bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conjugates of Tacrine with Aminomethylidene-Substituted Malonates: Synthesis and Biological Evaluation
Authors: Grishchenko M. V. , Elkina N. A. , Makhaeva G. F. , Burgart Ya. V. , Boltneva N. P. , Rudakova E. V. , Shchegolkov E. V. , Kovaleva N. V. , Serebryakova O. G. , Saloutin V. I. 
Published: December 2022

Abstract
The condensation of tacrine aminopolymethylene derivatives with diethyl (ethoxymethylidene)malonate led to the new hybrid compounds—conjugates, which were the effective inhibitors of acetylcholinesterase (AChE) (IC50 up to 0.538 μM) and butyrylcholinesterase (IC50 up to 0.0314 μM). They can displace propidium iodide from peripherical anionic site of AChE at the level of the reference drug donepezil and demonstrate a weak antioxidant activity. Conjugates are of interest for further extended research as potential drugs for the Alzheimer’s disease treatment.
Assessing widening disparities in HbA1c and systolic blood pressure retesting during the COVID-19 pandemic in an LGBTQ+-focused federally qualified health center in Chicago: a retrospective cohort study using electronic health records
Authors: Rivera Adovich S , Plank Megan , Davis Ash , Feinstein Matthew J , Rusie Laura K , Beach Lauren B 
Published: December 2022

IntroductionTo assess disparities in retesting for glycated hemoglobin (HbA1c) and systolic blood pressure (SBP) among people with diabetes mellitus (DM) and hypertension (HTN), respectively, we analyzed medical records from a lesbian, gay, bisexual, transgender, queer-specialized federally qualified health center with multiple sites in Chicago.Research design and methodsWe identified people with DM seen in 2018 and 2019 then assessed if individuals had HbA1c retested the following year (2019 and 2020). We repeated this using SBP for people with HTN. Rates of retesting were compared across gender, sexual orientation, and race and ethnicity and across the 2 years for each categorization with adjustment for socioeconomic indicators.ResultsRetesting rates declined from 2019 to 2020 for both HbA1c and SBP overall and across all groups. Cisgender women and transgender men with DM (vs cisgender men) and straight people (vs gay men) had significantly lower odds of HbA1c retesting for both years. There was evidence of widening of HbA1c retesting disparities in 2020 between gay men and other orientations. Cisgender women, straight people, and black people (vs white) with HTN had significantly lower odds of SBP retesting for both years. There was evidence of narrowing in the retesting gap between black and white people with HTN, but this was due to disproportionate increase in no retesting in white people rather than a decline in no retesting among black people with HTN.ConclusionsDisparities in DM and HTN care according to gender, race, ethnicity, and sexual orientation persisted during the pandemic with significant widening according to sexual orientation.
SP140 inhibits STAT1 signaling, induces IFN-γ in tumor-associated macrophages, and is a predictive biomarker of immunotherapy response
Authors: Tanagala Kranthi Kiran Kishore , Morin-Baxter Joshua , Carvajal Richard , Cheema Maryum , Dubey Sunil , Nakagawa Hiroshi , Yoon Angela , Cheng Yi-Shing L , Taylor Alison , Nickerson Jeffrey , Mintz Akiva , Momen-Heravi Fatemeh 
Published: December 2022

BackgroundUnderstanding the role and potential therapeutic targeting of tumor-associated macrophages (TAMs) is crucial to developing new biomarkers and therapeutic strategies for cancer immunotherapies. The epigenetic reader SP140 has emerged as a master regulator of macrophage transcriptional programs; however, its role in the signaling of TAMs and response to immunotherapy has not been investigated.MethodsWe evaluated the correlation between SP140 expression in head and neck squamous cell carcinoma (HNSCC) TAMs and clinical outcomes. We also used complementary bioinformatics and experimental approaches to study the association of SP140 expression with tumor mutation burden, patient survival, immunogenic signature of tumors, and signaling of TAMs. SP140 overexpression or knockdown was implemented to identify the role of SP140 in downstream signaling and production of inflammatory cytokine and chemokines. Chromatin immunoprecipitation and analysis of assay of transposase accessible chromatin sequencing data were used to demonstrate the direct binding of SP140 on the promoters of STAT1. Finally, correlation of SP140 with immune cell infiltrates and response to immune-checkpoint blockade in independent cohorts of HNSCC, metastatic melanoma, and melanoma was assessed.ResultsWe found that SP140 is highly expressed in TAMs across many cancer types, including HNSCCs. Interestingly, higher expression of SP140 in the tumors was associated with higher tumor mutation burden, improved survival, and a favorable response to immunotherapy. Tumors with high SP140 expression showed enrichment of inflammatory response and interferon-gamma (IFN-γ) pathways in both pan-cancer analysis and HNSCC-specific analysis. Mechanistically, SP140 negatively regulates transcription and phosphorylation of STAT1 and induces IFN-γ signaling. Activating SP140 in macrophages and TAMs induced the proinflammatory macrophage phenotype, increased the antitumor activity of macrophages, and increased the production of IFN-γ and antitumor cytokines and chemokines including interleukin-12 and CXCL10. SP140 expression provided higher sensitivity and specificity to predict antiprogrammed cell death protein 1 immunotherapy response compared with programmed death-ligand 1 in HNSCCs and lung cancer. In metastatic melanoma, higher levels of SP140 were associated with a durable response to immunotherapy, higher immune score estimates, high infiltrations of CD8+T cells, and inflammatory TAMs.ConclusionsOur findings suggest that SP140 could serve as both a therapeutic target and a biomarker to identify immunotherapy responders.
Association between haematological parameters and outcomes following transcatheter aortic valve implantation at mid-term follow-up
Authors: Abushouk Abdelrahman , Agrawal Ankit , Hariri Essa , Dykun Iryna , Kansara Tikal , Saad Anas , Abdelfattah Omar , Badwan Osamah , Jaggi Connor , Farwati Medhat , Harb Serge C , Puri Rishi , Reed Grant W , Krishnaswamy Amar , Yun James , Kapadia Samir 
Published: December 2022

BackgroundPatients undergoing transcatheter aortic valve implantation (TAVI) often have multiple comorbidities, such as anaemia and chronic inflammatory disorders. We sought to investigate the association between preoperative and postoperative haematological parameters and clinical outcomes in TAVI patients at mid-term follow-up.MethodsIn the present study, consecutive patients (N=908) who underwent TAVI at the Cleveland Clinic between 2017 and 2019 with available complete blood counts were studied. Data were collected on preoperative and postoperative anaemia and elevations in neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Survival analysis was used to study the association of haematologic parameters with all-cause mortality and major adverse cardiac and cerebrovascular events (MACCE).ResultsWe found that preoperative anaemia and elevated NLR were significantly associated with a higher risk of all-cause mortality (aHR=1.6 (95% CI: 1.1 to 2.0) and 1.4 (95% CI: 1.1 to 1.6), respectively) and MACCE (aHR=1.9 (95% CI: 1.3 to 2.8) and 1.6 (95% CI: 1.1 to 2.4), respectively). While an elevated preoperative PLR was not associated with increased mortality risk, it had a significant association with MACCE risk (aHR: 1.6 (95% CI: 1.1 to 2.4)). Further, postoperative anaemia, elevated NLR and PLR were associated with increased risks of all-cause mortality and MACCE.ConclusionPathological alterations in haematological parameters were associated with higher risks of post-TAVI mortality and MACCE at mid-term follow-up. Our findings advocate for further incorporating haematological parameters in the preoperative evaluation of TAVI candidates.
Association of Statin Use with the Risk of Incident Prostate Cancer: A Meta-Analysis and Systematic Review
Authors: Xu Meng-Yao , An Ye , Liu Chen-Qian , Xu Jin-Zhou , Zhong Xing-Yu , Zeng Na , Sun Jian-Xuan , Xia Qi-Dong , Wang Shao-Gang 
Published: December 2022

Background. With the growth and aging of population, the incidence of prostate cancer will increase year by year, which is bound to bring greater economic burden to the society. There has been greater interest in the anticancer effects of statin in recent years. It is controversial whether statin use is associated with the risk of prostate cancer (PCa). Thus, we conducted a meta-analysis and systematic review to explore the effects of statin use and their duration and cumulative dose on the overall incidence of PCa. Method. The study was conducted according to the latest guidelines for PRISMA 2020. We searched PubMed and other databases for studies about the association of statin use with the risk of incident prostate cancer between January 1, 1990, and April 11, 2022. Two independent researchers extracted data and evaluated the quality of the studies. R x64 4.1.2 and random-effects model were used for data statistics. Relative risk (RR) and odds ratio (OR) effective values with a 95% confidence interval (95% CI) were used to assess the main results. Results. The results of 6 RCT and 26 cohort studies showed that statins did not significantly associate with the incidence of PCa (RR = 0.94, 95% CI: 0.82–1.08). The similar results were obtained from 9 case-control studies (OR = 1.03, 95% CI: 0.99–1.07). However, statins were associated with a lower risk of Pca (RR = 0.44, 95% CI: 0.28–0.70) when the cumulative defined daily dose (cDDD) was high. Using statins for more than five years could be associated with a reduced incidence of Pca (RR = 0.47, 95% CI: 0.23–0.97). There was a significant heterogeneity in these studies (RCT and cohort study: I2 = 98%,

P

< 0.01; case-control study: I2 = 72%,

P

< 0.01). Conclusion. We concluded that statins had a neutral association with the overall risk of PCa. High cDDD and long duration were associated with a lower risk of PCa.
CSN6 Mediates Nucleotide Metabolism to Promote Tumor Development and Chemoresistance in Colorectal Cancer
Authors: Zou Shaomin , Qin Baifu , Yang Ziqing , Wang Wencong , Zhang Jieping , Zhang Yijing , Meng Manqi , Feng Junyan , Xie Yunling , Fang Ling , Xiao Lishi , Zhang Peng , Meng Xiangqi , Choi Hyun Ho , Wen Weijie , Pan Qihao , Ghesquière Bart , Lan Ping , Lee Mong-Hong , Fang Lekun 
Published: December 2022

Abstract

Metabolic reprogramming can contribute to colorectal cancer progression and therapy resistance. Identification of key regulators of colorectal cancer metabolism could provide new approaches to improve treatment and reduce recurrence. Here, we demonstrate a critical role for the COP9 signalosome subunit CSN6 in rewiring nucleotide metabolism in colorectal cancer. Transcriptomic analysis of colorectal cancer patient samples revealed a correlation between CSN6 expression and purine and pyrimidine metabolism. A colitis-associated colorectal cancer model established that Csn6 intestinal conditional deletion decreased tumor development and altered nucleotide metabolism. CSN6 knockdown increased the chemosensitivity of colorectal cancer cells in vitro and in vivo, which could be partially reversed with nucleoside supplementation. Isotope metabolite tracing showed that CSN6 loss reduced de novo nucleotide synthesis. Mechanistically, CSN6 upregulated purine and pyrimidine biosynthesis by increasing expression of PHGDH, a key enzyme in the serine synthesis pathway. CSN6 inhibited β-Trcp–mediated DDX5 polyubiquitination and degradation, which in turn promoted DDX5-mediated PHGDH mRNA stabilization, leading to metabolic reprogramming and colorectal cancer progression. Butyrate treatment decreased CSN6 expression and improved chemotherapy efficacy. These findings unravel the oncogenic role of CSN6 in regulating nucleotide metabolism and chemosensitivity in colorectal cancer.

Significance:
CSN6 deficiency inhibits colorectal cancer development and chemoresistance by downregulating PHGDH to block nucleotide biosynthesis, providing potential therapeutic targets to improve colorectal cancer treatment.
Extracellular Vesicle–Packaged circATP2B4 Mediates M2 Macrophage Polarization via miR-532-3p/SREBF1 Axis to Promote Epithelial Ovarian Cancer Metastasis
Authors: Wang Fang , Niu Yuequn , Chen Kelie , Yuan Xiaoyu , Qin Yuheng , Zheng Fang , Cui Zhenyan , Lu Weiguo , Wu Yihua , Xia Dajing 
Published: December 2022

Abstract

Ovarian cancer is one of the most common gynecologic malignancies with a highly immunosuppressive tumor microenvironment (TME) and poor prognosis. Circular RNA (circRNA) is a type of noncoding RNA with high stability, which has been shown to play an important role in biological processes and TME reprogramming in a variety of tumors. The biological function of a novel circRNA, circATP2B4, in epithelial ovarian cancer (EOC) was detected and evaluated. Transmission electron microscopy, differential ultracentrifugation and qRT-PCR were used to verify the existence of extracellular vesicles (EV)-packaged circATP2B4. Macrophage uptake of circATP2B4 was determined by EVs tracing. Dual luciferase reporter, FISH, Western blotting, and flow cytometry assays were used to investigate the interactions between circATP2B4 and miR-532-3p as well as sterol regulatory element-binding factor 1 (SREBF1) expression in macrophages. CircATP2B4 was upregulated in EOC tissues and positively correlated with ovarian cancer progression. Functionally, circATP2B4 promoted carcinogenic progression and metastasis of EOC both in vitro and in vivo. Mechanistically, EV-packaged circATP2B4 in EOC could be transmitted to infiltrated macrophages and acted as competing endogenous RNA of miR-532-3p to relieve the repressive effect of miR-532-3p on its target SREBF1. Furthermore, circATP2B4 induced macrophage M2 polarization by regulating the miR-532-3p/SREBF1/PI3Kα/AKT axis, thereby leading to immunosuppression and ovarian cancer metastasis. Collectively, these data indicate that circATP2B4-containing EVs generated by EOC cells promoted M2 macrophages polarization and malignant behaviors of EOC cells. Thus, targeting EVs-packaged circATP2B4 may provide a potential diagnosis and treatment strategy for ovarian cancer.
Communication for Real-Time Music Systems: An Overview of O2
Authors: Dannenberg Roger B. 
Published: December 2022

Abstract
Message passing between processes and across networks offers a powerful method to integrate and coordinate various music programs, facilitating software reuse, modularity, and parallel processing. Networking can integrate components that use different languages and hardware. In this article we describe O2, a flexible protocol for communication ranging from the thread level up to the level of global networks. Messages in O2 are similar to those of Open Sound Control, but O2 offers many additional features, including discovery, clock synchronization, a reliable message delivery option, and routing based on services rather than specific network addresses. A bridge mechanism extends the reach of O2 to web browsers, shared memory threads, and small microcontrollers. The design, implementation, and applications of O2 are described.
“Don’t Feel Like You Have to Do This All on Your Own”: Exploring Perceived Partner Support of Breastfeeding Among Black Women in Kentucky
Authors: Dogan Jardin , Hargons Candice , Stevens-Watkins Danelle 
Published: December 2022

Background: Few researchers have explored partner breastfeeding support among Black women, who report low breastfeeding rates compared to women of other cultural groups. Ways to encourage partner support of Black women’s breastfeeding can be understood from an Afrocentric perspective. Research Aim: To explore perceptions of partner support among Black mothers to develop a culturally relevant framework of partner breastfeeding support. Methods: Secondary data analyses of qualitative data from a larger prospective, cross-sectional mixed methods study were utilized. Participants from Kentucky ( N = 14), aged 23–71, who breastfed for at least 6 months, were recruited to participate in individual interviews. Professionally transcribed interviews were analyzed using Braun and Clarke’s (2006) thematic analysis. Results: By integrating the Breastfeeding Coparenting Framework and Optimal Conceptual Theory, we identified four culturally affirming partner support themes that participants believed impacted their breastfeeding experiences: (a) doing research, (b) offering care, (c) verbalizing praise, and (d) achieving teamwork, and three culturally incongruent partner support barrier themes: (e) withdrawing commitment, (f) politicking bodies, and (g) stripping agency. Conclusion: Participants who breastfed for at least 6 months largely attributed their breastfeeding success to the support received from their partners. Our findings offer a culturally relevant framework of partner breastfeeding support that can facilitate intervention efforts with participants and their partners to increase breastfeeding rates among this population.
The Role of Repetitive Transcranial Magnetic Stimulation in the Treatment of Autism Spectrum Disorder
Authors: Pal Mainak , Mandal Nikhiles , Ray Anirban , Saha Pradip Kumar 
Published: December 2022

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with impairments in language acquisition, social functioning, and restricted and repetitive behaviors. There is no definitive management for the ASD spectrum. The management options available are not beyond criticism. Hence, the search for new options is actively in progress. Noninvasive brain stimulation interventions such as repetitive transcranial magnetic stimulation (rTMS) appears to be a promising tool for the treatment of ASD. However, the available literature on TMS use in ASD is preliminary. Methods: This was a hospital-based longitudinal study conducted over 50 patients with ASD of 6 to 16 years of age. The Indian Scale for Assessment of Autism (ISAA) was used for the assessment of the extent of disability in these children. They were given 10 sessions of rTMS over a period of 10 days over the left dorsolateral prefrontal cortex (l-DLPFC) and reassessed for any improvement in ISAA score after 1 day and 3 months of completion of all the sessions of rTMS. Results: There was no statistically significant change in the total ISAA score or any of the 6 domains of ISAA after 1 day and 3 months of giving 10 sessions of TMS. There were no significant adverse effects after giving rTMS. In a few patients, mild headache, neck pain, or discomfort at the stimulation site was noted. Conclusion: This study has shown that low-frequency rTMS does not have any significant improvement on the various symptoms of ASD. However, there are no major adverse effects after giving rTMS. Also, it points toward the need for further studies.
Rib fracture-related morbidity and mortality for older persons in the era of fascial plane blocks: A cohort study
Authors: White Leigh D. , Riley Brooke , Seidel Davina , Davis Keiran , Mitchell Andrew , Abi-fares Catherine , Basson Willem , Anstey Chris 
Published: December 2022

Introduction Analgesia is key to successful conservative, nonsurgical management of patients admitted to the hospital with multiple rib fractures. Recently, new fascial plane regional anesthesia techniques have become widely available. We hypothesized that since the introduction of these new regional analgesia techniques, for patients over the age of 65 years, the effect of increasing numbers of rib fractures has been mitigated. Methods A retrospective study of patients admitted for the management of rib fractures between 2017 and 2020 was performed. Patients not admitted to the hospital, under the age of 65 years, or with chest trauma other than rib fractures were not eligible for inclusion. The primary outcome of interest was mortality. The secondary outcomes were the incidence of pneumonia and intensive care unit admission. Results were reported as the odds ratio and its 95% confidence interval and associated p-value. Statistical significance was set at [Formula: see text] < 0.05. Results Overall, 252 patients were included and 142 patients received a regional anesthesia. The mortality rate was 4% (n = 10) with no association between mortality and number of rib fractures ( p = 0.215). Twenty-four patients (9.5%) developed pneumonia during their hospital stay, again with no association with an increasing number of rib fractures. The intensive care unit admission rate was 13.1% (n = 33) and correlated with an increasing number of fractures (odds ratio = 1.15; 95% confidence interval = 1.01 to 1.31; p = 0.038). Conclusion Management including liberal utilization of regional anesthesia for at-risk patients appears to mitigate the effect of increasing numbers of rib fractures on the incidence of mortality and pneumonia.
Evaluation of taxonomic classification and profiling methods for long-read shotgun metagenomic sequencing datasets
Authors: Portik Daniel M. , Brown C. Titus , Pierce-Ward N. Tessa 
Published: December 2022

Abstract
Background
Long-read shotgun metagenomic sequencing is gaining in popularity and offers many advantages over short-read sequencing. The higher information content in long reads is useful for a variety of metagenomics analyses, including taxonomic classification and profiling. The development of long-read specific tools for taxonomic classification is accelerating, yet there is a lack of information regarding their relative performance. Here, we perform a critical benchmarking study using 11 methods, including five methods designed specifically for long reads. We applied these tools to several mock community datasets generated using Pacific Biosciences (PacBio) HiFi or Oxford Nanopore Technology sequencing, and evaluated their performance based on read utilization, detection metrics, and relative abundance estimates.

Results
Our results show that long-read classifiers generally performed best. Several short-read classification and profiling methods produced many false positives (particularly at lower abundances), required heavy filtering to achieve acceptable precision (at the cost of reduced recall), and produced inaccurate abundance estimates. By contrast, two long-read methods (BugSeq, MEGAN-LR & DIAMOND) and one generalized method (sourmash) displayed high precision and recall without any filtering required. Furthermore, in the PacBio HiFi datasets these methods detected all species down to the 0.1% abundance level with high precision. Some long-read methods, such as MetaMaps and MMseqs2, required moderate filtering to reduce false positives to resemble the precision and recall of the top-performing methods. We found read quality affected performance for methods relying on protein prediction or exact k-mer matching, and these methods performed better with PacBio HiFi datasets. We also found that long-read datasets with a large proportion of shorter reads (< 2 kb length) resulted in lower precision and worse abundance estimates, relative to length-filtered datasets. Finally, for classification methods, we found that the long-read datasets produced significantly better results than short-read datasets, demonstrating clear advantages for long-read metagenomic sequencing.

Conclusions
Our critical assessment of available methods provides best-practice recommendations for current research using long reads and establishes a baseline for future benchmarking studies.