bluuebunny/crossref_metadata_2025_split huggingface dataset:
High expression of ABCF1 is an independent predictor of poor prognosis in bladder cancer
Authors: Fan JiaWen , Ding Yi , Huang HaoXuan , Xiong ShiDa , He Liang , Guo Ju 
Published: March 2023

AbstractABCF1, a member of the ATP-binding cassette (ABC) transporter family, is involved in the malignant progression of tumors. However, the role of ABCF1 in bladder cancer is poorly understood. In our study, we explored the differential expression of ABCF1 in bladder cancer and normal bladder tissues based on bioinformatic analysis and immunohistochemical results. GSEA was performed to ascertain the potential related signaling pathways of ABCF1. The relationship between ABCF1 expression and bladder cancer progression was analyzed using the GSE13507 dataset. In addition, the differential expression of ABCF1 in the cell lines was verified by quantitative real-time polymerase chain reaction (qRT‒PCR) and Western blotting. ABCF1 was upregulated in bladder cancer, and the high expression of ABCF1 was closely related to sex (P = 0.00056), grade (P = 0.00049), T stage (P = 0.00007), and N stage (P = 0.0076). High expression of ABCF1 was correlated with poor overall survival in bladder cancer patients (P < 0.001). In addition, univariate and multivariate Cox regression analyses showed that high ABCF1 expression was an independent factor for poor prognosis in bladder cancer patients. Therefore, ABCF1 expression is closely related to the progression of bladder cancer and can be used as a potential indicator of poor prognosis and a therapeutic target for bladder cancer.
Tumor cell density dependent IL-8 secretion induces the fluctuation of tregs/CD8 + T cells infiltration in hepatocellular carcinoma: one prompt for the existence of density checkpoint
Authors: Yan Mengchao , Yao Jia , Lin Yan , Yan Jun , Xie Ye , Fu Zongli , Zhou Yongqiang , Wei Jiayun , Li Xun 
Published: March 2023

Abstract
Background
Tumor cell density is a basic pathological feature of solid tumors. Chemotherapy, radiotherapy, and targeted therapy reduce tumor cell density, whereas unrestricted tumor cell proliferation promotes this feature. The impact of tumor cells on the microenvironment following changes in tumor cell density is still unclear. In this study, we focused on the response of key immune cell subsets to tumor cell density in hepatocellular carcinoma (HCC).

Methods
We determined the density of tumor and immune cells in the same area by section staining. We then identified potential mediators using polymerase chain reaction (PCR), enzyme-linked immunofluorescence assay (ELISA), 3D and co-culture, flow cytometry, and lentivirus intervention. The mechanism of lactate promotion was verified using lactate tests, bioinformatics, western blotting, and the above methods. The IL-8/DAPK1/lactate/regulatory T cell (Treg) axis was verified using a mouse liver cancer model. Tumor mutation burden was calculated using maftools in R.

Results
We found that the Treg/CD8 + T cell ratio is not consistent with tumor cell density in HCC, and a decreased Treg/CD8 + T cell ratio in the range of 5000–6000 cells/mm2 may elicit the possibility for immunotherapy in an immunosuppressive microenvironment. We showed that IL-8 mediates this immune fluctuation and promotes the infiltration of Tregs through the DAPK1/pyruvate kinase activity/lactate axis in HCC. Based on tumor ploidy and mutation burden data, we discussed the potential significance of immune fluctuation in the homeostasis of HCC mutation burden and proposed a “density checkpoint” and “entropy model” to describe this phenomenon.

Conclusions
In summary, we report the mode of infiltration of Tregs/CD8 + T cells in response to tumor cell density and provide a new theoretical basis for IL-8 as a therapeutic target and the selection of an immunotherapy window in HCC.
H4-methylation regulators mediated epitranscriptome patterns and tumor microenvironment infiltration characterization in hepatocellular carcinoma
Authors: Yu Linyuan , Ji Tao , Liao Wei , Xu Yuyan , Fang Yinghao , Zhu Qing , Nie Jianmin , Yang Dinghua 
Published: March 2023

AbstractEpigenetic modifications are involved in the remodeling of the tumor microenvironment (TME) and the regulation of immune response. Nonetheless, the role of histone H4 methylation (H4M) modification in the TME and immune regulation of hepatocellular carcinoma (HCC) is unknown. As a result, the purpose of this research is to discover H4M-mediated modification patterns and their effects on TME and immunologic characteristics in HCC. A total of 2305 samples were enrolled from 13 different cohorts. With the help of consensus clustering analysis, three distinct H4M modification patterns were identified. The cell-infiltrating characteristics of TME under these three patterns were highly consistent with their enriched biological processes and clinical outcome. The H4Mscore was then created using principal component analysis algorithm to quantify the H4M modification pattern of each individual tumor and was systematically correlated with representative tumor characteristics. We found that analyzing H4M modification patterns within individual tumors could predict TME infiltration, homologous recombination deficiency (HRD), intratumor heterogeneity, proliferation activity, mRNA stemness index, and prognosis. The group with a low H4Mscore had an inflamed TME phenotype and a better immunotherapy response, as well as a better survival outcome. The prognostic value of H4Mscore was validated in three internal cohorts and five external cohorts, respectively. In external immunotherapy cohorts, the low H4Mscore was also linked to an enhanced response to anti-PD-1/L1 and anti-CTLA4 immunotherapy and a better prognosis. This study revealed that H4M modification played an important role in forming TME diversity and complexity. Evaluating the H4M modification pattern of individual tumors could help us learn more about TME and develop more effective immunotherapy strategies.
Outcome of patients with biochemical recurrence of prostate cancer after PSMA PET/CT-directed radiotherapy or surgery without systemic therapy
Authors: Harsini Sara , Wilson Don , Saprunoff Heather , Allan Hayley , Gleave Martin , Goldenberg Larry , Chi Kim N. , Kim-Sing Charmaine , Tyldesley Scott , Bénard François 
Published: March 2023

Abstract
Background
Radiotherapy (RT) and surgery are potential treatment options in patients with biochemical recurrence (BCR) following primary prostate cancer treatment. This study examines the value of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-informed surgery and RT in patients with BCR treated without systemic therapy.

Methods
This is a post-hoc subgroup analysis of a prospective clinical trial. Inclusion criteria were: histologically proven prostate cancer at initial curative-intent treatment, BCR after primary treatment with curative intent, having five or fewer lesions identified on [18F]DCFPyL PET/CT, and treatment with either PET/CT-directed RT or surgery without systemic therapy. The biochemical progression-free survival after PSMA ligand PET/CT-directed RT and surgery was determined. Uni- and multivariate Cox regression analyses were performed for the association of patients’ characteristics, tumor-specific variables, and PSMA PET/CT imaging results with biochemical progression at the last follow-up.

Results
Fifty-eight patients (30 in surgery and 28 in radiotherapy groups) met the inclusion criteria. A total of 87 PSMA-positive lesions were detected: 16 local recurrences (18.4%), 54 regional lymph nodes (62.1%), 6 distant lymph nodes (6,8%), and 11 osseous lesions (12.7%). A total of 85.7% (24 of 28) and 70.0% (21 of 30) of patients showed a ≥ 50% decrease in prostate-specific antigen (PSA) levels after RT and surgery, respectively. At a median follow-up time of 21 months (range, 6–32 months), the median biochemical progression-free survival was 19 months (range, 4 to 23 months) in the radiotherapy group, as compared with 16.5 months (range, 4 to 28 months) in the surgery group. On multivariate Cox regression analysis, the number of PSMA positive lesions (2–5 lesions compared to one lesion), and the anatomic location of the detected lesions (distant metastasis vs. local relapse and pelvic nodal relapse) significantly correlated with biochemical progression at the last follow-up, whereas other clinical, tumor-specific, and imaging parameters did not.

Conclusions
This study suggests that RT or surgery based on [18F]DCFPyL PET/CT are associated with high PSA response rates. The number and site of lesions detected on the PSMA PET/CT were predictive of biochemical progression on follow-up. Further studies are needed to assess the impact of targeting these sites on patient relevant outcomes.

Trial registration
Registered September 14, 2016; NCT02899312; https://clinicaltrials.gov/ct2/show/NCT02899312
Using Recurrent Neural Networks to Extract High-Quality Information From Lung Cancer Screening Computerized Tomography Reports for Inter-Radiologist Audit and Feedback Quality Improvement
Authors: Zhang Yucheng , Grant Benjamin M.M. , Hope Andrew J. , Hung Rayjean J. , Warkentin Matthew T. , Lam Andrew C.L. , Aggawal Reenika , Xu Maria , Shepherd Frances A. , Tsao Ming-Sound , Xu Wei , Pakkal Mini , Liu Geoffrey , McInnis Micheal C. 
Published: March 2023

PURPOSE Lung cancer screening programs generate a high volume of low-dose computed tomography (LDCT) reports that contain valuable information, typically in a free-text format. High-performance named-entity recognition (NER) models can extract relevant information from these reports automatically for inter-radiologist quality control. METHODS Using LDCT report data from a longitudinal lung cancer screening program (8,305 reports; 3,124 participants; 2006-2019), we trained a rule-based model and two bidirectional long short-term memory (Bi-LSTM) NER neural network models to detect clinically relevant information from LDCT reports. Model performance was tested using F1 scores and compared with a published open-source radiology NER model (Stanza) in an independent evaluation set of 150 reports. The top performing model was applied to a data set of 6,948 reports for an inter-radiologist quality control assessment. RESULTS The best performing model, a Bi-LSTM NER recurrent neural network model, had an overall F1 score of 0.950, which outperformed Stanza (F1 score = 0.872) and a rule-based NER model (F1 score = 0.809). Recall (sensitivity) for the best Bi-LSTM model ranged from 0.916 to 0.991 for different entity types; precision (positive predictive value) ranged from 0.892 to 0.997. Test performance remained stable across time periods. There was an average of a 2.86-fold difference in the number of identified entities between the most and the least detailed radiologists. CONCLUSION We built an open-source Bi-LSTM NER model that outperformed other open-source or rule-based radiology NER models. This model can efficiently extract clinically relevant information from lung cancer screening computerized tomography reports with high accuracy, enabling efficient audit and feedback to improve quality of patient care.
A Pilot Randomized Clinical Trial of Intranasal Oxytocin to Promote Weight Loss in Individuals With Hypothalamic Obesity
Authors: McCormack Shana E , Wang Zi , Wade Kristin L , Dedio Anna , Cilenti Nicolette , Crowley Julia , Plessow Franziska , Bamba Vaneeta , Roizen Jeffrey D , Jiang Yaoguang , Stylli Jack , Ramakrishnan Arjun , Platt Michael L , Shekdar Karuna , Fisher Michael J , Vetter Victoria L , Hocking Matthew , Xiao Rui , Lawson Elizabeth A 
Published: March 2023

Abstract

Context
Hypothalamic obesity is a rare, treatment-resistant form of obesity. In preliminary studies, the hypothalamic hormone oxytocin (OXT) has shown promise as a potential weight loss therapy.

Objective
To determine whether 8 weeks of intranasal OXT (vs 8 weeks of placebo) promotes weight loss in children, adolescents, and young adults with hypothalamic obesity.

Methods
This randomized, double-blind, placebo-controlled, crossover pilot trial (NCT02849743), conducted at an outpatient academic medical center, included patients aged 10 to 35 years with hypothalamic obesity from hypothalamic/pituitary tumors. Participants received intranasal OXT (Syntocinon, 40 USP units/mL, 4 IU/spray) vs excipient-matched placebo, 16 to 24 IU 3 times daily at mealtimes. Weight loss attributable to OXT vs placebo and safety (adverse events) were assessed.

Results
Of 13 individuals randomized (54% female, 31% pre-pubertal, median age 15.3 years, IQR 13.3-20.6), 10 completed the entire study. We observed a nonsignificant within-subject weight change of −0.6 kg (95% CI: −2.7, 1.5) attributable to OXT vs placebo. A subset (2/18 screened, 5/13 randomized) had prolonged QTc interval on electrocardiography prior to screening and/or in both treatment conditions. Overall, OXT was well-tolerated, and adverse events (epistaxis and nasal irritation, headache, nausea/vomiting, and changes in heart rate, blood pressure, and QTc interval) were similar between OXT and placebo. In exploratory analyses, benefits of OXT for anxiety and impulsivity were observed.

Conclusion
In this pilot study in hypothalamic obesity, we did not detect a significant impact of intranasal OXT on body weight. OXT was well-tolerated, so future larger studies could examine different dosing, combination therapies, and potential psychosocial benefits.
Proof-of-concept Application of Continuous Glucose Monitoring Data Analytics to Identify Diabetes Glucotypes
Authors: Steenkamp Devin W , Cheney Michael C , Ju Zhihui , Rodbard David , Wolpert Howard A 
Published: March 2023

AbstractBackgroundIn this proof-of-concept study, we evaluated if monogenic diabetes resulting from mutations of the HNF-1α gene (HNF1A-MODY) has a distinctive continuous glucose monitoring (CGM) glucotype, in comparison to type 1 diabetes (T1D).MethodsUsing CGM data from 5 subjects with HNF1A-MODY and 115 subjects with T1D, we calculated multiple glucose metrics, including measures of within- and between-day variability (such as coefficient variation for each hour [CVb_1h]).ResultsThe MODY and T1D cohorts had minimum CVb_1h of 11.3 ± 4.4 and 18.0 ± 4.9, respectively (P = .02) and maximum CVb_1h of 33.9 ± 5.0 and 50.3 ± 10, respectively (P &lt; .001). All subjects with HNF1A-MODY had a minimum %CVb_1h ≤ 17.3% and maximum %CVb_1h ≤ 37.1%. In contrast, only 12 of 115 subjects with T1D had both a minimum and maximum %CVb_1h below these thresholds (P &lt; .001).ConclusionHNF1A- MODY is characterized by a low hourly, between-day glucose variability. CGM-derived glucose metrics may have potential applicability for screening for atypical diabetes phenotypes in the T1D population.
Subversion of the Human Aura: A Crisis in Representation
Authors: Hayles N. Katherine 
Published: March 2023

AbstractThe human aura is now being subverted by a variety of simulacra. OpenAI’s language-generation program GPT-3 illustrates the challenges of interpreting algorithmic-generated texts. This article advocates interpretive strategies that recognize the profound differences (in the case of GPT-3) of language that issues from a program that has a model only of language, not of the world. Conscious robots, when and if they emerge, will have profoundly different embodiments than humans. Fictions that imagine conscious robots thus face a similar challenge presented by the GPT-3 texts: will they gloss over the differences, or will they enact strategies that articulate the differences and explore their implications for humans immersed in algorithmic cultures? The author analyzes three contemporary novels that engage with this challenge: Annalee Newitz’s Autonomous (2017), Kuzuo Ishiguro’s Klara and the Sun (2021), and Ian McEwan’s Machines like Me (2019). Each interrogates how the human aura is subverted by conscious robots. The article concludes by proposing how a reconfigured human aura should be constituted.
Outpatient Deep Brain Stimulation Surgery Is a Safe Alternative to Inpatient Admission
Authors: Thakur Vishal , Kessler Brice , Khan Muhammad Babar , Hodge Johnie O , Brandmeir Nicholas J 
Published: March 2023

BACKGROUND:
Deep brain stimulation (DBS) is usually performed as an inpatient procedure. The COVID-19 pandemic effected a practice change at our institution with outpatient DBS performed because of limited inpatient and surgical resources. Although this alleviated use of hospital resources, the comparative safety of outpatient DBS surgery is unclear.

OBJECTIVE:
To compare the safety and incidence of early postoperative complications in patients undergoing DBS procedures in the outpatient vs inpatient setting.

METHODS:
We retrospectively reviewed all outpatient and inpatient DBS procedures performed by a single surgeon between January 2018 and November 2022. The main outcome measures used for comparison between the 2 groups were total complications, length of stay, rate of postoperative infection, postoperative hemorrhage rate, 30-day emergency department (ED) visits and readmissions, and IV antihypertensive requirement.

RESULTS:
A total of 44 outpatient DBS surgeries were compared with 70 inpatient DBS surgeries. The outpatient DBS cohort had a shorter mean postoperative stay (4.19 vs 39.59 hours, P = .0015), lower total complication rate (2.3% vs 12.8%, P = .1457), and lower wound infection rate (0% vs 2.9%, P = .52) compared with the inpatient cohort, but the difference in complications was not statistically significant. In the 30-day follow-up period, ED visits were similar between the cohorts (6.8% vs 7.1%, P = .735), but no outpatient DBS patient required readmission, whereas all inpatient DBS patients visiting the ED were readmitted (P = .155).

CONCLUSION:
Our study demonstrates that DBS can be safely performed on an outpatient basis with same-day hospital discharge and close continuous monitoring.
Actores menores en la gran política: los conflictos armados de Kósovo y Georgia
Authors: Palacios Coronel José-Miguel 
Published: March 2023

En las relaciones internacionales, el juego de la gran política suele ser patrimonio de las grandes potencias; mientras que los actores menores deben adaptar sus prioridades a las de las potencias hegemónicas, bajo cuya influencia se encuentren. Existen casos, sin embargo, en que un pequeño actor ha sido capaz de imponer su línea política y sus prioridades a una gran potencia que, inicialmente, era muy reticente a asumirlas. El estudio comparado de los conflictos de Kósovo (1996-1999) y de Georgia (2008) es exploratorio y analiza el material publicado principalmente por medios de comunicación albaneses kosovares y la interpretación de los principales actores del conflicto georgiano diez años después. Como resultado del análisis, sugiere que ello solo es posible cuando el actor menor es capaz de aprovechar una “ventana de oportunidad” en la que sus objetivos particulares estén alineados con las prioridades políticas coyunturales de la gran potencia, que pueden, en ocasiones, contradecir su línea política a largo plazo.
Power Forward Performance in Semimartingale Markets with Stochastic Integrated Factors
Authors: Bo Lijun , Capponi Agostino , Zhou Chao 
Published: March 2023

We study the forward investment performance process (FIPP) in an incomplete semimartingale market model with closed and convex portfolio constraints, when the investor’s risk preferences are of the power form. We provide necessary and sufficient conditions for the existence of such a FIPP. In a semimartingale factor model, we show that the FIPP can be recovered as a triplet of processes that admit an integral representation with respect to semimartingales. Using an integrated stochastic factor model, we relate the factor representation of the triplet of processes to the smooth solution of an ill-posed partial integro-differential Hamilton–Jacobi–Bellman equation. We develop explicit constructions for the class of time-monotone FIPPs, generalizing existing results from Brownian to semimartingale market models. Funding: L. Bo was supported by the National Natural Science Foundation of China (NSFC) [Grant 11971368] and National Center for Applied Mathematics in Shaanxi (NCAMS). A. Capponi was supported in part by the National Science Foundation [Grant DMS-1716145]. C. Zhou was supported by the Singapore Ministry of Education Academic Research Fund [Grant R-146-000-271-112] and NSFC [Grant 11871364].
Relative cost-effectiveness of three compression bandages in treating newly diagnosed venous leg ulcers in the UK
Authors: Guest Julian F , Fuller Graham W 
Published: March 2023

Objective: To assess the clinical outcomes and cost-effectiveness of using a two-layer cohesive compression bandage (TLCCB; Coban 2, 3M, US) compared with a two-layer compression system (TLCS; KTwo, Urgo, France) and a cohesive inelastic bandage system (CIBR; Actico, L&R, Germany) in treating newly diagnosed venous leg ulcers (VLUs) in clinical practice, from the perspective of the UK's National Health Service (NHS). Method: This was a modelling study based on a retrospective cohort analysis of the case records of patients with a newly diagnosed VLU randomly extracted from the The Health Improvement Network (THIN) database who were treated with TLCCB, TLCS or CIBR. No significant differences were detected between the groups. Nevertheless, analysis of covariance was performed to enable differences in patients' outcomes between the groups to be adjusted for any heterogeneity in baseline covariates. Clinical outcomes and cost-effectiveness of the alternative compression systems were estimated over 12 months after starting treatment. Results: There were 250 patients in each group. Time from wound onset to starting compression was a mean of two months. The healing distribution of the TLCCB-treated patients was significantly different from that of the other two cohorts (p=0.003); the probability of healing at 12 months was 0.62, 0.51 and 0.49 in the TLCCB, TLCS and CIBR groups, respectively. Patients treated with TLCCB experienced better health-related quality of life (HRQoL) over 12 months (0.86 quality-adjusted life years (QALYs) per patient), compared with those treated with TLCS and CIBR (0.83 and 0.82 QALYs per patient, respectively). The 12-month NHS wound management cost was £3693, £4451 and £4399 per patient in the TLCCB, TLCS and CIBR groups, respectively. Conclusion: Within the model's limitations, treating newly diagnosed VLUs with TLCCB instead of the other two compression systems appears to afford a more cost-effective use of NHS-funded resources in clinical practice, since it is expected to result in increased healing, better HRQoL and a lower wound management cost for the NHS.