bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative evaluation of T-cell receptors in experimental glioma-draining lymph nodes
Authors: Blobner Jens , Kilian Michael , Tan Chin Leng , Aslan Katrin , Sanghvi Khwab , Meyer Jochen , Fischer Manuel , Jähne Kristine , Breckwoldt Michael O , Sahm Felix , von Deimling Andreas , Bendszus Martin , Wick Wolfgang , Platten Michael , Green Edward , Bunse Lukas 
Published: September 2021

Abstract

Background
Glioblastomas, the most common primary malignant brain tumors, are considered immunologically cold malignancies due to growth in an immune sanctuary site. While peptide vaccines have shown to generate intra-tumoral antigen-specific T cells, the identification of these tumor-specific T cells is challenging and requires detailed analyses of tumor tissue. Several studies have shown that CNS antigens may be transported via lymphatic drainage to cervical lymph nodes, where antigen-specific T-cell responses can be generated. Therefore, we investigated whether glioma-draining lymph nodes (TDLN) may constitute a reservoir of tumor-reactive T cells.

Methods
We addressed our hypothesis by flow cytometric analyses of chicken ovalbumin (OVA)-specific CD8+ T cells as well as T-cell receptor beta (TCRβ) next-generation-sequencing (TCRβ-NGS) of T cells from tumor tissue, TDLN, spleen, and inguinal lymph nodes harvested from experimental mouse GL261 glioma models.

Results
Longitudinal dextramer-based assessment of specific CD8+ T cells from TDLN did not show tumor model antigen reactivity. Unbiased immunogenomic analysis revealed a low overlap of TCRβ sequences from glioma-infiltrating CD8+ T cells between mice. Enrichment scores, calculated by the ratio of productive frequencies of the different TCRβ-CDR3 amino-acid (aa) rearrangements of CD8+ T cells derived from tumor, TDLN, inguinal lymph nodes, and spleen demonstrated a higher proportion of tumor-associated TCR in the spleen compared to TDLN.

Conclusions
In experimental glioblastoma, our data did not provide evidence that glioma-draining cervical lymph nodes are a robust reservoir for spontaneous glioma-specific T cells highlighting the requirement for detailed analyses of glioma-infiltrating T cells for the discovery of tumor-specific TCR.
Offspring of translocated individuals drive the successful reintroduction of Columbian Sharp-tailed Grouse in Nevada, USA
Authors: Mathews Steven R , Coates Peter S , Prochazka Brian G , Espinosa Shawn P , Delehanty David J 
Published: September 2021

Abstract
Translocations of North American prairie-grouse (genus Tympanuchus) present a conservation paradox wherein they are performed to augment, restore, or reintroduce populations, but translocated individuals exhibit a diminished ability to contribute to population restoration. For reintroduced populations without immigration, persistence can only be achieved through reproductive contributions by translocated individuals and their progeny. Due to the disruptive nature of translocation (e.g., physiological chronic stress), progeny produced at restoration sites may outperform founder populations in terms of demographics, but this hypothesis has yet to be tested. We reintroduced Columbian Sharp-tailed Grouse (T. phasianellus columbianus; CSTG) to north central Nevada from 2013 to 2017 and used integrated population models (IPMs) to evaluate the process of population establishment and estimate latent contributions of progeny hatched at the restoration site to population rate of change (λ^). Specifically, we used annual lek (i.e. communal breeding arenas) counts and demographic data from translocated individuals to build two separate IPMs to estimate λ^. While keeping demographic contributions by translocated individuals identical between models, one IPM assumed local progeny performance was demographically similar to translocated individuals (i.e. the baseline-IPM), and the second assumed that local progeny performed demographically similar to non-translocated CSTG (i.e. the informative-IPM). The baseline-IPM predicted strong population declines following the conclusion of translocations and extirpation by 2020, and it failed to predict observed lek counts. Conversely, the informative-IPM predicted population growth rates (λ^ = 1.17, 95% credible interval [CI]: 0.74–1.50) that were more similar to field observations. Offspring of translocated individuals likely perform at similar levels to non-translocated populations, and by not accounting for demographic differences between translocated individuals and non-translocated progeny hatched at the restoration site, managers could underestimate population performance and persistence. Thus, translocation practices that maximize the number of offspring immediately recruited into restoration sites are likely to be the most successful.
The treatment of Merkel cell carcinoma with immune checkpoint inhibitors: implications for patients with rheumatoid arthritis
Authors: Klee Gina , Kisch Tobias , Kümpers Christiane , Perner Sven , Schinke Susanne , Zillikens Detlef , Langan Ewan A , Terheyden Patrick 
Published: September 2021

Abstract

Objectives
Merkel cell carcinoma (MCC) is a rare, highly aggressive neuroendocrine skin cancer, which typically affects elderly and immunocompromised and/or immunosuppressed patients. The checkpoint inhibitor avelumab, a mAb targeting the anti-programmed cell death ligand 1 (anti-PD-L1), has revolutionized the treatment of metastatic MCC, achieving dramatic improvements in disease control and overall survival. However, checkpoint inhibitors are associated with the development of immune-related adverse events, such as exacerbation of pre-existing RA. Although most immune-related adverse events can be managed successfully with CSs, their frequent and/or long-term use runs the risk of undermining the efficacy of immune checkpoint inhibition.

Methods
We report two cases of MCC, in which immunosuppressive therapy for the management of RA was administered.

Results
Immunosuppression for (i) pre-existing and (ii) immune checkpoint inhibitor-exacerbated RA was associated with progression of metastatic MCC.

Conclusion
Any decision to initiate immunosuppressive treatment for RA in patients receiving immune checkpoint inhibitor therapy should include careful consideration of the risk of potentially fatal cancer progression and be taken after consultation with the patient’s oncologist and rheumatologist. When the immunosuppressive treatment is required, it should be administered for as short a time as possible and under strict clinical and radiological surveillance.
The Watchman device for preventing stroke in patients with atrial fibrillation
Authors: Zapata James , Paamoni Arielle , Rinard Benjamin , Abdou Amir , Zimmer Drew , Letherer Cathy Chang 
Published: September 2021

ABSTRACT
Atrial fibrillation (AF) is one of the most common sustained dysrhythmias that increases in prevalence with age, and is associated with strokes that can lead to significant patient morbidity and mortality. AF prevalence is projected to double over the next 25 years, demonstrating the need for innovative and effective stroke prevention modalities. Two options are direct oral anticoagulants and left atrial appendage occlusion. This article discusses the Watchman device, a left atrial appendage occlusion device that provides an option for patients with contraindications for anticoagulation.
Curriculum essentials of an entry-level PA doctoral degree
Authors: Kayingo Gerald , Gordes Karen L. , Jun Hyun-Jin , Fleming Shani , Kulo Violet , Cawley James F. 
Published: September 2021

ABSTRACT

Objectives:
With increasing discussion of physician assistant (PA) doctoral education, investigation of curriculum essentials and competencies has become relevant.

Methods:
We conducted a national mixed-methods study comprising a survey and semistructured interviews to capture stakeholders' views on essential curricular elements for PA doctoral education.

Results:
If the PA profession decides to transition to a terminal doctoral degree, 75% of respondents indicated this would require new content, with half indicating it would require significant change to the curriculum, enhance PA educational rigor, and change the competencies of the new graduate. The majority of respondents favored a bridge program model and the Doctor of Medical Science (DMSc) as the degree title.

Conclusions:
Overall, respondents agreed that transition to an entry-level PA doctoral degree would affect various aspects of the curriculum. As the prospect of an entry-level PA doctoral degree gains further attention, additional debate on curriculum essentials and competencies is warranted.
Screening pediatric surgical patients during the COVID-19 pandemic
Authors: Dibbs Rami P. , Ferry Andrew M. , Mehl Steven C. , Ferguson Susannah M. , Versalovic James , Dunn James J. , Enochs Joyce , Monson Laura A. , Hollier Larry H. 
Published: September 2021

ABSTRACT
SARS-CoV-2 has profoundly affected the way healthcare is delivered and has created significant strain on medical facilities globally. As a result, hospitals have had to continuously adapt in order to provide optimal patient care while minimizing the risk of SARS-CoV-2 transmission, particularly in the surgical setting. Texas Children's Hospital developed a set of protocols for surgical screening and clearance of patients in the context of the COVID-19 pandemic. These screening protocols were designed to mitigate the risk of exposing patients and healthcare providers to SARS-CoV-2 and have evolved significantly as a result of the emerging changes in medicine, technology, and governmental regulations. In this article, we share the reasoning behind the development, implementation, and successive modification of our institutional screening protocols.
Flying too close to the sun
Authors: Hickman Kevin A. 
Published: September 2021

ABSTRACT
Increasingly, physician assistants (PAs), advanced practice nurses, and physicians are financially involved with healthcare product manufacturers. Although the relationships themselves might not be illegal, when the transaction influences the healthcare provider's medical decision-making, patients can be harmed and the healthcare provider and manufacturer can face accusations of violating federal and state law. In 2019, the federal government recouped $2.6 billion from healthcare fraud and abuse by healthcare stakeholders. PAs' and NPs' behaviors violating the Anti-Kickback Statute (AKS) and False Claims Act (FCA) were partially responsible for the reported amount. To increase the transparency of the financial relationships between healthcare providers and healthcare manufacturers, the federal Centers for Medicare and Medicaid Services, under statutory obligation, created the Open Payments program, which will begin reporting PAs' and advanced practice nurses' financial relationships with manufacturers in 2022.
Perinatal depression screening
Authors: Ellington Kelly 
Published: September 2021

Abstract:
Recommendations for social distancing and avoidance of mass gatherings during the COVID-19 pandemic have correlated with increased depressive symptoms in some individuals, such as loss of interest in daily activities, sleeplessness, or sadness. Perinatal depression screening using established, validated tools can aid with early diagnosis, guide management strategies, and optimize outcomes for pregnant women and their families. Identifying at-risk patients early in pregnancy and implementing a plan of care with appropriate mental health resources such as counseling or therapy have been shown to decrease clinical depression by more than 40%.
Intraoperative Electrocochleography in Subjects Affected by Vestibular Schwannoma and Ménière’s Disease: Comparison of Results
Authors: Trecca Eleonora M. C. , Adunka Oliver F. , Hiss Meghan M. , Mattingly Jameson K. , Moberly Aaron C. , Dodson Edward E. , Cassano Michele , Prevedello Daniel M. , Riggs William J. 
Published: September 2021

Objectives:
Histologic reports of temporal bones of ears with vestibular schwannomas (VSs) have indicated findings of endolymphatic hydrops (ELH) in some cases. The main goal of this investigation was to test ears with VSs to determine if they exhibit electrophysiological characteristics similar to those of ears expected to experience ELH.

Design:
Fifty-three subjects with surgically confirmed VS aged ≥18 and with normal middle ear status were included in this study. In addition, a second group of adult subjects (n = 24) undergoing labyrinthectomy (n = 6) or endolymphatic sac decompression and shunt (ELS) placement (n = 18) for poorly controlled vestibular symptoms associated with Meniere’s disease (MD) participated in this research. Intraoperative electrocochleography (ECochG) from the round window was performed using tone burst stimuli. Audiometric testing and word recognition scores (WRS) were performed preoperatively. ECochG amplitudes, cochlear microphonic/auditory nerve neurophonic (ANN) in the form of the “ongoing” response and summation potential, were analyzed and compared between the two groups of subjects. In addition, to evaluate any effect of auditory nerve function, the auditory nerve score was calculated for each subject. Pure-tone averages were obtained using the average air conduction thresholds at 0.5, 1, and 2 kHz while WRS was assessed using Northwestern University Auditory Test No. 6 word lists.

Results:
In the VS group the average pure-tone averages and WRS were 59.6 dB HL and 44.8%, respectively, while in the MD group they were 52.3 dB HL and 73.8%. ECochG findings in both groups revealed a reduced trend in amplitude of the ongoing response with increased stimulus frequency. The summation potential amplitudes of subjects with VS were found to be less negative than the MD subjects for nearly all test frequencies. Finally, the VS group exhibited poorer amounts of auditory nerve function compared to the MD group.

Conclusions:
The current findings suggest cochlear pathology (e.g., hair cell loss) in both groups but do not support the hypothesis that VSs cause ELH.
Targeted Temperature Management in Out-of-Hospital Cardiac Arrest With Shockable Rhythm: A Post Hoc Analysis of the Coronary Angiography After Cardiac Arrest Trial
Authors: Spoormans Eva M. , Lemkes Jorrit S. , Janssens Gladys N. , van der Hoeven Nina W. , Jewbali Lucia S. D. , Dubois Eric A. , Meuwissen Martijn , Rijpstra Tom A. , Bosker Hans A. , Blans Michiel J. , Bleeker Gabe B. , Baak Remon , Vlachojannis Georgios J. , Eikemans Bob J. W. , Girbes Armand R. J. , van der Harst Pim , van der Horst Iwan C. C. , Voskuil Michiel , van der Heijden Joris J. , Beishuizen Albertus , Stoel Martin , Camaro Cyril , van der Hoeven Hans , Henriques José P. , Vlaar Alexander P. J. , Vink Maarten A. , van den Bogaard Bas , Heestermans Ton A. C. M. , de Ruijter Wouter , Delnoij Thijs S. R. , Crijns Harry J. G. M. , Jessurun Gillian A. J. , Oemrawsingh Pranobe V. , Gosselink Marcel T. M. , Plomp Koos , Magro Michael , van de Ven Peter M. , van Royen Niels , Elbers Paul W. G. 
Published: September 2021

OBJECTIVES:
The optimal targeted temperature in patients with shockable rhythm is unclear, and current guidelines recommend targeted temperature management with a correspondingly wide range between 32°C and 36°C. Our aim was to study survival and neurologic outcome associated with targeted temperature management strategy in postarrest patients with initial shockable rhythm.

DESIGN:
Observational substudy of the Coronary Angiography after Cardiac Arrest without ST-segment Elevation trial.

SETTING:
Nineteen hospitals in The Netherlands.

PATIENTS:
The Coronary Angiography after Cardiac Arrest trial randomized successfully resuscitated patients with shockable rhythm and absence of ST-segment elevation to a strategy of immediate or delayed coronary angiography. In this substudy, 459 patients treated with mild therapeutic hypothermia (32.0–34.0°C) or targeted normothermia (36.0–37.0°C) were included. Allocation to targeted temperature management strategy was at the discretion of the physician.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
After 90 days, 171 patients (63.6%) in the mild therapeutic hypothermia group and 129 (67.9%) in the targeted normothermia group were alive (hazard ratio, 0.86 [95% CI, 0.62–1.18]; log-rank p = 0.35; adjusted odds ratio, 0.89; 95% CI, 0.45–1.72). Patients in the mild therapeutic hypothermia group had longer ICU stay (4 d [3–7 d] vs 3 d [2–5 d]; ratio of geometric means, 1.32; 95% CI, 1.15–1.51), lower blood pressures, higher lactate levels, and increased need for inotropic support. Cerebral Performance Category scores at ICU discharge and 90-day follow-up and patient-reported Mental and Physical Health Scores at 1 year were similar in the two groups.

CONCLUSIONS:
In the context of out-of-hospital cardiac arrest with shockable rhythm and no ST-elevation, treatment with mild therapeutic hypothermia was not associated with improved 90-day survival compared with targeted normothermia. Neurologic outcomes at 90 days as well as patient-reported Mental and Physical Health Scores at 1 year did not differ between the groups.
Continuous Versus Routine Standardized Electroencephalogram for Outcome Prediction in Critically Ill Adults: Analysis From a Randomized Trial
Authors: Beuchat Isabelle , Rossetti Andrea O. , Novy Jan , Schindler Kaspar , Rüegg Stephan , Alvarez Vincent 
Published: September 2021

OBJECTIVES:
To investigate electroencephalogram (EEG) features’ relation with mortality or functional outcome after disorder of consciousness, stratifying patients between continuous EEG and routine EEG.

DESIGN:
Retrospective analysis of data from a randomized controlled trial.

SETTING:
Multiple adult ICUs.

PATIENTS:
Data from 364 adults with acute disorder of consciousness, randomized to continuous EEG (30–48 hr; n = 182) or repeated 20-minute routine electroencephalogram (n = 182).

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Correlations between electrographic features and mortality and modified Rankin scale at 6 months (good 0–2) were assessed. Background continuity, higher frequency, and reactivity correlated with survival and good modified Rankin scale. Rhythmic and periodic patterns carried dual prognostic information: lateralized periodic discharges were associated with mortality and bad modified Rankin scale. Generalized rhythmic delta activity correlated with survival, good modified Rankin scale, and lower occurrence of status epilepticus. Presence of sleep-spindles and continuous EEG background was associated with good outcome in the continuous EEG subgroup. In the routine EEG group, a model combining background frequency, continuity, reactivity, sleep-spindles, and lateralized periodic discharges was associated with mortality at 70.91% (95% CI, 59.62–80.10%) positive predictive value and 63.93% (95% CI, 58.67–68.89%) negative predictive value. In the continuous EEG group, a model combining background continuity, reactivity, generalized rhythmic delta activity, and lateralized periodic discharges was associated with mortality at 84.62% (95%CI, 75.02–90.97) positive predictive value and 74.77% (95% CI, 68.50–80.16) negative predictive value.

CONCLUSIONS:
Standardized EEG interpretation provides reliable prognostic information. Continuous EEG provides more information than routine EEG.
Association of Catecholamine Dose, Lactate, and Shock Duration at Vasopressin Initiation With Mortality in Patients With Septic Shock*
Authors: Sacha Gretchen L. , Lam Simon W. , Wang Lu , Duggal Abhijit , Reddy Anita J. , Bauer Seth R. 
Published: September 2021

OBJECTIVES:
To determine the association of catecholamine dose, lactate concentration, and timing from shock onset at vasopressin initiation with in-hospital mortality.

DESIGN:
Retrospective, observational study using segmented and multivariable logistic regression to evaluate the associations of catecholamine dose, lactate concentration, and timing from shock onset at vasopressin initiation with in-hospital mortality.

SETTING:
Multiple hospitals within the Cleveland Clinic Health System.

PATIENTS:
Adult patients who met criteria for septic shock based on the U.S. Centers for Disease Control and Prevention Adult Sepsis Event definition.

INTERVENTIONS:
All patients received continuous infusion vasopressin as an adjunct to catecholamine vasopressors.

MEASUREMENTS AND MAIN RESULTS:
In total, 1,610 patients were included with a mean Acute Physiology and Chronic Health Evaluation III 109.0 ± 35.1 and Sequential Organ Failure Assessment 14.0 ± 3.5; 41% of patients survived the hospital admission. At the time of vasopressin initiation, patients had median (interquartile range) lactate concentration 3.9 mmol/L (2.3–7.2 mmol/L), norepinephrine-equivalent dose 25 µg/min (18–40 µg/min), and 5.3 hours (2.1–12.2 hr) elapsed since shock onset. The odds of in-hospital mortality increased 20.7% for every 10 µg/min increase in norepinephrine-equivalent dose up to 60 µg/min at the time of vasopressin initiation (adjusted odds ratio, 1.21 [95% CI, 1.09–1.34]), but no association was detected when the norepinephrine-equivalent dose exceeded 60 µg/min (adjusted odds ratio, 0.96 [95% CI, 0.84–1.10]). There was a significant interaction between timing of vasopressin initiation and lactate concentration (p = 0.02) for the association with in-hospital mortality. A linear association between increasing in-hospital mortality was detected for increasing lactate concentration at the time of vasopressin initiation, but no association was detected for time elapsed from shock onset.

CONCLUSIONS:
Higher norepinephrine-equivalent dose at vasopressin initiation and higher lactate concentration at vasopressin initiation were each associated higher in-hospital mortality in patients with septic shock who received vasopressin.