bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural, photophysical, and electrochemical redox properties of meso-tetrakis(pentafluorophenyl)porphyrins
Authors: Deval Ankit Kumar , Sankar Muniappan 
Published: January 2024

This study delineates the synthesis and comprehensive characterization of metal complexes of meso-tetrakis(pentafluorophenyl)porphyrin (H2TPF[Formula: see text]P, 1) with first-row transition metal ions (M = Mn(III) 2, Fe(III) 3, Co(II) 4, Ni(II) 5, Cu(II) 6, and Zn(II) 7) to elucidate their structural, electronic spectral, and electrochemical redox properties. Co, Ni, Cu and Zn Complexes exhibit planar structure ([Formula: see text]24 = 0.003-0.021 Å and [Formula: see text]C[Formula: see text] = 0.004−0.041 Å) which is also confirmed by the single crystal data of complex ZnTPF[Formula: see text]P, 7 shows the planar geometry, while Fe and Mn complexes show the slightly nonplanar structure ([Formula: see text]24 = 0.101–0.143 Å and [Formula: see text]C[Formula: see text] = 0.080–0.112 Å), which are distorted due to their occupied axial sites by −Cl ligand as revealed by density functional theory (DFT) calculations. Furthermore, electronic spectroscopy revealed a gradual bathochromic shift following the order of NiTPF[Formula: see text]P < CoTPF[Formula: see text]P < CuTPF[Formula: see text]PCl < H2TPF[Formula: see text]P = FeTPF[Formula: see text]PCl < ZnTPF[Formula: see text]P < MnTPF[Formula: see text]PCl by appending different metal ions in the porphyrin core. MnTPF[Formula: see text]PCl exhibited the most significant bathochromic shift ([Formula: see text] = 63 nm) in the Soret band compared to H2TPF[Formula: see text]P. Also, MnTPF[Formula: see text]PCl and FeTPF[Formula: see text]PCl show a unique pattern of split Soret band at around 364 and 345 nm due to the interaction between the metal [Formula: see text]-orbitals and the surrounding ligands. The electrochemical redox potentials of the filled 3d orbital of Zn endow ZnTPF[Formula: see text]P (ring centered) with the lowest oxidation potential.
Exploiting Data-pattern-aware Vertical Partitioning to Achieve Fast and Low-cost Cloud Log Storage
Authors: Wei Junyu , Zhang Guangyan , Chen Junchao , Wang Yang , Zheng Weimin , Sun Tingtao , Wu Jiesheng , Jiang Jiangwei 
Published: January 2024

Cloud logs can be categorized into on-line, off-line, and near-line logs based on the access frequency. Among them, near-line logs are mainly used for debugging, which means they prefer a low query latency for better user experience. Besides, the storage system for near-line logs prefers a low overall cost including the storage cost to store compressed logs, and the computation cost to compress logs and execute queries. These requirements pose challenges to achieving fast and cheap cloud log storage.
This article proposes LogGrep, the first log compression and query tool that exploits both static and runtime patterns to properly structurize and organize log data in fine-grained units. The key idea of LogGrep is “vertical partitioning”: it stores each log entry into multiple partitions by first parsing logs into variable vectors according to static patterns and then extracting runtime pattern(s) automatically within each variable vector. Based on such runtime patterns, LogGrep further decomposes the variable vectors into fine-grained units called “Capsules” and stamps each Capsule with a summary of its values. During the query process, LogGrep can avoid decompressing and scanning Capsules that cannot match the keywords, with the help of the extracted runtime patterns and the Capsule stamps. We further show that the interactive debugging can well utilize the advantages of the vertical-partitioning-based method and mitigate its weaknesses as well. To this end, LogGrep integrates incremental locating and partial reconstruction to mitigate the read amplification incurred by vertical-partitioning-based method.
We evaluate LogGrep on 37 cloud logs from the production environment of Alibaba Cloud and the public datasets. The results show that LogGrep can reduce the query latency and the overall cost by an order of magnitude compared with state-of-the-art works. Such results have confirmed that it is worthwhile applying a more sophisticated vertical-partitioning-based method to accelerate queries on compressed cloud logs.
Lactate Utilization Enables Metabolic Escape to Confer Resistance to BET Inhibition in Acute Myeloid Leukemia
Authors: Monteith Andrew J. , Ramsey Haley E. , Silver Alexander J. , Brown Donovan , Greenwood Dalton , Smith Brianna N. , Wise Ashley D. , Liu Juan , Olmstead Sarah D. , Watke Jackson , Arrate Maria P. , Gorska Agnieszka E. , Fuller Londa , Locasale Jason W. , Stubbs Matthew C. , Rathmell Jeffrey C. , Savona Michael R. 
Published: January 2024

Abstract

Impairing the BET family coactivator BRD4 with small-molecule inhibitors (BETi) showed encouraging preclinical activity in treating acute myeloid leukemia (AML). However, dose-limiting toxicities and limited clinical activity dampened the enthusiasm for BETi as a single agent. BETi resistance in AML myeloblasts was found to correlate with maintaining mitochondrial respiration, suggesting that identifying the metabolic pathway sustaining mitochondrial integrity could help develop approaches to improve BETi efficacy. Herein, we demonstrated that mitochondria-associated lactate dehydrogenase allows AML myeloblasts to utilize lactate as a metabolic bypass to fuel mitochondrial respiration and maintain cellular viability. Pharmacologically and genetically impairing lactate utilization rendered resistant myeloblasts susceptible to BET inhibition. Low-dose combinations of BETi and oxamate, a lactate dehydrogenase inhibitor, reduced in vivo expansion of BETi-resistant AML in cell line and patient-derived murine models. These results elucidate how AML myeloblasts metabolically adapt to BETi by consuming lactate and demonstrate that combining BETi with inhibitors of lactate utilization may be useful in AML treatment.

Significance:
Lactate utilization allows AML myeloblasts to maintain metabolic integrity and circumvent antileukemic therapy, which supports testing of lactate utilization inhibitors in clinical settings to overcome BET inhibitor resistance in AML.
See related commentary by Boët and Sarry, p. 950
KDM5C-Mediated Recruitment of BRD4 to Chromatin Regulates Enhancer Activation and BET Inhibitor Sensitivity
Authors: Qiang Yulong , Fan Jiachen , Xie Chuanshuai , Yan Leilei , Song Xiaofei , Zhang Nan , Lin Yan , Xiong Jie , Zhang Wei , Liu Yu , Wei Lei , Li Yu , Chen Shizhen , Liang Kaiwei , Li Feng 
Published: January 2024

Abstract

The BET family member BRD4 is a bromodomain-containing protein that plays a vital role in driving oncogene expression. Given their pivotal role in regulating oncogenic networks in various cancer types, BET inhibitors (BETi) have been developed, but the clinical application has been impeded by dose-limiting toxicity and resistance. Understanding the mechanisms of BRD4 activity and identifying predictive biomarkers could facilitate the successful clinical use of BETis. Herein, we show that KDM5C and BRD4 cooperate to sustain tumor cell growth. Mechanistically, KDM5C interacted with BRD4 and stimulated BRD4 enhancer recruitment. Moreover, binding of the BRD4 C-terminus to KDM5C stimulated the H3K4 demethylase activity of KDM5C. The abundance of both KDM5C-associated BRD4 and H3K4me1/3 determined the transcriptional activation of many oncogenes. Notably, depletion or pharmacologic degradation of KDM5C dramatically reduced BRD4 chromatin enrichment and significantly increased BETi efficacy across multiple cancer types in both tumor cell lines and patient-derived organoid models. Furthermore, targeting KDM5C in combination with BETi suppressed tumor growth in vivo in a xenograft mouse model. Collectively, this work reveals a KDM5C-mediated mechanism by which BRD4 regulates transcription, providing a rationale for incorporating BETi into combination therapies with KDM5C inhibitors to enhance treatment efficacy.

Significance:
BRD4 is recruited to enhancers in a bromodomain-independent manner by binding KDM5C and stimulates KDM5C H3K4 demethylase activity, leading to synergistic effects of BET and KDM5C inhibitor combinations in cancer.
Pim Kinase Inhibitors Increase Gilteritinib Cytotoxicity in FLT3-ITD Acute Myeloid Leukemia Through GSK-3β Activation and c-Myc and Mcl-1 Proteasomal Degradation
Authors: Lee Jonelle K. , Chatterjee Aditi , Scarpa Mario , Bailey Christopher M. , Niyongere Sandrine , Singh Prerna , Mustafa Ali Moaath K. , Kapoor Shivani , Wang Yin , Silvestri Giovannino , Baer Maria R. 
Published: January 2024

Abstract

Acute myeloid leukemia (AML) with fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) has poor outcomes. FLT3-ITD drives constitutive and aberrant FLT3 signaling, activating STAT5 and upregulating the downstream oncogenic serine/threonine kinase Pim-1. FLT3 inhibitors are in clinical use, but with limited and transient efficacy. We previously showed that concurrent treatment with Pim and FLT3 inhibitors increases apoptosis induction in FLT3-ITD–expressing cells through posttranslational downregulation of Mcl-1. Here we further elucidate the mechanism of action of this dual targeting strategy. Cytotoxicity, apoptosis and protein expression and turnover were measured in FLT3-ITD–expressing cell lines and AML patient blasts treated with the FLT3 inhibitor gilteritinib and/or the Pim inhibitors AZD1208 or TP-3654. Pim inhibitor and gilteritinib cotreatment increased apoptosis induction, produced synergistic cytotoxicity, downregulated c-Myc protein expression, earlier than Mcl-1, increased turnover of both proteins, which was rescued by proteasome inhibition, and increased efficacy and prolonged survival in an in vivo model. Gilteritinib and Pim inhibitor cotreatment of Ba/F3-ITD cells infected with T58A c-Myc or S159A Mcl-1 plasmids, preventing phosphorylation at these sites, did not downregulate these proteins, increase their turnover or increase apoptosis induction. Moreover, concurrent treatment with gilteritinib and Pim inhibitors dephosphorylated (activated) the serine/threonine kinase glycogen synthase kinase-3β (GSK-3β), and GSK-3β inhibition prevented c-Myc and Mcl-1 downregulation and decreased apoptosis induction. The data are consistent with c-Myc T58 and Mcl-1 S159 phosphorylation by activated GSK-3β as the mechanism of action of gilteritinib and Pim inhibitor combination treatment, further supporting GSK-3β activation as a therapeutic strategy in FLT3-ITD AML.

Significance:
FLT3-ITD is present in 25% of in AML, with continued poor outcomes. Combining Pim kinase inhibitors with the FDA-approved FLT3 inhibitor gilteritinib increases cytotoxicity in vitro and in vivo through activation of GSK-3β, which phosphorylates and posttranslationally downregulates c-Myc and Mcl-1. The data support efficacy of GSK-3β activation in FLT3-ITD AML, and also support development of a clinical trial combining the Pim inhibitor TP-3654 with gilteritinib.
Longitudinal Position and Cancer Risk in the United States Revisited
Authors: Niu Jin , Brown Charlotte , Law Michael , Colacino Justin A. , Ritov Ya'acov 
Published: January 2024

Abstract

The debate over daylight saving time (DST) has surged, with interests in the effects of sunlight exposure on health. Prior studies simulated DST and standard time conditions by analyzing different locations within time zones and neighboring areas across time zone borders. We analyzed cancer incidence rates from various longitudinal positions within time zones and at time zone borders in the contiguous United States. Using data from State Cancer Profiles (2016–2020), we analyzed total cancer of 19 types and specific rates for eight cancers, adjusted for age and includes all demographics. log-linear regression is used to replicate a previous study, and spatial regression models are employed to explore discontinuities at borders. Cancer rate differences lack statistical significance within time zones and near borders for total cancer and most individual cancers. Exceptions included breast, prostate, and liver and bile duct cancers, which exhibited significant relationships with relative position at the 95% significance level. Breast and liver and bile duct cancers saw decreases, while prostate cancer incidence increased from west to east within time zones. Relative position does not have a significant impact on cancer incidence, hence cancer development in general. Isolated exceptions may warrant further investigation as more data become available. Our findings challenge prior research, revealing numerous inconsistencies. These disparities urge a reconsideration of the potential disparities in human health associated with DST and standard time. They offer insights contribute to the ongoing discussion surrounding the retention or abandonment of DST.

Significance:
In this article, we investigate the relation between the epidemiology of cancer incidence in the United States and time zone–related longitudinal positions. Our results differ from previous research, which were based on a subset of our data, and show that the time zone effect on cancer incidence rate is not significant. Our research provides implications on the implementation of DST by suggesting that there is no cancer-risk associated reason to prefer one time over the other. Our study also uses regression discontinuity design using natural splines, a more advanced statistical method, to increase robustness of our result. Our findings challenge prior research, revealing numerous inconsistencies. These disparities urge a reconsideration of the potential disparities in human health associated with DST and standard time. They offer insights contribute to the ongoing discussion surrounding the retention or abandonment of DST.
Artificial Intelligence Model Predicts Sudden Cardiac Arrest Manifesting With Pulseless Electric Activity Versus Ventricular Fibrillation
Authors: Holmstrom Lauri , Bednarski Bryan , Chugh Harpriya , Aziz Habiba , Pham Hoang Nhat , Sargsyan Arayik , Uy-Evanado Audrey , Dey Damini , Salvucci Angelo , Jui Jonathan , Reinier Kyndaron , Slomka Piotr J. , Chugh Sumeet S. 
Published: January 2024

BACKGROUND:
There is no specific treatment for sudden cardiac arrest (SCA) manifesting as pulseless electric activity (PEA) and survival rates are low; unlike ventricular fibrillation (VF), which is treatable by defibrillation. Development of novel treatments requires fundamental clinical studies, but access to the true initial rhythm has been a limiting factor.

METHODS:
Using demographics and detailed clinical variables, we trained and tested an AI model (extreme gradient boosting) to differentiate PEA-SCA versus VF-SCA in a novel setting that provided the true initial rhythm. A subgroup of SCAs are witnessed by emergency medical services personnel, and because the response time is zero, the true SCA initial rhythm is recorded. The internal cohort consisted of 421 emergency medical services-witnessed out-of-hospital SCAs with PEA or VF as the initial rhythm in the Portland, Oregon metropolitan area. External validation was performed in 220 emergency medical services-witnessed SCAs from Ventura, CA.

RESULTS:
In the internal cohort, the artificial intelligence model achieved an area under the receiver operating characteristic curve of 0.68 (95% CI, 0.61–0.76). Model performance was similar in the external cohort, achieving an area under the receiver operating characteristic curve of 0.72 (95% CI, 0.59–0.84). Anemia, older age, increased weight, and dyspnea as a warning symptom were the most important features of PEA-SCA; younger age, chest pain as a warning symptom and established coronary artery disease were important features associated with VF.

CONCLUSIONS:
The artificial intelligence model identified novel features of PEA-SCA, differentiated from VF-SCA and was successfully replicated in an external cohort. These findings enhance the mechanistic understanding of PEA-SCA with potential implications for developing novel management strategies.
Long-Term Durability of High- and Very High-Power Short-Duration PVI by Invasive Remapping: The HPSD Remap Study
Authors: Szegedi Nándor , Salló Zoltán , Nagy Vivien Klaudia , Osztheimer István , Hizoh István , Lakatos Bálint , Boussoussou Melinda , Orbán Gábor , Boga Márton , Ferencz Arnold Béla , Komlósi Ferenc , Tóth Patrik , Perge Péter , Kovács Attila , Merkely Béla , Gellér László 
Published: January 2024

BACKGROUND:
High-power short-duration ablation has shown impressive efficacy and safety for pulmonary vein isolation (PVI); however, initial efficacy results with very high power short-duration ablation were discouraging. This study compared the long-term durability of PVI performed with a 90- versus 50-W power setting.

METHODS:
Patients were randomized 1:1 to undergo PVI with the QDOT catheter using a power setting of 90 or 50 W. Three months after the index procedure, patients underwent a repeat electrophysiology study to identify pulmonary vein reconnections. Patients were followed for 12 months to detect AF recurrences.

RESULTS:

We included 46 patients (mean age, 64 years; women, 48%). Procedure (76 versus 84 minutes;
P
=0.02), left atrial dwell (63 versus 71 minutes;
P
=0.01), and radiofrequency (303 versus 1040 seconds;
P
<0.0001) times were shorter with 90- versus 50-W procedures, while the number of radiofrequency applications was higher with 90 versus 50 W (77 versus 67;
P
=0.01). There was no difference in first-pass isolation (83% versus 82%;
P
=1.0) or acute reconnection (4% versus 14%;
P
=0.3) rates between 90 and 50 W. Forty patients underwent a repeat electrophysiology study. Durable PVI on a per PV basis was present in 72/78 (92%) versus 68/77 (88%) PVs in the 90- and 50-W energy setting groups, respectively; effect size: 72/78−68/77=0.040, lower 95% CI=−0.051 (noninferiority limit=−0.1, ie, noninferiority is met). No complications occurred. There was no difference in 12-month atrial fibrillation-free survival between the 90- and 50-W groups (
P
=0.2).

CONCLUSIONS:
Similarly high rates of durable PVI and arrhythmia-free survival were achieved with 90 and 50 W. Procedure, left atrial dwell, and radiofrequency times were shorter with 90 W compared with 50 W. The sample size is too small to conclude the safety and long-term efficacy of the high and very high-power short-duration PVI; further studies are needed to address this topic.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT05459831.
Trajectories of Sleep Over Midlife and Incident Cardiovascular Disease Events in the Study of Women’s Health Across the Nation
Authors: Thurston Rebecca C. , Chang Yuefang , Kline Christopher E. , Swanson Leslie M. , El Khoudary Samar R. , Jackson Elizabeth A. , Derby Carol A. 
Published: January 2024

BACKGROUND:
Up to 50% of women report sleep problems in midlife, and cardiovascular disease (CVD) is the leading cause of death in women. How chronic poor sleep exposure over decades of midlife is related to CVD risk in women is poorly understood. We tested whether trajectories of insomnia symptoms or sleep duration over midlife were related to subsequent CVD events among SWAN (Study of Women’s Health Across the Nation) participants, whose sleep was assessed up to 16 times over 22 years.

METHODS:
At baseline, SWAN participants (n=2964) were 42 to 52 years of age, premenopausal or early perimenopausal, not using hormone therapy, and free of CVD. They completed up to 16 visits, including questionnaires assessing insomnia symptoms (trouble falling asleep, waking up several times a night, or waking earlier than planned ≥3 times/week classified as insomnia), typical daily sleep duration, vasomotor symptoms, and depressive symptoms; anthropometric measurements; phlebotomy; and CVD event ascertainment (ie, fatal or nonfatal myocardial infarction, stroke, heart failure, revascularization). Sleep trajectories (ie, insomnia, sleep duration) were determined by means of group-based trajectory modeling. Sleep trajectories were tested in relation to CVD in Cox proportional hazards models (multivariable models: site, age, race and ethnicity, education, CVD risk factors averaged over visits; additional covariates: vasomotor symptoms, snoring, depression).

RESULTS:

Four trajectories of insomnia symptoms emerged: low insomnia symptoms (n=1142 [39% of women]), moderate insomnia symptoms decreasing over time (n=564 [19%]), low insomnia symptoms increasing over time (n=590 [20%]), and high insomnia symptoms that persisted (n=668 [23%]). Women with persistently high insomnia symptoms had higher CVD risk (hazard ratio, 1.71 [95% CI, 1.19, 2.46],
P
=0.004, versus low insomnia; multivariable). Three trajectories of sleep duration emerged: persistently short (~5 hours: n=363 [14%]), moderate (~6 hours: n=1394 [55%]), and moderate to long (~8 hours: n=760 [30%]). Women with persistent short sleep had marginally higher CVD risk (hazard ratio, 1.51 [95% CI, 0.98, 2.33],
P
=0.06, versus moderate; multivariable). Women who had both persistent high insomnia and short sleep had significantly elevated CVD risk (hazard ratio, 1.75 [95% CI, 1.03, 2.98],
P
=0.04, versus low insomnia and moderate or moderate to long sleep duration; multivariable). Relations of insomnia to CVD persisted when adjusting for vasomotor symptoms, snoring, or depression.

CONCLUSIONS:
Insomnia symptoms, when persistent over midlife or occurring with short sleep, are associated with higher CVD risk among women.
Individualized epidemic spreading models predict epilepsy surgery outcomes: A pseudo-prospective study
Authors: Millán Ana P. , van Straaten Elisabeth C. W. , Stam Cornelis J. , Nissen Ida A. , Idema Sander , Van Mieghem Piet , Hillebrand Arjan 
Published: January 2024

Abstract
Epilepsy surgery is the treatment of choice for drug-resistant epilepsy patients, but up to 50% of patients continue to have seizures one year after the resection. In order to aid presurgical planning and predict postsurgical outcome on a patient-by-patient basis, we developed a framework of individualized computational models that combines epidemic spreading with patient-specific connectivity and epileptogeneity maps: the Epidemic Spreading Seizure and Epilepsy Surgery framework (ESSES). ESSES parameters were fitted in a retrospective study (N = 15) to reproduce invasive electroencephalography (iEEG)-recorded seizures. ESSES reproduced the iEEG-recorded seizures, and significantly better so for patients with good (seizure-free, SF) than bad (nonseizure-free, NSF) outcome. We illustrate here the clinical applicability of ESSES with a pseudo-prospective study (N = 34) with a blind setting (to the resection strategy and surgical outcome) that emulated presurgical conditions. By setting the model parameters in the retrospective study, ESSES could be applied also to patients without iEEG data. ESSES could predict the chances of good outcome after any resection by finding patient-specific model-based optimal resection strategies, which we found to be smaller for SF than NSF patients, suggesting an intrinsic difference in the network organization or presurgical evaluation results of NSF patients. The actual surgical plan overlapped more with the model-based optimal resection, and had a larger effect in decreasing modeled seizure propagation, for SF patients than for NSF patients. Overall, ESSES could correctly predict 75% of NSF and 80.8% of SF cases pseudo-prospectively. Our results show that individualised computational models may inform surgical planning by suggesting alternative resections and providing information on the likelihood of a good outcome after a proposed resection. This is the first time that such a model is validated with a fully independent cohort and without the need for iEEG recordings.