bluuebunny/crossref_metadata_2025_split huggingface dataset:
The B7-H3–Targeting Antibody–Drug Conjugate m276-SL-PBD Is Potently Effective Against Pediatric Cancer Preclinical Solid Tumor Models
Authors: Kendsersky Nathan M. , Lindsay Jarrett , Kolb E. Anders , Smith Malcolm A. , Teicher Beverly A. , Erickson Stephen W. , Earley Eric J. , Mosse Yael P. , Martinez Daniel , Pogoriler Jennifer , Krytska Kateryna , Patel Khushbu , Groff David , Tsang Matthew , Ghilu Samson , Wang Yifei , Seaman Steven , Feng Yang , Croix Brad St. , Gorlick Richard , Kurmasheva Raushan , Houghton Peter J. , Maris John M. 
Published: February 2021

Abstract

Purpose:
Patients with relapsed pediatric solid malignancies have few therapeutic options, and many of these patients die of their disease. B7-H3 is an immune checkpoint protein encoded by the CD276 gene that is overexpressed in many pediatric cancers. Here, we investigate the activity of the B7-H3–targeting antibody–drug conjugate (ADC) m276-SL-PBD in pediatric solid malignancy patient-derived (PDX) and cell line–derived xenograft (CDX) models.

Experimental Design:
B7-H3 expression was quantified by RNA sequencing and by IHC on pediatric PDX microarrays. We tested the safety and efficacy of m276-SL-PBD in two stages. Randomized trials of m276-SL-PBD of 0.5 mg/kg on days 1, 8, and 15 compared with vehicle were performed in PDX or CDX models of Ewing sarcoma (N = 3), rhabdomyosarcoma (N = 4), Wilms tumors (N = 2), osteosarcoma (N = 5), and neuroblastoma (N = 12). We then performed a single mouse trial in 47 PDX or CDX models using a single 0.5 m/kg dose of m276-SL-PBD.

Results:
The vast majority of PDX and CDX samples studied showed intense membranous B7-H3 expression (median H-score 177, SD 52). In the randomized trials, m276-SL-PBD showed a 92.3% response rate, with 61.5% of models showing a maintained complete response (MCR). These data were confirmed in the single mouse trial with an overall response rate of 91.5% and MCR rate of 64.4%. Treatment-related mortality rate was 5.5% with late weight loss observed in a subset of models dosed once a week for 3 weeks.

Conclusions:
m276-SL-PBD has significant antitumor activity across a broad panel of pediatric solid tumor PDX models.
Differential Expression of CD49a and CD49b Determines Localization and Function of Tumor-Infiltrating CD8+ T Cells
Authors: Melssen Marit M. , Lindsay Robin S. , Stasiak Katarzyna , Rodriguez Anthony B. , Briegel Amanda M. , Cyranowski Salwador , Rutkowski Melanie R. , Conaway Mark R. , Melief Cornelis J.M. , van der Burg Sjoerd H. , Eyo Ukpong , Slingluff Craig L. , Engelhard Victor H. 
Published: February 2021

Abstract
CD8+ T-cell infiltration and effector activity in tumors are correlated with better overall survival of patients, suggesting that the ability of T cells to enter and remain in contact with tumor cells supports tumor control. CD8+ T cells express the collagen-binding integrins CD49a and CD49b, but little is known about their function or how their expression is regulated in the tumor microenvironment (TME). Here, we found that tumor-infiltrating CD8+ T cells initially expressed CD49b, gained CD49a, and then lost CD49b over the course of tumor outgrowth. This differentiation sequence was driven by antigen-independent elements in the TME, although T-cell receptor (TCR) stimulation further increased CD49a expression. Expression of exhaustion markers and CD49a associated temporally but not mechanistically. Intratumoral CD49a-expressing CD8+ T cells failed to upregulate TCR-dependent Nur77 expression, whereas CD69 was constitutively expressed, consistent with both a lack of productive antigen engagement and a tissue-resident memory-like phenotype. Imaging T cells in live tumor slices revealed that CD49a increased their motility, especially of those in close proximity to tumor cells, suggesting that it may interfere with T-cell recognition of tumor cells by distracting them from productive engagement, although we were not able to augment productive engagement by short-term CD49a blockade. CD49b also promoted relocalization of T cells at a greater distance from tumor cells. Thus, our results demonstrate that expression of these integrins affects T-cell trafficking and localization in tumors via distinct mechanisms, and suggests a new way in which the TME, and likely collagen, could promote tumor-infiltrating CD8+ T-cell dysfunction.
Endovascular Treatment for Acute Ischemic Stroke in Children
Authors: van Es Adriaan C.G.M. , Hunfeld Maayke A.W. , van den Wijngaard Ido , Kraemer Ulrike , Engelen Marc , van Hasselt Boudewijn A.A.M. , Fransen Puck S.S. , Dippel Diederik W.J. , Majoie Charles B.L.M. , van der Lugt Aad , Emmer Bart J. ,   for the MR CLEAN Registry Investigators
Published: February 2021

Background and Purpose:
Multiple trials have shown the efficacy and safety of endovascular therapy (EVT) of acute ischemic stroke in adults. Trials in children are lacking and only case reports and case series exist. However, the long-term outcome of children with acute ischemic stroke can be devastating with significant mortality and morbidity. In this study, we describe the safety and efficacy of EVT in children with anterior circulation acute ischemic stroke who were included in the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands).

Methods:
Patients under the age of 18 years who were treated with EVT for acute ischemic stroke between March 2014 and July 2017 were retrospectively reviewed up to 6 months after EVT. Nine children, aged 13 months to 16 years (median 14 years, interquartile range, 3–15 years), underwent EVT. Stroke cause was thromboembolism in children with end-stage heart failure on left ventricular assist device (4 of these 9 cases). Median time from onset to imaging was 133 minutes. Four children received intravenous alteplase before EVT, with median onset to needle time of 165 minutes. In all but one patient, EVT was technically successful. No major periprocedural complications occurred.

Results:
At 24 hours after EVT, 3 children completely recovered and 4 children showed partial recovery (median National Institutes of Health Stroke Scale, 3.5), whereas 2 patients on left ventricular assist device died within the first week due to the occurrence of multiple strokes. One patient on left ventricular assist device developed a fatal massive intracranial hemorrhage and another child died due to left ventricular assist device-related complications. Among the 5 stroke survivors, all had a favorable outcome (modified Rankin Scale score, 0–2) at 6 months follow-up.

Conclusions:
EVT of children with acute ischemic stroke seems safe and feasible. However, these findings should be interpreted with caution as more and larger studies are needed to clarify the trade-off between risks and benefits of this treatment.
Brain Glucose Metabolism in Cerebral Amyloid Angiopathy
Authors: Bergeret Sébastien , Queneau Mathieu , Rodallec Mathieu , Landeau Brigitte , Chetelat Gaël , Hong Young T. , Dumurgier Julien , Hugon Jacques , Paquet Claire , Farid Karim , Baron Jean-Claude 
Published: February 2021

Background and Purpose:

The in vivo diagnosis of cerebral amyloid angiopathy (CAA) is currently based on the Boston criteria, which largely rely on hemorrhagic features on brain magnetic resonance imaging. Adding to these criteria
18
F-fluoro-deoxy-D-glucose (FDG) positron emission tomography, a widely available imaging modality, might improve their accuracy. Here we tested the hypothesis that FDG uptake is reduced in posterior cortical areas, particularly the primary occipital cortex, which pathologically bear the brunt of vascular Aβ deposition.

Methods:

From a large memory clinic database, we retrospectively included all patients in whom both brain magnetic resonance imaging and FDG positron emission tomography had been obtained as part of routine clinical care and who fulfilled the Boston criteria for probable CAA. None had a history of symptomatic intracerebral hemorrhage. FDG data processing involved (1) spatial normalization to the Montreal Neurology Institute/International Consortium for Brain Mapping 152 space and (2) generation of standardized FDG uptake (relative standardized uptake value; relative to the pons). The relative standardized uptake value data obtained in 13 regions of interest sampling key cortical areas and the cerebellum were compared between the CAA and age-matched control groups using 2 separate healthy subject databases and image-processing pipelines. The presence of significant hypometabolism (2-tailed
P
<0.05) was assessed for the bilaterally averaged regions-of-interest relative standardized uptake values.

Results:

Fourteen patients fulfilling the Boston criteria for probable CAA (≥2 exclusively lobar microbleeds) were identified. Significant hypometabolism (
P
range, 0.047 to <0.0001) consistently affected the posterior cortical areas, including the superior and inferior parietal, primary visual, lateral occipital, lateral temporal, precuneus, and posterior cingulate regions of interest. The anterior cortical areas were marginally or not significantly hypometabolic, and the cerebellum was spared.

Conclusions:
Supporting our hypothesis, significant glucose hypometabolism predominantly affected posterior cortical regions, including the visual cortex. These findings from a small sample may have diagnostic implications but require replication in larger prospective studies. In addition, whether they generalize to CAA-related symptomatic intracerebral hemorrhage warrants specific studies.
Simplicial and topological descriptions of human brain dynamics
Authors: Billings Jacob , Saggar Manish , Hlinka Jaroslav , Keilholz Shella , Petri Giovanni 
Published: February 2021

Abstract
While brain imaging tools like functional magnetic resonance imaging (fMRI) afford measurements of whole-brain activity, it remains unclear how best to interpret patterns found amid the data’s apparent self-organization. To clarify how patterns of brain activity support brain function, one might identify metric spaces that optimally distinguish brain states across experimentally defined conditions. Therefore, the present study considers the relative capacities of several metric spaces to disambiguate experimentally defined brain states. One fundamental metric space interprets fMRI data topographically, that is, as the vector of amplitudes of a multivariate signal, changing with time. Another perspective compares the brain’s functional connectivity, that is, the similarity matrix computed between signals from different brain regions. More recently, metric spaces that consider the data’s topology have become available. Such methods treat data as a sample drawn from an abstract geometric object. To recover the structure of that object, topological data analysis detects features that are invariant under continuous deformations (such as coordinate rotation and nodal misalignment). Moreover, the methods explicitly consider features that persist across multiple geometric scales. While, certainly, there are strengths and weaknesses of each brain dynamics metric space, wefind that those that track topological features optimally distinguish experimentally defined brain states.
The United Nations Convention against Transnational Organized Crime 20 Years from Its Adoption
Authors: Mejía Tania Bañuelos 
Published: February 2021

Abstract
In view of the approaching 20th anniversary, in 2020, of the adoption, by the General Assembly, of the United Nations Convention against Transnational Organized Crime, the present paper identifies and discusses the key strengths and achievements of this international legal instrument and challenges that lie ahead. The paper was written in the context of an academic seminar entitled The Palermo Convention against Transnational Organized Crime 2003–2018: Implementing the Treaty System organized by the University of Ferrara. The paper offers a reflection on what the Convention, the Conference of the Parties thereto, States parties themselves, and the Conference Secretariat have achieved in terms of implementation of the Convention, as well as some food for thought on remaining challenges in this regard.
International Cooperation for the Repression of Core Crimes
Authors: Annoni Alessandra 
Published: February 2021

Abstract
The burden of ensuring the repression of crimes that shock the conscience of mankind lies primarily with States. National prosecution of core crimes, however, relies heavily on inter-State cooperation. The obligation to cooperate in order to bring to justice the authors of war crimes, genocide and crimes against humanity may well be considered as a corollary of the erga omnes obligation to investigate and punish these crimes. The international instruments devoted to the repression of core crimes, however, fail to provide a sufficient regulatory framework for horizontal cooperation in this field, leaving it to States to make use of the tools established under domestic law, or provided by other existing treaties. The UNTOC and its Supplementing Protocols may prove useful in this framework. Even though these instruments were not expressly designed to tackle core crimes, some of the offences covered by them may indeed qualify as crimes against humanity or war crimes, if assisted by the ‘contextual element’ which characterizes the latter crimes. The UNTOC, moreover, can be used to further the prosecution of criminal groups that aid the commission of core crimes for profit.
Stratospheric and Tropospheric Flux Contributions to the Polar Cap Energy Budgets
Authors: Cardinale Christopher J. , Rose Brian E. J. , Lang Andrea L. , Donohoe Aaron 
Published: February 2021

AbstractThe flux of moist static energy into the polar regions plays a key role in the energy budget and climate of the polar regions. While usually studied from a vertically integrated perspective (Fwall), this analysis examines its vertical structure, using the NASA-MERRA-2 reanalysis to compute climatological and anomalous fluxes of sensible, latent, and potential energy across 70°N and 65°S for the period 1980–2016. The vertical structure of the climatological flux is bimodal, with peaks in the middle to lower troposphere and middle to upper stratosphere. The near-zero flux at the tropopause defines the boundary between stratospheric (Fstrat) and tropospheric (Ftrop) contributions toFwall. Especially at 70°N,Fstratis found to be important to the climatology and variability ofFwall, contributing 20.9 W m−2toFwall(19% ofFwall) during the winter and explaining 23% of the variance ofFwall. During winter, an anomalous poleward increase inFstratpreceding a sudden stratospheric warming is followed by an increase in outgoing longwave radiation anomalies, with little influence on the surface energy budget of the Arctic. Conversely, a majority of the energy input by an anomalous poleward increase inFtropgoes toward warming the Arctic surface. Overall,Ftropis found to be a better metric thanFwallfor evaluating the influence of atmospheric circulations on the Arctic surface climate.
Free and Forced Components of Shoaling Long Waves in the Absence of Short-Wave Breaking
Authors: Contardo Stephanie , Lowe Ryan J. , Hansen Jeff E. , Rijnsdorp Dirk P. , Dufois François , Symonds Graham 
Published: February 2021

AbstractLong waves are generated and transform when short-wave groups propagate into shallow water, but the generation and transformation processes are not fully understood. In this study we develop an analytical solution to the linearized shallow-water equations at the wave-group scale, which decomposes the long waves into a forced solution (a bound long wave) and free solutions (free long waves). The solution relies on the hypothesis that free long waves are continuously generated as short-wave groups propagate over a varying depth. We show that the superposition of free long waves and a bound long wave results in a shift of the phase between the short-wave group and the total long wave, as the depth decreases prior to short-wave breaking. While it is known that short-wave breaking leads to free-long-wave generation, through breakpoint forcing and bound-wave release mechanisms, we highlight the importance of an additional free-long-wave generation mechanism due to depth variations, in the absence of breaking. This mechanism is important because as free long waves of different origins combine, the total free-long-wave amplitude is dependent on their phase relationship. Our free and forced solutions are verified against a linear numerical model, and we show how our solution is consistent with prior theory that does not explicitly decouple free and forced motions. We also validate the results with data from a nonlinear phase-resolving numerical wave model and experimental measurements, demonstrating that our analytical model can explain trends observed in more complete representations of the hydrodynamics.
Effectiveness of transcutaneous electrical nerve stimulation as an adjunct to selected physical therapy exercise program on male patients with pudendal neuralgia: A randomized controlled trial
Authors: Eid Marwa M , Rawash Mohamed F , Sharaf Moussa A , Eladl Hadaya Mosaad 
Published: February 2021

Objective: To assess the effectiveness of Transcutaneous Electrical Nerve Stimulation (TENS) combined with selected physical therapy exercise program on male patients with pudendal neuralgia. Design: A double-blinded randomized controlled study. Setting: Out-patient setting. Participants: Fifty-two male participants with pudendal neuralgia (30–50 years) were allocated randomly into two groups; study and control. The same physical therapy exercises were applied to all participants, plus the same prescribed analgesic medication (Etodolac). Participants in the study group received additional TENS and sham TENS were given to those in control group. Intervention: Intervention lasted for 12 weeks, three sessions per week (60 minutes/session). Outcome measures: Numerical pain rating scale and daily Etodolac intake dose were measured before and after intervention. Results: Statistically significant differences were detected in numerical pain rating scale and daily Etodolac intake in favor of the study group ( P < 0.05). After 12 weeks of intervention, the mean ± SD for numerical pain rating scale and daily Etodolac intake were 4.25 ± 1.9 and 259.25 ± 84.4 mg, in the study group, and 6.22 ± 2.22 and 355.55 ± 93.36 mg in the control group, respectively. The mean difference (95% CI) for numerical pain rating scale and daily Etodolac intake was −1.97 (−3.09: −0.83) and −96.3 (−144.9: −47.69), between groups post treatment, respectively. Conclusion: Adding TENS to physical therapy exercise program is more effective than physical therapy program alone in improving pain in male patients with pudendal neuralgia as measured by numerical pain rating scale and daily analgesic intake dose.
Hybrid Repair With Endovascular Debranching of the Aberrant Right Subclavian Artery for Complicated Type B Aortic Dissection in Patients With Kommerell’s Diverticulum
Authors: Chien Yu-Chen , Chou Nai-Kuan , Wu I-Hui 
Published: February 2021

Purpose: Aberrant right subclavian artery (ARSA) associated with Kommerell’s diverticulum (KD) is a common congenital arch anomaly. It can be complicated by type B aortic dissection (TBAD) or aneurysmal formation at its ostium. Recently, hybrid repair with thoracic endovascular aortic repair (TEVAR) has appeared to be more favorable. Due to the normal anatomic proximity of the ARSA to the left subclavian artery (LSA) orifice in KD, coverage of the bilateral subclavian arteries (SCAs) to obtain an adequate proximal landing zone (PLZ) is usually required, and double cervicotomy for SCA revascularization potentially increases the risk of complications. Technique: This technique was demonstrated on a 50-year-old man presenting with progressive aneurysmal formation of KD with ARSA after chronic TBAD. A 3-step technique, namely left cervical debranching with a left common carotid artery to LSA bypass graft, TEVAR, and an LSA-to-ARSA endovascular debranching with a self-expanding covered stent by a through-and-through wire from the right brachial artery to the bypass graft, was performed in a 1-stage repair to cover the primary tear of TBAD and preserve the bilateral SCAs. The postoperative course was uneventful. Conclusion: This technique can prevent complications from double cervicotomy and achieve an adequate PLZ with preservation of the bilateral SCAs for TEVAR.
Label-Free Quantitative Comparison of Cervical Mucus Peptides in Subjects With Endocervical Adenocarcinoma and Adenocarcinoma in Situ
Authors: Shi Feng , Li Xiaohui , Ma Zhifang , Luan Ting , Zhong Tianying , Gu Yun 
Published: February 2021

Purpose: To uncover potential diagnostic biomarkers for endocervical adenocarcinoma (EAC) and adenocarcinoma in situ (AIS). Experimental design: Quantitative label-free liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) peptidomics strategies were employed to profile 8 cervical mucus (CM) samples, including 3 EAC cases, 2 AIS cases and 3 normal controls (Ctrl). Results: Among the 3721 exclusive peptides identified, 12 (5 up-regulated and 7 down-regulated) endogenous peptides were significantly expressed in EAC compared to healthy controls (EAC/Ctrl); 10 (7 up-regulated and 3 down-regulated) endogenous peptides were significantly expressed in AIS compared to healthy controls (AIS/Ctrl); 11 (6 up-regulated and 5 down-regulated) endogenous peptides were significantly expressed in EAC compared to AIS (EAC/AIS) (absolute fold change ≥1.5, Benjamini-Hochberg adjusted p-value ≤0.05). Among these identifications, annexin A1 (ANXA1) was found to be down-regulated both in EAC and AIS, and its unique peptide (FIENEEQEYVQTVK) may be promising indicators for cervical glandular epithelial lesions. Conclusion: This is the first study to utilize CM peptidomics in cervical glandular malignancies, which may reveal the novel noninvasive biomarkers for EAC and AIS.
Posterior Vertebral Column Resection (pVCR) for Severe Thoracolumbar Kyphosis in Patients With Achondroplasia
Authors: Wang Hai , Wang Shengru , Wu Nan , Wang Shujie , Qiu Guixing , Zhang Jianguo 
Published: February 2021

Study Design: Retrospective cohort study. Objective: We aimed to evaluate the safety and validity of posterior vertebral column resection (pVCR) for severe thoracolumbar kyphosis (TLK) in the achondroplasia (ACH) patients. Methods: Seven ACH patients (male: female = 6:1) who underwent pVCR procedures due to severe TLK from December 2008 to December 2017 in the authors’ hospital were included in this retrospective study. Their mean follow-up duration was 67 ± 35 months. Their clinical characteristics, radiologic characteristics, surgical characteristics and surgical complications were reviewed. Results: A total of 8 vertebrae were removed with an average of 5 ± 2 levels of decompression and 9 ± 2 segments instrumented. The mean correction rates of TLKs and the main curves were 73 ± 15% and 87 ± 6%, respectively. Five patients (71%) had preoperative neurological symptoms with a mean Japanese Orthopedic Association (JOA) score of 8 ± 3 points. Their neurological functions were all improved, with a recovery rate of 78 ± 32% for the JOA score at the last follow-up. Four patients (57%) suffered from surgical complications, including rod breakages (43%), neurological complications (28%), dural tears (14%), cerebrospinal fluid leaks (14%) and proximal junction kyphosis (14%). Conclusions: pVCR can offer a good correction for TLK and improve neurological function with extensive laminectomies in ACH patients. But the morbidity of surgical complications is relatively high. Therefore, it is a reserved surgical option for severe TLK in ACH patients by experienced spinal surgeons, especially with apical markedly hypoplastic vertebrae.