bluuebunny/crossref_metadata_2025_split huggingface dataset:
Probody Therapeutic Design of 89Zr-CX-072 Promotes Accumulation in PD-L1–Expressing Tumors Compared to Normal Murine Lymphoid Tissue
Authors: Giesen Danique , Broer Linda N. , Lub-de Hooge Marjolijn N. , Popova Irina , Howng Bruce , Nguyen Margaret , Vasiljeva Olga , de Vries Elisabeth G.E. , Pool Martin 
Published: January 2020

AbstractPurpose:Probody therapeutic CX-072 is a protease-activatable antibody that is cross-reactive with murine and human programmed death-ligand 1 (PD-L1). CX-072 can be activated in vivo by proteases present in the tumor microenvironment, thereby potentially reducing peripheral, anti–PD-L1-mediated toxicities. To study its targeting of PD-L1–expressing tissues, we radiolabeled CX-072 with the PET isotope zirconium-89 (89Zr).Experimental Design:89Zr-labeled CX-072, nonspecific Probody control molecule (PbCtrl) and CX-072 parental antibody (CX-075) were injected in BALB/c nude mice bearing human MDA-MB-231 tumors or C57BL/6J mice bearing syngeneic MC38 tumors. Mice underwent serial PET imaging 1, 3, and 6 days after intravenous injection (pi), followed by ex vivo biodistribution. Intratumoral 89Zr-CX-072 distribution was studied by autoradiography on tumor tissue sections, which were subsequently stained for PD-L1 by IHC. Activated CX-072 species in tissue lysates were detected by Western capillary electrophoresis.Results:PET imaging revealed 89Zr-CX-072 accumulation in MDA-MB-231 tumors with 2.1-fold higher tumor-to-blood ratios at 6 days pi compared with 89Zr-PbCtrl. Tumor tissue autoradiography showed high 89Zr-CX-072 uptake in high PD-L1–expressing regions. Activated CX-072 species were detected in these tumors, with 5.3-fold lower levels found in the spleen. Furthermore, 89Zr-CX-072 uptake by lymphoid tissues of immune-competent mice bearing MC38 tumors was low compared with 89Zr-CX-075, which lacks the Probody design.Conclusions:89Zr-CX-072 accumulates specifically in PD-L1–expressing tumors with limited uptake in murine peripheral lymphoid tissues. Our data may enable clinical evaluation of 89Zr-CX-072 whole-body distribution as a tool to support CX-072 drug development (NCT03013491).
Determining the Optimal Adjuvant Therapy for Improving Survival in Elderly Patients with Glioblastoma: A Systematic Review and Network Meta-analysis
Authors: Nassiri Farshad , Taslimi Shervin , Wang Justin Z. , Badhiwala Jetan H. , Dalcourt Tatyana , Ijad Nazanin , Pirouzmand Neda , Almenawer Saleh , Stupp Roger , Zadeh Gelareh 
Published: January 2020

Abstract

Purpose:
Older patients with glioblastoma (GBM) are underrepresented in clinical trials. Several abbreviated and standard chemoradiotherapy regimens are advocated with no consensus on the optimal approach. Our objective was to quantitatively evaluate which of these regimens would provide the most favorable survival outcomes in older patients with GBM using a network meta-analysis.

Experimental Design:
MEDLINE, Embase, Google Scholar, and the Cochrane Library were searched. Patients &gt;60 years of age with histologically confirmed GBM were included. Primary outcome of interest was the pooled HR from randomized controlled trials (RCTs). Secondary outcomes of interest included pooled HR from studies controlling for MGMT promoter methylation status, and safety.

Results:
Fourteen studies, including 5 RCTs, reporting 4,561 patients were included. Using highest quality data from RCTs, our network-based approach demonstrated that standard radiotherapy (SRT) and temozolomide (TMZ) provided similar survival benefit when compared with hypofractionated radiotherapy (HRT) and TMZ [HR = 0.90; 95% confidence interval (CI), 0.43–1.87], TMZ alone (HR 1.25; 95% CI, 0.69–2.26), HRT alone (HR = 1.34; 95% CI, 0.73–2.45), or SRT alone (HR = 1.43; 95% CI, 0.87–2.36). HRT-TMZ had the highest probability (85%) of improving survival in older patients with GBM followed by SRT-TMZ (72%). Pooled analysis of trials controlling for MGMT promoter methylation status demonstrated that TMZ monotherapy confers similar survival benefit to combined chemoradiotherapy.

Conclusions:
Statistical comparisons using a network approach demonstrates that the common treatment regimens for older patients with GBM in previous RCTs confer similar survival benefits. Adjustments for MGMT promoter methylation status demonstrated that radiotherapy alone was inferior to TMZ-based approaches. Head-to-head comparison of TMZ monotherapy to combined TMZ and radiation is warranted.
Стан системи антиоксидантного захисту в піддослідних тварин внаслідок модельованої поєднаної абдоміно-скелетної травми та ішемії-реперфузії нижніх кінцівок
Authors: Garian S. V. 
Published: January 2020

Мета роботи: вивчити вплив реперфузії кінцівки в моделі поєднаної абдоміно-скелетної травми на зміни показників антиоксидантного захисту.
Матеріали і методи. В експерименті використали 130 статевозрілих білих щурів-самців лінії Wistar масою 190–220 г, які знаходилися на стандартному раціоні віварію.
Усіх тварин поділили на групи: контрольну (КГ) та три дослідні (ГД): контрольна група – інтактні тварини (10 тварин); перша дослідна група (ГД–1) – моделювали перелом стегна, масивну зовнішню кровотечу та ішемію-реперфузію нижніх кінцівок (40 тварин); друга дослідна група (ГД–2) – моделювали перелом стегна, масивну зовнішню крововтрату та закриту травму органів черевної порожнини (40 тварин); третя дослідна група (ГД–3) – моделювали закриту травму органів черевної порожнини, скелетну травму, масивну зовнішню крововтрату та ішемію-реперфузію нижніх кінцівок (40 тварин).
Тварин дослідних груп виводили з експерименту в умовах тіопентало- натрієвого наркозу методом тотального кровопускання з серця через 3, 7, 14 та 21 добу після моделювання травм. Для дослідження забирали кров тварин.
У сироватці крові визначали активність каталази, та враховуючи отримані попередньо дані щодо вмісту реагентів до тіобарбітурової кислоти (ТБК-активних продуктів), розраховували антиоксидантно-прооксидантний індекс.
Результати досліджень та їх обговорення. Отримані результати дають змогу стверджувати, що реперфузія кінцівки зумовлює розвиток тривалого оксидативного стресу, у відповідь на який зростає рівень каталази. Найбільш виражені зміни зафіксовано у групі піддослідних тварин, де поряд з поєднаною абдоміно-скелетною травмою була наявна ішемія реперфузія нижніх кінцівок. Саме вона була причиною розвитку тривалих системних змін та відповідно дисбалансу адаптаційно-компенсаторних механізмів, спрямованих на ліквідацію патологічних чинників.
Поєднання абдоміно-скелетної травми та ішемії-реперфузії нижніх кінцівок викликає спричиняє оксидативний стрес та виснаження антиоксидантних систем, про що свідчить зниження рівня АПІ, який через 21 добу був статистично менше контрольних показників (р<0,05) на 13,3 %.
Вплив експериментальної гострої крововтрати, ускладненої ішемією-реперфузією кінцівки, на діурез і швидкість клубочкової фільтрації
Authors: Shatsky V. V. , Hudyma A. A. , Blyzniuk R. V. 
Published: January 2020

Мета роботи: зʼясувати вплив гострої крововтрати, ускладненої ішемією-реперфузією кінцівки, на діурез і швидкість клубочкової фільтрації та оцінити ефективність карбацетаму в корекції виявлених порушень.
Матеріали і методи. Експерименти виконано на 96 нелінійних щурах-самцях масою 160–180 г. Усіх тварин поділили на пʼять груп: контрольну та чотири дослідних (по 6 щурів у групі). До першої дослідної групи увійшли тварини, яким під тіопентал-натрієвим наркозом моделювали двогодинну ішемію кінцівки з наступною реперфузією. У другій дослідній групі в умовах знеболення тваринам моделювали гостру крововтрату в обсязі 20–22 % обʼєму циркулюючої крові шляхом пересікання стегнової вени. У третій дослідній групі дані ушкодження поєднували. У четвертій дослідній групі тваринам з гострою крововтратою, ускладненою ішемією-реперфузією кінцівки, з метою корекції внутрішньоочеревинно вводили карбацетам (Інститут фізико-органічної хімії та вуглехімії НАН України, Донецьк) в дозі 5 мг на кілограм маси тварини. В контрольній групі тваринам вводили в наркоз, застосовуючи еквівалентну дозу тіопенталу натрію, накладали джгут на 2 год без припинення кровотоку і в подальшому брали для досліджень через одну годину.
Через 1 і 2 год, а також через 1, 7 і 14 діб у піддослідних тварин визначали функціональний стан нирок методом водного навантаження. Сечу збирали протягом 2 год і визначали діурез. Після забору сечі під тіопентал-натрієвим знеболенням щурів виводили з експерименту методом тотального кровопускання із серця. У сечі і сироватці крові визначали концентрацію креатиніну. Швидкість клубочкової фільтрації (ШКФ) оцінювали за кліренсом ендогенного креатиніну.
Результати досліджень та їх обговорення. Встановлено, що реперфузія після двогодинної ішемії супроводжується істотним порушенням функціонального стану нирок, що виявляється зниженням діурезу та ШКФ, величина яких до першої доби досягає мінімального рівня, проте до 14 доби – нормалізується. На тлі гострої крововтрати досліджувані показники знижувалися ще більше. У всі терміни спостереження діурез і ШКФ були статистично вірогідно меншими, ніж у тварин з ішемією-реперфузією кінцівки. За умов моделювання гострої крововтрати та ішемії-реперфузії кінцівки у всі терміни реперфузійного періоду величина діурезу виявилася істотно меншою, ніж за умов самої крововтрати. У свою чергу, ШКФ за цих умов статистично вірогідно знижувалася через 4 год і 7 діб реперфузійного періоду. Дослідження впливу карбацетаму показало, що його застосування в реперфузійному періоді вже через 7 діб привело до статистично значущого зростання діурезу та ШКФ у тварин з гострою крововтратою, ускладненою ішемією-реперфузією кінцівки. Ефект ставав ще більшим через 14 діб. Отже, карбацетам нівелює патогенні прояви гострої крововтрати та ішемії-реперфузії кінцівки і знижує прояви ниркової дисфункції, що свідчить про його перспективність як засобу системної корекції.
A Risk Score Including Carotid Plaque Inflammation and Stenosis Severity Improves Identification of Recurrent Stroke
Authors: Kelly Peter J. , Camps-Renom Pol , Giannotti Nicola , Martí-Fàbregas Joan , McNulty Jonathan P. , Baron Jean-Claude , Barry Mary , Coutts Shelagh B. , Cronin Simon , Delgado-Mederos Raquel , Dolan Eamon , Fernández-León Alejandro , Foley Shane , Harbison Joseph , Horgan Gillian , Kavanagh Eoin , Marnane Michael , McCabe John , McDonnell Ciaran , Sharma Vijay K. , Williams David J. , O’Connell Martin , Murphy Sean 
Published: January 2020

Background and Purpose—

In randomized trials of symptomatic carotid endarterectomy, only modest benefit occurred in patients with moderate stenosis and important subgroups experienced no benefit. Carotid plaque
18
F-fluorodeoxyglucose uptake on positron emission tomography, reflecting inflammation, independently predicts recurrent stroke. We investigated if a risk score combining stenosis and plaque
18
F-fluorodeoxyglucose would improve the identification of early recurrent stroke.

Methods—

We derived the score in a prospective cohort study of recent (<30 days) non-severe (modified Rankin Scale score ≤3) stroke/transient ischemic attack. We derived the SCAIL (symptomatic carotid atheroma inflammation lumen-stenosis) score (range, 0–5) including
18
F-fluorodeoxyglucose standardized uptake values (SUV
max
<2 g/mL, 0 points; SUV
max
2–2.99 g/mL, 1 point; SUV
max
3–3.99 g/mL, 2 points; SUV
max
≥4 g/mL, 3 points) and stenosis (<50%, 0 points; 50%–69%, 1 point; ≥70%, 2 points). We validated the score in an independent pooled cohort of 2 studies. In the pooled cohorts, we investigated the SCAIL score to discriminate recurrent stroke after the index stroke/transient ischemic attack, after positron emission tomography-imaging, and in mild or moderate stenosis.

Results—

In the derivation cohort (109 patients), recurrent stroke risk increased with increasing SCAIL score (
P
=0.002, C statistic 0.71 [95% CI, 0.56–0.86]). The adjusted (age, sex, smoking, hypertension, diabetes mellitus, antiplatelets, and statins) hazard ratio per 1-point SCAIL increase was 2.4 (95% CI, 1.2–4.5,
P
=0.01). Findings were confirmed in the validation cohort (87 patients, adjusted hazard ratio, 2.9 [95% CI, 1.9–5],
P
<0.001; C statistic 0.77 [95% CI, 0.67–0.87]). The SCAIL score independently predicted recurrent stroke after positron emission tomography-imaging (adjusted hazard ratio, 4.52 [95% CI, 1.58–12.93],
P
=0.005). Compared with stenosis severity (C statistic, 0.63 [95% CI, 0.46–0.80]), prediction of post-positron emission tomography stroke recurrence was improved with the SCAIL score (C statistic, 0.82 [95% CI, 0.66–0.97],
P
=0.04). Findings were confirmed in mild or moderate stenosis (adjusted hazard ratio, 2.74 [95% CI, 1.39–5.39],
P
=0.004).

Conclusions—
The SCAIL score improved the identification of early recurrent stroke. Randomized trials are needed to test if a combined stenosis-inflammation strategy improves selection for carotid revascularization where benefit is currently uncertain.
Modulation of Body Representation Impacts on Efferent Autonomic Activity
Authors: D'Alonzo Marco , Mioli Alessandro , Formica Domenico , Di Pino Giovanni 
Published: January 2020

Abstract
The afferent branch of the autonomic nervous system contributes with interoception to the multimodal sensory correlation continuously needed to update our representation of the body. To test whether the modulation of body representation would have an impact on the efferent branch of the autonomic nervous system, nonspecific skin conductance has been measured in three rubber hand illusion (RHI) experiments, controlled with asynchronous brush-stroking and incongruent fake hand position. Nonspecific skin conductance standard deviation (SCSD) computed along the whole 90 sec of stroking was found to be increased by the illusion and to correlate with all the typical measures of embodiment. Computing SCSD in shorter time windows strongly enhanced the difference between illusion and controls. The highest difference was found in the 10–55 sec window, being the 14–34 sec window as the most informative one. The higher correlations with the validated measures of embodiment (all but the proprioceptive drift) were found for time windows ranging between 35 and 65 sec. The SCSD was no longer significantly higher when the RHI was repeated twice (two trials each iteration), but it was still significantly higher in synchronous stroking even when considering only the second trial. However, after the first iteration of the RHI paradigm, the effect of the embodiment on nonspecific skin conductance response results to be attenuated, suggesting that novelty in presentation of the RHI can contribute to the effect on nonspecific skin conductance response. Results candidate SCSD as a noninvasive, cheap, easy, and objective measure of embodiment, especially sensible to onset and strength of the illusion. Alike the already known enhanced autonomic reaction to a threatening, SCSD does not interfere with the collection of other behavioral measures. Correlations and their dynamics, presence of the effect in the second presentation of the setup but relative low robustness against multiple repetition, suggest that the increased fluctuations of skin conductance caught by SCSD are not just the effect of different presented sensory stimuli but more likely a stronger arousal response to the novelty of the updated perceptual status.
Regional to Global Evolution of Impacts of Parameterized Mountain-Wave Drag in the Lower Stratosphere
Authors: Kruse Christopher G. 
Published: January 2020

AbstractMountain ranges are regional features on Earth, as are the regions of mountain-wave drag (MWD) exerted by dissipating atmospheric gravity waves generated by flow over them. However, these regional drags have significant global- or zonal-mean impacts on Earth’s atmospheric general circulation (e.g., slowing of the polar night jet). The objective of this work is to understand the regional to global evolution of these impacts. The approach is to track the evolution of MWD-generated potential vorticity (PV) over the winter using the Whole Atmosphere Community Climate Model (WACCM). Within an ensemble of winter-long runs with and without MWD, lower-stratospheric PV is generated over mountains and advected downstream, generating large-scale PV banners. These PV banners are diffused but survive this diffusion and are reinforced over downstream mountain ranges, accumulating into zonal-mean or global features within WACCM. A simple 2D model representing sources, advection, and diffusion of “passive PV” recreates the salient features in the WACCM results, suggesting the winter-long evolution of MWD-generated PV can be crudely understood in terms of horizontal advection and diffusion within a global vortex. In the Northern Hemisphere, cyclonic, equatorward PV banners accumulate zonally into a single zonally symmetric positive PV anomaly. The anticyclonic, poleward PV banners also accumulate into a zonally symmetric feature, but then diffuse over the North Pole into a negative PV polar cap. In the Southern Hemisphere, the same processes are at work, though the different geographic configuration of mountain ranges leads to different patterns of impacts.
Global and Regional Entropy Production by Radiation Estimated from Satellite Observations
Authors: Kato Seiji , Rose Fred G. 
Published: January 2020

AbstractVertical profiles of shortwave and longwave irradiances computed with satellite-derived cloud properties and temperature and humidity profiles from reanalysis are used to estimate entropy production. Entropy production by shortwave radiation is computed by the absorbed irradiance within layers in the atmosphere and by the surface divided by their temperatures. Similarly, entropy production by longwave radiation is computed by emitted irradiance to space from layers in the atmosphere and surface divided by their temperatures. Global annual mean entropy production by shortwave absorption and longwave emission to space are, respectively, 0.852 and 0.928 W m−2 K−1. With a steady-state assumption, entropy production by irreversible processes within the Earth system is estimated to be 0.076 W m−2 K−1 and by nonradiative irreversible processes to be 0.049 W m−2 K−1. Both global annual mean entropy productions by shortwave absorption and longwave emission to space increase with increasing shortwave absorption (i.e., with decreasing the planetary albedo). The increase of entropy production by shortwave absorption is, however, larger than the increase of entropy production by longwave emission to space. The result implies that global annual mean entropy production by irreversible processes decreases with increasing shortwave absorption. Input and output temperatures derived by dividing the absorbed shortwave irradiance and emitted longwave irradiance to space by respective entropy production are, respectively, 282 and 259 K, which give the Carnot efficiency of the Earth system of 8.5%.
Protocolized use of catheter-directed thrombolysis and echocardiography is highly effective in reversing acute right heart dysfunction in severe submassive pulmonary embolism patients
Authors: Guliani Sundeep , Das Gupta Jaideep , Osofsky Robin , Marek John , Rana Muhammad Ali , Marinaro Jon 
Published: January 2020

Objective: The objective of this study was to evaluate the efficacy of protocolized use of catheter-directed thrombolysis and echocardiography in submassive pulmonary embolism patients. Methods: A retrospective study at a single institution of 28 patients that presented with submassive pulmonary embolism from July 2016 to September 2019 was performed. All patients were diagnosed using chest computed tomography demonstrating a pulmonary embolism and abnormal right ventricular to left ventricular ratio. Patients with severe right heart dysfunction (right ventricular to left ventricular ratio ⩾1.4) were protocolized to receive catheter-directed thrombolysis via EkoSonic catheters (EKOS Corporation, Bothell, WA, United States). Transthoracic echocardiogram was performed after 24 hours to assess right ventricular function and determine the need to continue thrombolysis. Patients after discharge then received follow-up echocardiograms at 6 weeks to determine new post-treatment baseline. Results: The mean patient age was 54.6 years, mean body mass index was 35.0, and mean right ventricular to left ventricular ratio on admission computed tomography imaging was 1.70. Interval mean right ventricular to left ventricular ratio on echocardiography during thrombolysis therapy was 1.01 (p < 0.00001). Patients were tachycardic on admission (mean heart rate 102.2 beats per minute) with improvement by completion of thrombolysis (mean heart rate 72.9 beats per minute) (p < 0.00001). There was a 0% incidence of periprocedural complications. Overall 30-day complication rate was 7.1% (n = 1 arrhythmia, n = 1 delayed intracranial hemorrhage). At 6-week follow-up, 91% of the patients who received echocardiography had normal right ventricular function. Conclusion: This retrospective study demonstrates the effectiveness of protocolized use of catheter-directed thrombolysis and echocardiography in reversing severe right heart dysfunction in submassive pulmonary embolism patients.
Shorter training intervals increase high school students’ awareness of cardiopulmonary resuscitation: a questionnaire study
Authors: Tang Hong-mei , Wu Xiao , Jin Yin , Jin Yi-qing , Wang Zi-jun , Luo Jin-yan , Hu Yan-qi , Jin Ting , Shang Moses , Chang Qing , Wang Fei 
Published: January 2020

Objective To explore training-related independent factors affecting the awareness of cardiopulmonary resuscitation (CPR) in senior high school students in Shanghai. Methods Questionnaires measuring CPR-related knowledge were distributed to 430 senior high school students in Shanghai. Results The overall CPR qualification rate was 7.7%. Qualification rate increased significantly with training frequency (5.5% vs. 9.3% vs. 20%), personal willingness to perform CPR (3.7% vs. 9.5%) and smaller training intervals (12.8% vs. 5.3% vs. 1.8%). After adjustment, training interval <6 months (odds ratio [OR] 6.078, 95% confidence interval [CI] 1.367–27.014) remained an independent predictor of qualifying rate. In unqualified students, willingness to implement CPR (72.4% vs. 66.2% vs. 54.8%) and training interval <6 months (23.8% vs. 15.8% vs. 6.8%) decreased as school grade increased. Worries about CPR not meeting professional standards, especially in females (OR 1.72, 95% CI 1.065–2.776), and legal responsibility for failed CPR were the main reasons for reduced willingness to implement CPR. Conclusion The CPR qualifying rate of senior high school students in Shanghai is low. It could be improved by reducing training intervals to consolidate learning. It may also be necessary to promote laws about first aid to senior high school students.
Assessment of the relationship between knee ultrasound and clinical symptoms in patients with thyroid dysfunction
Authors: Kim Bo Young , Kim Sung-Soo , Park Hyeong Kyu , Kim Hyun-Sook 
Published: January 2020

Objective To determine whether musculoskeletal ultrasound (MSUS) abnormalities were associated with thyroid dysfunction. Methods This study included 109 patients with thyroid diseases, including thyroid dysfunction or autoimmune thyroid disease. Patients were categorized as euthyroid, hypothyroid, or hyperthyroid based on their recent thyroid function tests. To evaluate MSUS, an experienced rheumatologist examined the presence of synovial fluid, synovial hypertrophy, and grade of inflammation in both gray-scale and power Doppler scans of the knee joint. Associations between MSUS abnormalities, thyroid status, visual analog scale (VAS) score for knee pain, and presence of thyroid autoantibodies were investigated. Results MSUS abnormalities were more frequently associated with hyperthyroid or hypothyroid states than with a euthyroid state. High knee VAS score was significantly associated with overall MSUS severity score regardless of knee osteoarthritis. However, there was no difference in MSUS abnormalities based on the presence of thyroid autoantibodies. Conclusions Both hypothyroid and hyperthyroid states were associated with MSUS abnormalities and knee arthralgia. MSUS examination may be helpful in uncontrolled thyroid dysfunction and knee arthralgia.