bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of everolimus for recurrent or progressive pediatric ependymoma
Authors: Bowers Daniel C , Rajaram Veena , Karajannis Matthias A , Gardner Sharon L , Su Jack Meng-Fen , Baxter Patricia , Partap Sonia , Klesse Laura J 
Published: February 2023

AbstractBackgroundPreclinical studies have suggested that mTOR pathway signaling may be a potential therapeutic target for childhood ependymoma.MethodsA phase II clinical trial (ClinicalTrials.gov identifier: NCT02155920) of single-agent everolimus was performed to test the hypothesis that mTOR pathway inhibition would result in tumor responses for children with recurrent and/or progressive ependymomas.ResultsEleven subjects [sex: 4 females (36.4%); median age: 8 years (range: 2-15 years); race: 9 white; prior therapies: median 6 (range: 3-9)] were enrolled on the study. Ten primary tumors were located in the posterior fossa and one primary tumor was located in the spinal cord. Eight of 9 tumors were PF-A subtype epenydmomas. All subjects were treated with oral everolimus 4.5 mg/m2/day (each cycle = 28 days) that was titrated to achieve serum trough levels of 5-15 ng/ml. Overall, everolimus was well tolerated; except for a single event of grade 3 pneumonia, all adverse events were grade 1-2. No objective tumor responses were observed. Participating subjects experienced tumor progression and discontinued therapy after a median of 2 cycles of therapy (1 cycle = 2; 2 cycles = 6; 3, 4, and 8 cycles = 1 each).ConclusionsEverolimus does not appear to have activity for children with recurrent or progressive PF-A ependymoma.
Genomic decoding of breeding history to guide breeding-by-design in rice
Authors: Chen Zhuo , Bu Qingyun , Liu Guifu , Wang Maoqing , Wang Hongru , Liu Huazhao , Li Xiufeng , Li Hong , Fang Jun , Liang Yan , Teng Zhenfeng , Kang Sai , Yu Hong , Cheng Zhukuan , Xue Yongbiao , Liang Chengzhi , Tang Jiuyou , Li Jiayang , Chu Chengcai 
Published: February 2023

ABSTRACTDeciphering the intrinsic molecular logic of empirical crop breeding from a genomic perspective is a decisive prerequisite for breeding-by-design (BbD), but remains not well established. Here, we decoded the historical features of past rice breeding by phenotyping and haplotyping 546 accessions covering the majority of cultivars bred in the history of Northeast China (NEC). We revealed that three groups founded the genetic diversities in NEC rice with distinct evolution patterns and traced and verified the breeding footprints to known or genome-wide association study (GWAS)-detected quantitative trait loci (QTLs), or introgressions from indica sub-species with chronological changes in allele frequencies. Then we summarized a rice breeding trend/principle in NEC, and combined with the successful example in breeding and application of Zhongkefa5 to demonstrate the guiding value of our conclusion for BbD in practice. Our study provides a paradigm for decoding the breeding history of a specific crop to guide BbD, which may have implications in different crop breeding.
Eczema Monkeypoxicum in a Female Patient With Atopic Dermatitis
Authors: Napoli Emma , Frizzell Madeline , Gravell Clark , Vallejo Sergio , Theodore Shasta , Chen Karen , Siddiqui Huma , Dunn Justin , Marrufo Dora , Cadena Jose , Danaher Patrick J 
Published: February 2023

AbstractA female patient with atopic dermatitis who had recently received a tattoo presented with severe right ear pain and several vesiculopustular lesions. Over 1 week, she developed approximately 80 widely distributed lesions. Laboratory testing confirmed mpox (previously monkeypox) virus, and no further lesions developed after initiation of oral tecovirimat.
Polysulfide metabolizing enzymes influence SqrR-mediated sulfide-induced transcription by impacting intracellular polysulfide dynamics
Authors: Shimizu Takayuki , Ida Tomoaki , Antelo Giuliano T , Ihara Yuta , Fakhoury Joseph N , Masuda Shinji , Giedroc David P , Akaike Takaaki , Capdevila Daiana A , Masuda Tatsuru 
Published: February 2023

Abstract
Sulfide plays essential roles in controlling various physiological activities in almost all organisms. Although recent evidence has demonstrated that sulfide is endogenously generated and metabolized into polysulfides inside the cells, the relationship between polysulfide metabolism and polysulfide-sensing mechanisms is not well understood. To better define this interplay between polysulfide metabolism and sensing in cells, we investigated the role of polysulfide-metabolizing enzymes such as sulfide:quinone oxidoreductase (SQR) on the temporal dynamics of cellular polysulfide speciation and on the transcriptional regulation by the persulfide-responsive transcription factor SqrR in Rhodobacter capsulatus. We show that disruption of the sqr gene resulted in the loss of SqrR repression by exogenous sulfide at longer culture times, which impacts the speciation of intracellular polysulfides of Δsqr vs. wild-type strains. Both the attenuated response of SqrR and the change in polysulfide dynamics of the Δsqr strain is fully reversed by the addition to cells of cystine-derived polysulfides, but not by glutathione disulfide (GSSG)-derived polysulfides. Furthermore, cysteine persulfide (CysSSH) yields a higher rate of oxidation of SqrR relative to glutathione persulfide (GSSH), which leads to DNA dissociation in vitro. The oxidation of SqrR was confirmed by a mass spectrometry-based kinetic profiling strategy that showed distinct polysulfide-crosslinked products obtained with CysSSH vs. GSSH. Taken together, these results establish a novel association between the metabolism of polysulfides and the mechanisms for polysulfide sensing inside the cells.
Vitamin D status in ANCA-associated vasculitis
Authors: Doubelt Irena , Cuthbertson David , Carette Simon , Khalidi Nader A , Koening Curry L , Langford Carol , McAlear Carol A , Moreland Larry W , Monach Paul , Seo Philip , Specks Ulrich , Warrington Kenneth J , Merkel Peter A , Pagnoux Christian 
Published: February 2023

AbstractObjectiveVitamin D might participate in the pathogenesis of several immune-mediated diseases, but few related data are available for ANCA-associated vasculitis (AAV). In this study, we analysed the association between vitamin D status and disease in patients with AAV.MethodsSerum levels of 25(OH)D2/3 were measured in 125 randomly selected patients with AAV [granulomatosis with polyangiitis (n = 50), eosinophilic granulomatosis with polyangiitis (n = 50) or microscopic polyangiitis (n = 25)] enrolled in the Vasculitis Clinical Research Consortium Longitudinal Studies at the time of enrolment and a subsequent relapse visit. Sufficient, insufficient and deficient vitamin D status were defined as 25(OH)D3 levels &gt;30, 20–30 and ˂20 ng/ml, respectively.ResultsSeventy of 125 patients (56%) were female, with a mean age of 51.5 (16) years at diagnosis; 84 (67%) were ANCA positive. Mean 25(OH)D was 37.6 (16) ng/ml, with vitamin D deficiency in 13 (10.4%) and insufficiency in 26 (20.8%). In univariate analysis, lower vitamin D status was associated with male sex (P = 0.027) and disease activity (P = 0.047). In univariate and multivariate analyses, deficient vitamin D status was associated with disease activity (P = 0.015). Mean 25(OH)D status in the 21 patients with a subsequent relapse did not differ between baseline and relapse visit [37.8 (16) vs 38.0 (10) ng/ml, respectively; P = 0.92].ConclusionMost patients with AAV have sufficient 25(OH)D levels, although those with lower vitamin D status were more likely to be male and to have active disease. Whether optimization of vitamin D status alters disease manifestations or activity in AAV remains to be determined.Trial RegistrationVasculitis Clinical Research Consortium (VCRC) Longitudinal Study (LS), NCT00315380, https://clinicaltrials.gov/ct2/show/NCT00315380
Surgical Site Infection After Primary Spinal Fusion Surgery for Adolescent Idiopathic Scoliosis
Authors: Rudic Theodore N. , Althoff Alyssa D. , Kamalapathy Pramod , Bachmann Keith R. 
Published: February 2023

Study Design.
Retrospective review.

Objective.
The purpose of this study was to quantify the incidence and factors associated with surgical site infection (SSI) in pediatric patients undergoing spinal fusion for adolescent idiopathic scoliosis (AIS).

Summary of Background Data.
Infection is a morbid complication after spinal fusion. The incidence of SSI after pediatric spinal fusion is likely underestimated; the use of a national database allows for a comprehensive assessment of this rare outcome.

Materials and Methods.
The PearlDiver Database was used to identify AIS patients who underwent primary instrumented spinal fusion between 2010 and 2019 and relevant patient records were queried to identify infections within 7, 30, and 90 postoperative days. Patients with nonidiopathic scoliosis were excluded. Logistic regression was used to evaluate risk factors associated with postoperative infection.

Results.
Out of 9801 patients who underwent primary fusion for AIS, 44 patients (0.4%) developed an infection within 7 postoperative days. The 30 days and 90 days incidences were 1.9% and 2.7%, respectively. Within 90 days, 154 (57.7%) of the patients with infection had undergone reoperation, of whom 72 underwent multiple reoperations. Obesity and male sex (P < 0.05) were significantly associated with postoperative infection. The length of fusion was not a significant factor in the development of SSI (P > 0.05). Eleven patients underwent an operation requiring hardware removal within 90 days. There were no significant factors associated with those undergoing hardware removal compared with those undergoing surgical debridement.

Conclusions.
The study identified a 2.7% 90 days incidence of SSI after posterior spinal fusion for AIS, with 57.7% of all infections requiring a return to the operating room. Preoperative patient-related characteristics associated with increased risk of postoperative SSI were male sex and obesity. The current study can be used to provide preoperative counseling regarding the risk of this postoperative complication.

Level of Evidence.
Level III.
Annexin A2 Loss After Cardiopulmonary Bypass and Development of Acute Postoperative Respiratory Dysfunction in Children
Authors: Hsing Deyin D. , Stock Arabela C. , Greenwald Bruce M. , Bacha Emile A. , Flynn Patrick A. , Carroll Sheila J. , Dayton Jeffrey D. , Prockop Susan E. , Qiu Yuqing , Almeida Dena , Tamura Shoran , Hajjar Katherine A. 
Published: February 2023

IMPORTANCE AND OBJECTIVES:
The primary objective of this study was to determine whether expression of the multifunctional and adherens junction-regulating protein, annexin A2 (A2), is altered following cardiopulmonary bypass (CPB). A secondary objective was to determine whether depletion of A2 is associated with post-CPB organ dysfunction in children.

DESIGN:
In a prospective, observational study conducted over a 1-year period in children undergoing cardiac surgery requiring CPB, we analyzed A2 expression in peripheral blood mononuclear cells at different time points. We then assessed the relationship of A2 expression with organ function at each time point in the early postoperative period.

SETTING:
Twenty-three-bed mixed PICU in a tertiary academic center.

PARTICIPANTS:
Patients 1 month to 18 years old undergoing cardiac surgery requiring CPB.

MEAN OUTCOME MEASUREMENTS AND RESULTS:
We analyzed A2 expression in 22 enrolled subjects (n = 9, 1–23 mo old; n = 13, 2–18 yr old) and found a proteolysis-mediated decline in intact A2 immediately after bypass (p = 0.0009), reaching a median of 4% of baseline at 6 hours after bypass (p < 0.0001), and recovery by postoperative day 1. The degree of A2 depletion immediately after bypass in 1–23-month-olds correlated strongly with the extent of organ dysfunction, as measured by PICU admission Vasoactive-Ventilation-Renal (p = 0.004) and PEdiatric Logistic Organ Dysfunction-2 (p = 0.039) scores on postoperative day 1. A2 depletion immediately after bypass also correlated with more protracted requirement for both respiratory support (p = 0.007) and invasive ventilation (p = 0.013) in the 1–23-month-olds.

CONCLUSIONS AND RELEVANCE:
The degree of depletion of A2 following CPB correlates with more severe organ dysfunction, especially acute respiratory compromise in children under 2 years. These findings suggest that loss of A2 may contribute to pulmonary microvascular leak in young children following CPB.
Obesity Paradox and Functional Outcomes in Sepsis: A Multicenter Prospective Study
Authors: Yeo Hye Ju , Kim Tae Hwa , Jang Jin Ho , Jeon Kyeongman , Oh Dong Kyu , Park Mi Hyeon , Lim Chae-Man , Kim Kipoong , Cho Woo Hyun ,   on behalf of the Korean Sepsis Alliance (KSA) Investigators
Published: February 2023

OBJECTIVES:
In Asian populations, the correlation between sepsis outcomes and body mass is unclear. A multicenter, prospective, observational study conducted between September 2019 and December 2020 evaluated obesity’s effects on sepsis outcomes in a national cohort.

SETTING:
Nineteen tertiary referral hospitals or university-affiliated hospitals in South Korea.

PATIENTS:
Adult patients with sepsis (n = 6,424) were classified into obese (n = 1,335) and nonobese groups (n = 5,089).

MEASUREMENTS AND RESULTS:
Obese and nonobese patients were propensity score-matched in a ratio of 1:1. Inhospital mortality was the primary outcome. After propensity score matching, the nonobese group had higher hospital mortality than the obese group (25.3% vs 36.7%; p < 0.001). The obese group had a higher home discharge rate (70.3% vs 65.2%; p < 0.001) and lower median Clinical Frailty Scale (CFS) (4 vs 5; p = 0.007) at discharge than the nonobese group, whereas the proportion of frail patients at discharge (CFS ≥ 5) was significantly higher in the nonobese group (48.7% vs 54.7%; p = 0.011). Patients were divided into four groups according to the World Health Organization body mass index (BMI) classification and performed additional analyses. The adjusted odds ratio of hospital mortality and frailty at discharge for underweight, overweight, and obese patients relative to normal BMI was 1.25 (p = 0.004), 0.58 (p < 0.001), and 0.70 (p = 0.047) and 1.53 (p < 0.001), 0.80 (p = 0.095), and 0.60 (p = 0.022), respectively.

CONCLUSIONS:
Obesity is associated with higher hospital survival and functional outcomes at discharge in Asian patients with sepsis.
Obstructive sleep apnea and cardiovascular events in acute coronary syndrome: a meta-analysis
Authors: Tong Jiangtao , Yu Qian , Li Yuan , Du Jianbo , Qiu Jian 
Published: February 2023

Objective
Obstructive sleep apnea (OSA) in patients with the acute coronary syndrome (ACS) were at high risk for cardiovascular events, but the results are currently inconclusive. We aimed to conduct a systematic review to determine the incidence of cardiovascular events among ACS patients with OSA by a meta-analysis of observational studies.

Methods
PubMed, Embase, and Cochrane Library were searched for studies related to the association between OSA and the risk of cardiovascular events in patients with ACS. Risk of bias in observational studies was assessed according to the Risk Of Bias In the Non-randomized Studies-Of Interventions tool.
We performed a meta-analysis using a random-effects model to calculate estimates of pooled hazard ratios (HR) with 95% confidence intervals (CI), and heterogeneity was assessed using the statistics.

Results
A total of 12 studies evaluating ACS patients with OSA were included in the meta-analysis. OSA was related to the increased risk of MACE (HR = 2.2; 95% CI, 1.274–3.805, I
2 = 76.1%). The effect of OSA on MACCE (HR = 1.921; 95% CI, 1.45–2.546; I
2 = 19.1%) and readmission for unstable angina (HR = 3.137, 95% CI, 1.06–9.283; I
2 = 52.4%) were statistically significant in the pooled analysis. All of the outcomes in the included studies had a serious risk of bias and the Grading of Recommendation, Assessment, Development, and Evaluation evidence level of all the evaluation results were very low.

Conclusions
OSA was associated with a significant increase in the risk of cardiovascular events for patients with ACS. Additional randomized controlled trial studies are required to confirm the results and to prove the treatment of OSA can change the prognosis.
Meta-analysis of the effect of colchicine on C-reactive protein in patients with acute and chronic coronary syndromes
Authors: Alam Mustafa , Kontopantelis Evangelos , Mamas Mamas A. , Savinova Olga V. , Jhaveri Amit , Siddiqui Emaad , Jhamnani Sunny 
Published: February 2023

Objective
The anti-inflammatory drug colchicine has recently shown benefits in the prevention of major adverse cardiovascular events (MACE) in patients with the acute coronary syndrome (ACS) and chronic coronary syndromes (CCS). This meta-analysis focuses on understanding Colchicine’s effects on the high-sensitivity C-reactive protein (hs-CRP) to provide mechanistic insight to explain its clinical event reduction.

Methods
A computerized search of MEDLINE was conducted to retrieve journal articles with studies performed on humans from 1 January 2005 to 1 January 2022, using keywords: ‘Colchicine AND Coronary’, ‘Colchicine AND CRP’, and ‘Colchicine AND Coronary Artery Disease’. Studies were included if they measured hs-CRP changes from baseline, and colchicine or placebo were given to patients with ACS or CCS.

Results
Thirteen studies with a biomarker subgroup population of 1636 patients were included in the hs-CRP meta-analysis. Of those 13 studies, 8 studies with a total population of 6016 reported clinical events defined as myocardial infarction (MI), stroke, cardiovascular death, periprocedural MI, repeat angina after PCI and repeat revascularization. Multivariate analysis revealed a weak negative correlation of −0.1056 (P = 0.805) between change in CRP and clinical events. Overall, colchicine treatment resulted in a greater reduction in hs-CRP levels compared with placebo (Mean Difference: -1.59; 95% Confidence Interval, −2.40 to −0.79, P = 0.0001) and clinical events (Odds Ratio: 0.78; 95% Confidence Interval 0.64 to 0.95, P = 0.01)

Conclusion
Colchicine therapy is associated with a reduction in hs-CRP and clinical events in patients with ACS and CCS. This finding supports colchicine’s anti-inflammatory efficacy via CRP reduction to explain its clinical benefit.
Intracoronary thrombus assessment with cardiac computed tomography angiography in a deferred stenting strategy: the MATURE prospective study (MSCT to Assess ThrombUs REsolution)
Authors: Osinalde Eduardo Pozo , Bastante Teresa , Cecconi Alberto , Muñiz Álvaro Montes , García-Guimaraes Marcos , Rivero Fernando , Rojas-González Antonio , Olivera María José , Salamanca Jorge , de Isla Leopoldo Pérez , De Agustín Jose Alberto , Caballero Paloma , Torres Rio Aguilar , Jiménez-Borreguero Luis Jesús , Alfonso Fernando 
Published: February 2023

Background
Cardiac computed tomography angiography (CCTA) is precise in noninvasive coronary atherosclerosis characterization but its value in the diagnosis of intracoronary thrombus remains unknown. Therefore, our aim was to evaluate CCTA for intracoronary thrombus and stenosis detection in patients with acute coronary syndromes with high thrombus burden selected for a deferred stenting strategy.

Methods
We systematically performed a CCTA in consecutive patients following a deferred stenting strategy, 24 h before the scheduled repeated coronary angiography including optical coherence tomography (OCT) imaging. Intracoronary thrombus and residual stenosis were blindly and independently evaluated by both techniques. Agreement was determined per lesion using the weighted Kappa (K) coefficient and absolute intraclass correlation coefficient (ICC). A stratified analysis according to OCT-detected thrombus burden was also performed.

Results
Thirty lesions in 28 consecutive patients were analyzed. Concordance between CCTA and repeated coronary angiography in thrombus detection was good (K = 0.554; P < 0.001), but both showed poor agreement with OCT. CCTA needed >11.5% thrombus burden on OCT to obtain adequate diagnostic accuracy. The lesions detected by angiography were more frequently classified as red thrombus (76.5 vs. 33.3%; P = 0.087) on OCT. CCTA showed an excellent concordance with coronary angiography in diameter measurement (ICC = 0.85; P < 0.001) and was able to identify all the patients with severe residual stenosis.

Conclusions
Although CCTA showed just a good concordance with angiography in intracoronary thrombus detection, the agreement in residual stenosis was excellent. Thus, in patients with a high-thrombus burden selected for a deferred stenting strategy CCTA may substitute repeat angiography.
Gut–lung crosstalk during critical illness
Authors: Nath Sridesh , Kitsios Georgios D. , Bos Lieuwe D.J. 
Published: February 2023

Purpose of review
Study of organ crosstalk in critical illness has uncovered complex biological communication between different organ systems, but the role of microbiota in organ crosstalk has received limited attention. We highlight the emerging understanding of the gut–lung axis, and how the largest biomass of the human body in the gut may affect lung physiology in critical illness.

Recent findings
Disruption of healthy gut microbial communities and replacement by disease-promoting pathogens (pathobiome) generates a maladaptive transmitter of messages from the gut to the lungs, connected via the portal venous and the mesenteric lymphatic systems. Gut barrier impairment allows for microbial translocation (living organisms or cellular fragments) to the lungs. Host-microbiota interactions in the gut mucosa can also impact lung physiology through microbial metabolite secretion or host-derived messengers (hormones, cytokines or immune cells). Clinical examples like the prevention of ventilator-associated pneumonia by selective decontamination of the digestive tract show that the gut–lung axis can be manipulated therapeutically.

Summary
A growing body of evidence supports the pathophysiological relevance of the gut–lung axis, yet we are only at the brink of understanding the therapeutic and prognostic relevance of the gut microbiome, metabolites and host-microbe interactions in critical illness.
Ventilatory targets following brain injury
Authors: Taran Shaurya , Wahlster Sarah , Robba Chiara 
Published: February 2023

Purpose of review
Recent studies have focused on identifying optimal targets and strategies of mechanical ventilation in patients with acute brain injury (ABI). The present review will summarize these findings and provide practical guidance to titrate ventilatory settings at the bedside, with a focus on managing potential brain-lung conflicts.

Recent findings
Physiologic studies have elucidated the impact of low tidal volume ventilation and varying levels of positive end expiratory pressure on intracranial pressure and cerebral perfusion. Epidemiologic studies have reported the association of different thresholds of tidal volume, plateau pressure, driving pressure, mechanical power, and arterial oxygen and carbon dioxide concentrations with mortality and neurologic outcomes in patients with ABI. The data collectively make clear that injurious ventilation in this population is associated with worse outcomes; however, optimal ventilatory targets remain poorly defined.

Summary
Although direct data to guide mechanical ventilation in brain-injured patients is accumulating, the current evidence base remains limited. Ventilatory considerations in this population should be extrapolated from high-quality evidence in patients without brain injury – keeping in mind relevant effects on intracranial pressure and cerebral perfusion in patients with ABI and individualizing the chosen strategy to manage brain-lung conflicts where necessary.