bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune dysfunction revealed by digital spatial profiling of immuno-oncology markers in progressive stages of renal cell carcinoma and in brain metastases
Authors: Schoenfeld David A , Moutafi Myrto , Martinez Sandra , Djureinovic Dijana , Merkin Ross D , Adeniran Adebowale , Braun David A , Signoretti Sabina , Choueiri Toni K , Parisi Fabio , Hurwitz Michael , Rimm David L , Wei Wei , Jilaveanu Lucia , Kluger Harriet M 
Published: August 2023

BackgroundThe tumor microenvironment (TME) contributes to cancer progression and treatment response to therapy, including in renal cell carcinoma (RCC). Prior profiling studies, including single-cell transcriptomics, often involve limited sample sizes and lack spatial orientation. The TME of RCC brain metastases, a major cause of morbidity, also remains largely uncharacterized.MethodsWe performed digital spatial profiling on the NanoString GeoMx platform using 52 validated immuno-oncology markers on RCC tissue microarrays representing progressive stages of RCC, including brain metastases. We profiled 76 primary tumors, 27 adjacent histologically normal kidney samples, and 86 metastases, including 24 brain metastases.ResultsWe observed lower immune checkpoint (TIM-3 and CTLA-4), cytolytic (GZMA and GZMB), and T cell activation (CD25) protein expression in metastases compared with primary tumors in two separate cohorts. We also identified changes in macrophages in metastases, with brain metastases-susceptible patients showing less M1-like, inflammatory macrophage markers (HLA-DR and CD127) in metastatic samples. A comparison of brain metastases to extracranial metastases revealed higher expression of the anti-apoptotic, BCL-2-family protein BCL-XL and lower expression of the innate immune activator STING in brain metastases. Lower TIM-3 and CD40 in the TME of brain metastases appear to be associated with longer survival, a finding that requires further validation.ConclusionsCompared with primary tumors, RCC metastases, including brain metastases, express lower levels of numerous markers of immune activation and current or investigational therapeutic targets. Our findings may have important implications for designing future biomarker and treatment studies and may aid in development of brain metastases-specific therapies.
Deep phenotyping of the neuroimaging and skeletal features in KBG syndrome: a study of 53 patients and review of the literature
Authors: Peluso Francesca , Caraffi Stefano G , Contrò Gianluca , Valeri Lara , Napoli Manuela , Carboni Giorgia , Seth Alka , Zuntini Roberta , Coccia Emanuele , Astrea Guja , Bisgaard Anne-Marie , Ivanovski Ivan , Maitz Silvia , Brischoux-Boucher Elise , Carter Melissa T , Dentici Maria Lisa , Devriendt Koenraad , Bellini Melissa , Digilio Maria Cristina , Doja Asif , Dyment David A , Farholt Stense , Ferreira Carlos R , Wolfe Lynne A , Gahl William A , Gnazzo Maria , Goel Himanshu , Grønborg Sabine Weller , Hammer Trine , Iughetti Lorenzo , Kleefstra Tjitske , Koolen David A , Lepri Francesca Romana , Lemire Gabrielle , Louro Pedro , McCullagh Gary , Madeo Simona F , Milone Annarita , Milone Roberta , Nielsen Jens Erik Klint , Novelli Antonio , Ockeloen Charlotte W. , Pascarella Rosario , Pippucci Tommaso , Ricca Ivana , Robertson Stephen P , Sawyer Sarah , Falkenberg Smeland Marie , Stegmann Sander , Stumpel Constanze T , Goel Amy , Taylor Juliet M , Barbuti Domenico , Soresina Annarosa , Bedeschi Maria Francesca , Battini Roberta , Cavalli Anna , Fusco Carlo , Iascone Maria , Van Maldergem Lionel , Venkateswaran Sunita , Zuffardi Orsetta , Vergano Samantha , Garavelli Livia , Bayat Allan 
Published: August 2023

BackgroundKBG syndrome is caused by haploinsufficiency ofANKRD11and is characterised by macrodontia of upper central incisors, distinctive facial features, short stature, skeletal anomalies, developmental delay, brain malformations and seizures. The central nervous system (CNS) and skeletal features remain poorly defined.MethodsCNS and/or skeletal imaging were collected from molecularly confirmed individuals with KBG syndrome through an international network. We evaluated the original imaging and compared our results with data in the literature.ResultsWe identified 53 individuals, 44 with CNS and 40 with skeletal imaging. Common CNS findings included incomplete hippocampal inversion and posterior fossa malformations; these were significantly more common than previously reported (63.4% and 65.9% vs 1.1% and 24.7%, respectively). Additional features included patulous internal auditory canal, never described before in KBG syndrome, and the recurrence of ventriculomegaly, encephalic cysts, empty sella and low-lying conus medullaris. We found no correlation between these structural anomalies and epilepsy or intellectual disability. Prevalent skeletal findings comprised abnormalities of the spine including scoliosis, coccygeal anomalies and cervical ribs. Hand X-rays revealed frequent abnormalities of carpal bone morphology and maturation, including a greater delay in ossification compared with metacarpal/phalanx bones.ConclusionThis cohort enabled us to describe the prevalence of very heterogeneous neuroradiological and skeletal anomalies in KBG syndrome. Knowledge of the spectrum of such anomalies will aid diagnostic accuracy, improve patient care and provide a reference for future research on the effects ofANKRD11variants in skeletal and brain development.
Reconstruction of the sphenoid sinus erosion or dehiscence after treatment of unruptured intracavernous aneurysms with flow diverter stents
Authors: Lorga Tiago , Pizzuto Silvia , Coskun Oguzhan , Sgreccia Alessandro , Cavazza Martino , Rahman Mohammad Habibur , Rodesch Georges , Di Maria Federico , Consoli Arturo 
Published: August 2023

BackgroundIntracavernous carotid aneurysms (ICCAs) are rare, frequently asymptomatic, with a low rupture risk, which, however, can lead to life-threatening epistaxis. The aim of this study was to assess the effect of the treatment of asymptomatic ICCAs with flow diverters (FD) on sphenoid bone erosion or dehiscence in a selected cohort of patients.MethodsWe retrospectively reviewed all asymptomatic ICCAs with sphenoid bone erosion or dehiscence detected on cone beam CT (CBCT) and treated with FD between December 2018 and December 2022. Patients were followed-up with CBCT and bone reconstruction was blindly evaluated by two interventional neuroradiologists and classified as unchanged, partial, or complete.ResultsA total of 10 patients (women: 90%, mean age 58 years) treated with an FD for an asymptomatic ICCA with associated sphenoid bone erosion or dehiscence were included in this cohort. Sphenoid bone erosion was present in seven patients and dehiscence was observed in the remaining three. After treatment with FD, complete reconstruction of the sphenoid sinus wall occurred in seven cases, and partial reconstruction in two cases. Sphenoid bone erosion remained unchanged after treatment in only one patient.ConclusionsThe decision to treat asymptomatic and unruptured ICCAs remains challenging due to their benign natural history and low hemorrhagic risk. The presence of sphenoid sinus erosion or dehiscence should not be overlooked since it could be considered as an indication for prophylactic treatment of life-threatening epistaxis. The mechanisms of bone erosion by the aneurysm and of reconstruction after treatment are still to be fully elucidated.
Impact of diabetes on remodelling, microvascular function and exercise capacity in aortic stenosis
Authors: Dattani Abhishek , Brady Emer M , Alfuhied Aseel , Gulsin Gaurav S , Steadman Christopher D , Yeo Jian L , Aslam Saadia , Banovic Marko , Jerosch-Herold Michael , Xue Hui , Kellman Peter , Costet Philippe , Cvijic Mary Ellen , Zhao Lei , Ebert Christina , Liu Laura , Gunawardhana Kushan , Gordon David , Chang Ching-Pin , Arnold J Ranjit , Yates Thomas , Kelly Damian , Hogrefe Kai , Dawson Dana , Greenwood John , Ng Leong L , Singh Anvesha , McCann Gerry P 
Published: August 2023

ObjectiveTo characterise cardiac remodelling, exercise capacity and fibroinflammatory biomarkers in patients with aortic stenosis (AS) with and without diabetes, and assess the impact of diabetes on outcomes.MethodsPatients with moderate or severe AS with and without diabetes underwent echocardiography, stress cardiovascular magnetic resonance (CMR), cardiopulmonary exercise testing and plasma biomarker analysis. Primary endpoint for survival analysis was a composite of cardiovascular mortality, myocardial infarction, hospitalisation with heart failure, syncope or arrhythmia. Secondary endpoint was all-cause death.ResultsDiabetes (n=56) and non-diabetes groups (n=198) were well matched for age, sex, ethnicity, blood pressure and severity of AS. The diabetes group had higher body mass index, lower estimated glomerular filtration rate and higher rates of hypertension, hyperlipidaemia and symptoms of AS. Biventricular volumes and systolic function were similar, but the diabetes group had higher extracellular volume fraction (25.9%±3.1% vs 24.8%±2.4%, p=0.020), lower myocardial perfusion reserve (2.02±0.75 vs 2.34±0.68, p=0.046) and lower percentage predicted peak oxygen consumption (68%±21% vs 77%±17%, p=0.002) compared with the non-diabetes group. Higher levels of renin (log10renin: 3.27±0.59 vs 2.82±0.69 pg/mL, p<0.001) were found in diabetes. Multivariable Cox regression analysis showed diabetes was not associated with cardiovascular outcomes, but was independently associated with all-cause mortality (HR 2.04, 95% CI 1.05 to 4.00; p=0.037).ConclusionsIn patients with moderate-to-severe AS, diabetes is associated with reduced exercise capacity, increased diffuse myocardial fibrosis and microvascular dysfunction, but not cardiovascular events despite a small increase in mortality.
Model based on single-nucleotide polymorphism to discriminate aspirin resistance patients
Authors: Liu Qingyuan , Guo Shuaiwei , Wang Nuochuan , Wang Kaiwen , Mo Shaohua , Li Xiong , Zhang Yanan , He Hongwei , Wang Shuo , Wu Jun 
Published: August 2023

Background
Aspirin is widely used for preventing ischaemic events. About 20%–40% of patients have aspirin resistance (ASR), which prevents them from benefiting from aspirin medication. This study aimed to develop and validate a model based on single-nucleotide polymorphism (SNP) to distinguish ASR patients.

Methods
We included patients with spontaneous intracerebral haemorrhage and continuing antiplatelet therapy from a multicentre, prospective cohort study as the derivation cohort. Thromboelastography (inhibition of arachidonic acid channel<50%) was used to identify ASR. Genotyping was performed to identify the ASR-related SNP. Based on the result of the logistic analysis, the aspirin resistance in the Chinese population score (ASR-CN score) was established, and its accuracy was evaluated using the area under the curve (AUC). Patients receiving dual antiplatelet therapy for unruptured intracranial aneurysm embolism were prospectively included in the validation cohort. After embolism, 30-day ischaemic events, including ischaemic stroke, new or more frequent transient ischaemic attack, stent thrombosis and cerebrovascular death, were recorded.

Results

The derivation cohort included 212 patients (155 male patients and the median age as 59). 87 (41.0%) individuals were identified with ASR. The multivariate logistic analysis demonstrated six SNPs of
GP1BA, TBXA2R, PTGS2
and
NOS3
as risk factors related to ASR. The ASR-CN score integrating these SNPs performed well to discriminate ASR patients from non-ASR patients (AUC as 0.77). Based on the validation cohort of 372 patients receiving antiplatelet therapy after embolism (including 130 ASR patients), the ASR-CN score continued to distinguish ASR patients with good accuracy (AUC as 0.80). Patients with high a ASR-CN score were more likely to suffer from 30-day ischaemic events after embolism (OR, 1.28; 95% CI, 1.10 to 1.50; p=0.002).

Conclusion

GP1BA, TBXA2R, PTGS2
and
NOS3
were SNPs related to ASR. The ASR-CN score is an effective tool to discriminate ASR patients, which may guide antiplatelet therapy.

Clinical trial registration

Surgical Treatments of Antiplatelet Intracerebral Hemorrhage cohort (unique identifier: ChiCTR1900024406,
http://www.chictr.org.cn/edit.aspx?pid=40640&htm=4
).
Stereotactic radiosurgery for haemorrhagic cerebral cavernous malformation: a multi-institutional, retrospective study
Authors: Dumot Chloe , Mantziaris Georgios , Dayawansa Sam , Xu Zhiyuan , Pikis Stylianos , Peker Selcuk , Samanci Yavuz , Ardor Gokce D , Nabeel Ahmed M , Reda Wael A , Tawadros Sameh R , Abdelkarim Khaled , El-Shehaby Amr M N , Emad Eldin Reem M , Elazzazi Ahmed H , Moreno Nuria Martínez , Martínez Álvarez Roberto , Liscak Roman , May Jaromir , Mathieu David , Tourigny Jean-Nicolas , Tripathi Manjul , Rajput Akshay , Kumar Narendra , Kaur Rupinder , Picozzi Piero , Franzini Andrea , Speckter Herwin , Hernandez Wenceslao , Brito Anderson , Warnick Ronald E , Alzate Juan , Kondziolka Douglas , Bowden Greg N , Patel Samir , Sheehan Jason 
Published: August 2023

Background
Cerebral cavernous malformations (CCMs) frequently manifest with haemorrhages. Stereotactic radiosurgery (SRS) has been employed for CCM not suitable for resection. Its effect on reducing haemorrhage risk is still controversial. The aim of this study was to expand on the safety and efficacy of SRS for haemorrhagic CCM.

Methods
This retrospective multicentric study included CCM with at least one haemorrhage treated with single-session SRS. The annual haemorrhagic rate (AHR) was calculated before and after SRS. Recurrent event analysis and Cox regression were used to evaluate factors associated with haemorrhage. Adverse radiation effects (AREs) and occurrence of new neurological deficits were recorded.

Results
The study included 381 patients (median age: 37.5 years (Q1–Q3: 25.8–51.9) with 414 CCMs. The AHR from diagnosis to SRS excluding the first haemorrhage was 11.08 per 100 CCM-years and was reduced to 2.7 per 100 CCM-years after treatment. In recurrent event analysis, SRS, HR 0.27 (95% CI 0.17 to 0.44), p<0.0001 was associated with a decreased risk of haemorrhage, and the presence of developmental venous anomaly (DVA) with an increased risk, HR 1.60 (95% CI 1.07 to 2.40), p=0.022. The cumulative risk of first haemorrhage after SRS was 9.4% (95% CI 6% to 12.6%) at 5 years and 15.6% (95% CI% 9 to 21.8%) at 10 years. Margin doses> 13 Gy, HR 2.27 (95% CI 1.20 to 4.32), p=0.012 and the presence of DVA, HR 2.08 (95% CI 1.00 to 4.31), p=0.049 were factors associated with higher probability of post-SRS haemorrhage. Post-SRS haemorrhage was symptomatic in 22 out of 381 (5.8%) patients, presenting with transient (15/381) or permanent (7/381) neurological deficit. ARE occurred in 11.1% (46/414) CCM and was responsible for transient neurological deficit in 3.9% (15/381) of the patients and permanent deficit in 1.1% (4/381) of the patients. Margin doses >13 Gy and CCM volume >0.7 cc were associated with increased risk of ARE.

Conclusion
Single-session SRS for haemorrhagic CCM is associated with a decrease in haemorrhage rate. Margin doses ≤13 Gy seem advisable.
Invitation strategies and participation in a community-based lung cancer screening programme located in areas of high socioeconomic deprivation
Authors: Goodley Patrick , Balata Haval , Alonso Alberto , Brockelsby Christopher , Conroy Matthew , Cooper-Moss Nicola , Craig Christopher , Evison Matthew , Hewitt Kath , Higgins Coral , Johnson William , Lyons Judith , Merchant Zoe , Rowlands Ailsa , Sharman Anna , Sinnott Nicola , Sperrin Matthew , Booton Richard , Crosbie Philip A J 
Published: August 2023

IntroductionAlthough lung cancer screening is being implemented in the UK, there is uncertainty about the optimal invitation strategy. Here, we report participation in a community screening programme following a population-based invitation approach, examine factors associated with participation, and compare outcomes with hypothetical targeted invitations.MethodsLetters were sent to all individuals (age 55–80) registered with a general practice (n=35 practices) in North and East Manchester, inviting ever-smokers to attend a Lung Health Check (LHC). Attendees at higher risk (PLCOm2012NoRacescore≥1.5%) were offered two rounds of annual low-dose CT screening. Primary care recorded smoking codes (live and historical) were used to model hypothetical targeted invitation approaches for comparison.ResultsLetters were sent to 35 899 individuals, 71% from the most socioeconomically deprived quintile. Estimated response rate in ever-smokers was 49%; a lower response rate was associated with younger age, male sex, and primary care recorded current smoking status (adjOR 0.55 (95% CI 0.52 to 0.58), p<0.001). 83% of eligible respondents attended an LHC (n=8887/10 708). 51% were eligible for screening (n=4540/8887) of whom 98% had a baseline scan (n=4468/4540). Screening adherence was 83% (n=3488/4199) and lung cancer detection 3.2% (n=144) over 2 rounds. Modelled targeted approaches required 32%–48% fewer invitations, identified 94.6%–99.3% individuals eligible for screening, and included 97.1%–98.6% of screen-detected lung cancers.DiscussionUsing a population-based invitation strategy, in an area of high socioeconomic deprivation, is effective and may increase screening accessibility. Due to limitations in primary care records, targeted approaches should incorporate historical smoking codes and individuals with absent smoking records.
Competing Engagement of β-arrestin Isoforms Balances IGF1R/p53 Signaling and Controls Melanoma Cell Chemotherapeutic Responsiveness
Authors: Cismas Sonia , Pasca Sylvya , Crudden Caitrin , Trocoli Drakensjo Iara , Suleymanova Naida , Zhang Simin , Gebhard Benjamin , Song Dawei , Neo Shiyong , Shibano Takashi , Smith Terry J. , Calin George A. , Girnita Ada , Girnita Leonard 
Published: August 2023

Abstract

Constraints on the p53 tumor suppressor pathway have long been associated with the progression, therapeutic resistance, and poor prognosis of melanoma, the most aggressive form of skin cancer. Likewise, the insulin-like growth factor type 1 receptor (IGF1R) is recognized as an essential coordinator of transformation, proliferation, survival, and migration of melanoma cells. Given that β-arrestin (β-arr) system critically governs the anti/pro-tumorigenic p53/IGF1R signaling pathways through their common E3 ubiquitin-protein ligase MDM2, we explore whether unbalancing this system downstream of IGF1R can enhance the response of melanoma cells to chemotherapy. Altering β-arr expression demonstrated that both β-arr1-silencing and β-arr2-overexpression (-β-arr1/+β-arr2) facilitated nuclear-to-cytosolic MDM2 translocation accompanied by decreased IGF1R expression, while increasing p53 levels, resulting in reduced cell proliferation/survival. Imbalance towards β-arr2 (-β-arr1/+β-arr2) synergizes with the chemotherapeutic agent, dacarbazine, in promoting melanoma cell toxicity. In both 3D spheroid models and in vivo in zebrafish models, this combination strategy, through dual IGF1R downregulation/p53 activation, limits melanoma cell growth, survival and metastatic spread. In clinical settings, analysis of the TCGA-SKCM patient cohort confirms β-arr1−/β-arr2+ imbalance as a metastatic melanoma vulnerability that may enhance therapeutic benefit. Our findings suggest that under steady-state conditions, IGF1R/p53-tumor promotion/suppression status-quo is preserved by β-arr1/2 homeostasis. Biasing this balance towards β-arr2 can limit the protumorigenic IGF1R activities while enhancing p53 activity, thus reducing multiple cancer-sustaining mechanisms. Combined with other therapeutics, this strategy improves patient responses and outcomes to therapies relying on p53 or IGF1R pathways.

Implications:
Altogether, β-arrestin system bias downstream IGF1R is an important metastatic melanoma vulnerability that may be conductive for therapeutic benefit.
Theta-band Connectivity within Cognitive Control Brain Networks Suggests Common Neural Mechanisms for Cognitive and Implicit Emotional Control
Authors: Adamczyk Agnieszka K. , Wyczesany Miroslaw 
Published: August 2023

Abstract
Self-control is a core aspect of adaptive human behavior. It allows the attainment of personal goals by regulating unwanted thoughts, emotions, and behavior. Previous research highlighted the crucial role of cognitive control for explicitly pursued self-control and explicit emotion regulation strategies (such as cognitive reappraisal or attentional distraction). The present study investigated whether similar neural mechanisms would be involved in an implicit self-control task that acted as a covert emotion regulation strategy. Thirty-six female participants unscrambled sentences of either neutral (no-regulation condition) or neutral and self-control-related content (regulation condition) before passively viewing negative and neutral pictures. Compared with the no-regulation condition, implicit induction of self-control reduced the amplitude of the late positive potential to negative pictures, indicating successful emotion downregulation. Crucially, implicit self-control enhanced connectivity within the two cognitive control brain networks in the theta frequency band. Specifically, for the frontoparietal network, increased connectivity from the dorsolateral PFC to the intraparietal cortex was observed. For the cingulo-opercular network, increased connectivity from dorsal anterior cingulate cortex to the left anterior insula/frontal operculum and from the right anterior insula/frontal operculum to the dorsal anterior cingulate cortex was observed. These effects were accompanied by a decrease in prestimulus alpha power in the right primary visual cortex, suggesting adjustment of attentional and perceptual processes in preparation for the upcoming affective stimulation. Together, our results indicate that self-control enhances cognitive control that is necessary for setting, maintaining, and monitoring the achievement of self-control behavior, as well as regulation of attentional and emotional processes.
Speaker-induced Suppression in EEG during a Naturalistic Reading and Listening Task
Authors: Kurteff Garret L. , Lester-Smith Rosemary A. , Martinez Amanda , Currens Nicole , Holder Jade , Villarreal Cassandra , Mercado Valerie R. , Truong Christopher , Huber Claire , Pokharel Paranjaya , Hamilton Liberty S. 
Published: August 2023

Abstract
Speaking elicits a suppressed neural response when compared with listening to others' speech, a phenomenon known as speaker-induced suppression (SIS). Previous research has focused on investigating SIS at constrained levels of linguistic representation, such as the individual phoneme and word level. Here, we present scalp EEG data from a dual speech perception and production task where participants read sentences aloud then listened to playback of themselves reading those sentences. Playback was separated into immediate repetition of the previous trial and randomized repetition of a former trial to investigate if forward modeling of responses during passive listening suppresses the neural response. Concurrent EMG was recorded to control for movement artifact during speech production. In line with previous research, ERP analyses at the sentence level demonstrated suppression of early auditory components of the EEG for production compared with perception. To evaluate whether linguistic abstractions (in the form of phonological feature tuning) are suppressed during speech production alongside lower-level acoustic information, we fit linear encoding models that predicted scalp EEG based on phonological features, EMG activity, and task condition. We found that phonological features were encoded similarly between production and perception. However, this similarity was only observed when controlling for movement by using the EMG response as an additional regressor. Our results suggest that SIS operates at a sensory representational level and is dissociated from higher order cognitive and linguistic processing that takes place during speech perception and production. We also detail some important considerations when analyzing EEG during continuous speech production.