bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blockade Of PD-1 Attenuated Postsepsis Aspergillosis Via The Activation of IFN-γ and The Dampening of IL-10
Authors: Vu Chau Tran Bao , Thammahong Arsa , Yagita Hideo , Azuma Miyuki , Hirankarn Nattiya , Ritprajak Patcharee , Leelahavanichkul Asada 
Published: July 2019

ABSTRACT

Background:
Nosocomial aspergillosis in patients with sepsis has emerged in the past few years. Blockade of PD-1/PD-L pathway has tended to become a promising therapeutic strategy as it improved the outcome of bacterial sepsis and postsepsis secondary fungal infection. Recently, the controversial effects of PD-1 blockade on infectious diseases, including aspergillosis, have been demonstrated; therefore, the efficacy of anti-PD-1 drug still remains to be elucidated.

Methods:
Cecal ligation and puncture (CLP) was conducted as a mouse sepsis model. Aspergillus fumigatus spores were intravenously inoculated on day 5 post-CLP, when the immune cells succumbed to exhaustion. Amphotericin B was medicated together with or without anti-PD-1 treatment after Aspergillus infection.

Results:
Amphotericin B alone was not effective to treat the CLP-mice with secondary aspergillosis. In contrast, antifungal medication with the adjunctive anti-PD-1 treatment attenuated the fungal burdens in blood and internal organs, and improved the survival rate of the mice with secondary aspergillosis. These outcomes of PD-1 blockade were concurring with the enhanced CD86 expression on splenocytes, the augmented serum IFN-γ, and the dampened IL-10. Activated T cells from anti-PD-1-treated mice also highly increased IFN-γ and diminished IL-10 production.

Conclusion:
The blockade of PD-1 on postsepsis aspergillosis presumably reinvigorated exhausted antigen-presenting cells and T cells by upregulating CD86 expression and IFN-γ production, and dampened IL-10 production, which consequently leaded to the attenuation of secondary aspergillosis. The adjunctive anti-PD-1 therapy may become a promising strategy for the advanced immunotherapy against lethal fungal infection.
Influence of Hyperglycemia During Different Phases of Ischemic Preconditioning on Cardioprotection—A Focus on Apoptosis and Aggregation of Granulocytes
Authors: Goergens Jessica I. , Heinen Nicole M. , Zoller Jan , Preckel Benedikt , Bauer Inge , Huhn Ragnar , Ebel Dirk , Raupach Annika 
Published: July 2019

ABSTRACT

Background:
Ischemic preconditioning (IPC) protects the myocardium against ischemia/reperfusion injury. Evidence suggests that hyperglycemia inhibits IPC-induced cardioprotection. The effects of hyperglycemia initiated during different phases of IPC on myocardial injury were characterized with emphasis on apoptosis and aggregation of polymorphonuclear granulocytes (PMN).

Methods:
Male Wistar rats were subjected to 35 min of myocardial ischemia and 2 h of reperfusion. Control animals were not further treated. IPC was induced by three cycles of 3 min ischemia and 5 min of reperfusion before major ischemia. Hyperglycemia (blood glucose more than 22.2 mmol/L) was induced by glucose administration with or without IPC during different phases (trigger- (before ischemia), mediator- (during ischemia), early reperfusion-phase). One additional group received an anti-PMN-antibody before ischemia. Infarct size was quantified by triphenyltetrazolium chloride staining. Cytochrome C release and B-cell lymphoma two (Bcl-2) expression were assessed by western blot analysis. Poly-ADP-Ribose staining and PMN accumulation were quantified with immunohistochemistry and histochemistry.

Results:
IPC reduced infarct size compared with control. Hyperglycemia completely abolished IPC-induced cardioprotection independent of the time point of initiation. Hyperglycemia before and during major ischemia but without IPC also slightly reduced infarct size. IPC reduced the accumulation of PMNs. This effect was reversed by hyperglycemia during trigger- and mediator-phase but not by hyperglycemia during reperfusion. Hyperglycemia alone had no effect on PMN accumulation. In all treatment groups, signs of myocardial apoptosis were reduced compared with control. IPC alone, combined with hyperglycemia and anti-PMN treatment, reduced apoptosis by a Bcl-2-associated mechanism. Hyperglycemia alone reduced apoptosis by a Bcl-2-independent pathway.

Conclusion:
Hyperglycemia inhibits IPC-induced cardioprotection independent of its onset. Furthermore, hyperglycemia prevents apoptosis and IPC-induced reduction of PMN aggregation.
A Randomized Controlled Trial Evaluating the BREASTChoice Tool for Personalized Decision Support About Breast Reconstruction After Mastectomy
Authors: Politi Mary C. , Lee Clara N. , Philpott-Streiff Sydney E. , Foraker Randi E. , Olsen Margaret A. , Merrill Corinne , Tao Yu , Myckatyn Terence M. 
Published: July 2019

Objective:To evaluate a web-based breast reconstruction decision aid,BREASTChoice.Summary and Background Data:Although postmastectomy breast reconstruction can restore quality of life and body image, its morbidity remains substantial. Many patients lack adequate knowledge to make informed choices. Decisions are often discordant with patients’ preferences.Methods:Adult women with stages 0–III breast cancer considering postmastectomy breast reconstruction with no previous reconstruction were randomized toBREASTChoiceor enhanced usual care (EUC).Results:Three hundred seventy-six patients were screened; 120 of 172 (69.8%) eligible patients enrolled. Mean age = 50.7 years (range 25–77). Most were Non-Hispanic White (86.3%) and had a college degree (64.3%). Controlling for health literacy and provider seen,BREASTChoiceusers had higher knowledge than those in EUC (84.6% vs. 58.2% questions correct;P< 0.001). Those usingBREASTChoicewere more likely to know that reconstruction typically requires more than 1 surgery, delayed reconstruction lowers one's risk, and implants may need replacement over time (all ps < 0.002).BREASTChoicecompared to EUC participants also felt more confident understanding reconstruction information (P= 0.009). There were no differences between groups in decisional conflict, decision process quality, shared decision-making, quality of life, or preferences (all ps > 0.05). There were no differences in consultation length betweenBREASTChoiceand EUC groups (mean = 29.7 vs. 30.0 minutes;P> 0.05).BREASTChoicehad high usability (mean score = 6.3/7). Participants completedBREASTChoicein about 27 minutes.Conclusions:BREASTChoicecan improve breast reconstruction decision quality by improving patients’ knowledge and providing them with personalized risk estimates. More research is needed to facilitate point-of-care decision support and examineBREASTChoice'simpact on patients’ decisions over time.
Recurrent Urinary Tract Infection in Women: Primary Care Referral Patterns in a Tertiary Care Center
Authors: Samimi Parisa , Ackerman Anne Lenore , Handler Stephanie , Eilber Karyn S. , Anger Jennifer 
Published: July 2019

Objectives
With more than 150 million urinary tract infections (UTIs) diagnosed globally per year, the impact on patient care is significant. We sought to examine appropriateness of management of recurrent UTI before referral to a female pelvic medicine and reconstructive surgery practice, as well as the characteristics of patients referred.

Methods
The medical records of 100 consecutive women with a diagnosis of “recurrent UTI” at a single institution between November 2010 and December 2015 were reviewed. The baseline clinical characteristics, laboratory testing, and treatments before and at referral to the female pelvic medicine and reconstructive surgery were examined by descriptive statistics.

Results
The evaluation and treatment patterns for recurrent UTI before specialist referral varied widely. Pelvic examination was performed in only 20.8% of patients before referral. Although most women had at least 1 culture performed (65.2%), treatments were variable. Only 42.7% of patients received recommended first-line antibiotic therapy. At symptom recurrence, only 47.2% of patients received a urine culture; most were empirically treated. Approximately 35.0% of patients received the same antibiotic upon their first recurrence.

Conclusions
A large proportion of patients referred for recurrent UTI to a specialty practice had no prior culture, physical examination, or symptom-specific evaluation before referral. Despite existing guidelines, the evaluation, treatment, and referral patterns for recurrent UTI are highly varied and rarely conform to recommendations. Further studies are needed to confirm these trends and determine interventions to improve the efficacy and efficiency of primary care for women with recurrent UTI.
Low Interrater Reliability of Videourodynamic Diagnosis of Detrusor External Sphincter Dyssynergia
Authors: Miller Brandi D. , Tallman Christopher T. , Boone Timothy B. , Khavari Rose 
Published: July 2019

Objectives
Complex bladder dysfunction requires urodynamic testing, often under fluoroscopy termed videourodynamic study (VUDS), to assist the diagnosis and management. Videourodynamic study is an objective tool with high interrater reliability (IRR) for identifying detrusor overactivity. However, IRR has not been validated with disorders associated with neurogenic bladder (NGB). We aim to investigate the IRR of VUDS to diagnose detrusor external sphincter dyssynergia (DESD) among NGB patients and hypothesize a high IRR to DESD diagnosis on VUDS.

Methods
Videourodynamics tracings with fluoroscopic images were rated either positive or negative for evidence of DESD by 4 raters (2 neurourologists, neurourology fellow, and urology postgraduate year 2 resident), in patients who underwent VUDS from 2013 to 2017. The study population had known NGB without previous bladder reconstruction. The IRR was determined using percent agreement and κ values.

Results
The experts had a percent agreement of 82.1% (κ = 0.26). Expert 1 and expert 2 had a percent agreement of 63.6% (κ = 0.1497) and 68.9% (κ = 0.2967), respectively, when compared with the fellow. Sensitivity and specificity ranged from 28% to 75% and 64% to 93%, respectively. The negative predictive values ranged from 90% to 95%.

Conclusions
The IRR to diagnose DESD on VUDS was much lower than expected, even among experts, and was likely multifactorial and partially owing to lack of clinical context and lack of standardized VUDS interpretation of the electromyogram. A high negative predictive value was found among all participants. Further research is needed to evaluate factors contributing to the low reproducibility of DESD diagnosis on VUDS.
Nonfatal motor vehicle related injuries among deployed US Service members: Characteristics, trends, and risks for limb amputations
Authors: Schweizer Marc A. , Janak Jud C. , Graham Brock , Mazuchowski Edward L. , Gurney Jennifer M. , Shackelford Stacy A. , Stockinger Zsolt T. , Monchal Tristan 
Published: July 2019

BACKGROUND
Motor vehicle-related (MVR) incidents are important causes of morbidity among deployed US service members (SMs). Nonbattle MVR injuries are usually similar to civilian MVR injuries, while battle MVR injuries are often unique due to the blast effects from precipitating explosive mechanisms. Our primary objective was to describe the characteristics and trends of nonfatal MVR injuries sustained by deployed US SMs. A second objective was to assess the association between mechanism of injury (i.e., explosive vs. nonexplosive) and limb amputation.

METHODS
We conducted a retrospective cross-sectional analysis using data from the Department of Defense Trauma Registry collected from October 2001 to December 2018. Descriptive statistics were reported stratified by mechanism of injury (explosive vs. nonexplosive). The association between mechanism of injury and limb amputation was assessed using logistic regression models.

RESULTS
There were 3,119 US casualties who sustained nonfatal MVR injuries, 2,380 (76.3%) SMs sustained nonexplosive MVR injuries while 739 (23.7%) sustained explosive MVR injuries. Of all MVR casualties, 2,085 (66.9%) were in Iraq or Syria and 1034 (33.1%) in Afghanistan. The annual prevalence of nonfatal MVR battle casualties was highest in Iraq and Syria from 2003 to 2009 and Afghanistan from 2009 to 2014, ranging overall 15 to 50 MVR casualties per 1,000 wounded in action. There were 92 limb amputations associated with MVR incidents. Compared with nonexplosive MVR mechanisms, explosive MVR mechanisms had higher association with limb amputation (adjusted odds ratio, 2.6; confidence interval, 1.7–3.9), even after adjusting for injury year and Injury Severity Score (AOR, 2.1; confidence interval: 1.4–3.4).

CONCLUSION
Motor vehicle-related incidents are an important cause of injury in US military operations. Compared with nonexplosive MVR incidents, explosive MVR incidents result in more severe injuries, and have a higher associated risk of limb amputation. Continued efforts to improve injury prevention through protective equipment and medical training specific to MVR injuries are needed.

LEVEL OF EVIDENCE
Prognostic and epidemiological study, Level III.
Effect of partial and complete aortic balloon occlusion on survival and shock in a swine model of uncontrolled splenic hemorrhage with delayed resuscitation
Authors: Kauvar David S. , Schechtman David W. , Thomas Sarah B. , Prince M. Dale , De Guzman Rodolfo , Polykratis I. Amy , Kheirabadi Bijan S. , Dubick Michael A. 
Published: July 2019

BACKGROUND
Resuscitative endovascular balloon occlusion of the aorta (REBOA) is accepted as a resuscitation adjunct and bridge to definitive hemostasis. The ischemic burden of REBOA may be mitigated by a partial REBOA (P-REBOA) strategy permitting longer occlusion times and military use for combat trauma. We evaluated REBOA and P-REBOA in a swine multiple trauma model with uncontrolled solid organ hemorrhage and delayed resuscitation and surgical hemostasis.

METHODS
Anesthetized swine (51.9 ± 2.2 kg) had 20 mL/kg hemorrhage and closed femur fracture. Splenic transection was performed and free bleeding permitted for 10 minutes. Controls (n = 5) were hemorrhaged but had no REBOA, REBOA (n = 8) had 60 minutes complete zone 1 occlusion, P-REBOA (n = 8) had 15 minutes complete occlusion and 45 minutes 50% occlusion. Splenectomy was performed and plasma (15 mL/kg) resuscitation initiated 5 minutes prior to deflation. Resuscitation goal was 80 mm Hg systolic with epinephrine as needed. Animals were monitored for 6 hours.

RESULTS
An initial study with 120-minute occlusion had universal fatality in three REBOA (upon deflation) and three P-REBOA animals (after 60 minutes inflation). With 60-minute occlusion, mortality was 100%, 62.5%, and 12.5% in the control, REBOA, and P-REBOA groups, respectively (p < 0.05). Survival time was shorter in controls (120 ± 89 minutes) than REBOA and P-REBOA groups (241 ± 139, 336 ± 69 minutes). Complete REBOA hemorrhaged less during inflation (1.1 ± 0.5 mL/kg) than Control (5.6 ± 1.5) and P-REBOA (4.3 ± 1.4), which were similar. Lactate was higher in the REBOA group compared with the P-REBOA group after balloon deflation, remaining elevated. Potassium increased in REBOA after deflation but returned to similar levels as P-REBOA by 120 minutes.

CONCLUSION
In a military relevant model of severe uncontrolled solid organ hemorrhage 1-hour P-REBOA improved survival and mitigated hemodynamic and metabolic shock. Two hours of partial aortic occlusion was not survivable using this protocol due to ongoing hemorrhage during inflation. There is potential role for P-REBOA as part of an integrated minimally invasive field-expedient hemorrhage control and resuscitation strategy.
Resilience and long-term outcomes after trauma: An opportunity for early intervention?
Authors: Nehra Deepika , Herrera-Escobar Juan P. , Al Rafai Syeda S. , Havens Joaquim , Askari Reza , Nitzschke Stephanie , Velmahos George , Kasotakis George , Brasel Karen J. , Levy-Carrick Nomi , Salim Ali , Haider Adil 
Published: July 2019

BACKGROUND
Resilience, or the ability to cope with difficulties, influences an individual's response to life events including unexpected injury. We sought to assess the relationship between patient self-reported resilience traits and functional and psychosocial outcomes 6 months after traumatic injury.

METHODS
Adult trauma patients 18 years to 64 years of age with moderate to severe injuries (Injury Severity Score, ≥9) admitted to one of three Level I trauma centers between 2015 and 2017 were contacted by phone at 6 months postinjury and asked to complete a validated Trauma Quality of Life (T-QoL) survey and PTSD screen. Patients were classified into “low” and “high” resilience categories. Long-term outcomes were compared between groups. Adjusted logistic regression models were built to determine the association between resilience and each of the long-term outcomes.

RESULTS
A total of 305 patients completed the 6-month interview. Two hundred four (67%) of the 305 patients were classified as having low resilience. Mean age was 42 ± 14 years, 65% were male, 91% suffering a blunt injury, and average Injury Severity Score was 15.4 ± 7.9. Patients in the low-resilience group had significantly higher odds of functional limitations in activities of daily living (odds ratio [OR], 4.81; 95% confidence interval [CI], 2.48–9.34). In addition, patients in the lower resilience group were less likely to have returned to work/school (OR, 3.25; 95% CI, 1.71–6.19), more likely to report chronic pain (OR, 2.57; 95% CI, 1.54–4.30) and more likely to screen positive for PTSD (OR, 2.96; 95% CI, 1.58–5.54).

CONCLUSION
Patients with low resilience demonstrated worse functional and psychosocial outcomes 6 months after injury. These data suggest that screening for resilience and developing and deploying early interventions to improve resilience-associated traits as soon as possible after injury may hold promise for improving important long-term functional outcomes.

LEVEL OF EVIDENCE
Prognostic, level II.
Artifact Mimicking Ictal Epileptiform Activity in EEG
Authors: McKay Jake H. , Tatum William O. 
Published: July 2019

Summary:Although the EEG is designed to record cerebral activity, it also frequently records activity from extracerebral sources, leading to artifact. Differentiating rhythmical artifact from true electrographic ictal activity remains a substantial challenge to even experienced electroencephalographers because the sources of artifact able to mimic ictal activity on EEG have continued to increase with the advent of technology. Knowledge of the characteristics of the polarity and physiologic electrical fields of the brain, as opposed to those generated by the eyes, heart, and muscles, allows the electroencephalographer to intuitively recognize noncerebrally generated waveforms. In this review, we provide practical guidelines for the EEG interpreter to correctly identify physiologic and nonphysiologic artifacts capable of mimicking electrographic seizures. In addition, we further elucidate the common pitfalls in artifact interpretation and the costly impact of epilepsy misdiagnosis due to artifact.
Alternative Splicing of MR1 regulates antigen presentation to MAIT cells
Authors: Narayanan Gitanjali A. , Nellore Abhinav , Tran Jessica G. , Worley Aneta H. , Meermeier Erin W. , Karamooz Elham , Huber Megan , Kurapova Regina , Tafesse Fikadu , Harriff Melanie J. , Lewinsohn David M. 
Published: July 2019

AbstractMucosal Associated Invariant T (MAIT) cells can sense intracellular infection by a broad array of pathogens. These cells are activated upon encountering microbial antigen(s) displayed by MR1 on the surface of an infected cell. Human MR1 undergoes alternative splicing. The full length isoform, MR1A, can activate MAIT cells, while the function of the isoforms, MR1B and MR1C, are not well characterized.In this report, we sought to characterize these splice variants. Using a transcriptomic analysis in conjunction with qPCR, we find that that MR1A and MR1B transcripts are widely expressed. Despite the widespread expression of MR1A and MR1B, only MR1A can present mycobacterial antigen to MAIT cells. Coexpression of MR1B with MR1A serves to decrease MAIT cell activation following bacterial infection. However, expression of MR1B prior to MR1A lowers total MR1A abundance, suggesting competition between MR1A and MR1B for either ligands or chaperones required for folding and/or trafficking. Finally, we evaluated CD4/CD8 double positive thymocytes expressing surface MR1. RelativeMR1A/MR1Bexpression in MR1-expressing thymocytes is associated with their prevalence.Our results suggest alternative splicing of MR1 represents a means of regulating MAIT activation in response to microbial ligand.FundingThis work was supported by NIH T32HL083808 (EK, GAN, EM), VA Merit Award I01CX001562 (MJH), NIH R01AI29976 (MJH), NIH R01AI048090 (DML), NIH R21AI124225-01A1 (FT) and VA Merit Award I01BX000533 (DML). The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government.
Ultraconserved non-coding DNA within insect phyla
Authors: Brody Thomas , Yavatkar Amar , Kuzin Alexander , Odenwald Ward F. 
Published: July 2019

AbstractPresence of ultra-conserved sequence elements in vertebrate enhancers suggest that transcription factor regulatory interactions are shared across phylogenetically diverse species. To date evidence for similarly conserved elements among evolutionarily distant insects such as flies, mosquitos, ants and bees, has been elusive. This study has taken advantage of the availability of the assembled genomic sequence of these insects to explore the presence of ultraconserved sequence elements in these phylogenetic groups. To investigate the integrity of fly regulatory sequences across ~100 million years of evolutionary divergence from the fruitfly Drosophila melanogaster, we compared Drosophila non-coding sequences to those of Ceratitis capitata, the Mediterranean fruit fly and Musca domestica, the domestic housefly. Using various alignment techniques, Blastn, Clustal, Blat, EvoPrinter and Needle, we show that many of the conserved sequence blocks (CSBs) that constitute Drosophila cis-regulatory DNA, recognized by EvoPrinter alignment protocols, are also conserved in Ceratitis and Musca. We term the sequence elements shared among these species ultraconserved CSBs (uCSBs). The position of the uCSBs with respect to flanking genes is also conserved. The results suggest that CSBs represent the point of interaction of multiple trans-regulators whose functions and interactions are conserved across divergent genera. Blastn alignments also detect putative cis-regulatory sequences shared among evolutionarily distant mosquitos Anopheles gambiae and Culex pipiens and Aedes aegypti. We have also identified conserved sequences shared among bee species. Side by side comparison of bee and ant EvoPrints identify uCSBs shared between the two taxa, as well as more poorly conserved CSBs in either one or the other taxon but not in both. Analysis of uCSBs in dipterans, mosquitos and bees will lead to a greater understanding of their evolutionary origin and the function of their conserved sequences.