtained after the completion of a rehabilitation program was used to evaluate responsiveness with MANOVA analysis and standard response mean (SRM) calculation. Predictive validity was assessed with receiver-operating characteristic curves and area under the curve (AUC) analysis regarding falls occurrence. Slower walkers detection thresholds were computed by receiver-operating characteristic curves for the Frail’BESTest and the Tinetti test.

Results
The concurrent validity of the test was good (r = 0.74; p < 0.001). The Standard Error of measurement was at 2.81 points and the Minimal Detectable Change at 7.79 points for the total score of the Frail’BESTest. The SRM was at 0.41 for the Tinetti test and 0.56 for the Frail’BESTest. The AUC, computed according to fall occurrence, was at 0.71 for the Gait Speed test, 0.673 for the Tinetti test and 0.693 for the Frail’BESTest. Both the Tinetti (AUC = 0.87) and the Frail’BESTest (AUC = 0.88) were found suitable for tracking slower walkers.

Conclusion
Concurrent validity and responsiveness of the Frail’BESTest were good. As for the Tinetti and the Frail’BESTest, they were unable to predict efficiently falls occurrence in the tested sample. The Frail’BESTest seems enough sensitive to spot the slower walkers efficiently, using a 15/20 threshold method. The Frail’BESTest was found to be a valid and responsive clinical test, therefore it can be recommended as an outcome measure in clinical practice.
A cis-regulatory element promoting increased transcription at low temperature in cultured ectothermic Drosophila cells
Authors: Bai Yu , Caussinus Emmanuel , Leo Stefano , Bosshardt Fritz , Myachina Faina , Rot Gregor , Robinson Mark D. , Lehner Christian F. 
Published: October 2021

Abstract
Background
Temperature change affects the myriad of concurrent cellular processes in a non-uniform, disruptive manner. While endothermic organisms minimize the challenge of ambient temperature variation by keeping the core body temperature constant, cells of many ectothermic species maintain homeostatic function within a considerable temperature range. The cellular mechanisms enabling temperature acclimation in ectotherms are still poorly understood. At the transcriptional level, the heat shock response has been analyzed extensively. The opposite, the response to sub-optimal temperature, has received lesser attention in particular in animal species. The tissue specificity of transcriptional responses to cool temperature has not been addressed and it is not clear whether a prominent general response occurs. Cis-regulatory elements (CREs), which mediate increased transcription at cool temperature, and responsible transcription factors are largely unknown.

Results
The ectotherm Drosophila melanogaster with a presumed temperature optimum around 25 °C was used for transcriptomic analyses of effects of temperatures at the lower end of the readily tolerated range (14–29 °C). Comparative analyses with adult flies and cell culture lines indicated a striking degree of cell-type specificity in the transcriptional response to cool. To identify potential cis-regulatory elements (CREs) for transcriptional upregulation at cool temperature, we analyzed temperature effects on DNA accessibility in chromatin of S2R+ cells. Candidate cis-regulatory elements (CREs) were evaluated with a novel reporter assay for accurate assessment of their temperature-dependency. Robust transcriptional upregulation at low temperature could be demonstrated for a fragment from the pastrel gene, which expresses more transcript and protein at reduced temperatures. This CRE is controlled by the JAK/STAT signaling pathway and antagonizing activities of the transcription factors Pointed and Ets97D.

Conclusion
Beyond a rich data resource for future analyses of transcriptional control within the readily tolerated range of an ectothermic animal, a novel reporter assay permitting quantitative characterization of CRE temperature dependence was developed. Our identification and functional dissection of the pst_E1 enhancer demonstrate the utility of resources and assay. The functional characterization of this CoolUp enhancer provides initial mechanistic insights into transcriptional upregulation induced by a shift to temperatures at the lower end of the readily tolerated range.
COVID-19 underreporting and its impact on vaccination strategies
Authors: Albani Vinicius , Loria Jennifer , Massad Eduardo , Zubelli Jorge 
Published: October 2021

Abstract
Background
Underreporting cases of infectious diseases poses a major challenge in the analysis of their epidemiological characteristics and dynamical aspects. Without accurate numerical estimates it is difficult to precisely quantify the proportions of severe and critical cases, as well as the mortality rate. Such estimates can be provided for instance by testing the presence of the virus. However, during an ongoing epidemic, such tests’ implementation is a daunting task. This work addresses this issue by presenting a methodology to estimate underreported infections based on approximations of the stable rates of hospitalization and death.

Methods
We present a novel methodology for the stable rate estimation of hospitalization and death related to the Corona Virus Disease 2019 (COVID-19) using publicly available reports from various distinct communities. These rates are then used to estimate underreported infections on the corresponding areas by making use of reported daily hospitalizations and deaths. The impact of underreporting infections on vaccination strategies is estimated under different disease-transmission scenarios using a Susceptible-Exposed-Infective-Removed-like (SEIR) epidemiological model.

Results
For the considered locations, during the period of study, the estimations suggest that the number of infected individuals could reach 30% of the population of these places, representing, in some cases, more than six times the observed numbers. These results are in close agreement with estimates from independent seroprevalence studies, thus providing a strong validation of the proposed methodology. Moreover, the presence of large numbers of underreported infections can reduce the perceived impact of vaccination strategies in reducing rates of mortality and hospitalization.

Conclusions
pBy using the proposed methodology and employing a judiciously chosen data analysis implementation, we estimate COVID-19 underreporting from publicly available data. This leads to a powerful way of quantifying underreporting impact on the efficacy of vaccination strategies. As a byproduct, we evaluate the impact of underreporting in the designing of vaccination strategies.