bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative Single-Cell and Bulk Transcriptomes Analyses Identify Intrinsic HNSCC Subtypes with Distinct Prognoses and Therapeutic Vulnerabilities
Authors: Dai Yibin , Wang Ziyu , Xia Yingchao , Li Jin , Wu Yaping , Wang Yanling , Jiang Hongbing , Cheng Jie 
Published: June 2023

Abstract

Purpose:
Tumor heterogeneity in head and neck squamous cell carcinoma (HNSCC) profoundly compromises patient stratification, personalized treatment planning, and prognostic prediction, which underscores the urgent need for more effective molecular subtyping for this malignancy. Here, we sought to define the intrinsic epithelial subtypes for HNSCC by integrative analyses of single-cell and bulk RNA sequencing datasets from multiple cohorts and assess their molecular features and clinical significance.

Experimental Design:
Malignant epithelial cells were identified from single-cell RNA sequencing (scRNA-seq) datasets and subtyped on the basis of differentially expressed genes. Subtype-specific genomic/epigenetic abnormalities, molecular signaling, genetic regulatory network, immune landscape, and patient survival were characterized. Therapeutic vulnerabilities were further predicted on the basis of drug sensitivity datasets from cell lines, patient-derived xenograft models, and real-world clinical outcomes. Novel signatures for prognostication and therapeutic prediction were developed by machine learning and independently validated.

Results:
Three intrinsic consensus molecular subtypes (iCMS1–3) for HNSCC were proposed from scRNA-seq analyses and recapitulated in 1,325 patients from independent cohorts using bulk-sequencing datasets. iCMS1 was characterized by EGFR amplification/activation, stromal-enriched environment, epithelial-to-mesenchymal transition, worst survival, and sensitivities to EGFR inhibitor. iCMS2 was featured by human papillomavirus–positive oropharyngeal predilection, immune-hot, susceptibilities to anti–PD-1, and best prognosis. Moreover, iCMS3 displayed immune-desert and sensitivities to 5-FU and MEK, STAT3 inhibitors. Three novel, robust signatures derived from iCMS subtype-specific transcriptomics features were developed by machine learning for patient prognostication and cetuximab and anti–PD-1 response predictions.

Conclusions:
These findings reiterate molecular heterogeneity of HNSCC and advantages of scRNA-seq in pinpointing cellular diversities in complex cancer ecosystems. Our HNSCC iCMS regime might facilitate accurate patient stratification and individualized precise treatment.
Longitudinal Hemodynamic Correlates of and Sex Differences in the Evolution of Blood Pressure Across the Adult Lifespan: The Framingham Heart Study
Authors: Mitchell Gary F. , Rong Jian , Larson Martin G. , Cooper Leroy L. , Xanthakis Vanessa , Benjamin Emelia J. , Hamburg Naomi M. , Vasan Ramachandran S. 
Published: June 2023

Background
Systolic blood pressure increases with age after midlife, particularly in women, and contributes to development of wide pulse pressure hypertension in middle‐aged and older adults. Relative contributions of aortic stiffness and premature wave reflection to increases in pulse pressure remain controversial.

Methods and Results

We evaluated visit‐specific values and change in key correlates of pulse pressure, aortic characteristic impedance, forward and backward wave amplitude, and global reflection coefficient, at 3 sequential examinations of the Framingham Generation 3 (N=4082), Omni‐2 (N=410), and New Offspring Spouse (N=103) cohorts (53% women). Data were analyzed using repeated‐measures linear mixed models adjusted for age, sex, and risk factor exposures. Pulse pressure increased markedly with age after midlife (age and age‐squared terms,
P
<0.0001), particularly in women (age slope 3.1±0.2 mm Hg/decade higher in women,
P
<0.0001). In sex‐specific models, change in pulse pressure was closely related (all
P
<0.0001) to baseline (6.7±0.2 and 7.3±0.2 mm Hg/SD in men and women, respectively) and change (11.8±0.1 and 11.7±0.1 mm Hg/SD) in forward wave amplitude, whereas relations with baseline (2.1±0.15 and 2.0±0.14 mm Hg/SD) and change (4.0±0.13 and 3.4±0.11 mm Hg/SD) in global reflection coefficient were weaker. Global reflection coefficient fell as aortic characteristic impedance increased (
P
<0.0001), consistent with the hypothesis that impedance matching reduces relative wave reflection in the arterial system.

Conclusions
Proximal aortic stiffening, as assessed by higher aortic characteristic impedance and larger forward wave amplitude, is strongly associated with longitudinal increase in pulse pressure, especially in women, whereas wave reflection has more modest relations.
Comparative Outcomes of Interventions for Femoropopliteal Chronic Total Occlusion Versus Non–Chronic Total Occlusion Lesions From the Multicenter XLPAD Registry
Authors: Tsai Shirling , Liu Yulun , Hoang Lawrence , Vu Michael , Lu Hua , Ramanan Bala , Fernandez Vazquez David , Rosol Zachary , Sayfo Sameh , Alaiti Mohamad Amer , Koutakis Panagiotis , Brilakis Emmanouil S. , Shishehbor Mehdi H. , Banerjee Subhash 
Published: June 2023

Background
Endovascular intervention of femoropopliteal chronic total occlusions (CTOs) is technically more complex. However, there is lack of comparative analysis between CTO and non‐CTO femoropopliteal interventions.

Methods and Results

We report procedural details and outcomes of patients treated for femoropopliteal CTO and non‐CTO lesions in the XLPAD (Excellence in Peripheral Artery Disease) registry (NCT01904851) between 2006 and 2019. Primary outcomes were procedural success and 1‐year major adverse limb events, a composite of all‐cause death, target limb revascularization, or major amputation. Analysis included 2895 patients (CTO: n=1516 patients; non‐CTO: n=1379 patients) with 3658 lesions (CTO: n=1998 lesions; non‐CTO: n=1660 lesions). Conventional balloon angioplasty (20.86% versus 33.48%,
P
<0.001) or drug‐coated balloon angioplasty (1.26% versus 2.93%,
P
<0.001) were more frequent in the non‐CTO group, whereas bare‐metal stents (28.09% versus 20.22%,
P
<0.001) or covered stents (4.08% versus 1.83%,
P
<0.001) were more frequent in the CTO group. Debulking procedures were more commonly performed in the non‐CTO group (41.44% versus 53.13%,
P
<0.001), despite a similar degree of calcification between the 2 groups. Procedural success was higher in the non‐CTO group (90.12% versus 96.79%,
P
<0.001). Procedural complications were higher in the CTO group (7.21% versus 4.66%,
P
=0.002), mainly due to excess distal embolization (1.5% versus 0.6%,
P
=0.015). Adjusted 1‐year major adverse limb events were higher in the CTO group (22.47% versus 18.77%,
P
=0.019), driven mainly by target limb revascularization (19.00% versus 15.34%,
P
=0.013).

Conclusions
Procedural success is lower for endovascular treatment of femoropopliteal CTO compared with non‐CTO lesions. CTO lesions are associated with higher rates of periprocedural complications and reinterventions after 1 year.
Lymphatic Abnormalities on Magnetic Resonance Imaging in Single‐Ventricle Congenital Heart Defects Before Glenn Operation
Authors: Kristensen Rasmus , Kelly Benjamin , Kim Emily , Dori Yoav , Hjortdal Vibeke E. 
Published: June 2023

Background
In the palliative pathway of single‐ventricle physiology, lymphatic abnormalities on T2‐weighted magnetic resonance imaging have been shown after the Glenn operation. It is believed that postsurgical hemodynamic changes contribute to the lymphatic changes.However, little is known about how early these abnormalities occur. Our purpose was to determine if lymphatic abnormalities occur as early as before the Glenn operation.

Methods and Results

We retrospectively reviewed patients with single‐ventricle physiology and a T2‐weighted magnetic resonance imaging scan before their Glenn operation (superior cavopulmonary connection) at The Children's Hospital of Philadelphia from 2012 to 2022. Lymphatic perfusion patterns on T2‐magnetic resonance imaging were categorized from type 1 (no supraclavicular T2‐signal) to type 4 (supraclavicular, mediastinal, lung parenchymal T2‐signal). Types 1 and 2 were considered normal variants. Distribution of lymphatic abnormalities were tabulated, as well as secondary outcomes including chylothorax and mortality. Comparison was done using analysis of variance, Kruskal–Wallis test, and Fisher's exact test. Seventy‐one children were included: 30 with hypoplastic left heart syndrome and 41 with nonhypoplastic left heart syndrome. Lymphatic abnormalities were present before Glenn operation in 21% (type 3) and 20% (type 4), and normal lymphatic perfusion patterns (type 1–2) were seen in 59% of patients. Chylothorax was present in 17% (only types 3 and 4). Pre‐Glenn mortality and mortality at any time was significantly increased when having a type 4 lymphatic abnormality compared with types 1 and 2 (
P
=0.04).

Conclusions
Lymphatic abnormalities can be found on T2‐weighted magnetic resonance imaging in children with single‐ventricle physiology before their Glenn operation. Mortality and chylothorax were more prevalent with advancing grade of lymphatic abnormality.
The Parallelism Tradeoff: Limitations of Log-Precision Transformers
Authors: Merrill William , Sabharwal Ashish 
Published: June 2023

AbstractDespite their omnipresence in modern NLP, characterizing the computational power of transformer neural nets remains an interesting open question. We prove that transformers whose arithmetic precision is logarithmic in the number of input tokens (and whose feedforward nets are computable using space linear in their input) can be simulated by constant-depth logspace-uniform threshold circuits. This provides insight on the power of transformers using known results in complexity theory. For example, if L≠P (i.e., not all poly-time problems can be solved using logarithmic space), then transformers cannot even accurately solve linear equalities or check membership in an arbitrary context-free grammar with empty productions. Our result intuitively emerges from the transformer architecture’s high parallelizability. We thus speculatively introduce the idea of a fundamental parallelism tradeoff: any model architecture as parallelizable as the transformer will obey limitations similar to it. Since parallelism is key to training models at massive scale, this suggests a potential inherent weakness of the scaling paradigm.
Atezolizumab-induced cerebellar ataxia in a patient with metastatic small cell lung cancer: A case report and literature review
Authors: Kapagan Tanju , Aksu Faruk , Yuzkan Sabahattin , Bulut Nilufer , Erdem Gokmen Umut 
Published: June 2023

Introduction The use of immune checkpoint inhibitors, which have an important role in the treatment of malignant tumors, is increasing. Although rarely observed, neurological immune-related adverse events associated with immune checkpoint inhibitors result in high morbidity and mortality. Small cell lung cancer is a common cause of neurological paraneoplastic syndromes. The differentiation between paraneoplastic syndromes and neurological immune-related adverse events is important in patients using immune checkpoint inhibitors. Cerebellar ataxia caused by atezolizumab is a rare immune-related adverse event. Case report In this context, we present a 66-year-old man with small cell lung cancer who developed immune-mediated cerebellar ataxia after three cycles of atezolizumab, a programmed cell death ligand-1 inhibitor. The admission of brain and spinal gadolinium-based contrast-enhanced magnetic resonance imaging supported the preliminary diagnosis and indicated leptomeningeal involvement. However, the blood tests and a lumbar puncture did not reveal any structural, biochemical, paraneoplastic, or infectious cause. Management and outcome High-dose steroid treatment resulted in an improvement in the radiological involvement, as evidenced both clinically and on follow-up whole spine magnetic resonance imaging. Therefore, the immunotherapy was discontinued. The patient was discharged on day 20 without neurological sequelae. Discussion In light of this, we present this case to emphasize the differential diagnosis of neurological immune-related adverse events originating from immune checkpoint inhibitors, which require rapid diagnosis and treatment, and clinically similar paraneoplastic syndromes and radiologically similar leptomeningeal involvement, in a case of small cell lung cancer.
Safety and efficacy of Vitamin C, Vitamin E, and selenium supplementation in the oncology setting: A systematic review
Authors: Barnhart AS , Anthony AL , Conaway KR , Sibbitt BG , Delaney E , Haluschak J , Kathula S , Chen AMH 
Published: June 2023

Objective With rising rates of complementary and alternative medicine (CAM) use, the exploration of CAM integration into oncology treatments is becoming increasingly prevalent. Antioxidants have been proposed as potentially beneficial to prevent or treat cancer. However, evidence summaries are limited, and the United States Preventive Services Task Force has recently recommended the use of Vitamin C and E supplementation for cancer prevention. Thus, the objective of this systematic review is to evaluate the existing literature on the safety and efficacy of antioxidant supplementation in oncology patients. Methods A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using prespecified search terms in PubMed and CINAHL. Two reviewers independently reviewed titles, abstracts, and full-text articles, with a third reviewer resolving conflicts, before the included articles underwent data extraction and quality appraisal. Results Twenty-four articles met the inclusion criteria. Of the included studies, nine evaluated selenium, eight evaluated Vitamin C, four evaluated Vitamin E, and three of these studies included a combination of two or more of these agents. The most frequently evaluated cancer types included colorectal cancer ( n = 4), leukemias ( n = 4), breast cancer ( n = 3), and genitourinary cancers ( n = 3). Most of the studies focused on the antioxidants’ therapeutic efficacy ( n = 15) or their use in protecting against chemotherapy- or radiation-induced side effects ( n = 8), and one study evaluated the role of an antioxidant in protection against cancer. Findings were generally favorable among the studies, and adverse effects of supplementation were limited. Furthermore, the average score for all the included articles on the Mixed Methods Appraisal Tool was 4.2, indicating the high quality of the studies. Conclusions Antioxidant supplements may provide benefits in reducing incidence or severity of treatment-induced side effects with limited risk for adverse effects. Large, randomized controlled trials are needed to confirm these findings among various cancer diagnoses and stages. Healthcare providers should understand the safety and efficacy of these therapies to address questions that arise in caring for those with cancer.
8-Hydroxy-2′-deoxyguanosine and malondialdehyde in plasma and their association with disease severity in 20 cats with chronic kidney disease
Authors: Nishi Reo , Harada Airi , Hori Koji , Maeda Shingo , Momoi Yasuyuki , Yonezawa Tomohiro 
Published: June 2023

Objectives Oxidative stress is associated with the development and progression of chronic kidney disease (CKD) in humans. The aim of this study was to evaluate the concentrations of oxidative stress markers, 8-hydroxy-2′-deoxyguanosine (8-OHdG) and malondialdehyde (MDA), in the plasma and urine of cats with different stages of CKD. Methods Plasma and urine samples were collected from cats with CKD that were referred to the Veterinary Medical Center of the University of Tokyo between April 2019 and October 2022. Plasma and urine samples were collected from healthy cats (n = 6 at most), cats with stage 2 CKD (n = 8) and stage 3–4 CKD (n = 12), and cats with idiopathic cystitis (disease control, n = 5). Plasma and urine concentrations of 8-OHdG and MDA were measured using ELISA and thiobarbituric acid reactive substances assay kits, respectively. Results The median plasma 8-OHdG concentrations were 0.156 ng/ml (<0.125–0.210 ng/ml) in the healthy group, <0.125 ng/ml (range <0.125 ng/ml) in the idiopathic cystitis group, 0.246 ng/ml (range 0.170–0.403 ng/ml) in cats with stage 2 CKD and 0.433 ng/ml (range 0.209–1.052 ng/ml) in cats with stage 3–4 CKD. Concentrations in stage 3–4 CKD were significantly higher than those in the healthy and disease control groups. Plasma MDA concentrations were low in the healthy and disease control groups and significantly higher in cats with stage 3–4 CKD. In every cat with CKD, plasma 8-OHdG and MDA concentrations were positively correlated with plasma creatinine concentrations (8-OHdG, rs = 0.68; MDA, rs = 0.67). Urinary 8-OHdG/urinary creatinine (u-CRE) and urinary MDA/u-CRE levels did not differ significantly between the groups; however, it was difficult to evaluate them because of the small sample size. Conclusions and relevance This report shows that plasma 8-OHdG and MDA concentrations increase with the severity of feline CKD. These markers may be useful for assessing oxidative stress in cats with CKD.
Evaluating the efficacy and safety of transitioning patients with multiple sclerosis from natalizumab to ocrelizumab (OCTAVE)
Authors: Smoot Kyle , Marginean Horia , Gervasi-Follmar Tiffany , Chen Chiayi , Repovic Pavle , Cohan Stanley 
Published: June 2023

Introduction: Natalizumab is associated with a risk of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients infected with John Cunningham virus (JCV). Ocrelizumab has demonstrated efficacy to treat MS; however, its safety in patients previously treated with natalizumab is unclear. Objective: To evaluate the safety and efficacy of ocrelizumab in patients with relapsing MS (RMS) previously treated with natalizumab. Methods: Clinically and radiographically stable RMS patients, ages 18–65 treated with natalizumab for ⩾ 12 months, were enrolled in the study and initiated ocrelizumab 4–6 weeks after their final dose of natalizumab. Relapse assessment, expanded disability status scale, and brain magnetic resonance imaging (MRI) were performed prior to starting ocrelizumab and at months 3, 6, 9, and 12. Results: Forty-three patients were enrolled, and 41 (95%) completed the study. Two patients had a relapse while on ocrelizumab, one at month 9 and the other at month 12, without changes on brain MRI. Two additional patients had new brain MRI lesions detected at month 3, with no new symptoms. Thirteen serious adverse events (SAEs) were recorded, four of which were considered possibly related to ocrelizumab. Conclusion: Overall, our study indicates clinical and MRI stability for most patients transitioning from natalizumab to ocrelizumab. ClinicalTrials.gov Identifier: NCT03157830
Numerical simulation on the acoustic wave scattering and fluid perturbations inside confined orifice flow
Authors: Chen Wenyu , Wang Peng , Liu Yingzheng 
Published: June 2023

Acoustic wave scattering and fluid perturbations produced by interactions between incident acoustic wave and confined orifice flow were investigated by a combined numerical solution containing nonlinear flow simulation and linearized acoustic simulation. In flow simulations, the mainstream Reynolds number was fixed at 10,000, which relates to the cooling pipe system of lithography. Turbulent flow fields corresponding to different orifice geometries were solved by an opensource finite volume solver OpenFOAM with Reynolds-averaged Navier–Stokes turbulence model. The turbulence database could efficiently improve the accuracy of subsequent linearized acoustic simulations as the viscosity dissipations were considered. In acoustic simulations, the linearized Navier-Stokes equations were solved by a finite element solver with transformation into frequency domain. The incident acoustic waves with varying frequencies from 500 Hz to 4000 Hz were arranged first at the inlet and then the outlet surfaces, enabling a two-port analysis on the transmission and reflection coefficients of acoustic waves. The numerical setup and the two-port model were well validated by results in literature. Generally, acoustic waves tend to gradually dissipate as their frequencies increase or the opening ratio of the ducted orifice decreases. However, the nonlinear variation in the transmission and reflection coefficients against the frequency variation of the incident acoustic waves could be investigated by increasing the thickness ratio. The acoustically induced fluid perturbations that were characterized by the Q-criterion could form a ring shape vortex structure in the vicinity of the orifice edge and then develop into disk-like packets. When the circumferential shape of the orifice was changed to a square, the attenuation of the incident acoustic waves corresponded to the intensity of the three-dimensionality of the acoustic-induced vortex structures, which indicated a greater energy transfer from the acoustic waves to the fluid perturbations.
Open Emergency Repair of a Thoracoabdominal Aortic Aneurysm on a 12-Year-Old Boy With Tuberous Sclerosis
Authors: Corso-Ramirez Julian M. , López Mariana Molina , Flórez Paula Camila , Barrera-Carvajal Juan Guillermo , Mackenzie Jaime Camacho 
Published: June 2023

Tuberous sclerosis complex is a neurocutaneous syndrome caused by an autosomal dominant genetic disorder. This condition can lead to the expression of many vascular anomalies especially, in the pediatric population. Likewise, it has been linked with aortic aneurysm development. We report a case of a 12-year-old boy who presented a 97 × 70 mm Crawford type IV thoracoabdominal aortic aneurysm. Satisfactory open surgical repair was performed with an 18-mm multibranched dacron tube graft. Clinical and imaging findings revealed a de novo tuberous sclerosis diagnosis. The patient was discharged uneventfully during a 1-month follow-up.
Informed consent process for emergency surgery: A scoping review of stakeholders’ perspectives, challenges, ethical concepts, and policies
Authors: Kituuka Olivia , Munabi Ian Guyton , Mwaka Erisa Sabakaki , Galukande Moses , Harris Michelle , Sewankambo Nelson 
Published: June 2023

Background: A scoping review of literature about the informed consent process for emergency surgery from the perspectives of the patients, next of kin, emergency staff, and available guiding policies. Objectives: To provide an overview of the informed consent process for emergency surgery; the challenges that arise from the perspectives of the patients, emergency staff, and next of kin; policies that guide informed consent for emergency surgery; and to identify any knowledge gaps that could guide further inquiry in this area. Methods: We searched Google Scholar, PubMed/MEDLINE databases as well as Sheridan Libraries and Welch Medical Library from 1990 to 2021. We included journal articles published in English and excluded non-peer-reviewed journal articles, unpublished manuscripts, and conference abstracts. The themes explored were emergency surgery consent, ethical and theoretical concepts, stakeholders’ perceptions, challenges, and policies on emergency surgery. Articles were reviewed by three independent reviewers for relevance. Results: Of the 65 articles retrieved, 18 articles were included. Of the 18 articles reviewed, 5 addressed emergency informed consent, 9 stakeholders’ perspectives, 7 the challenges of emergency informed consent, 3 ethical and theoretical concepts of emergency informed consent, and 3 articles addressed policies of emergency surgery informed consent. Conclusion: There is poor satisfaction in the informed consent process in emergency surgery. Impaired capacity to consent and limited time are a challenge. Policies recommend that informed consent should not delay life-saving emergency care and patient’s best interests must be upheld.