bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hospital efficiency measurement in the west of Iran: data envelopment analysis and econometric approach
Authors: Yousefi Nayer Mohamad , Fazaeli Ali Akbar , Hamidi Yadollah 
Published: February 2022

Abstract
Objective
Measuring hospital efficiency is one of the way how to use resources.The optimal hospital performance is the goals of healthcare policymakers. This study aimed to the current study was conducted to evaluate the efficiency the current study was conducted to evaluate the efficiency and assess the association between hospital size and hospital area population with technical efficiency in public hospitals.

Methods
In this descriptive-analytical study, the statistical population consisted of 15 public hospitals in the west of Iran. First, the data envelopment analysis (DEA) method was used to evaluate technical efficiency. inputs included staff and beds, and outputs consisted of the number of surgeries, the number of patients, and the average length of stay. Then, according to the public ownership of all hospitals, their educational and therapeutic activities, as well as their size and population were considered as the environmental factor affecting efficiency. Thus, regression was applied to measure their effects on efficiency.

Results
The average technical efficiency of the studied hospitals, the average management efficiency, and the average efficiency of the scale were 0.935, 0.961, and 0.987, respectively. Out of the total evaluated hospitals, six and nine hospitals had an efficiency of less than one and one, respectively. Moreover, the size of the hospital and the population as the environment variable were significant in the Tobit model. Our regression demonstrated that although the size of the hospital is positively associated with its technical efficiency, the hospital population negatively affects hospital efficiency.

Conclusion
According to the size and area population of the hospitals, they decrease their inputs to maximize their efficacy by optimizing their surplus amounts. Tobit regression analysis concludes that hospital size and population covered by the hospital significant effect on hospitals' efficiency.
Controlled human exposure to diesel exhaust: results illuminate health effects of traffic-related air pollution and inform future directions
Authors: Long Erin , Carlsten Christopher 
Published: February 2022

AbstractAir pollution is an issue of increasing interest due to its globally relevant impacts on morbidity and mortality. Controlled human exposure (CHE) studies are often employed to investigate the impacts of pollution on human health, with diesel exhaust (DE) commonly used as a surrogate of traffic related air pollution (TRAP). This paper will review the results derived from 104 publications of CHE to DE (CHE-DE) with respect to health outcomes. CHE-DE studies have provided mechanistic evidence supporting TRAP’s detrimental effects on related to the cardiovascular system (e.g., vasomotor dysfunction, inhibition of fibrinolysis, and impaired cardiac function) and respiratory system (e.g., airway inflammation, increased airway responsiveness, and clinical symptoms of asthma). Oxidative stress is thought to be the primary mechanism of TRAP-induced effects and has been supported by several CHE-DE studies. A historical limitation of some air pollution research is consideration of TRAP (or its components) in isolation, limiting insight into the interactions between TRAP and other environmental factors often encountered in tandem. CHE-DE studies can help to shed light on complex conditions, and several have included co-exposure to common elements such as allergens, ozone, and activity level. The ability of filters to mitigate the adverse effects of DE, by limiting exposure to the particulate fraction of polluted aerosols, has also been examined. While various biomarkers of DE exposure have been evaluated in CHE-DE studies, a definitive such endpoint has yet to be identified. In spite of the above advantages, this paradigm for TRAP is constrained to acute exposures and can only be indirectly applied to chronic exposures, despite the critical real-world impact of living long-term with TRAP. Those with significant medical conditions are often excluded from CHE-DE studies and so results derived from healthy individuals may not apply to more susceptible populations whose further study is needed to avoid potentially misleading conclusions. In spite of limitations, the contributions of CHE-DE studies have greatly advanced current understanding of the health impacts associated with TRAP exposure, especially regarding mechanisms therein, with important implications for regulation and policy.
Incidence of calcaneal apophysitis (Sever’s disease) and return-to-play in adolescent athletes of a German youth soccer academy: a retrospective study of 10 years
Authors: Belikan Patrick , Färber Lars-Christopher , Abel Frédéric , Nowak Tobias E. , Drees Philipp , Mattyasovszky Stefan G. 
Published: February 2022

Abstract
Background
Calcaneal apophysitis, or Sever's disease, is the most common cause of heel pain in childhood and adolescence. It is regarded as an overuse syndrome. Studies on the incidence of calcaneal apophysitis in young athletes and their associated return-to-play time are lacking in the current literature. The aim of our current study was to identify the incidence of calcaneal apophysitis in professional youth soccer, the associated time to return-to-play, predisposing factors and their impact on time to return-to-play.

Methods
Retrospective evaluation of injury data gathered from a German youth soccer academy in the years 2009–2018. In total, 4326 injury cases in 612 players were included in the study. The diagnosis and the follow-up visits were carried out in a weekly consultation hour at the youth academy.

Results
During the observation period of 10 years, 22 cases of calcaneal apophysitis were detected. The incidence of calcaneal apophysitis per 100 athletes per year was found to be 0.36. The mean age of the affected athletes at the time of diagnosis was 11.8 ± 2.1 years (MW ± SD). The complaints were unilateral in 20 and bilateral in two cases. Three of the 22 detected cases of calcaneal apophysitis (13.6%) were recurrent injuries. The mean time to return-to-play of the affected athletes was 60.7 ± 64.9 days (MW ± SD). Athletes with recurrent complaints showed longer recovery time and time to return-to-play when compared to players with primary diagnosed disease. Our results could show that neither age nor body mass index at the time of diagnosis had an impact on time to return-to-play.

Conclusions
This is the first study investigating the incidence of calcaneal apophysitis and the associated time to return-to-play in youth elite soccer. Calcaneal apophysitis results in substantial time loss for the athletes. Further prospective clinical studies are required to fully understand the etiology and risk factors for calcaneal apophysitis and therefore develop preventive strategies.
A large-scale genome and transcriptome sequencing analysis reveals the mutation landscapes induced by high-activity adenine base editors in plants
Authors: Li Shaofang , Liu Lang , Sun Wenxian , Zhou Xueping , Zhou Huanbin 
Published: February 2022

Abstract
Background
The high-activity adenine base editors (ABEs), engineered with the recently-developed tRNA adenosine deaminases (TadA8e and TadA9), show robust base editing activity but raise concerns about off-target effects.

Results
In this study, we perform a comprehensive evaluation of ABE8e- and ABE9-induced DNA and RNA mutations in Oryza sativa. Whole-genome sequencing analysis of plants transformed with four ABEs, including SpCas9n-TadA8e, SpCas9n-TadA9, SpCas9n-NG-TadA8e, and SpCas9n-NG-TadA9, reveal that ABEs harboring TadA9 lead to a higher number of off-target A-to-G (A>G) single-nucleotide variants (SNVs), and that those harboring CRISPR/SpCas9n-NG lead to a higher total number of off-target SNVs in the rice genome. An analysis of the T-DNAs carrying the ABEs indicates that the on-target mutations could be introduced before and/or after T-DNA integration into plant genomes, with more off-target A>G SNVs forming after the ABEs had integrated into the genome. Furthermore, we detect off-target A>G RNA mutations in plants with high expression of ABEs but not in plants with low expression of ABEs. The off-target A>G RNA mutations tend to cluster, while off-target A>G DNA mutations rarely clustered.

Conclusion
Our findings that Cas proteins, TadA variants, temporal expression of ABEs, and expression levels of ABEs contribute to ABE specificity in rice provide insight into the specificity of ABEs and suggest alternative ways to increase ABE specificity besides engineering TadA variants.
An improved repertoire of splicing variants and their potential roles in Arabidopsis photomorphogenic development
Authors: Huang Chun-Kai , Lin Wen-Dar , Wu Shu-Hsing 
Published: February 2022

Abstract
Background
Light switches on the photomorphogenic development of young plant seedlings, allowing young seedlings to acquire photosynthetic capacities and gain survival fitness. Light regulates gene expression at all levels of the central dogma, including alternative splicing (AS) during the photomorphogenic development. However, accurate determination of full-length (FL) splicing variants has been greatly hampered by short-read RNA sequencing technologies.

Result
In this study, we adopt PacBio isoform sequencing (Iso-seq) to overcome the limitation of the short-read RNA-seq technologies. Normalized cDNA libraries used for Iso-seq allows for comprehensive and effective identification of FL AS variants. Our analyses reveal more than 30,000 splicing variant models from approximately 16,500 gene loci and additionally identify approximately 700 previously unannotated genes. Among the variants, approximately 12,000 represent new gene models. Intron retention (IR) is the most frequently observed form of variants, and many IR-containing AS variants show evidence of engagement in translation. Our study reveals the formation of heterodimers of transcription factors composed of annotated and IR-containing AS variants. Moreover, transgenic plants overexpressing the IR forms of two B-BOX DOMAIN PROTEINs exhibits light-hypersensitive phenotypes, suggesting their regulatory roles in modulating optimal light responses.

Conclusions
This study provides an accurate and comprehensive portrait of full-length transcript isoforms and experimentally confirms the presence of de novo synthesized AS variants that impose regulatory functions in photomorphogenic development in Arabidopsis.
Time to response for clinical and patient-reported outcomes in patients with psoriatic arthritis treated with tofacitinib, adalimumab, or placebo
Authors: Gladman Dafna D. , Coates Laura C. , Wu Joseph , Fallon Lara , Bacci Elizabeth D. , Cappelleri Joseph C. , Bushmakin Andrew G. , Helliwell Philip S. 
Published: February 2022

AbstractBackgroundThis study examined the time to clinically meaningful response in patients with active psoriatic arthritis treated with tofacitinib, adalimumab, or placebo switching to tofacitinib.MethodsData were from two phase 3 studies, OPAL Broaden (12 months) and OPAL Beyond (6 months). Patients received tofacitinib 5 or 10 mg twice daily (BID), adalimumab 40 mg once every 2 weeks (OPAL Broaden only), or placebo switching to tofacitinib 5 or 10 mg BID at month 3. Baseline to initial response time was according to pre-defined clinically meaningful criteria on Health Assessment Questionnaire-Disability Index (HAQ-DI; ≥ 0.35-point improvement), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F; ≥ 4-point improvement), Psoriatic Arthritis Disease Activity Score (PASDAS; post-baseline score ≤ 3.2 and > 1.6-point improvement from baseline), and minimal disease activity (MDA; meeting at least 5 of 7 criteria) composite.ResultsIn OPAL Broaden, median time to initial HAQ-DI score response was 29, 53, and 30 days in patients treated with tofacitinib 5 mg BID, tofacitinib 10 mg BID, or adalimumab, compared with 162 and 112 days in patients treated with placebo switching to tofacitinib 5 or 10 mg BID at month 3, respectively. Across studies, median time to initial FACIT-F total score response was shorter in patients receiving tofacitinib 5 mg BID (31 days) vs other groups (84–92 days). Median time to initial response was approximately 11 (MDA)/6–9 months (PASDAS) in tofacitinib/adalimumab groups in OPAL Broaden.ConclusionThis analysis demonstrates tofacitinib’s efficacy on most patient-reported and clinical endpoints over time and shows a shorter time to initial, clinically meaningful response in patients receiving tofacitinib vs patients switching from placebo to tofacitinib.Trial registrationClinicalTrials.gov, NCT01877668. Registered June 12, 2013.ClinicalTrials.gov, NCT01882439. Registered June 18, 2013.
A comparison between tau and amyloid-β cerebrospinal fluid biomarkers in chronic traumatic encephalopathy and Alzheimer disease
Authors: Turk Katherine W. , Geada Alexandra , Alvarez Victor E. , Xia Weiming , Cherry Jonathan D. , Nicks Raymond , Meng Gaoyuan , Daley Sarah , Tripodis Yorghos , Huber Bertrand R. , Budson Andrew E. , Dwyer Brigid , Kowall Neil W. , Cantu Robert C. , Goldstein Lee E. , Katz Douglas I. , Stern Robert A. , Alosco Michael L. , Mez Jesse , McKee Ann C. , Stein Thor D. 
Published: February 2022

Abstract
Background
Cerebrospinal fluid (CSF) tau and beta-amyloid levels in chronic traumatic encephalopathy (CTE), a disease which can be clinically indistinguishable from Alzheimer’s disease (AD), are largely unknown. We examined postmortem CSF analytes among participants with autopsy confirmed CTE and AD.

Methods
In this cross-sectional study 192 participants from the Boston University AD Research Center, VA-BU-CLF Center, and Framingham Heart Study (FHS) had post-mortem CSF collected at autopsy. Participants were divided into pathological groups based on AD and CTE criteria, with 61 CTE participants (18 low, 43 high stage), 79 AD participants (23 low, 56 intermediate to high), 11 participants with CTE combined with AD, and 41 participants lacking both CTE and AD neuropathology. The Meso Scale Discovery immunoassay system was utilized to measure amyloid-beta (Aβ1-40, Aβ1-42), total tau (t-tau), and phosphorylated tau (p-tau181 and p-tau231). CSF analytes were then compared across the pathological groups: no CTE/no AD (control), Low CTE, Low AD, High CTE, Intermediate/High AD, and AD+CTE.

Results
Among the Low disease state groups, the Low CTE group had significantly higher levels of p-tau231 versus the control group and compared to the Low AD group. The Low CTE group was also found to have significantly lower levels of Aβ1-42 compared to the control group. The high CTE group had higher levels of p-tau231 and lower levels of Aβ1-42 compared to Intermediate/High AD group.

Conclusions
Importantly, p-tau231 and Aβ1-42 were predictors of diagnosis of CTE vs. control and CTE vs. AD. Increased CSF p-tau231 is a promising potentially sensitive biomarker of CTE, and CSF Aβ1-42 needs further investigation in CTE.
Duplication and expression patterns of CYCLOIDEA-like genes in Campanulaceae
Authors: Tong Jingjing , Knox Eric B. , Morden Clifford W. , Cellinese Nico , Mossolem Fatima , Zubair Aarij S. , Howarth Dianella G. 
Published: February 2022

AbstractBackgroundCYCLOIDEA (CYC)-like transcription factors pattern floral symmetry in most angiosperms. In core eudicots, two duplications led to three clades ofCYC-like genes:CYC1,CYC2,andCYC3, with orthologs of theCYC2clade restricting expression dorsally in bilaterally symmetrical flowers. Limited data fromCYC3suggest that they also play a role in flower symmetry in some asterids. We examine the evolution of these genes in Campanulaceae, a group that contains broad transitions between radial and bilateral floral symmetry and 180° resupination (turning upside-down by twisting pedicle).ResultsWe identify here all three paralogousCYC-likeclades across Campanulaceae. Similar to other core eudicots, we show thatCamCYC2duplicated near the time of the divergence of the bilaterally symmetrical and resupinate Lobelioideae. However, in non-resupinate, bilaterally symmetrical Cyphioideae,CamCYC2appears to have been lost andCamCYC3duplicated, suggesting a novel genetic basis for bilateral symmetry in Cyphioideae. We additionally, utilized qRT-PCR to examine the correlation betweenCYC-like gene expression and shifts in flower morphology in four species of Lobelioideae. As expected,CamCYC2gene expression was dorsoventrally restricted in bilateral symmetrical flowers. However, because Lobelioideae have resupinate flowers, bothCamCYC2AandCamCYC2Bare highly expressed in the finally positioned ventral petal lobes, corresponding to the adaxial side of the flower relative to meristem orientation.ConclusionsOur sequences across Campanulaceae of all three of these paralogous groups suggests that radially symmetrical Campanuloideae duplicatedCYC1, Lobelioideae duplicatedCYC2and lostCYC3early in their divergence, and that Cyphioideae lostCYC2and duplicatedCYC3. This suggests a dynamic pattern of duplication and loss of major floral patterning genes in this group and highlights the first case of a loss ofCYC2in a bilaterally symmetrical group. We illustrate here thatCYCexpression is conserved along the dorsoventral axis of the flower even as it turns upside-down, suggesting that at least lateCYCexpression is not regulated by extrinsic factors such as gravity. We additionally show that while the pattern of dorsoventral expression of each paralog remains the same,CamCYC2Ais more dominant in species with shorter relative finally positioned dorsal lobes, andCamCYC2Bis more dominant in species with long dorsal lobes.
Subtyping of high grade serous ovarian carcinoma: histopathological and immunohistochemical approach
Authors: Khashaba Marwa , Fawzy Mohamed , Abdel-Aziz Azza , Eladawei Ghada , Nagib Reham 
Published: February 2022

Abstract
Background
High-grade serous ovarian carcinoma (HGSOC) is classified into four molecular subtypes; mesenchymal, proliferative, immunoreactive, and differentiated, with suggested different prognosis. Addressing the presence of histopathological and immunohistochemical differences in HGSOC that parallel the molecular subtypes can help in tailoring the management protocol to improve therapeutic response and patient outcome.

Methods
This retrospective study was conducted on 85 specimens for cases of HGSOC. Cases were classified according to histopathological findings into mesenchymal, proliferative, immunoreactive, and differentiated subtypes. Cases were immunostained with ER, PR, Ki67, CD8, E-cadherin, and vimentin.

Results
By applying histopathological data, cases were subdivided into 4 groups; mesenchymal type represented by 25 cases, proliferative type which included 14 cases, the immunoreactive type included 14 cases, and differentiated type represented by 32 cases; 13 of them had SET features and 19 had papillary architectural features. A significant correlation was found between Ki67 and proliferative subtype, as well as between CD8 and immunoreactive subtype. ER showed significantly higher expression in proliferative subtype in the group treated by primary debulking. CD8 showed a significant correlation with solid endometroid transitional (SET) pattern in the group that underwent interval debulking. In terms of prognosis, the shortest median progression-free survival (PFS) was for mesenchymal subtype, while the longest median PFS was for differentiated subtype with SET architectural pattern with statistically significant correlation. No correlation was found between any of the studied parameters and overall survival.

Conclusion
Histopathological features and immunohistochemistry can help to stratify HGSOC into prognostic distinct groups.
Classification of suicidal thoughts and behaviour in children: results from penalised logistic regression analyses in the Adolescent Brain Cognitive Development study
Authors: van Velzen Laura S. , Toenders Yara J. , Avila-Parcet Aina , Dinga Richard , Rabinowitz Jill A. , Campos Adrián I. , Jahanshad Neda , Rentería Miguel E. , Schmaal Lianne 
Published: February 2022

BackgroundDespite efforts to predict suicide risk in children, the ability to reliably identify who will engage in suicide thoughts or behaviours has remained unsuccessful.AimsWe apply a novel machine-learning approach and examine whether children with suicide thoughts or behaviours could be differentiated from children without suicide thoughts or behaviours based on a combination of traditional (sociodemographic, physical health, social–environmental, clinical psychiatric) risk factors, but also more novel risk factors (cognitive, neuroimaging and genetic characteristics).MethodThe study included 5885 unrelated children (50% female, 67% White, 9–11 years of age) from the Adolescent Brain Cognitive Development (ABCD) study. We performed penalised logistic regression analysis to distinguish between: (a) children with current or past suicide thoughts or behaviours; (b) children with a mental illness but no suicide thoughts or behaviours (clinical controls); and (c) healthy control children (no suicide thoughts or behaviours and no history of mental illness). The model was subsequently validated with data from seven independent sites involved in the ABCD study (n = 1712).ResultsOur results showed that we were able to distinguish the suicide thoughts or behaviours group from healthy controls (area under the receiver operating characteristics curve: 0.80 child-report, 0.81 for parent-report) and clinical controls (0.71 child-report and 0.76–0.77 parent-report). However, we could not distinguish children with suicidal ideation from those who attempted suicide (AUROC: 0.55–0.58 child-report; 0.49–0.53 parent-report). The factors that differentiated the suicide thoughts or behaviours group from the clinical control group included family conflict, prodromal psychosis symptoms, impulsivity, depression severity and history of mental health treatment.ConclusionsThis work highlights that mostly clinical psychiatric factors were able to distinguish children with suicide thoughts or behaviours from children without suicide thoughts or behaviours. Future research is needed to determine if these variables prospectively predict subsequent suicidal behaviour.
Yang-Mills instantons in an asymptotically locally flat background: Taub-NUT vs. Taub-Bolt
Authors: Radu E. 
Published: February 2022

Abstract
We present arguments for the existence of a one-parameter family of self-dual Yang-Mills instantons in the background of Taub-NUT and Taub-Bolt spaces. These solutions are finite everywhere and generically carry a non-integer Pontryagin charge. The Taub-NUT space configurations can be considered as interpolating (when varying the NUT parameter) between the Prasad-Sommerfield and BPST instantons.