bluuebunny/crossref_metadata_2025 huggingface dataset:
Multimorbidity Among Adolescent and Young Adult Thyroid Cancer Survivors: A Report From the AYA VOICE Study
Authors: Ou JY , Kirchhoff AC , Li J , AbrahÃ£o R , Li Q , Kaddas KK , Brunson A , Kushi LH , Chubak J , Keegan TH
Published: May 2024

Background: Thyroid cancer is one of the most common cancers in adolescents and young adults (AYA, 15 to 39), with excellent 5-year survival of 98%. However, treatments for thyroid cancer such as radioactive iodine and thyroid hormone suppression may increase the risk for multiple late effects (LE). We investigated the incidence of severe LE that cluster in AYA thyroid cancer survivors in a large population-based cohort. Methods: We used California Cancer Registry records to identify AYAs diagnosed with first primary thyroid cancer during 2006–2018 linked to statewide hospitalization, ambulatory surgery, and emergency department data. Cohort entry began 2 years from diagnosis. Severe LE included cardiovascular, respiratory, endocrine, renal, and liver diseases, and second cancers. Cumulative incidence of each LE, accounting for the competing risk of death, was calculated. Latent class analysis (LCA) identified clustering of LE overall and in <5 and ≥5-year survivors. The number of LE classes was identified by selecting models with the lowest likelihood-ratio G2 statistic, Akaike's Information Criterion, and Bayesian Information Criterion. Probabilities of each LE are presented in each class. Results: Of 12,224 survivors, 83% were female, 34% were Hispanic, and 62% aged 30–39 years at diagnosis. Mean follow-up time was 7.9 years. Five-year cumulative incidence was highest for endocrine (27.9%, 95% CI 27.0–28.8), respiratory (5.1%, 95% CI 4.6–5.5), and cardiovascular (2.1%, 95% CI 1.8–2.4) diseases. The LCA model identified 3 classes: 78.6% were ‘healthy survivors’ with a low probability of any LE, 19.8% experienced a high probability of endocrine (95%) conditions, and the remaining 1.6% were ‘multimorbidity survivors,’ experiencing a high probability of all LEs, particularly endocrine (94%), cardiovascular (61%), renal (55%), and respiratory (46%) conditions, followed by liver disease (25%) and second cancers (9%). No differences were found in the LCA classes among <5 and ≥5-year survivors. Conclusion: While most survivors of AYA thyroid cancer have few severe LEs, >20% have a high probability of endocrine conditions or multimorbidities. Multidisciplinary survivorship care may be vital to supporting thyroid cancer survivors experiencing multiple LEs.
Abstract A003: Characterization of circulating tumor cells from patients with metastatic bladder cancer
Authors: Niu Zeqi , Kozminski Molly , Day Kathleen C. , Broses Luke , Henderson Marian L. , Merajver Sophia , Udager Aaron , Palmbos Phillip L. , Nagrath Sunitha , Day Mark L.
Published: May 2024

Assessing the molecular profile of bladder tumors from patients with metastatic disease is crucial for implementing personalized treatment. Current standards are based on highly invasive biopsies. Alternatively, liquid biopsies of tumor cells, proteins, and nucleic acids allows longitudinal profiling in a less invasive manner. Circulating tumor cells (CTCs) isolated from blood are a key analyte of liquid biopsy. In this study, we developed a protein and transcriptomic co-analysis workflow for bladder cancer CTCs utilizing the graphene oxide (GO) microfluidic chip conjugated with antibodies against both EpCAM and EGFR to isolate CTCs from blood of patients with metastatic bladder cancer. Following CTC capture, protein and mRNA were analyzed using immunofluorescent staining and ion-torrent whole transcriptome sequencing. This is the first time that whole transcriptome sequencing was used in a downstream application for the GO microfluidic platform. We found that elevated CTC counts were significantly associated with patient disease status at the time of blood draw and that greater than 2 CTCs per mL were associated with shorter overall survival. Invasive markers, including EGFR, HER-2, CD31, and ADAM15, were detected in subpopulations of CTCs. Targeted whole transcriptome sequencing showed distinct expression profiles from patients with metastatic burden at the time of blood draw. In these patients, we found significant upregulation of several metastasis-related and chemotherapy-resistant genes demonstrating the capability of identifying tumor-related RNA signatures from circulating CTCs using immune-affinity GO chip-based assays. In addition, this workflow highlights the prognostic potential of CTCs in metastatic bladder cancer patients.

Citation Format: Zeqi Niu, Molly Kozminski, Kathleen C. Day, Luke Broses, Marian L. Henderson, Sophia Merajver, Aaron Udager, Phillip L. Palmbos, Sunitha Nagrath, Mark L. Day. Characterization of circulating tumor cells from patients with metastatic bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A003.
Abstract A012: Kmt2c/d loss primes urothelium for tumorigenesis and redistributes Menin to bivalent promoters
Authors: Wang Naitao , Pachai Mohini , Li Dan , Lee Cindy , Warda Sarah , Khudoynazarova Makhzuna , Cho Woo Hyun , Xie Guojia , Kuo Fengshen , Shah Sagar , Yao Li , Qian Cheng , Wong Elissa , Yan Juan , Tomas Fanny , Hu Wenhuo , Gao Sizhi , Smith Alison , Han Ming , Gao Dong , Ge Kai , Yu Haiyuan , Chandarlapaty Sarat , Iyer Gopakumar , Rosenberg Jonathan , Solit David , AI-Ahmadie Hikmat , Chi Ping , Chen Yu
Published: May 2024

Urothelial carcinoma arises from a “field” of precancerous but histologically normal urothelium. The KMT2C/D-KDM6A complexes known to bind and activate enhancers are frequently mutated in urothelial carcinoma and in histologically normal urothelium. Here, using a genetically engineered mouse model, we demonstrate that knockout of Kmt2c and/or Kmt2d induced a histologically normal, pre-tumorigenic state characterized by impaired differentiation from basal state and by augmented responses to growth and inflammatory stimuli. This sensitized the urothelium to transformation by known oncogenic drivers in urothelial carcinoma. Mechanistically, Kmt2d localized to both active enhancers and a small group of CpG-poor promoters and Kmt2c/d knockout led to diminished H3K4me1, H3K27ac and nascent RNA transcription at these sites, which together led to downregulation of the urothelial differentiation program. We further observed that Menin distributed extensively to Kmt2d localized enhancers and Kmt2c/d knockout led to redistribution of Menin to CpG-high and particularly bivalent promoters, resulting in transcriptional de-repression of bivalent genes. Blockade of Kmt2a/b-Menin interaction partially rescued the transcriptional changes that induced by Kmt2c/d deletion. Therapeutically, Kmt2c/d knockout maintained a basal state that upregulated EGFR signaling and conferred vulnerability to EGFR inhibitors. Together, our data posits that functional loss of Kmt2c/d licenses a molecular “field effect” priming histologically normal urothelium for oncogenic transformation and leading to therapeutic vulnerabilities to EGFR signaling pathway inhibition.

Citation Format: Naitao Wang, Mohini Pachai, Dan Li, Cindy Lee, Sarah Warda, Makhzuna Khudoynazarova, Woo Hyun Cho, Guojia Xie, Fengshen Kuo, Sagar Shah, Li Yao, Cheng Qian, Elissa Wong, Juan Yan, Fanny Tomas, Wenhuo Hu, Sizhi Gao, Alison Smith, Ming Han, Dong Gao, Kai Ge, Haiyuan Yu, Sarat Chandarlapaty, Gopakumar Iyer, Jonathan Rosenberg, David Solit, Hikmat AI-Ahmadie, Ping Chi, Yu Chen. Kmt2c/d loss primes urothelium for tumorigenesis and redistributes Menin to bivalent promoters [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A012.
Abstract A015: Novel genetic driver for the genesis of muscle invasion in bladder cancer
Authors: Mohanvelu Sreenidhi , Subramanian Poorvi , Salim Sabir , Somasundaram Dinesh Babu , Aravindan Sheeja , Aravindan Natarajan
Published: May 2024

Non-muscle invasive bladder cancer (NMIBC) is a heterogeneous type of urothelial carcinoma with a substantial risk (>50%) of tumor progression and muscle invasion. Our sequential studies uniquely unveiled the availability of Retinal Degeneration Protein 3 (RD3) in human adult/fetal tissues and recognized its functional significance in tumor evolution. Herein, we investigated the relevance of RD3 in coordinating de novo MIBC from NMIBC. Compared to the low-grade tumor, RD3 is significantly lost (mRNA, qPCR; protein, ELISA) in grade III and IV patient derived NMIBC cells. In a cohort of (n=55) NMIBC patients, RD3-loss associated with increased tumor invasive potential (complete loss in highly invasive T4), metastasis (vs. primary tumors), therapy pressure (insignificant levels in progressive disease that defies therapy), disease recurrence, and death (custom archived TMA with automated RD3 IHC).Crucially, we observed a significant low-is-worse association to overall survival (p=7.30E-03, hazard ratio (HR) of 5.161), relapse-free survival (p=4.464E-02, HR = 2.328), and progression-free survival (p=7.00E-0.4, HR = 3.264). Further, radio-resistant cells exposed to fractionated irradiation (FIR, 2Gy/Day for 5 days) to a total dose of 10 or 20Gy displayed a dose dependent loss of RD3 recognizing an ongoing acquisition of RD3-loss with therapy pressure. More interestingly, Grade I or III bystander cells (BSE) co-cultured with FIR-exposed cells displayed anew acquisition of RD3-loss and displayed tumor grade-dependent increase (vs. mock-irradiated) in NFkB transcriptional activity (EMSA) and the activation of NFkB trans-activated pro-survival molecules (QPCR profiling of 89 NFkB targets). Together, these results clearly depict that RD3 regulates NMIBC disease pathogenesis, dissemination, acquired loss of RD3 with therapy pressure and further implies its role in the evolution of de novo MIBC from NMIBC. Funding: DOD CA-210339, OCAST-HR19-045, NIH-P20GM103639, NIH-NCI-P30CA225520 and TSET-R23-03.

Citation Format: Sreenidhi Mohanvelu, Poorvi Subramanian, Sabir Salim, Dinesh Babu Somasundaram, Sheeja Aravindan, Natarajan Aravindan. Novel genetic driver for the genesis of muscle invasion in bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A015.
Abstract A026: PIN1 isomerase promotes the initiation and progression of bladder cancer through SREBP2-mediated cholesterol biosynthesis pathway
Authors: Wang Xue , Hunter Tony
Published: May 2024

Bladder cancer, one of the most commonly diagnosed cancers worldwide, is associated with high morbidity, mortality, and a poor prognosis. The PIN1 phospho-dependent prolyl isomerase is frequently overexpressed in many human cancer types and affects tumor initiation and progression through disrupting the balance of oncoprotein and tumor suppressor protein signaling. However, the functional pSer/Thr.Pro protein substrates of PIN1 and its effects on downstream signaling in bladder carcinogenesis remain largely unknown. Phenotypically, we discovered that ablation of Pin1 in human/mouse bladder cancer cells and organoids formed from mouse primary urothelial cells resulted in decreased cell proliferation, stemness maintenance, cell invasion, migration, urothelium clearance capacity, and reduced free/total cholesterol levels in vitro. Re-expressing Pin1 in Pin1 knockout cells reversed the defects caused by lack of Pin1. Moreover, in vivo subcutaneous xenograft and allograft transplantation mouse models combined with an orthotopic implantation model were utilized to confirm a positive role for Pin1 in controlling tumor growth and potential metastasis. Therapeutically, a combination of the sulfopin PIN1 inhibitor and the simvastatin HMGCR inhibitor was shown to suppress cell proliferation in vitro and tumor growth in vivo synergistically. Mechanistically, we observed a negative enrichment of SREBP2-driven cholesterol metabolism pathways in PIN1 knockout cells via RNA-sequencing and used a suite of diverse molecular and biochemical approaches to show that PIN1 directly binds to JNK-dependent phosphorylated SREBP2 (Ser455) and vice versa. These results indicate that active cholesterol biosynthesis pathway in bladder cancer cells is regulated by PIN1-mediated isomerization and JNK-mediated phosphorylation of its key transcriptional factor SREBP2. These findings emphasize that PIN1 can act as a regulator and potential therapeutic target in bladder cancer.

Citation Format: Xue Wang, Tony Hunter. PIN1 isomerase promotes the initiation and progression of bladder cancer through SREBP2-mediated cholesterol biosynthesis pathway [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A026.
Abstract B009: Targeting bladder cancer-macrophage interactions by SPARC peptides
Authors: Diab Mariam , Said Neveen
Published: May 2024

Bladder cancer is one of the privileged cancers treated with two modalities of immune therapeutics: intravesical Bacille Calmette-Guérin (BCG) for non-muscle invasive disease and immune checkpoint inhibitors for advanced metastatic muscle invasive disease. However, recurrence, intolerance and adverse events are encountered in both modalities with limited second and third line treatment options. Clinical data indicated that pretreatment infiltration of bladder tumors with tumor associated macrophages (TAMs) is associated with BCG failure, resistance to standard of care chemo- and immune-therapy and poor disease outcome. Preclinical studies indicated that macrophage infiltration is the forerunner of carcinogen-induced preneoplastic bladder lesions and progresses throughout overt neoplastic and metastatic disease. Thus, TAMs represent a plausible therapeutic target for bladder cancer. Capitalizing on our earlier report that SPARC, as tumor suppressor of BCa, we developed peptides mapping the biologically active domains of SPARC and investigated their direct effect on tumor cell malignant phenotype. In tandem, we determined the effect of SPARC-peptides on macrophage differentiation, polarization, and anti-tumor effects. We identified a potent inhibitory effect of our peptides on a panel of bladder cancer cell survival and invasiveness in 2D and 3D cultures. Using macrophage cell lines as well as bone marrow-derived myeloid cells, we found these peptides induced an M1 phenotype in response to cytokine stimulation, with enhanced phagocytic activity and macrophage-induced tumor cell killing in vitro. Moreover, SPARC-peptides inhibited macrophage polarization to M2 phenotype. Our data strongly suggest that SPARC-peptides are promising therapeutic candidates for bladder cancer.

Citation Format: Mariam Diab, Neveen Said. Targeting bladder cancer-macrophage interactions by SPARC peptides [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr B009.
Abstract B020: Development of novel Src-targeting strategies to block bladder cancer invasive progression
Authors: Jerome Nicole A. , Wang Yin , Henderson Marian L. , Broses Luke , Day Kathleen C. , Day Mark L. , Soellner Matthew B. , Palmbos Phillip L.
Published: May 2024

Background: Treatment of muscle-invasive bladder cancer remains challenging and, BCG, one of the few treatments that prevents progression of high-risk non-muscle invasive tumors to invasive metastatic disease, is difficult to obtain. Thus, development of new treatment approaches to block progression to muscle invasive disease is essential. We find that TRIM29 (tripartite motif containing 29, also known as ATDC), drives bladder cancer invasive progression through modulation of focal adhesions containing FAK and c-Src (Src). Despite this, literature has reported conflicting effects of Src knockdown and Src kinase inhibition on migration, perhaps due to separable pro- and anti-invasive functions of Src in bladder cancer. Hypothesis: Src drives bladder cancer invasive progression specifically through its tyrosine kinase activity within focal adhesions. Methods: We used 2D live cell migration assays and 3D spheroid invasion assays to test dasatinib, highly specific, novel conformation inhibitors of Src, a novel Src PROTAC, and siRNA against Src on bladder cancer migration and invasion. Results: Dasatinib and our novel conformation-specific inhibitors inhibited Src kinase activity and both siRNA and the novel PROTAC reduced total Src expression in vitro. Neither dasatinib, conformation inhibitors, siRNA, nor the PROTAC impacted bladder cancer cell viability in UM-UC5, UM-UC9 or UM-UC14 cell lines. Interestingly, we found that inhibiting Src’s kinase activity with either dasatinib or conformation-specific inhibitors abrogated bladder cancer migration. Conclusion: These results point to the selective importance of Src in regulating bladder cancer migration and invasion. They also suggest that novel Src targeting agents have potential clinical utility in the prevention of bladder cancer invasive progression.

Citation Format: Nicole A. Jerome, Yin Wang, Marian L. Henderson, Luke Broses, Kathleen C. Day, Mark L. Day, Matthew B. Soellner, Phillip L. Palmbos. Development of novel Src-targeting strategies to block bladder cancer invasive progression [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr B020.
Abstract IA003: Molecular subtypes and clinical benefit from neoadjuvant chemotherapy: A ten-year update
Authors: McConkey David J
Published: May 2024

Ten years ago TCGA and two private groups reported that muscle-invasive bladder cancers (MIBCs) could be grouped into basal and luminal molecular subtypes that shared features with the corresponding subtypes of breast cancer. These and earlier studies by the group at Lund University demonstrated that molecular subtype membership was prognostic: patients whose tumors were assigned to basal/squamous subtypes had shorter survival than did patients whose tumors were assigned to the luminal subtypes, and these relationships were confirmed in subsequent studies. In addition, one of the studies included tumors from patients treated with neoadjuvant cisplatin-based combination chemotherapy (NAC), where patients whose tumors were infiltrated with smooth muscle cells and fibroblasts (the MD Anderson p53-like subtype) had the lowest response rates. Parallel comparisons of patients who either did or did not receive NAC concluded that patients with basal tumors derived the most clinical benefit in terms of disease-specific or overall survival. Thus, in addition to being prognostic, there was a suggestion that molecular subtypes might also be used to predict resistance to NAC. This work led to the design of two large collaborative projects that were designed to validate these observations and the conclusion that inactivating mutations in several DNA damage and repair (DDR) genes were also associated with response. One leveraged the S1314 Phase-2 “CoXEN” trial that was designed to prospectively validate another gene expression-based biomarker, and the other exploited pretreatment samples from the CALGB/Alliance 90601 Phase-3 trial of gemcitabine/cisplatin with or without bevacizumab in patients with advanced or metastatic disease. Comparisons of response rates as a function of molecular subtype membership in S1314 failed to validate the original link between the MD Anderson p53-like subtype and resistance, and patients with basal/squamous tumors in 90601 did not have better outcomes than did patients with luminal tumors. Thus, while the prognostic value of molecular subtype membership was confirmed, the predictive value was not. Developing biomarkers to predict response to chemotherapy remains a challenge not only for bladder cancer but also for other solid and hematopoietic malignancies. It seems likely that success will require the integration of measurements using multiple platforms, including liquid biopsies and others. The exciting results of the EV-302 clinical trial of enfortumab vedotin plus pembrolizumab have shifted the focus of biomarker work to these and other novel agents.

Citation Format: David J McConkey. Molecular subtypes and clinical benefit from neoadjuvant chemotherapy: A ten-year update [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr IA003.
Abstract IA012: Novel approaches to the management of non-muscle invasive bladder cancer
Authors: Kamat Ashish M.
Published: May 2024

Non-muscle invasive bladder cancer (NMIBC) is a prevalent disease with a high recurrence rate and the potential to progress to muscle-invasive stages. While transurethral resection and bacillus Calmette-Guerin (BCG) immunotherapy remain the mainstay of treatment, limitations exist, particularly for high-grade and BCG-unresponsive NMIBC. This necessitates the exploration of novel therapeutic strategies. This talk will explore promising avenues in NMIBC management, including combination intravesical therapies, enhanced delivery methods for existing treatments, and emerging fields like gene therapy, targeted therapy, immunotherapy variants, and photodynamic therapy. These approaches hold the potential to improve bladder preservation rates, reduce recurrence, and ultimately enhance patient outcomes across the entire spectrum of NMIBC disease.

Citation Format: Ashish M. Kamat. Novel approaches to the management of non-muscle invasive bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr IA012.
Colon Age: A Metric for Whether and How to Screen Male Veterans for Early-Onset Colorectal Cancer
Authors: Imperiale Thomas F. , Myers Laura J. , Barker Barry C. , Stump Timothy E. , Daggy Joanne K.
Published: May 2024

We aimed to develop a metric for estimating risk for early-onset colorectal cancer (EOCRC) to help decide whether and how to screen persons < age 50. We used risk prediction models derived and validated on male veterans to calculate the RRs for six scenarios: one low-risk scenario (no risk factors present), four intermediate risk scenarios (some risk factors present), and one high-risk scenario (all risk factors present) for three age groups (35–39, 40–44, and 45–49 years). For each scenario, we estimated absolute colorectal cancer risk using Surveillance Epidemiology and End Results colorectal cancer incidence rates and each scenario’s RR. We identified the current Surveillance Epidemiology and End Results 5-year age group to which the revised estimate was closest and refer to the midpoint of this group as the “colon age.” When the revised estimate equals or exceeds that for 50- to 54-year-olds and for 70- to 74-year-olds, respective recommendations were made for (any) colorectal cancer screening and screening with colonoscopy. Among the scenarios, there was inconsistency between the two models for the 35 to 39 and 40 to 44 age groups, with only the 15-variable model recommending screening for the higher-risk 35- to 39-year-olds. Both models recommended screening for some intermediate risk and high-risk 40- to 44-year-olds. The models were well aligned on whether and how to screen most 45- to 49-year-olds. Using risk factors for EOCRC with colorectal cancer incidence rates, “colon age” may be useful for shared decision-making about whether and how to screen male veterans <50 years. For 45- to 49-year-olds, the 7-variable model may be preferred by patients, providers, and health systems.

Prevention Relevance: A new metric known as “colon age” expresses risk of EOCRC based on biological risk and may be useful for providers to explain and for patients to understand colorectal cancer risk when considering whether and how to be screened for colorectal cancer prior to age 45 or 50.
Devassa nas Minas Gerais: observações sobre casos de concubinato
Authors: Luna Francisco Vidal , Costa Iraci del Nero da
Published: May 2024

In this article we considere some characteristics — like sex, colour, economic activity and others — of persons who were sententiated due to the Devassa (religious inquiry at bishopric levei) effectuated in Minas Gerais in 1738. We have more interest in persons condamned by concubinage, because they represented about nine decimais of the total number of sententiated persons. We used the information we found in the manuscripts of the archive of the archbishopric of Mariana (Minas Gerais). In these manuscripts there is information about tweenty one parishes situated in Minas Gerais. With reference to concubinage, we verified that among the senten­tiated, there were persons belonging various social extracts and different economic, administrative and religious activities. It is possible to affirm that the concubinage was present at all the society of Minas Gerais and that there was not, with reference to the Devassas, privilege of any social extract. The major part of the sententiated were unmarried. Free men and slave and emancipated women predominated. The free women joined in marriage with members of his proper social extract, while the emancipated and slaves women, in the major part, were joined in marriage with free men (members of another social extract that was not the hers). It was not observed any correlation between the activities developped by men and the colour, the civil situation or the women’s social extract. Due to the exposed, the diffuse and indiscriminate character of the events of concubinage considered in this study.
Prognostic Impact of Heart Rhythm Shockability Trajectory in Out-of-Hospital Cardiac Arrest: A Multicenter Retrospective Study
Authors: Wang Chih-Hung , Lu Tsung-Chien , Tay Joyce , Wu Cheng-Yi , Wu Meng-Che , Su Pei-I. , Huang Chun-Yen , Tsai Chu-Lin , Huang Chien-Hua , Chen Wen-Jone
Published: May 2024

BACKGROUND:

This study aimed to investigate the association between the temporal transitions in heart rhythms during cardiopulmonary resuscitation (CPR) and outcomes after out-of-hospital cardiac arrest.

METHODS:

This was an analysis of the prospectively collected databases in 3 academic hospitals in northern and central Taiwan. Adult patients with out-of-hospital cardiac arrest transported by emergency medical service between 2015 and 2022 were included. Favorable neurological recovery and survival to hospital discharge were the primary and secondary outcomes, respectively. Time-specific heart rhythm shockability was defined as the probability of shockable rhythms at a particular time point during CPR. The temporal changes in the time-specific heart rhythm shockability were calculated by group-based trajectory modeling. Multivariable logistic regression analyses were performed to examine the association between the trajectory group and outcomes. Subgroup analyses examined the effects of extracorporeal CPR in different trajectories.

RESULTS:

The study comprised 2118 patients. The median patient age was 69.1 years, and 1376 (65.0%) patients were male. Three distinct trajectories were identified: high-shockability (52 patients; 2.5%), intermediate-shockability (262 patients; 12.4%), and low-shockability (1804 patients; 85.2%) trajectories. The median proportion of shockable rhythms over the course of CPR for the 3 trajectories was 81.7% (interquartile range, 73.2%–100.0%), 26.7% (interquartile range, 16.7%–37.5%), and 0% (interquartile range, 0%–0%), respectively. The multivariable analysis indicated both intermediate- and high-shockability trajectories were associated with favorable neurological recovery (intermediate-shockability: adjusted odds ratio [aOR], 4.98 [95% CI, 2.34–10.59]; high-shockability: aOR, 5.40 [95% CI, 2.03–14.32]) and survival (intermediate-shockability: aOR, 2.46 [95% CI, 1.44–4.18]; high-shockability: aOR, 2.76 [95% CI, 1.20–6.38]). The subgroup analysis further indicated extracorporeal CPR was significantly associated with favorable neurological outcomes (aOR, 4.06 [95% CI, 1.11–14.81]) only in the intermediate-shockability trajectory.

CONCLUSIONS:

Heart rhythm shockability trajectories were associated with out-of-hospital cardiac arrest outcomes, which may be a supplementary factor in guiding the allocation of medical resources, such as extracorporeal CPR.
Instruction on the Scientific Method Provides (Some) Protection Against Illusions of Causality
Authors: Chow Julie Y. L. , Goldwater Micah B. , Colagiuri Ben , Livesey Evan J.
Published: May 2024

People tend to overestimate the efficacy of an ineffective treatment when they experience the treatment and its supposed outcome co-occurring frequently. This is referred to as the outcome density effect. Here, we attempted to improve the accuracy of participants’ assessments of an ineffective treatment by instructing them about the scientific practice of comparing treatment effects against a relevant base-rate, i.e., when no treatment is delivered. The effect of these instructions was assessed in both a trial-by-trial contingency learning task, where cue administration was either decided by the participant (Experiments 1 & 2) or pre-determined by the experimenter (Experiment 3), as well as in summary format where all information was presented on a single screen (Experiment 4). Overall, we found two means by which base-rate instructions influence efficacy ratings for the ineffective treatment: 1) When information was presented sequentially, the benefit of base-rate instructions on illusory belief was mediated by reduced sampling of cue-present trials, and 2) When information was presented in summary format, we found a direct effect of base-rate instruction on reducing causal illusion. Together, these findings suggest that simple instructions on the scientific method were able to decrease participants’ (over-)weighting of cue-outcome coincidences when making causal judgements, as well as decrease their tendency to over-sample cue-present events. However, the effect of base-rate instructions on correcting illusory beliefs was incomplete, and participants still showed illusory causal judgements when the probability of the outcome occurring was high. Thus, simple textual information about assessing causal relationships is partially effective in influencing people’s judgements of treatment efficacy, suggesting an important role of scientific instruction in debiasing cognitive errors.
How Do You Know If You Were Mind Wandering? Dissociating Explicit Memories of Off Task Thought From Subjective Feelings of Inattention
Authors: Mathews Nathan K. , Bin Faiz Umer , Brosowsky Nicholaus P.
Published: May 2024

Mind wandering is a common experience in which your attention drifts away from the task at hand and toward task-unrelated thoughts. To measure mind wandering we typically use experience sampling and retrospective self-reports, which require participants to make metacognitive judgments about their immediately preceding attentional states. In the current study, we aimed to better understand how people come to make such judgments by introducing a novel distinction between explicit memories of off task thought and subjective feelings of inattention. Across two preregistered experiments, we found that participants often indicated they were “off task” and yet had no memory of the content of their thoughts—though, they were less common than remembered experiences. Critically, remembered experiences of mind wandering and subjective feelings of inattention differed in their behavioral correlates. In Experiment 1, we found that only the frequency of remembered mind wandering varied with task demands. In contrast, only subjective feelings of inattention were associated with poor performance (Experiments 1 and 2) and individual differences in executive functioning (Experiment 2). These results suggest that the phenomenology of mind wandering may differ depending on how the experiences are brought about (e.g., executive functioning errors versus excess attentional resources), and provide preliminary evidence of the importance of measuring subjective feelings of inattention when assessing mind wandering.
Toward the Emergence of Intelligent Control: Episodic Generalization and Optimization
Authors: Giallanza Tyler , Campbell Declan , Cohen Jonathan D.
Published: May 2024

Human cognition is unique in its ability to perform a wide range of tasks and to learn new tasks quickly. Both abilities have long been associated with the acquisition of knowledge that can generalize across tasks and the flexible use of that knowledge to execute goal-directed behavior. We investigate how this emerges in a neural network by describing and testing the Episodic Generalization and Optimization (EGO) framework. The framework consists of an episodic memory module, which rapidly learns relationships between stimuli; a semantic pathway, which more slowly learns how stimuli map to responses; and a recurrent context module, which maintains a representation of task-relevant context information, integrates this over time, and uses it both to recall context-relevant memories (in episodic memory) and to bias processing in favor of context-relevant features and responses (in the semantic pathway). We use the framework to address empirical phenomena across reinforcement learning, event segmentation, and category learning, showing in simulations that the same set of underlying mechanisms accounts for human performance in all three domains. The results demonstrate how the components of the EGO framework can efficiently learn knowledge that can be flexibly generalized across tasks, furthering our understanding of how humans can quickly learn how to perform a wide range of tasks—a capability that is fundamental to human intelligence.
Orbitacolax kyphosi sp. nov. (Copepoda, Cyclopoida, Bomolochidae) recovered from the brassy chub Kyphosus vaigiensis (Quoy & Gaimard, 1825) (Actinopterygii) in Japan
Authors: Izawa Kunihiko
Published: May 2024

Orbitacolax kyphosi sp. nov. is described based on a single specimen of the female recovered from washing fluid of the brassy chub Kyphosus vaigiensis (Quoy & Gaimard, 1825) (Centrachiformes, Kyphosidae) in Japan. K. vaigiensis is a new host and Kyphosidae is a new host group for the genus.
On the identity of Paranotonyx curtipes Nobili, 1906 (Brachyura, Thoracotremata, Varunidae)
Authors: Ng Peter K. L. , Davie Peter J. F.
Published: May 2024

Paranotonyx curtipes Nobili, 1906a, has not been reported since it was described from the Red Sea. Originally placed in the Goneplacidae, the genus has been associated with the Rhizopinae Stimpson, 1858 (Pilumnidae), since Tesch (1918). A re-examination of the holotype female shows that Paranotonyx is actually a member of the Gaeticinae Davie & N.K. Ng, 2007 (Varunidae). Records from Madagascar and Pakistan previously doubtfully referred to “Acmaeopleura balssi Shen, 1932” are here shown to be conspecific with P. curtipes. Paranotonyx is redescribed and figured, and compared with the allied Acmaeopleura Stimpson, 1858, and Sestrostoma Davie & N.K. Ng, 2007, genera that are restricted to the western Pacific.
Surface drag on deformed topographic boundaries: Tests using a semi-idealized model
Authors: Li Yi , Epifanio Craig
Published: May 2024

The physics of the surface drag (or surface stress) boundary condition is explored
in the context of semi-idealized flows past realistic terrain. Numerical experiments are presented to explore the impact of the drag condition on flows past a region of complex topography, with a particular focus on the dependence on terrain geometry. Arguments are presented to show that the drag condition depends on the geometry of the terrain in two respects: (i) a dependence on terrain slope, as represented by a normal gradient term; and (ii) a dependence on the curvature, which appears in the drag condition as a Dirichlet term. The dependence on the geometry is illustrated through a series of numerical experiments in which simulations using the full form of the drag condition are compared to companion simulations using one of two widely used approximations: (a) the normal gradient condition, which accounts for the terrain slope but neglects curvature; and (b) the flat boundary assumption, which neglects both slope and curvature. The results show that the role of the terrain geometry in the drag condition is strongly dependent on grid spacing, with more highly resolved topography leading to a stronger dependence on the slope and curvature. For sufficiently high resolutions, the dependence on the geometry becomes significant, to the extent that simulations using the approximate drag conditions fail to capture important aspects of the flow. Some basic implications of these results for the problem of high resolution wind energy forecasting are discussed.
Large-Scale Climate Modes Drive Low-Frequency Regional Arctic Sea Ice Variability
Authors: Wyburn-Powell Christopher , Jahn Alexandra
Published: May 2024

Summer Arctic sea ice is declining rapidly but with superimposed variability on multiple time scales that introduces large uncertainties in projections of future sea ice loss. To better understand what drives at least part of this variability, we show how a simple linear model can link dominant modes of climate variability to low-frequency regional Arctic sea ice concentration (SIC) anomalies. Focusing on September, we find skillful projections from global climate models (GCMs) from phase 6 of the Coupled Model Intercomparison Project (CMIP6) at lead times of 4–20 years, with up to 60% of observed low-frequency variability explained at a 5-yr lead time. The dominant driver of low-frequency SIC variability is the interdecadal Pacific oscillation (IPO) which is positively correlated with SIC anomalies in all regions up to a lead time of 15 years but with large uncertainty between GCMs and internal variability realization. The Niño-3.4 index and Atlantic multidecadal oscillation have better agreement between GCMs of being positively and negatively related, respectively, with low-frequency SIC anomalies for at least 10-yr lead times. The large variations between GCMs and between members within large ensembles indicate the diverse simulation of teleconnections between the tropics and Arctic sea ice and the dependence on the initial climate state. Further, the influence of the Niño-3.4 index was found to be sensitive to the background climate. Our results suggest that, based on the 2022 phases of dominant climate variability modes, enhanced loss of sea ice area across the Arctic is likely during the next decade.

Significance Statement

The purpose of this study is to better understand the drivers of low-frequency variability of Arctic sea ice. Teasing out the complicated relationships within the climate system takes a large number of examples. Here, we use 42 of the latest generation of global climate models to construct a simple linear model based on dominant named climate features to predict regional low-frequency sea ice anomalies at a lead time of 2–20 years. In 2022, these modes of variability happen to be in the phases most conducive to low Arctic sea ice concentration anomalies. Given the context of the longer-term trend of sea ice loss due to global warming, our results suggest accelerated Arctic sea ice loss in the next decade.
The E592K variant of SF3B1 creates unique RNA missplicing and associates with high-risk MDS without ring sideroblasts
Authors: Choi In Young , Ling Jonathan P. , Zhang Jian , Helmenstine Eric , Walter Wencke , Tsakiroglou Panagiotis , Bergman Riley E. , Philippe Céline , Manley James L. , Rouault-Pierre Kevin , Li Bing , Wiseman Daniel H. , Batta Kiran , Ouseph Madhu , Bernard Elsa , Dubner Benjamin , Li Xiao , Haferlach Torsten , Koget Anna , Fazal Salman , Jain Tania , Gocke Christopher D. , DeZern Amy E. , Dalton William Brian
Published: May 2024

Among the most common genetic alterations in myelodysplastic syndromes (MDS) are mutations in the spliceosome gene SF3B1. Such mutations induce specific RNA missplicing events, directly promote ring sideroblast (RS) formation, and generally associate with a more favorable prognosis. However, not all SF3B1 mutations are the same, and little is known about how distinct hotspots influence disease. Here, we report that the E592K variant of SF3B1 associates with high-risk disease features in MDS, including a lack of RS, increased myeloblasts, a distinct comutation pattern, and a lack of favorable survival seen with other SF3B1 mutations. Moreover, compared with other hot spot SF3B1 mutations, E592K induces a unique RNA missplicing pattern, retains an interaction with the splicing factor SUGP1, and preserves normal RNA splicing of the sideroblastic anemia genes TMEM14C and ABCB7. These data have implications for our understanding of the functional diversity of spliceosome mutations, as well as the pathobiology, classification, prognosis, and management of SF3B1-mutant MDS.
Optimization Mechanism of Mechanical Properties of Basalt Fiber-Epoxy Resin Composites by Interfacially Enriched Distribution of Nano-Starch Crystals
Authors: Wei Yanpeng , Zhao Jiale , Zhuang Jian , Zhang Peng , Han Zhiwu
Published: May 2024

Fibre reinforced polymer composites have become a new generation of structural materials due to their unique advantages such as high specific strength, designability, good dimensional stability and ease of large-area monolithic forming. However, the problem of interfacial bonding between the resin matrix and the fibres limits the direct use of reinforcing fibres and has become a central difficulty in the development of basalt fibre-epoxy composites. This paper proposes a solution for enhancing the strength of the fibre-resin interface using maize starch nanocrystals, which are highly yield and eco-friendly. Firstly, in this paper, corn starch nanocrystals (SNC) were prepared by hydrolysis, and were deposited on the surface of basalt fibers by electrostatic adsorption. After that, in order to maximize the modification effect of nano-starch crystals on the interface, the basalt fiber-epoxy resin composite samples were prepared by mixing in a pressureless molding method. The test results shown that the addition of basalt fibers alone led to a reduction in the strength of the sample. Deposition of 0.1 wt% SNC on the surface of basalt fibers can make the strength consistent with pure epoxy resin. When the adsorption amount of SNC reached 0.5 wt%, the tensile strength of the samples was 23.7% higher than that of pure epoxy resin. This is due to the formation of ether bond homopolymers between the SNC at the fibre-epoxy interface and the epoxy resin, which distorts the originally smooth interface, leading to increased stress concentration and the development of cracks. This enhances the binding of basalt fibers. The conclusions of this paper can provide an effective, simple, low-cost and non-polluting method of interfacial enhancement modification.
Facile synthesis of hierarchical W18O49 microspheres by solvothermal method and their optical absorption properties
Authors: Xiong Yuanpeng , Wu Bo , Lin Yuanzhi , Zhang Mingwen , Chen Jintian
Published: May 2024

In this study, a simple route for the synthesis of hierarchical W18O49 assembled by nanowires is reported. The morphologies and formation of W18O49 single-crystal could be controlled by changing the concentration of WCl6-ethanol solution. This synthesis strategy has the advantages that the hierarchical W18O49 microspheres could be economic synthesized at 180 °C without adding additives. Furthermore, efficient optical absorption properties in ultraviolet, visible and near-infrared region were obtained for the hierarchical W18O49 microspheres comparing with nanowires. These results will further promote the research of tungsten-based oxide nanomaterials.

Graphical abstract
Single-cell transcriptomic landscape and the microenvironment of normal adjacent tissues in hypopharyngeal carcinoma
Authors: Guan Rui , Li Ce , Gu Fangmeng , Li Wenming , Wei Dongmin , Cao Shengda , Chang Fen , Lei Dapeng
Published: May 2024

Background

The cellular origin of hypopharyngeal diseases is crucial for further diagnosis and treatment, and the microenvironment in tissues may also be associated with specific cell types at the same time. Normal adjacent tissues (NATs) of hypopharyngeal carcinoma differ from non-tumor-bearing tissues, and can influenced by the tumor. However, the heterogeneity in kinds of disease samples remains little known, and the transcriptomic profile about biological information associated with disease occurrence and clinical outcome contained in it has yet to be fully evaluated. For these reasons, we should quickly investigate the taxonomic and transcriptomic information of NATs in human hypopharynx.

Results

Single-cell suspensions of normal adjacent tissues (NATs) of hypopharyngeal carcinoma were obtained and single-cell RNA sequencing (scRNA-seq) was performed. We present scRNA-seq data from 39,315 high-quality cells in the hypopharyngeal from five human donors, nine clusters of normal adjacent human hypopharyngeal cells were presented, including epithelial cells, endothelial cells (ECs), mononuclear phagocyte system cells (MPs), fibroblasts, T cells, plasma cells, B cells, mural cells and mast cells. Nonimmune components in the microenvironment, including epithelial cells, endothelial cells, fibroblasts and the subpopulations of them were performed.

Conclusions

Our data provide a solid basis for the study of single-cell landscape in human normal adjacent hypopharyngeal tissues biology and related diseases.
Performance comparison of BD Phoenix CPO detect panel with Cepheid Xpert Carba-R assay for the detection of carbapenemase-producing Klebsiella pneumoniae isolates
Authors: Tüzemen Nazmiye Ülkü , Önal Uğur , Merdan Osman , Akca Bekir , Ener Beyza , Akalın Halis , Özakın Cüneyt
Published: May 2024

Background

We aimed to compare the performance of carbapenemase classification in carbapenem-resistant Klebsiella pneumoniae (CRKP) obtained using the BD Phoenix CPO Detect panel (CPO panel) and Cepheid Xpert Carba-R assays. We analyzed 55 CRKP strains from clinical specimens collected between November 2020 and November 2022. The CPO panel was used to detect both antibiotic susceptibility and phenotypic carbapenemase classes, while Xpert Carba-R was employed to identify KPC, NDM, VIM, OXA-48, and IMP genes. Due to the limited availability of molecular kits, we arbitrarily selected 55 isolates, identified as carbapenemase-producing according to the CPO panel and with meropenem minimum inhibitory concentration values > 8 mg/L.

Results

According to the Xpert Carba-R assay, 16 of the 55 isolates (29.1%) were categorised as Ambler Class A (11 of which matched CPO panel Class A identification); three isolates (5.5%) were identified as Class B and 27 isolates (49.1%) as Class D (in both cases consistent with CPO panel B and D classifications). A further eight isolates (14.5%) exhibited multiple carbapenemase enzymes and were designated as dual-carbapenemase producers, while one isolate (1.8%) was identified as a non-carbapenemase-producer. The CPO panel demonstrated positive and negative percent agreements of 100% and 85.7% for Ambler Class A, 100% and 100% for Class B, and 96.4% and 100% for Class D carbapenemase detection, respectively.

Conclusion

While the CPO panel’s phenotypic performance was satisfactory in detecting Class B and D carbapenemases, additional confirmatory testing may be necessary for Class A carbapenemases as part of routine laboratory procedures.