bluuebunny/crossref_metadata_2025_split huggingface dataset:
A combined nutritional risk index and carcinoembryonic antigen score predicts the outcome in radically resected colorectal cancer
Authors: Chen Guanzhou , Xie Jiang , Li Panhua , Wang Qin , Ye Qianwen , Feng Shouhan 
Published: July 2024

AbstractBackgroundNutritional risk index (NRI) and carcinoembryonic antigen (CEA) are useful prognostic markers in colorectal cancer (CRC); however, the prognostic value of a combination of the NRI and CEA, namely, the NRI and CEA score (NCS), needs further investigation.MethodsStage I‐III CRC patients were collected and then divided into three subgroups by counting the NCS: NCS 1: high NRI with normal CEA; NCS 2: high NRI with elevated CEA or low NRI with normal CEA; and NCS 3: low NRI with elevated CEA. The differences in outcome, counted as disease‐free survival (DFS) and overall survival (OS), were tested among the subgroups.ResultsA total of 285 patients were enrolled, with 108 in NCS 1, 118 in NCS 2 and 59 in NCS 3. Patient features, including age, tumour deposit, T stage, N stage and TNM stage, were significantly different in the NCS subgroups. Both the DFS (log‐rank = 26.06, P<0.001) and OS (log‐rank = 39.10, P<0.001) were significant in different NCS subgroups, even in maximum tumour diameter ≤4 cm cases (DFS: log‐rank = 21.42, P<0.001; OS: log‐rank = 30.95, P<0.001), and NCS 1 patients displayed the best outcome compared with the rest of the subgroups. NCS was also found to be an independent risk factor for both DFS and OS.ConclusionsNCS was a useful prognostic indicator in stages I–III CRC patients.
Re‐imagining the future state of the ventricular assist device controller interface through human‐centered design
Authors: Hough Rosie , Dunn Jessica Lea , Hepburn Leigh‐Anne 
Published: July 2024

AbstractBackgroundVentricular assist devices (VADs) are effective therapy for patients with end‐stage heart failure. Current VAD controllers offer improved interactivity, yet limitations of the visual, tactile, and auditory interface persist that impact patient experience and quality of life (QoL). This study explores how VAD controllers can be redesigned using a human‐centered design approach to enhance the emotional and functional experience of the device for patients.MethodsVAD patients (n = 21), caregivers (n = 4) and healthcare practitioners (n = 24) were interviewed to uncover design opportunities. From this, a series of realistic scenarios to design for emerged. A “design by analogy” method took inspiration from existing consumer products to ideate new functionality for the VAD wearable system, creating concepts for a controller interface and paired wearable device. An additional 15 patients and 2 caregivers were engaged to explore current VAD controller experiences and evaluate the future‐state concepts.ResultsThis research validated the need for increased automation and emergency functionality in VAD controllers, including remote monitoring of data, accurate communication of battery status, and automated medical alerts for critical device alarms. “Manage my health,” “Feeling normal,” “Social belonging,” “Feeling safe,” and “Sense of control” emerged as key patient concerns to be met by future VAD controller designs.ConclusionsThe study demonstrated an innovative and relevant approach to improve usability of future VAD peripherals. By considering both emotional and functional perspectives in the design of lifesaving medical devices such as VADs, device manufacturers can uncover new opportunities to improve patient QoL through improved user experiences.
How the manner in which data is visualized affects and corrects (mis)perceptions of political polarization
Authors: Tartaglione JonRobert , de‐Wit Lee 
Published: July 2024

AbstractWhile the mechanisms underlying polarization are complex, scholars have consistently found a pervasive overestimation of perceptions of polarization to be a contributing factor. We argue that one mitigation strategy that can work at scale to address such misperceptions might be relatively straightforward: better data visualizations of cross‐party attitudes on key issues. In a large‐scale (N = 6603), international replication, we find that mode of presentation—or the manner in which data are visually presented—plays a significant role in moderating perceptions of polarization, even for longstanding, divisive issues for which partisans would likely hold strong prior beliefs. Additionally, we find the effects that different modes of presentation have on issue‐specific polarization also extend to participant beliefs about overall interparty polarization, with certain modes proving capable of not only promoting less polarized views but also enabling more accurate estimates of the extent to which political groups agree. Finally, our findings also suggest that the manner in which intergroup data are visualized may also exert influence over the degree to which political groups are essentialized—a finding with implications for not only political perception but also for apolitical social psychological phenomena such as dehumanization.
Pathological concordance rate and outcomes by subtype in advanced papillary renal cell carcinoma
Authors: Tripathi Abhishek , Tangen Catherine M. , Plets Melissa , Li Xiaochen , Tretiakova Maria , Humphrey Peter A. , Adeniran Adebowale , Barata Pedro C. , Gulati Shuchi , Bergerot Cristiane D. , Pruthi Deepak K. , Thompson Ian M. , Lara Primo N. , Lerner Seth P. , Pal Sumanta K. , Shuch Brian M. 
Published: July 2024

ObjectiveTo evaluate the clinical significance of subtyping (type 1 vs 2) of papillary renal cell carcinoma (PRCC) in patients treated with targeted therapy, as well as the concordance, sensitivity and positive predictive value (PPV) of local review pathology review.MethodsPatients with advanced refractory PRCC were randomised to receive sunitinib or cabozantinib, crizotinib or savolitinib, stratified by PRCC subtype (type 1, type 2, or not otherwise specified [NOS]/mixed) by local review. Central review was retrospectively conducted by three expert genitourinary pathologists who independently reviewed cases. The sensitivity and PPV of local review were estimated and outcomes [objective response rate (ORR), progression‐free survival (PFS)] were summarised for treatment groups stratified by subtypes by central review.ResultsAmongst the 147 patients reviewed, the prevalence of individual subtypes varied by local or central review (type 1: 17.7% vs 29.3%; type 2: 53.1% vs 45.6%; NOS/mixed: 29.3% vs 25.2%), respectively. Individual cases were frequently reclassified and local pathology review demonstrated low sensitivity (type 1: 48%, 95% confidence interval [CI] 33, 65; type 2: 67%, 95% CI 55, 78; NOS/mixed: 43%, 95% CI 27, 61). The PPVs of local review were 80%, 57.7% and 37% for type 1, 2 and NOS/mixed, respectively. Compared to sunitinib, cabozantinib demonstrated improved PFS for both type 1 and type 2 PRCC subgroups (7.4 vs 9.0 and 2.9 vs 5.6 months, respectfully) as well as higher ORR.ConclusionsThe PRCC subtype assignment did not identify a subset of patients with greater clinical benefit from cabozantinib, with significant discordance between local and central review. Our findings confirm the limited clinical value of pathological subtyping of metastatic PRCC, in line with the recent World Health Organisation 2022 guidelines.Patient summaryIn this study, categorising papillary renal cell carcinoma into type 1 or 2 subtypes showed limited concordance between central and local pathological review and did not enrich for patients more likely to benefit from cabozantinib in the S1500 PAPMET trial.
Advanced optical imaging techniques for bladder cancer detection and diagnosis: a systematic review
Authors: Remmelink Marinka J. , Rip Yael , Nieuwenhuijzen Jakko A. , Ket Johannes C.F. , Oddens Jorg R. , de Reijke Theo M. , de Bruin Daniel M. 
Published: July 2024

ObjectivesTo systematically assess the current available literature concerning advanced optical imaging methods for the detection and diagnosis of bladder cancer (BCa), focusing particularly on the sensitivity and specificity of these techniques.MethodsFirst a scoping search was performed to identify all available optical techniques for BCa detection and diagnosis. The optical imaging techniques used for detecting BCa are: the Storz professional image enhancement system (IMAGE1 S), narrow‐band imaging (NBI), photoacoustic imaging (PAI), autofluorescence imaging (AFI), photodynamic diagnosis (PDD), and scanning fibre endoscopy (SFE). The staging and grading techniques for BCa are: optical coherence tomography (OCT), confocal laser endomicroscopy (CLE), Raman spectroscopy, endocytoscopy, and non‐linear optical microscopy (NLO). Then a systematic literature search was conducted using MEDLINE, EMBASE and Web of Science from inception to 21 November 2023. Articles were screened and selected by two independent reviewers. Inclusion criteria were: reporting on both the sensitivity and specificity of a particular technique and comparison to histopathology, and in the case of a detection technique comparison to white light cystoscopy (WLC).ResultsOut of 6707 articles, 189 underwent full‐text review, resulting in 52 inclusions. No articles met criteria for IMAGE1 S, PAI, SFE, Raman spectroscopy, and endocytoscopy. All detection techniques showed higher sensitivity than WLC, with NBI leading (87.8–100%). Overall, detection technique specificity was comparable to WLC, with PDD being most specific (23.3–100%). CLE and OCT varied in sensitivity and specificity, with OCT showing higher specificity for BCa diagnosis, notably for carcinoma in situ (97–99%) compared to CLE (62.5–81.3%). NLO demonstrated high sensitivity and specificity (90–97% and 77–100%, respectively) based on limited data from two small ex vivo studies.ConclusionsOptical techniques with the most potential are PDD for detecting and OCT for staging and grading BCa. Further research is crucial to validate their integration into routine practice and explore the value of other imaging techniques.
UBA2 SUMOylates NQO1 and promotes the proliferation of hepatocellular carcinoma by modulating the MAPK pathway
Authors: Chen Hailong , Li Huifang , He Minke , Lai Zhicheng , Huang Lichang , Wen Dongsheng , Shi Ming , Kan Anna 
Published: July 2024

AbstractIn our previous study, we found that small ubiquitin‐related modifier (SUMO)‐activating enzyme ubiquitin‐associated‐2 domain (UBA2) was upregulated in hepatocellular carcinoma (HCC) patients who were insensitive to chemoembolization. In this study, we aimed to investigate the role of UBA2 in HCC progression. Three cohorts were used to evaluate the efficacy of UBA2 as a prognostic factor for HCC. Our results indicated that UBA2 was associated with aggressive clinical behaviors and was a strong indicator of poor prognosis in HCC. In vitro experiments demonstrated that UBA2 accelerated cell growth, invasion, and migration. These results were further supported by in vivo experiments. RNA‐sequencing analysis indicated NQO1 as a target of UBA2, with its levels altering following UBA2 manipulation. The results were verified by western blotting (WB) and quantitative PCR. The SUMOplot Analysis Program predicted lysine residue K240 as a modification target of UBA2, which was confirmed by immunoprecipitation (IP) assays. Subsequent mutation of NQO1 at K240 in HCC cell lines and functional assays revealed the significance of this modification. In addition, the oncogenic effect of UBA2 could be reversed by the SUMO inhibitor ML792 in vivo and in vitro. In conclusion, our study elucidated the regulatory mechanism of UBA2 in HCC and suggested that the SUMO inhibitor ML792 may be an effective combinatory treatment for patients with aberrant UBA2 expression.
Therapeutic potential and recent progression of BTK inhibitors against rheumatoid arthritis
Authors: Paliwal Swati , Bawa Sandhya , Shalmali Nishtha , Tonk Rajiv K. 
Published: July 2024

AbstractRheumatoid arthritis (RA) is a complex chronic inflammatory illness that affects the entire physiology of human body. It has become one of the top causes of disability worldwide. The development and progression of RA involves a complex interplay between an individual's genetic background and various environmental factors. In order to effectively manage RA, a multidisciplinary approach is required, as this disease is complicated and its pathophysiological mechanism is not fully understood yet. In majority of arthritis patients, the presence of abnormal B cells and autoantibodies, primarily anti‐citrullinated peptide antibodies and rheumatoid factor affects the progression of RA. Therefore, drugs targeting B cells have now become a hot topic in the treatment of RA which is quite evident from the recent trends seen in the discovery of various B cell receptors (BCRs) targeting agents. Bruton's tyrosine kinase (BTK) is one of these recent targets which play a role in the upstream phase of BCR signalling. BTK is an important enzyme that regulates the survival, proliferation, activation and differentiation of B‐lineage cells by preventing BCR activation, FC‐receptor signalling and osteoclast development. Several BTK inhibitors have been found to be effective against RA during the in vitro and in vivo studies conducted using diverse animal models. This review focuses on BTK inhibition mechanism and its possible impact on immune‐mediated disease, along with the types of RA currently being investigated, preclinical and clinical studies and future prospective.
MK2 inhibitor PF‐3644022 shows protective effect in mouse microglial N9 cell line induced with cigarette smoke extract
Authors: Asthana Shikha , Pandey Shivam Kumar , Gautam Avtar Singh , Singh Rakesh Kumar 
Published: July 2024

AbstractNeuroinflammation is suggested as one of the potential links between CS‐induced neuronal dysfunction. Cigarette smoke (CS) is one of the significant contributors of neuroinflammation, consequently leading to cognitive impairment and neurodegeneration. Microglia are the key resident macrophage cells in the brain with cell surface TLR4 receptor for responding to various stress signals. The CS constituents promote inflammation and oxidative stress in microglia leading to cytotoxicity through the TLR4‐MK2 axis. However, the role of MK2 kinase in CS‐induced microglial inflammation is not yet clearly understood. Therefore, we have used an MK2 inhibitor, PF‐3644022 to study modulation of CS‐extract induced oxidative and inflammatory signaling in a mouse microglial cell line, Furthermore, we also evaluated the enzymatic activity of acetylcholinesterase (AChE) on a direct exposure of enzyme with CS. CS exposure led to microglial cytotoxicity and enhanced the level of oxidative stress and proinflammatory cytokine release by microglial cells. The microglial cells pretreated with MK2 inhibitor, PF‐3644022 significantly reduced the levels of oxidative stress markers, proinflammatory markers, and improved the level of antioxidant proteins in these cells. In addition, direct exposure of CS showed reduction in the enzymatic activity of AChE.
Clinical and molecular characterization of limb‐girdle muscular dystrophy 2G/R7 in a large cohort of Brazilian patients
Authors: Gaviraghi Tobias , Cavalcanti Eduardo B. U. , Lorenzoni Paulo José , Cotta Ana , de Souza Paulo V. S. , de Oliveira André D. , de Moraes Maria T. , Marques Marcos V. O. , Donis Karina C. , Winckler Pablo B. , Costa e Silva Cynthia , Pinto Wladimir B. V. R. , Kay Cláudia S. K. , Ducci Renata D. , Rodrigues Paula R. V. P. , Fustes Otto J. H. , da Silva André M. S. , Zanoteli Edmar , França Marcondes C. , Sobreira Cláudia F. R. , Oliveira Acary S. B. , Carvalho Elmano H. T. , Scola Rosana H. , Carvalho Alzira A. S. , Saute Jonas Alex Morales 
Published: July 2024

AbstractLimb‐girdle muscular dystrophy type 2G/R7 (LGMD2G/R7) is an ultra‐rare condition initially identified within the Brazilian population. We aimed to expand clinical and genetic information about this disease, including its worldwide distribution. A multicenter historical cohort study was performed at 13 centers in Brazil in which data from index cases and their affected relatives from consecutive families with LGMD2G/R7 were reviewed from July 2017 to August 2023. Additionally, a systematic literature review was conducted to identify case reports and series of the disease worldwide. Forty‐one LGMD2G/R7 cases were described in the Brazilian cohort, being all subjects homozygous for the c.157C>T/(p.Gln53*) variant in TCAP. Survival curves showed that the median disease duration before individuals required walking aids was 21 years. Notably, women exhibited a slower disease progression, requiring walking aids 13 years later than men. LGMD2G/R7 was frequently reported not only in Brazil but also in China and Bulgaria, with 119 cases identified globally, with possible founder effects in the Brazilian, Eastern European, and Asian populations. These findings are pivotal in raising awareness of LGMD2G/R7, understanding its progression, and identifying potential modifiers. This can significantly contribute to the development of future natural history studies and clinical trials for this disease.
A predictive model combining connectomics and entropy biomarkers to discriminate long‐term vagus nerve stimulation efficacy for pediatric patients with drug‐resistant epilepsy
Authors: Cheng Tung‐yang , Hu Yingbing , Qin Xiaoya , Ma Jiayi , Zha Daqi , Xie Han , Ji Taoyun , Liu Qingzhu , Wang Zhiyan , Hao Hongwei , Wu Ye , Li Luming 
Published: July 2024

AbstractAimsTo predict the vagus nerve stimulation (VNS) efficacy for pediatric drug‐resistant epilepsy (DRE) patients, we aim to identify preimplantation biomarkers through clinical features and electroencephalogram (EEG) signals and thus establish a predictive model from a multi‐modal feature set with high prediction accuracy.MethodsSixty‐five pediatric DRE patients implanted with VNS were included and followed up. We explored the topological network and entropy features of preimplantation EEG signals to identify the biomarkers for VNS efficacy. A Support Vector Machine (SVM) integrated these biomarkers to distinguish the efficacy groups.ResultsThe proportion of VNS responders was 58.5% (38/65) at the last follow‐up. In the analysis of parieto‐occipital α band activity, higher synchronization level and nodal efficiency were found in responders. The central‐frontal θ band activity showed significantly lower entropy in responders. The prediction model reached an accuracy of 81.5%, a precision of 80.1%, and an AUC (area under the receiver operating characteristic curve) of 0.838.ConclusionOur results revealed that, compared to nonresponders, VNS responders had a more efficient α band brain network, especially in the parieto‐occipital region, and less spectral complexity of θ brain activities in the central‐frontal region. We established a predictive model integrating both preimplantation clinical and EEG features and exhibited great potential for discriminating the VNS responders. This study contributed to the understanding of the VNS mechanism and improved the performance of the current predictive model.
Systolic blood pressure and early neurological deterioration in minor stroke: A post hoc analysis of ARAMIS trial
Authors: Cui Yu , Zhao Zi‐Ai , Wang Jia‐Qi , Qiu Si‐Qi , Shen Xin‐Yu , Li Ze‐Yu , Hu Hai‐Zhou , Chen Hui‐Sheng 
Published: July 2024

AbstractBackgroundSystolic blood pressure (SBP) was a predictor of early neurological deterioration (END) in stroke. We performed a secondary analysis of ARAMIS trial to investigate whether baseline SBP affects the effect of dual antiplatelet versus intravenous alteplase on END.MethodsThis post hoc analysis included patients in the as‐treated analysis set. According to SBP at admission, patients were divided into SBP ≥140 mmHg and SBP <140 mmHg subgroups. In each subgroup, patients were further classified into dual antiplatelet and intravenous alteplase treatment groups based on study drug actually received. Primary outcome was END, defined as an increase of ≥2 in the NIHSS score from baseline within 24 h. We investigated effect of dual antiplatelet vs intravenous alteplase on END in SBP subgroups and their interaction effect with subgroups.ResultsA total of 723 patients from as‐treated analysis set were included: 344 were assigned into dual antiplatelet group and 379 into intravenous alteplase group. For primary outcome, there was more treatment effect of dual antiplatelet in SBP ≥140 mmHg subgroup (adjusted RD, −5.2%; 95% CI, −8.2% to −2.3%; p < 0.001) and no effect in SBP <140 mmHg subgroup (adjusted RD, −0.1%; 95% CI, −8.0% to 7.7%; p = 0.97), but no significant interaction between subgroups was found (adjusted p = 0.20).ConclusionsAmong patients with minor nondisabling acute ischemic stroke, dual antiplatelet may be better than alteplase with respect to preventing END within 24 h when baseline SBP ≥140 mmHg.
Reduced hepatic impairment study to evaluate pharmacokinetics and safety of zavegepant and to inform dosing recommendation for hepatic impairment
Authors: Bhardwaj Rajinder , Donohue Mary K. , Madonia Jennifer , Morris Beth , Marbury Thomas C. , Matschke Kyle T. , Croop Robert , Bertz Richard , Liu Jing 
Published: July 2024

AbstractZavegepant, a high‐affinity, selective, small‐molecule calcitonin gene‐related peptide (CGRP) receptor antagonist, is approved in the United States for acute treatment of migraine in adults. The effects of moderate hepatic impairment (8 participants with Child‐Pugh score 7–9 points) on the pharmacokinetics of a single 10‐mg intranasal dose of zavegepant versus eight matched participants with normal hepatic function were evaluated in a phase I study. Pharmacokinetic sampling determined total and unbound plasma zavegepant concentrations. Moderate hepatic impairment increased the exposure of total zavegepant (~2‐fold increase in AUC0–inf and 16% increase in Cmax) versus normal hepatic function, which is not considered clinically meaningful. The geometric least squares mean ratios (moderate impairment/normal) of plasma zavegepant AUC0−inf and Cmax were 193% (90% confidence interval [CI]: 112, 333; p = 0.051) and 116% (90% CI: 69, 195; p = 0.630), respectively. The geometric mean fraction unbound of zavegepant was similar for participants with moderate hepatic impairment (0.13; coefficient of variation [CV] 13.71%) versus those with normal hepatic function (0.11; CV 21.43%). Similar exposure findings were observed with unbound zavegepant versus normal hepatic function (~2.3‐fold increase in AUC0−inf and 39% increase in Cmax). One treatment‐emergent adverse event (mild, treatment‐related headache) was reported in a participant with normal hepatic function. No dosage adjustment of intranasal zavegepant is required in adults with mild or moderate hepatic impairment.