bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 vaccination in patients with immune thrombocytopenia
Authors: Visser Chantal , Swinkels Maurice , van Werkhoven Erik D. , Croles F. Nanne , Noordzij-Nooteboom Heike S. , Eefting Matthijs , Last-Koopmans Suzanne M. , Idink Cecile , Westerweel Peter E. , Santbergen Bart , Jobse Pieter A. , Baboe Fazil ,   RECOVAC-IR Consortium, te Boekhorst Peter A. W. , Leebeek Frank W. G. , Levin Mark-David , Kruip Marieke J. H. A. , Jansen A. J. Gerard 
Published: December 2021

Abstract
Immune thrombocytopenia (ITP) is an acquired autoimmune disorder that is characterized by low platelet count and increased bleeding risk. COVID-19 vaccination has been described as a risk factor for de novo ITP, but the effects of COVID-19 vaccination in patients with ITP are unknown. We aimed to investigate the effects of COVID-19 vaccination in patients with ITP on platelet count, bleeding complications, and ITP exacerbation (≥50% decline in platelet count, or nadir platelet count &lt; 30 × 109/L with a &gt;20% decrease from baseline, or use of rescue therapy). Platelet counts in patients with ITP and healthy controls were collected immediately before and 1 and 4 weeks after the first and second vaccinations. Linear mixed-effects modeling was applied to analyze platelet counts over time. We included 218 patients with ITP (50.9% female; mean age, 55 years; and median platelet count, 106 × 109/L) and 200 healthy controls (60.0% female; mean age, 58 years; median platelet count, 256 × 109/L). Platelet counts decreased by 6.3% after vaccination. We did not observe any difference in decrease between the groups. Thirty patients with ITP (13.8%; 95% confidence interval [CI], 9.5-19.1) had an exacerbation and 5 (2.2%; 95% CI, 0.7-5.3) suffered from a bleeding event. Risk factors for ITP exacerbation were platelet count &lt; 50 × 109/L (odds ratio [OR], 5.3; 95% CI, 2.1-13.7), ITP treatment at time of vaccination (OR, 3.4; 95% CI, 1.5-8.0), and age (OR, 0.96 per year; 95% CI, 0.94-0.99). Our study highlights the safety of COVID-19 vaccination in patients with ITP and the importance of the close monitoring of platelet counts in a subgroup of patients with ITP. Patients with ITP with exacerbation responded well on therapy.
Emergency medicine in Brazil: historical perspective, current status, and future challenges
Authors: Oliveira J. e Silva Lucas , Herpich Henrique , Puls Henrique Alencastro , Myers Justin Guy , Schubert Daniel Ujakow Correa , Freitas Ana Paula , Santos Jule , Melo de Andrade Marcus Vinicius , Penna Guimarães Hélio 
Published: December 2021

Abstract
Background
Emergency medicine (EM) in Brazil has achieved critical steps toward its development in the last decades including its official recognition as a specialty in 2016. In this article, we worked in collaboration with the Brazilian Association of Emergency Medicine (ABRAMEDE) to describe three main aspects of EM in Brazil: (1) brief historical perspective; (2) current status; and (3) future challenges.

Main text
In Brazil, the first EM residency program was created in 1996. Only 20 years later, the specialty was officially recognized by national regulatory bodies. Prior to recognition, there were only 2 residency programs. Since then, 52 new programs were initiated. Brazil has now 54 residency programs in 16 of the 27 federative units. As of December 2020, 192 physicians have been board certified as emergency physicians in Brazil. The shortage of formal EM-trained physicians is still significant and at this point it is not feasible to have all Brazilian emergency care units and EDs staffed only with formally trained emergency physicians. Three future challenges were identified including the recognition of EM specialists in the house of Medicine, the need of creating a reliable training curriculum despite highly heterogeneous emergency care practice across the country, and the importance of fostering the development of academic EM as a way to build a strong research agenda and therefore increase the knowledge about the epidemiology and organization of emergency care.

Conclusion
Although EM in Brazil has accomplished key steps toward its development, there are several obstacles before it becomes a solid medical specialty. Its continuous development will depend on special attention to key challenges involving recognition, reliability, and research.
In-depth assembly of organ and development dissected Picrorhiza kurroa proteome map using mass spectrometry
Authors: Kumari Manglesh , Pradhan Upendra Kumar , Joshi Robin , Punia Ashwani , Shankar Ravi , Kumar Rajiv 
Published: December 2021

Abstract
Background
Picrorhiza kurroa Royle ex Benth. being a rich source of phytochemicals, is a promising high altitude medicinal herb of Himalaya. The medicinal potential is attributed to picrosides i.e. iridoid glycosides, which synthesized in organ-specific manner through highly complex pathways. Here, we present a large-scale proteome reference map of P. kurroa, consisting of four morphologically differentiated organs and two developmental stages.

Results
We were able to identify 5186 protein accessions (FDR < 1%) providing a deep coverage of protein abundance array, spanning around six orders of magnitude. Most of the identified proteins are associated with metabolic processes, response to abiotic stimuli and cellular processes. Organ specific sub-proteomes highlights organ specialized functions that would offer insights to explore tissue profile for specific protein classes. With reference to P. kurroa development, vegetative phase is enriched with growth related processes, however generative phase harvests more energy in secondary metabolic pathways. Furthermore, stress-responsive proteins, RNA binding proteins (RBPs) and post-translational modifications (PTMs), particularly phosphorylation and ADP-ribosylation play an important role in P. kurroa adaptation to alpine environment. The proteins involved in the synthesis of secondary metabolites are well represented in P. kurroa proteome. The phytochemical analysis revealed that marker compounds were highly accumulated in rhizome and overall, during the late stage of development.

Conclusions
This report represents first extensive proteomic description of organ and developmental dissected P. kurroa, providing a platform for future studies related to stress tolerance and medical applications.
Comparison between 5-aminolevulinic acid photodynamic diagnosis and narrow-band imaging for bladder cancer detection
Authors: Hagimoto Hiroki , Makita Noriyuki , Mine Yuta , Kokubun Hidetoshi , Murata Shiori , Abe Yohei , Kubota Masashi , Tsutsumi Naofumi , Yamasaki Toshinari , Kawakita Mutsushi 
Published: December 2021

Abstract
Background
To compare 5-aminolevulinic acid (5-ALA)-mediated photodynamic diagnosis (PDD) with narrow-band imaging (NBI) for cancer detection during transurethral resection of bladder tumour (TURBT).

Methods
Between June 2018 and October 2020, 114 patients and 282 lesions were included in the analysis. Patients were orally administered 5-ALA (20 mg/kg) 2 h before TURBT. The bladder was inspected with white light (WL), PDD, and NBI for each patient, and all areas positive by at least one method were resected or biopsied. The imaging data were then compared to the pathology results.

Results
The sensitivities of WL, PDD, and NBI for detecting urothelial carcinoma were 88.1%, 89.6%, and 76.2%, respectively. The specificity, positive predictive value, and negative predictive value for detecting urothelial carcinoma were 47.5%, 80.9%, and 61.3%, respectively, for WL; 22.5%, 74.5%, and 46.2%, respectively, for PDD; and 46.3%, 78.2%, and 43.5%, respectively, for NBI. PDD was significantly more sensitive than NBI for all lesions (p < 0.001) and carcinoma in situ (CIS) lesions (94.6% vs. 54.1%, p < 0.001).

Conclusions
PDD can increase the detection rate of bladder cancer, compared to NBI, by greater than 10%. Therefore, 100% of CIS lesions can be detected by adding PDD to WL.
Tocilizumab improves 28-day survival in hospitalized patients with severe COVID-19: an open label, prospective study
Authors: Karampitsakos Theodoros , Malakounidou Elli , Papaioannou Ourania , Dimakopoulou Vasilina , Zarkadi Eirini , Katsaras Matthaios , Tsiri Panagiota , Tsirikos Georgios , Georgiopoulou Vasiliki , Oikonomou Ioanna , Davoulos Christos , Velissaris Dimitrios , Sampsonas Fotios , Marangos Markos , Akinosoglou Karolina , Tzouvelekis Argyris 
Published: December 2021

Abstract
Background
Data on the safety and efficacy profile of tocilizumab in patients with severe COVID-19 needs to be enriched.

Methods
In this open label, prospective study, we evaluated clinical outcomes in consecutive patients with COVID-19 and PaO2/FiO2 < 200 receiving tocilizumab plus usual care versus usual care alone. Tocilizumab was administered at the time point that PaO2/FiO2 < 200 was observed. The primary outcome was 28-day mortality. Secondary outcomes included time to discharge, change in PaO2/FiO2 at day 5 and change in WHO progression scale at day 10.

Findings
Overall, 114 patients were included in the analysis (tocilizumab plus usual care: 56, usual care: 58). Allocation to usual care was associated with significant increase in 28-day mortality compared to tocilizumab plus usual care [Cox proportional-hazards model: HR: 3.34, (95% CI: 1.21–9.30), (p = 0.02)]. There was not a statistically significant difference with regards to hospital discharge over the 28 day period for patients receiving tocilizumab compared to usual care [11.0 days (95% CI: 9.0 to 16.0) vs 14.0 days (95% CI: 10.0–24.0), HR: 1.32 (95% CI: 0.84–2.08), p = 0.21]. ΔPaO2/FiO2 at day 5 was significantly higher in the tocilizumab group compared to the usual care group [42.0 (95% CI: 23.0–84.7) vs 15.8 (95% CI: − 19.4–50.3), p = 0.03]. ΔWHO scale at day 10 was significantly lower in the tocilizumab group compared to the usual care group (-0.5 ± 2.1 vs 0.6 ± 2.6, p = 0.005).

Conclusion
Administration of tocilizumab, at the time point that PaO2/FiO2 < 200 was observed, improved survival and other clinical outcomes in hospitalized patients with severe COVID-19 irrespective of systemic inflammatory markers levels.
Engineering Rhodosporidium toruloides for limonene production
Authors: Liu Sasa , Zhang Mengyao , Ren Yuyao , Jin Guojie , Tao Yongsheng , Lyu Liting , Zhao Zongbao K. , Yang Xiaobing 
Published: December 2021

Abstract
Background
Limonene is a widely used monoterpene in the production of food, pharmaceuticals, biofuels, etc. The objective of this work was to engineer Rhodosporidium toruloides as a cell factory for the production of limonene.

Results
By overexpressing the limonene synthase (LS), neryl pyrophosphate synthase (NPPS)/geranyl pyrophosphate synthase and the native hydroxy-methyl-glutaryl-CoA reductase (HMGR), we established a baseline for limonene production based on the mevalonate route in Rhodosporidium toruloides. To further enhance the limonene titer, the acetoacetyl-CoA thiolase/HMGR (EfMvaE) and mevalonate synthase (EfMvaS) from Enterococcus faecalis, the mevalonate kinase from Methanosarcina mazei (MmMK) and the chimeric enzyme NPPS-LS were introduced in the carotenogenesis-deficient strain. The resulting strains produced a maximum limonene titer of 393.5 mg/L.

Conclusion
In this study, we successfully engineered the carotenogenesis yeast R. toruloides to produce limonene. This is the first report on engineering R. toruloides toward limonene production based on NPP and the fusion protein SltNPPS-CltLS. The results demonstrated that R. toruloides is viable for limonene production, which would provide insights into microbial production of valuable monoterpenes.
Dentoskeletal effects of early class III treatment protocol based on timing of intervention in children
Authors: Nucci Ludovica , Costanzo Caterina , Carfora Marco , d’Apuzzo Fabrizia , Franchi Lorenzo , Perillo Letizia 
Published: December 2021

Abstract
Background
To detect the optimal timing of intervention based on different cervical vertebral maturation stage (CS1-2 vs. CS3-4) for the treatment of Class III malocclusion with early Class III protocol.

Methods
A total sample of 43 patients (23 females, 20 males) ranging between 7 and 13 years of age with dentoskeletal Class III malocclusion treated with the modified SEC III (Splints, Elastic and Chincup) protocol divided into two groups based on the cervical vertebral maturation stages (CS1-2 and CS3-4) was included in this retrospective observational longitudinal study. Patient compliance was assessed using a 2-point Likert scale. Statistical comparisons between the two groups were performed with independent sample t tests.

Results
No statistically significant differences for any of the cephalometric variables describing the baseline dentoskeletal features were found between the two groups except for the mandibular unit length that was significantly greater in the pubertal group (P = 0.005). The modified SEC III protocol produced favorable sagittal outcomes in both groups, whereas no statistically significant T1-T2 changes were found between the CS1-2 and CS3-4 groups for any of the angular and linear measurements. No significant differences were found in the prevalence rates of the degree of collaboration between the two groups (P = 1.000).

Conclusions
No significant differences between prepubertal and pubertal patients were found in the sagittal and vertical dentoskeletal changes with the modified SEC III protocol. Thus, this early Class III treatment produced similar favorable effects in growing subjects regardless of the cervical vertebral maturation stages from CS1 to CS4.
Prevalence and risk factors of burnout among Lebanese community pharmacists in the era of COVID-19 pandemic: results from the first national cross-sectional survey
Authors: Youssef Dalal , Youssef Janet , Hassan Hamad , Abou-Abbas Linda 
Published: December 2021

Abstract
Background
Community pharmacists (CPs) are increasingly facing occupational challenges as a result of the COVID-19 pandemic, putting them at high risk of burnout. This study aimed to assess the prevalence of burnout among Lebanese CPs during the COVID-19 pandemic and to identify its associated factors.

Methods
An online survey was conducted among Lebanese CPs between February 1st and March 30, 2021. Collected data included information on sociodemographic characteristics, exposure and work-related variables, the Copenhagen burnout inventory (CBI), and the COVID-19 threat perception scale. Prevalence of burnout was calculated. Multiple logistic regressions were performed to identify the factors associated with the three burnout domains.

Results
A total of 387 CPs participated in the survey. Of the total, 53.7% were females; and 43.2% were aged less than 40 years old. The prevalence of moderate-to-high personal, work-related and client-related burnout was 77.8%, 76.8, and 89.7%, respectively. Younger age, staff pharmacist, working more than 40 h per week, high perceived COVID-19 threat were associated with a moderate-to-high likelihood of burnout in all three domains. However, altruistically accepting the risks of caring for COVID-19 patients was the only variable that was associated with a lower likelihood of burnout in all three domains.

Conclusion
An alarming prevalence of personal, work-related and client-related burnout was revealed among Lebanese CPs. This study has many implications for practice and provides a framework for establishing policy interventions to reduce burnout levels among Lebanese CPs. Preventive strategies and interventions on individual and organizational basis are recommended.
Exercise Training Intensity and the Fitness-Fatness Index in Adults with Metabolic Syndrome: A Randomized Trial
Authors: Ramos Joyce S. , Dalleck Lance C. , Fennell Mackenzie , Martini Alex , Welmans Talita , Stennett Rebecca , Keating Shelley E. , Fassett Robert G. , Coombes Jeff S. 
Published: December 2021

Abstract
Background
Cardiorespiratory fitness and fatness (notably central obesity) are mediating factors of the metabolic syndrome (MetS) and consequent cardiovascular disease (CVD)/mortality risk. The fitness-fatness index (FFI) combines these factors and has been reported to be a better indicator of CVD and all-cause mortality risk, beyond the capacity of either fitness or fatness alone.

Objective
This study sought to investigate the effects of different exercise intensities on FFI in adults with MetS.

Methods
This was a sub-study of the ‘Exercise in the prevention of Metabolic Syndrome’ (EX-MET) multicentre trial. Ninety-nine adults diagnosed with MetS according to the International Diabetes Federation criteria were randomized to one of the following 16-week exercise interventions: i) moderate-intensity continuous training (MICT) at 60–70% HRpeak for 30 min/session (n = 34, 150 min/week); ii) 4 × 4 min bouts of high-intensity interval training at 85–95% HRpeak, interspersed with 3-min active recovery at 50–70% HRpeak (n = 34, 38 min/session, 114 min/week); and iii) 1 × 4 min bout of HIIT at 85–95% HRpeak (n = 31, 17 min/session, 51 min/week). Cardiorespiratory fitness (peak oxygen uptake, V̇O2peak) was determined via indirect calorimetry during maximal exercise testing and fatness was the ratio of waist circumference-to-height (WtHR). FFI was calculated as V̇O2peak in metabolic equivalents (METs) divided by WtHR. A clinically meaningful response to the exercise intervention was taken as a 1 FFI unit increase.

Results
Seventy-seven participants completed pre and post testing to determine FFI. While there was no significant between group difference (p = 0.30), there was a small group x time interaction effect on FFI [F(2, 73) = 1.226; η2 = 0.01], with numerically greater improvements following HIIT (4HIIT, + 16%; 1HIIT, + 11%) relative to MICT (+ 7%). There was a greater proportion of participants who had a clinically meaningful change in FFI following high-volume HIIT (60%, 15/25) and low-volume HIIT (65%, 17/26) compared to MICT (38%, 10/26), but with no significant between-group difference (p = 0.12). A similar trend was found when a sub-analysis comparing the FFI between those with type 2 diabetes (MICT, 33%, 3/9; high-volume HIIT, 64%, 7/11; and low-volume HIIT, 58%, 7/12) and without type 2 diabetes (MICT, 41%, 7/17; high-volume HIIT, 57%, 8/14; low-volume HIIT, 71%, 10/14).

Conclusion
Although there were no statistically significant differences detected between groups, this study suggests that the response to changes in FFI in adults with MetS may be affected by exercise intensity, when numerical differences between exercise groups are considered. Further research is warranted.
Trial registration number and date of registration: ClinicalTrials.gov NCT01676870; 31/08/2012.
Modeling the Cost-Effectiveness of Adjuvant Chemotherapy for Stage III Colon Cancer in South African Public Hospitals
Authors: Pumpalova Yoanna , Rogers Alexandra M. , Tan Sarah Xinhui , Herbst Candice-lee , Ruff Paul , Neugut Alfred I. , Hur Chin 
Published: December 2021

PURPOSE Cancer incidence is rising in low- and middle-income countries, where resource constraints often complicate therapeutic decisions. Here, we perform a cost-effectiveness analysis to identify the optimal adjuvant chemotherapy strategy for patients with stage III colon cancer treated in South African (ZA) public hospitals. METHODS A decision-analytic Markov model was developed to compare lifetime costs and outcomes for patients with stage III colon cancer treated with six adjuvant chemotherapy regimens in ZA public hospitals: fluorouracil, leucovorin, and oxaliplatin for 3 and 6 months; capecitabine and oxaliplatin (CAPOX) for 3 and 6 months; capecitabine for 6 months; and fluorouracil/leucovorin for 6 months. Transition probabilities were derived from clinical trials to estimate risks of toxicity, disease recurrence, and survival. Societal costs and utilities were obtained from literature. The primary outcome was the incremental cost-effectiveness ratio in international dollars (I$) per disability-adjusted life-year (DALY) averted, compared with no therapy, at a willingness-to-pay (WTP) threshold of I$13,006.56. RESULTS CAPOX for 3 months was cost-effective (I$5,381.17 and 5.74 DALYs averted) compared with no adjuvant chemotherapy. Fluorouracil, leucovorin, and oxaliplatin for 6 months was on the efficiency frontier with 5.91 DALYs averted but, with an incremental cost-effectiveness ratio of I$99,021.36/DALY averted, exceeded the WTP threshold. CONCLUSION In ZA public hospitals, CAPOX for 3 months is the cost-effective adjuvant treatment for stage III colon cancer. The optimal strategy in other settings may change according to local WTP thresholds. Decision analytic tools can play a vital role in selecting cost-effective cancer therapeutics in resource-constrained settings.
Identification of Genetic Risk Factors for Familial Urinary Bladder Cancer: An Exome Sequencing Study
Authors: Pemov Alexander , Wegman-Ostrosky Talia , Kim Jung , Koutros Stella , Douthitt Brenna , Jones Kristine , Zhu Bin , Baris Dalsu , Schwenn Molly , Johnson Alison , Karagas Margaret R. , Carter Brian D. , McCullough Marjorie L. , Landi Maria Teresa , Freedman Neal D. , Albanes Demetrius , Silverman Debra T. , Rothman Nathaniel , Caporaso Neil E. , Greene Mark H. , Fraumeni Joseph F. , Stewart Douglas R. 
Published: December 2021

PURPOSE Previous studies have shown an approximately two-fold elevation in the relative risk of urinary bladder cancer (UBC) among people with a family history that could not be entirely explained by shared environmental exposures, thus suggesting a genetic component in its predisposition. Multiple genome-wide association studies and recent gene panel sequencing studies identified several genetic loci that are associated with UBC risk; however, the list of UBC-associated variants and genes is incomplete. MATERIALS AND METHODS We exome sequenced eight patients from three multiplex UBC pedigrees and a group of 77 unrelated familial UBC cases matched to 241 cancer-free controls. In addition, we examined pathogenic germline variation in 444 candidate genes in 392 The Cancer Genome Atlas UBC cases. RESULTS In the pedigrees, segregating variants were family-specific although the identified genes clustered in common pathways, most notably DNA repair ( MLH1 and MSH2) and cellular metabolism ( IDH1 and ME1). In the familial UBC group, the proportion of pathogenic and likely pathogenic variants was significantly higher in cases compared with controls ( P = .003). Pathogenic and likely pathogenic variant load was also significantly increased in genes involved in cilia biogenesis ( P = .001). In addition, a pathogenic variant in CHEK2 (NM_007194.4:c.1100del; p.T367Mfs*15) was over-represented in cases (variant frequency = 2.6%; 95% CI, 0.71 to 6.52) compared with controls (variant frequency = 0.21%; 95% CI, 0.01 to 1.15), but was not statistically significant. CONCLUSION These results point to a complex polygenic predisposition to UBC. Despite heterogeneity, the genes cluster in several biologically relevant pathways and processes, for example, DNA repair, cilia biogenesis, and cellular metabolism. Larger studies are required to determine the importance of CHEK2 in UBC etiology.