bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carfilzomib Treatment Causes Molecular and Functional Alterations of Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes
Authors: Forghani Parvin , Rashid Aysha , Sun Fangxu , Liu Rui , Li Dong , Lee Megan R. , Hwang Hyun , Maxwell Joshua T. , Mandawat Anant , Wu Ronghu , Salaita Khalid , Xu Chunhui 
Published: December 2021

Background
Anticancer therapies have significantly improved patient outcomes; however, cardiac side effects from cancer therapies remain a significant challenge. Cardiotoxicity following treatment with proteasome inhibitors such as carfilzomib is known in clinical settings, but the underlying mechanisms have not been fully elucidated.

Methods and Results

Using human induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) as a cell model for drug‐induced cytotoxicity in combination with traction force microscopy, functional assessments, high‐throughput imaging, and comprehensive omic analyses, we examined the molecular mechanisms involved in structural and functional alterations induced by carfilzomib in hiPSC‐CMs. Following the treatment of hiPSC‐CMs with carfilzomib at 0.01 to 10 µmol/L, we observed a concentration‐dependent increase in carfilzomib‐induced toxicity and corresponding morphological, structural, and functional changes. Carfilzomib treatment reduced mitochondrial membrane potential, ATP production, and mitochondrial oxidative respiration and increased mitochondrial oxidative stress. In addition, carfilzomib treatment affected contractility of hiPSC‐CMs in 3‐dimensional microtissues. At a single cell level, carfilzomib treatment impaired Ca
2+
transients and reduced integrin‐mediated traction forces as detected by piconewton tension sensors. Transcriptomic and proteomic analyses revealed that carfilzomib treatment downregulated the expression of genes involved in extracellular matrices, integrin complex, and cardiac contraction, and upregulated stress responsive proteins including heat shock proteins.

Conclusions
Carfilzomib treatment causes deleterious changes in cellular and functional characteristics of hiPSC‐CMs. Insights into these changes could be gained from the changes in the expression of genes and proteins identified from our omic analyses.
Endovascular Thrombectomy in Young Patients With Stroke: A MR CLEAN Registry Study
Authors: Brouwer Josje , Smaal Johanna A. , Emmer Bart J. , de Ridder Inger R. , van den Wijngaard Ido R. , de Leeuw Frank-Erik , Hofmeijer Jeannette , van Zwam Wim H. , Martens Jasper M. , Roos Yvo B.W.E.M. , Majoie Charles B. , van Oostenbrugge Robert J. , Coutinho Jonathan M. ,   on behalf of the MR CLEAN Registry Investigators†
Published: December 2021

Background and Purpose:
Acute ischemic stroke due to large vessel occlusion is uncommon in young adults. We assessed stroke cause in young patients and compared their outcomes after endovascular thrombectomy with older patients.

Methods:
We used data (March 2014 until November 2017) of patients with an anterior circulation large vessel occlusion stroke from the MR CLEAN (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry, a nationwide, prospective study on endovascular thrombectomy in the Netherlands. We compared young patients (18–49 years) with older patients (≥50 years). Outcomes included modified Rankin Scale score after 90 days (both shift and dichotomized analyses), expanded Thrombolysis in Cerebral Infarction score, and symptomatic intracranial hemorrhage. Analyses were adjusted for confounding.

Results:

We included 3256 patients, 310 (10%) were 18 to 49 years old. Young patients had lower median National Institutes of Health Stroke Scale scores (14 versus 16,
P
<0.001) and less cardiovascular comorbidities than older patients. Stroke etiologies in young patients included carotid dissection (16%), cardio-embolism (15%), large artery atherosclerosis (10%), and embolic stroke of undetermined source (31%). Clinical outcome was better in young than older patients (acOR for modified Rankin Scale shift: 1.8 [95% CI, 1.5–2.2]; functional independence [modified Rankin Scale score 0–2] 61 versus 39% [adjusted odds ratio, 2.1 [95% CI, 1.6–2.8]); mortality 7% versus 32%, adjusted odds ratio, 0.2 [95% CI, 0.1–0.3]). Symptomatic intracranial hemorrhage occurred less frequently in young patients (3% versus 6%, adjusted odds ratio, 0.5 [95% CI, 0.2–1.00]). Successful reperfusion (expanded Thrombolysis in Cerebral Infarction Score 2b-3) did not differ between groups. Onset to reperfusion time was shorter in young patients (253 versus 255 minutes, adjusted B in minutes 12.4 [95% CI, 2.4–22.5]).

Conclusions:
Ten percent of patients with acute ischemic stroke undergoing endovascular thrombectomy were younger than 50. Cardioembolism and carotid dissection were common underlying causes in young patients. In one-third of cases, no cause was identified, indicating the need for more research on stroke cause in young patients. Young patients had better prognosis and lower risk of symptomatic intracranial hemorrhage than older patients.
Comparison of Two Automated Computed Tomography Perfusion Applications to Predict the Final Infarct Volume After Thrombolysis in Cerebral Infarction 3 Recanalization
Authors: Muehlen Iris , Sprügel Maximilian , Hoelter Philip , Hock Stefan , Knott Michael , Huttner Hagen B. , Schwab Stefan , Kallmünzer Bernd , Doerfler Arnd 
Published: December 2021

Background:
Several automated computed tomography perfusion software applications have been developed to provide support in the definition of ischemic core and penumbra in acute ischemic stroke. However, the degree of interchangeability between software packages is not yet clear. Our study aimed to evaluate 2 commonly used automated perfusion software applications (Syngo.via and RAPID) for the indication of ischemic core with respect to the follow-up infarct volume (FIV) after successful recanalization and with consideration of the clinical impact.

Methods:
Retrospectively, 154 patients with large vessel occlusion of the middle cerebral artery or the internal carotid artery, who underwent endovascular therapy with a consequent Thrombolysis in Cerebral Infarction 3 result within 2 hours after computed tomography perfusion, were included. Computed tomography perfusion core volumes were assessed with both software applications with different thresholds for relative cerebral blood flow (rCBF). The results were compared with the FIV on computed tomography within 24 to 36 hours after recanalization. Bland-Altman was applied to display the levels of agreement and to evaluate systematic differences.

Results:

Highest correlation between ischemic core volume and FIV without significant differences was found at a threshold of rCBF<38% for the RAPID software (
r
=0.89,
P
<0.001) and rCBF<25% for the Syngo software (
r
=0.87,
P
<0.001). Bland-Altman analysis revealed best agreement in these settings. In the vendor default settings (rCBF<30% for RAPID and rCBF<20% for Syngo) correlation between ischemic core volume and FIV was also high (RAPID:
r
=0.88, Syngo:
r
=0.86,
P
<0.001), but mean differences were significant (
P
<0.001). The risk of critical overestimation of the FIV was higher with rCBF<38% (RAPID) and rCBF<25% (Syngo) than in the default settings.

Conclusions:
By adjusting the rCBF thresholds, comparable results with reliable information on the FIV after complete recanalization can be obtained both with the RAPID and Syngo software. Keeping the software specific default settings means being more inclusive in patient selection, but forgo the highest possible accuracy in the estimation of the FIV.
Adherence to the EAT-Lancet Diet and Risk of Stroke and Stroke Subtypes: A Cohort Study
Authors: Ibsen Daniel B. , Christiansen Anne H. , Olsen Anja , Tjønneland Anne , Overvad Kim , Wolk Alicja , Mortensen Janne K. , Dahm Christina C. 
Published: December 2021

Background and Purpose:
We investigated the association between adherence to the EAT-Lancet diet, a sustainable and mostly plant-based diet, and risk of stroke and subtypes of stroke in a Danish population. For comparison, we also investigated the Alternate Healthy Eating Index-2010 (AHEI).

Methods:
We used the Danish Diet, Cancer and Health cohort (n=55 016) including adults aged 50 to 64 years at baseline (1993–1997). A food frequency questionnaire was used to assess dietary intake and group participants according to adherence to the diets. Stroke cases were identified using a national registry and subsequently validated by review of medical records (n=2253). Cox proportional hazards models were used to estimate hazard ratios and 95% CIs for associations with the EAT-Lancet diet or the AHEI and risk of stroke and stroke subtypes.

Results:
Adherence to the EAT-Lancet diet was associated with a lower risk of stroke, although not statistically significant (highest versus lowest adherence: hazard ratio, 0.91 [95% CI, 0.76–1.09]). A lower risk was observed for AHEI (0.75 [95% CI, 0.64–0.87]). For stroke subtypes, we found that adherence to the EAT-Lancet diet was associated with a lower risk of subarachnoid hemorrhage (0.30 [95% CI, 0.12–0.73]), and the AHEI was associated with a lower risk of ischemic stroke (0.76 [95% CI, 0.64–0.90]) and intracerebral hemorrhage (0.58 [95% CI, 0.36–0.93]).

Conclusions:
Adherence to the EAT-Lancet diet in midlife was associated with a lower risk of subarachnoid stroke, and the AHEI was associated with a lower risk of total stroke, mainly ischemic stroke and intracerebral hemorrhage.
Design, Control, and Evaluation of Mixed-Order, Compact Spherical Loudspeaker Arrays
Authors: Riedel Stefan , Zotter Franz 
Published: December 2021

Abstract
Beamforming on the icosahedral loudspeaker (IKO), a compact, spherical loudspeaker array, was recently established and investigated as an instrument to produce auditory sculptures (i.e., 3-D sonic imagery) in electroacoustic music. Sound beams in the horizontal plane most effectively and expressively produce auditory objects via lateral reflections on sufficiently close walls and baffles. Can there be 3-D-printable arrays at drastically reduced cost and transducer count, but with similarly strong directivity in the horizontal plane? To find out, we adopt mixed-order Ambisonics schemes to control fewer, and predominantly horizontal, beam patterns, and we propose the 3|9|3 array as a suitable design, with beamforming crossing over to Ambisonics panning at high frequencies. Analytic models and measurements on hardware prototypes permit a comparison between the new design and the IKO regarding beamforming capacity. Moreover, we evaluate our 15-channel 3|9|3 prototype in listening experiments to find out whether the sculptural qualities and auditory object trajectories it produces are comparable to those of the 20-channel IKO.
The Interplay between Heritage Learners’ Prior Knowledge and Instruction on a Linguistically Complex Structure
Authors: Bowles Melissa A. 
Published: December 2021

Abstract
Current HL pedagogy recommends focus on form approaches (Beaudrie, Ducar, & Potowski, 2014; Kisselev, Dubinina, & Polinsky, 2020) but within this broad category there are many techniques. To date only a few studies have compared HL learning gains on explicit and implicit focus on form instruction, and these have found explicit instruction to be more beneficial. The present study isolated the role of rule presentation on learning gains by comparing Spanish HL learners in a Processing Instruction condition (n = 26) who received rule presentation and explicit information about the target structure (indicative and subjunctive in adverbial clauses of time) prior to structured input, to HL learners in a Structured Input condition (n = 16) who received only structured input. Pretest/posttest/delayed posttest comparisons revealed that both PI and SI resulted in lasting learning gains, as well as a complex interplay between learners’ initial knowledge of the structure and the type of instruction, such that learners with little or no initial knowledge benefited from rule presentation, whereas learners with greater initial knowledge did not. Furthermore, data from think-alouds and retrospective interviews shows that all learners did not process the instruction similarly, and pedagogical implications are discussed.
Code-Switching Knowledge as Heritage Grammar Attainment: A Case Study
Authors: Lipski John M. 
Published: December 2021

Abstract
This study examines sensitivity to putative grammatical constraints on intra-sentential code-switching, viewed as a relative measure of attainment in heritage bilingual grammars. This is exemplified by a series of interactive tasks carried out with heritage Portuguese speakers in Misiones Province, Argentina. The results demonstrate the viability of deploying a range of experimental techniques in field settings with heritage speakers who do not engage in habitual code switching.
A Man of Our Times: Muḥammad ibn Dāwūd al-Iṣbahānī’s Pioneering Vision of Male Love
Authors: Tobkin Jennifer 
Published: December 2021

Abstract
The ghazal chapters of Muḥammad b. Dāwūd al-Iṣbahānī’s poetry anthology Kitāb al-Zahrah include 109 brief poems attributed to baʿḍ ahl hādhā al-ʿaṣr (a Man of Our Times). Ibn Dāwūd has conventionally been assumed to be the author of these poems. The “Man of Our Times” poems stand out among ‘Abbāsid ghazal because of their focus on justice, their appeals to reason, and their depiction of brotherly friendship (ikhā’) imbued with passionate love (hawā). Moreover, their repurposing of motifs from the poetic canon, such as the lover’s desert wanderings and nature’s lamentation in sympathy with him, adds to their tone of erudition. This gives the impression that the relationship they describe is an intense friendship between educated men of similar age. As with other early ʿAbbāsid bodies of ghazal, the poems can be categorized according to rhetorical function. For the “Man of Our Times” poems, these subcategories are 1) personal messages, 2) aphorisms, 3) petitions for justice, 4) alienation narratives, and 5) urban narratives.
The Bear and the Dragon
Authors: Paige Tamsin Phillipa 
Published: December 2021

Abstract
Within the ideological confines of Western liberal democracies, two ‘truths’ are held to be self-evident: that Russia and China are opportunistic in their behaviour, and that this behaviour is strategic rather than sincere. This article is a short, empirical analysis of the justifications of Russia and China when determining a ‘threat to the peace’ in accordance with Article 39 of the Charter of the United Nations. Examining how Russia and China have justified their decisions where this concept was significantly under debate, I find that their behaviour is not as opportunistic as believed. Rather, it is consistent with ideals of pragmatism and state-centric interpretations of international law. I further suggest that the consistency of their approaches means it is of little consequence if their arguments are strategic in nature.
Preventing the Forcibly Displaced from Returning as Persecution and Inhumane Act under International Criminal Law and the Rome Statute
Authors: Katselli Proukaki Elena 
Published: December 2021

Abstract
Preventing the forcibly displaced from returning to the territory from which they were unlawfully expelled has not received adequate attention under international criminal law. This article addresses this gap by focusing on denial of return as a crime against humanity. It evaluates international criminal jurisprudence including the proceedings concerning the Rohingya and evolving human rights standards to show that prevention from returning is a serious and continuing denial of fundamental human rights which inflicts great suffering. As such, it may qualify as persecution and/or an inhumane act under the Rome Statute. The ramifications of this on the temporal and territorial jurisdiction of the International Criminal Court and the principle of legality are important especially in situations of protracted displacement. The article demonstrates that although criminalisation of denial of return is not a panacea, it is instrumental in tackling forced displacement which affects millions across the world.
Multidecadal Sea Level Rise in the Southeast Indian Ocean: The Role of Ocean Salinity Change
Authors: Lu Ying , Li Yuanlong , Duan Jing , Lin Pengfei , Wang Fan 
Published: December 2021

AbstractRegional sea level rise in the southeast Indian Ocean (SEIO) exerts growing threats to the surrounding Australian and Indonesian coasts, but the mechanisms of sea level rise have not been firmly established. By analyzing observational datasets and model results, this study investigates multidecadal steric sea level (SSL) rise of the SEIO since the mid-twentieth century, underscoring a significant role of ocean salinity change. The average SSL rising rate from 1960 through 2018 was 7.4 ± 2.4 mm decade−1, and contributions of the halosteric and thermosteric components were ∼42% and ∼58%, respectively. The notable salinity effect arises primarily from a persistent subsurface freshening trend at 400–1000 m. Further insights are gained through the decomposition of temperature and salinity changes into the heaving (vertical displacements of isopycnal surfaces) and spicing (density-compensated temperature and salinity change) modes. The subsurface freshening trend since 1960 is mainly attributed to the spicing mode, reflecting property modifications of the Subantarctic Mode Water (SAMW) and Antarctic Intermediate Water (AAIW) in the southern Indian Ocean. Also noteworthy is a dramatic acceleration of SSL rise (20.3 ± 7.0 mm decade−1) since ∼1990, which was predominantly induced by the thermosteric component (16.3 ± 5.5 mm decade−1) associated with the heaving mode. Enhanced Ekman downwelling by surface winds and radiation forcing linked to global greenhouse gas warming mutually caused the depression of isopycnal surfaces, leading to the accelerated SSL rise through thermosteric effect. This study highlights the complexity of regional sea level rise in a rapidly changing climate, in which the role of ocean salinity is vital and time-varying.
On the Discrete Normal Modes of Quasigeostrophic Theory
Authors: Yassin Houssam , Griffies Stephen M. 
Published: December 2021

AbstractThe discrete baroclinic modes of quasigeostrophic theory are incomplete, and the incompleteness manifests as a loss of information in the projection process. The incompleteness of the baroclinic modes is related to the presence of two previously unnoticed stationary step-wave solutions of the Rossby wave problem with flat boundaries. These step waves are the limit of surface quasigeostrophic waves as boundary buoyancy gradients vanish. A complete normal-mode basis for quasigeostrophic theory is obtained by considering the traditional Rossby wave problem with prescribed buoyancy gradients at the lower and upper boundaries. The presence of these boundary buoyancy gradients activates the previously inert boundary degrees of freedom. These Rossby waves have several novel properties such as the presence of multiple modes with no internal zeros, a finite number of modes with negative norms, and the fact that their vertical structures form a basis capable of representing any quasigeostrophic state with a differentiable series expansion. These properties are a consequence of the Pontryagin-space setting of the Rossby wave problem in the presence of boundary buoyancy gradients (as opposed to the usual Hilbert-space setting). We also examine the quasigeostrophic vertical velocity modes and derive a complete basis for such modes as well. A natural application of these modes is the development of a weakly nonlinear wave-interaction theory of geostrophic turbulence that takes topography into account.
Hand Motion Analysis Illustrates Differences When Drilling Cadaveric and Printed Temporal Bone
Authors: Hochman Jordan B. , Pisa Justyn , Kazmerik Katrice , Unger Bertram 
Published: December 2021

Objective: Temporal bone simulation is now commonly used to augment cadaveric education. Assessment of these tools is ongoing, with haptic modeling illustrating dissimilar motion patterns compared to cadaveric opportunities. This has the potential to result in maladaptive skill development. It is hypothesized that trainee drill motion patterns during printed model dissection may likewise demonstrate dissimilar hand motion patterns. Methods: Resident surgeons dissected 3D-printed temporal bones generated from microCT data and cadaveric simulations. A magnetic position tracking system (TrakSTAR Ascension, Yarraville, Australia) captured drill position and orientation. Skill assessment included cortical mastoidectomy, thinning procedures (sigmoid sinus, dural plate, posterior canal wall) and facial recess development. Dissection was performed by 8 trainees (n = 5 < PGY3 > n = 3) using k-cos metrics to analyze drill strokes within position recordings. K-cos metrics define strokes by change in direction, providing metrics for stroke duration, curvature, and length. Results: T-tests between models showed no significant difference in drill stroke frequency (cadaveric = 1.36/s, printed = 1.50/s, P < .40) but demonstrate significantly shorter duration (cadaveric = 0.37 s, printed = 0.16 s, P < .01) and a higher percentage of curved strokes (cadaveric = 31, printed = 67, P < .01) employed in printed bone dissection. Junior staff used a higher number of short strokes (junior = 0.54, senior = 0.38, P < .01) and higher percentage of curved strokes (junior = 35%, senior = 21%, P < .01). Conclusions: Significant differences in hand motions were present between simulations, however the significance is unclear. This may indicate that printed bone is not best positioned to be the principal training schema.
Impact of Stress Ulcer Prophylaxis Discontinuation Guidance in Mechanically Ventilated, Critically Ill Patients: A Pre-Post Cohort Study
Authors: Jones Christopher A. , Betthauser Kevin D. , Lizza Bryan D. , Juang Paul A. , Micek Scott T. , Kollef Marin H. 
Published: December 2021

Purpose: Recent data highlight unclear efficacy and potential negative sequelae of stress ulcer prophylaxis (SUP) in the intensive care unit (ICU). Minimizing SUP exposure has pertinent clinical and other implications. This study assessed medication use and clinical outcomes before and after implementation of a practice guideline promoting early discontinuation of SUP in mechanically ventilated ICU patients. Methods: Retrospective, single-center, pre-post cohort study within a medical ICU at a large, academic medical center. Adult patients requiring mechanical ventilation and receiving SUP via a histamine-2 receptor antagonist (H2RA) or proton pump inhibitor (PPI) were eligible for inclusion. The clinical practice guideline was implemented on January 1, 2020. The impact of implementation was assessed via percent of patient-days with inappropriate SUP. Incidence of clinically important GI bleed was the primary safety outcome. Results: A total of 137 pre-guideline and 112 post-guideline patients were included. Comorbidity burden was similar between groups. A higher prevalence of baseline vasopressor receipt (39% vs 67%, P < .01) and acute kidney injury (56% vs 69%, P = .04) was observed in post-guideline patients. Post-guideline patients experienced a significantly lower percentage of patient-days of inappropriate SUP (25% vs 50%, P < .01) as well as higher rates of SUP discontinuation before extubation (71% vs 12%, P < .01) and during ICU stay (93% vs 50%, P < .01). Post-guideline patients observed a significantly lower incidence of SUP at hospital discharge (4% vs 35%, P < .01). No differences in bleeding outcomes were observed, though post-guideline patients experienced longer durations of mechanical ventilation, ICU stay, and hospital stay. Conclusions: Implementation of an early SUP discontinuation guideline was associated with significant improvements in SUP prescribing practices. Baseline differences between groups likely explain observed differences in clinical outcomes.