bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B033: Direct and sensitive in-situ detection of DNA breaks by STRIDE and its potential as a new biomarker
Authors: Solarczyk Kamil , Patterson Brian 
Published: January 2024

Abstract
DNA damage is usually detected using indirect methods which require active signaling and triggered DNA repair mechanisms. These methods, although relatively sensitive, are prone to false (positive or negative) results. Methods for direct DNA damage detection, on the other hand, suffer from low sensitivity or require DNA isolation, what can result in misleading artefactual readouts of the analysis. Here we present a method called STRIDE (SensiTive Recognition of Individual DNA Ends), which allows for specific, very sensitive in-situ detection of DNA breaks. This fluorescence-based method, in its two variants (dSTRIDE and sSTRIDE), allows selective labelling of double-or single-strand breaks, respectively. STRIDE enables highly sensitive and specific detection and quantification of single and double-strand DNA breaks in cultured cells and FFPE human tissues, both PBMCs as well as solid tumors. STRIDE is superior to classic methods used to measure DNA damage, as it combines a direct detection that is independent of DNA repair mechanisms with an unprecedented sensitivity. With its versatility it can be used in any type of biological material, including liquid biopsies as well as different types of tumors. STRIDE has the potential to become a very useful biomarker reporting about the efficiency of therapies based on DNA damage induction, such as DNA repair inhibitors or radiotherapy.
Citation Format: Kamil Solarczyk, Brian Patterson. Direct and sensitive in-situ detection of DNA breaks by STRIDE and its potential as a new biomarker [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr B033.
Abstract IA017: Drugging the DNA damage response (DDR) in the Clinic: Going beyond the approved PARP inhibitors
Authors: Yap Timothy A. 
Published: January 2024

Abstract
Genomic instability is a key hallmark of cancer that arises owing to defects in the DNA damage response (DDR) and/or increased replication stress. These alterations promote the clonal evolution of cancer cells via the accumulation of driver aberrations, including gene copy-number changes, rearrangements, and mutations; however, these same defects also create vulnerabilities that are relatively specific to cancer cells, which could potentially be exploited to increase the therapeutic index of anticancer treatments and thereby improve patient outcomes. The discovery that BRCA-mutant cancer cells are exquisitely sensitive to inhibition of poly(ADP-ribose) polymerase has ushered in a new era of research on biomarker-driven synthetic lethal treatment strategies for different cancers. The therapeutic landscape of antitumor agents targeting the DDR has rapidly expanded to include inhibitors of other key mediators of DNA repair and replication, such as ATR, ATM, CHK1, WEE1, PKMYT1 and PARG. Efforts to optimize these therapies are ongoing across a range of cancers, involving the development of predictive biomarker assays of response (beyond BRCA mutations), assessment of the mechanisms underlying intrinsic and acquired resistance, and evaluation of rational combinations to improve patient outcomes and widen the application of DDR agents.
Citation Format: Timothy A. Yap. Drugging the DNA damage response (DDR) in the Clinic: Going beyond the approved PARP inhibitors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr IA017.
Abstract PR006: Elucidating the effect of PARP inhibitors on MMEJ-mediated DNA repair
Authors: Ortega Raquel , Arnoult Nausica , Bitler Benjamin G 
Published: January 2024

Abstract
First-line maintenance treatment for homologous recombination (HR)-deficient (HRD, e.g., BRCA1/2 mutations) cancers includes poly ADP-ribose inhibitors (PARPi, e.g., olaparib, niraparib). PARPi are lethal through multiple mechanisms, including PARP trapping and PARP activity inhibition, which both destabilize the replication fork machinery in the absence of BRCA1/2. However, only 50% of HRD tumors respond to PARPi treatment due to intrinsic resistance and of those that respond, most tumors eventually relapse due to acquired drug resistance. Because MMEJ is essential in HRD-cancers, it has emerged as a promising target to combat PARPi resistance, with POLQ inhibitors currently in clinical trials. Thus, understanding the interplay between MMEJ and PARP inhibitors is critical. While PARP1 is proposed to promote MMEJ, PARP regulates numerous aspects of DSB repair, and therefore its overall impact on MMEJ levels remains unclear. For instance, the effect of PARP inhibition on DSB end-resection, a critical step of MMEJ, remains controversial. Utilizing a DNA repair reporter, we assessed MMEJ levels following treatment with various PARP inhibitors, including those with minimal PARP trapping activity. Remarkably, we find that PARP inhibition systematically leads to elevated MMEJ levels in a POLQ-dependent fashion. Furthermore, PARP inhibition also induces higher MMEJ levels in cells treated with NHEJ inhibitors as well as in HR-deficient cells, including an HRD ovarian cancer cell line (PEO1, BRCA2mut). Therefore, this MMEJ upregulation cannot be simply attributed to a PARPi-mediated suppression of NHEJ or HR activity. Taken together, our data suggests that the overall effect of PARP inhibitors may lead to upregulation, rather than suppression, of MMEJ activity. We are currently assessing the contribution of PARP1 and PARP2 in MMEJ regulation and are testing whether PARPi also increase MMEJ levels at sites of replication induced DSBs. We hypothesize that PARPi could upregulate MMEJ through modulating DSB end-resection. This insight bears significant implications for the development of combination therapies of MMEJ and PARP inhibitors in treating HRD cancers.
Citation Format: Raquel Ortega, Nausica Arnoult, Benjamin G Bitler. Elucidating the effect of PARP inhibitors on MMEJ-mediated DNA repair [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr PR006.
REPRODUCTIVE BIOLOGY OF THE FRESHWATER CLAM POKEA (Batissa violacea var. celebensis, VON MARTEN 1897) (Bivalvia: Corbiculidae) IN THE POHARA RIVER, SOUTHEAST SULAWESI, INDONESIA
Authors: Bahtiar Bahtiar , Anadi La , Nurgayah Wa , Hamzah Muhaimin , Hernawan Udhi Eko 
Published: January 2024

The freshwater clam, locally known as Pokea, (Batissa violaceaÂ varÂ celebensis, von Martens 1897; Bivalvia: Corbulidae) is a popular and widely consumed food in Kendari, Southeast Sulawesi. Despite its popularity, basic information required for conservation managenment, such as reproductive biology, is lacking. This study aims to examine the reproductive biology of the clam obtained from the Pohara River, Kendari. Pokea samples were collected monthly from February 2012 to January 2013. We recorded parameters of reproductive biology, including sex ratio, stage of gonadal maturity, gonadosomatic index (GSI), fecundity, and size of the first mature gonad from each sample. Data were analysed using chi-square test andÂ linear regression in the package Sigma Plot v.6.0. Pokea population in the Pohara River was male-biased. The population spawns throughout the year and the peak spawning season was August-September. Mature gonad was found at small shell size (indicating early sexual maturity). Food availability might have influenced the gonadal development in Pokea. This baseline information is very relevant for conservation practices of Pokea population in the Pohara River.
Hospital Variation in Skilled Nursing Facility Use After Coronary Artery Bypass Graft Surgery
Authors: Stewart James W. , Hou Hechuan , Hawkins Robert B. , Pagani Francis D. , Sterling Madeline R. , Likosky Donald S. , Thompson Michael P. 
Published: January 2024

Background
Over 20% of patients are discharged to a skilled nursing facility (SNF) after coronary artery bypass graft surgery, but little is known about specific drivers for postdischarge SNF use. The purpose of this study was to evaluate hospital variation in SNF use and its association with postoperative outcomes after coronary artery bypass graft.

Methods and Results

A retrospective study design utilizing Medicare Provider Analysis and Review files was used to evaluate SNF use among 70 509 beneficiaries undergoing coronary artery bypass graft, with or without valve procedures, between 2016 and 2018. A total of 17 328 (24.6%) were discharged to a SNF, ranging from 0% to 88% across 871 hospitals. Multilevel logistic regression models identified significant patient‐level predictors of discharge to SNF including increasing age, comorbidities, female sex, Black race, dual eligibility, and postoperative complications. After adjusting for patient and hospital factors, 15.6% of the variation in hospital SNF use was attributed to the discharging hospital. Compared with the lower quartile of hospital SNF use, hospitals in the top quartile of SNF use had lower risk‐adjusted 1‐year mortality (12.5% versus 8.6%,
P
<0.001) and readmission (59.9% versus 49.8%,
P
<0.001) rates for patients discharged to a SNF.

Conclusions
There is high variability in SNF use among hospitals that is only partially explained by patient characteristics. Hospitals with higher SNF utilization had lower risk‐adjusted 1‐year mortality and readmission rates for patients discharged to a SNF. More work is needed to better understand underlying provider and hospital‐level factors contributing to SNF use variability.
Remote Heart Failure Symptoms Assessment After Myocardial Infarction Identifies Patients at Risk for Death
Authors: Wohlfahrt Peter , Jenča Dominik , Melenovský Vojtěch , Stehlik Josef , Spertus John A. , Mrázková Jolana , Šramko Marek , Kotrč Martin , Želízko Michael , Adámková Věra , Piťha Jan , Kautzner Josef 
Published: January 2024

Background
Heart failure is a common complication after myocardial infarction (MI) and is associated with increased mortality. Whether remote heart failure symptoms assessment after MI can improve risk stratification is unknown. The authors evaluated the association of the 23‐item Kansas City Cardiomyopathy Questionnaire (KCCQ) with all‐cause mortality after MI.

Methods and Results

Prospectively collected data from consecutive patients hospitalized for MI at a large tertiary heart center between June 2017 and September 2022 were used. Patients remotely completed the KCCQ 1 month after discharge. A total of 1135 (aged 64±12 years, 26.7% women) of 1721 eligible patients completed the KCCQ. Ranges of KCCQ scores revealed that 30 (2.6%), 114 (10.0%), 274 (24.1%), and 717 (63.2%) had scores <25, 25 to 49, 50 to 74, and ≥75, respectively. During a mean follow‐up of 46 months (interquartile range, 29–61), 146 (12.9%) died. In a fully adjusted analysis, KCCQ scores <50 were independently associated with mortality (hazard ratio [HR], 6.05 for KCCQ <25, HR, 2.66 for KCCQ 25–49 versus KCCQ ≥50; both
P
<0.001). Adding the 30‐day KCCQ to clinical risk factors improved risk stratification: change in area under the curve of 2.6 (95% CI, 0.3–5.0), Brier score of −0.6 (95% CI, −1.0 to −0.2), and net reclassification improvement of 0.71 (95% CI, 0.45–1.04). KCCQ items most strongly associated with mortality were walking impairment, leg swelling, and change in symptoms.

Conclusions
Remote evaluation of heart failure symptoms using the KCCQ among patients recently discharged for MI identifies patients at risk for mortality. Whether closer follow‐up and targeted therapy can reduce mortality in high‐risk patients warrants further study.
Hungary and the Dissolution of the Warsaw Pact (1988–1991)
Authors: Békés Csaba 
Published: January 2024

Abstract
After the demise of Communism in East-Central Europe in 1989–1990, the new, non-Communist governments in the region had to consolidate their countries’ independence. The basic institutions of Soviet domination in East-Central Europe—the Warsaw Pact, the Council for Economic Mutual Assistance (CMEA), four large contingents of Soviet troops, and various other mechanisms of intra-bloc integration—still existed, and Soviet leaders hoped they could preserve most of those features in some form. Officials in East-Central Europe soon realized that they would have to take the initiative in eliminating all vestiges of Soviet hegemony in the region. The main impetus came from Hungary and Czechoslovakia and eventually Poland. Acting as a pressure group, they achieved agreement in the first half of 1991 on the dismantling of the alliance's military structures and then, by mid-1991, the dissolution of both the Warsaw Pact and CMEA. This article draws on recently declassified Hungarian, Soviet, East German, and Bulgarian archival sources to tell the behind-the-scenes endgame of the Warsaw Pact.
The Long Misunderstanding: Cuba's Economic Ties with the Soviet Bloc
Authors: Yordanov Radoslav 
Published: January 2024

Abstract
This article examines the political and economic issues that arose in relations between the Soviet bloc and Cuba from 1959 through 1991, including the admission of Cuba into the Soviet-dominated Council for Economic Mutual Assistance (CMEA) in the early 1970s. The article breaks new ground by consulting previously unseen primary documents originating from the East European states and Cuba, which highlight the often contentious ties between the European CMEA states and Cuba. The East European governments were often dismayed by the egregious economic mismanagement of Fidel Castro's regime and tried, mostly unsuccessfully, to encourage better policies. The relationship that emerged was shaped in part by Cuba's ever-increasing demands, by the East European states’ own economic limitations, and by the Soviet Union's far-reaching political objectives.
The Olympics and the Cold War: A Historiography
Authors: Sarantakes Nicholas Evan 
Published: January 2024

Abstract
This article is a historiographic review of the literature on the Olympic Games and the Cold War. The topic has been a growth area among scholars of both diplomatic history and the history of sports over the past three decades. Most of the literature has been in English, but a significant amount of work has appeared in French, German, and a few other languages. Despite the proliferation and richness of the historiography, some large gaps in coverage still exist, and some important issues still need to be explored.
Génétique animale et modernisation de l’élevage dans la France de l’après-guerre. Essai d’épistémologie historique de la sélection
Authors: Cornu Pierre 
Published: January 2024

Résumé
De la fondation de l’INRA en 1946 à la loi sur l’élevage de 1966, la génétique animale française vit une période d’une exceptionnelle intensité, qui la fait passer de la marge de la recherche nationale à une position de carrefour entre science, société et politiques agricoles. Les archives et la mémoire des acteurs de la recherche et de l’appui technique mettent en lumière cette histoire : la fabrique d’une véritable économie politique du cheptel, marquée au sceau de la rationalisation des bioressources, dans une dynamique hybride de biosciences appliquées, de « politique des grands nombres » et d’imaginaire du « progrès ». Une analyse diachronique en termes d’économie de la connaissance offre un récit intégrateur de la modernisation agricole dans ses dimensions biologique, sociale, technique et politique, en en restituant la conflictualité interne, mais également le rôle insoupçonné dans l’émergence d’une réflexivité critique au sein même du dispositif génétique.
Observations of Parametric Subharmonic Instability of Diurnal Internal Tides in the Northwest Pacific
Authors: Wang Yifan , Guan Shoude , Zhang Zhiwei , Zhou Chun , Xu Xin , Guo Chuncheng , Zhao Wei , Tian Jiwei 
Published: January 2024

Abstract
Based on yearlong observations from three moorings at 12°, 14°, and 16°N in the northwest Pacific, this study presents observational evidence for the occurrence and behavior of parametric subharmonic instability (PSI) of diurnal internal tides (ITs) both in the upper and abyssal ocean around the critical latitudes (O1 IT: 13.44°N; K1 IT: 14.52°N), which is relatively less explored in comparison with PSI of M2 ITs. At 14°N, near-inertial waves (NIWs) feature a “checkerboard” pattern with comparable upward- and downward-propagating components, while the diurnal ITs mainly feature a low-mode structure. The near-inertial kinetic energy at 14°N, correlated fairly well with the diurnal KE, is the largest among three moorings. The bicoherence analysis, and a causality analysis method newly introduced here, both show statistically significant phase locking between PSI triads at 14°N, while no significant signals emerge at 12° and 16°N. The estimated PSI energy transfer rate shows a net energy transfer from diurnal ITs to NIWs with an annual-mean value of 1.5 × 10−10 W kg−1. The highly sheared NIWs generated by PSI result in a 2–6 times larger probability of shear instability events at 14°N than 12° and 16°N. Through swinging the local effective inertial frequency close to either O1 or K1 subharmonic frequencies, the passages of anticyclonic and cyclonic eddies both result in elevated NIWs and shear instability events by enhancing PSI efficiency. Particularly, different from the general understanding that cyclonic eddies usually expel NIWs, enhanced NIWs and instability are observed within cyclonic eddies whose relative vorticity can modify PSI efficiency.

Significance Statement
Parametric subharmonic instability (PSI) effectively transfers energy from low-mode internal tides (ITs) to high-mode near-inertial waves (NIWs), triggering elevated mixing around critical latitudes. This study provides observational evidence for the occurrence of PSI of diurnal ITs in the northwest Pacific and its role in enhancing shear instability. Generally, anticyclonic eddies act to trap NIWs while cyclonic eddies tend to expel NIWs. Here we document elevated NIWs and shear instability within both anticyclonic and cyclonic eddies, which shift the local effective inertial frequency close to either O1 or K1 subharmonic frequencies, thereby enhancing PSI efficiency. Processes associated with PSI and the modulation of PSI efficiency by mesoscale eddies have significant implications for improving mixing parameterizations in ocean circulation and climate models.
Improvement of Albedo and Snow-Cover Simulation during Snow Events over the Tibetan Plateau
Authors: Liu Lian , Ma Yaoming 
Published: January 2024

Abstract
The snow albedo is a vital component of land–atmosphere coupling models. It plays a critical role in regulating land surface energy exchange by controlling incoming solar radiation absorbed by the land surface and influencing the timing and rate of snowmelt. Accurate snow albedo simulation is essential to obtain surface energy balance and snow-cover estimates. Here, the simulation of albedo and snow cover using the Weather Research and Forecasting Model and an improved snow albedo scheme is verified against satellite-retrieved products during and immediately following eight snowfall events over the Tibetan Plateau. The improved model successfully characterizes the spatial pattern and inverted U-shaped temporal pattern of albedo over the entire Tibetan Plateau. This is attributed to the local optimization of snow-age parameters and explicit consideration of snow depth in the improved scheme. Compared with the previous model, the model proposed herein greatly decreases the overestimated albedo (by 0.13–0.27), yielding a bias range of ±0.08, mean relative bias decrease of 70%, and significant increase in the spatial correlation coefficient of 0.03–0.39 (mean: 0.13). The significant improvements of albedo estimates appear in deep snow-covered regions, largely attributed to parameter optimization related to snow albedo decay, while less improvements appear over the shallow snow-covered regions. Accurate reproduction of the spatiotemporal variation in albedo alleviated snow-cover overestimation by small amounts. For snow-cover estimates, the improved model consistently decreases the false-alarm rate by 0.03, and increases the overall accuracy and equitable threat score by 0.04 and 0.03, respectively. Moreover, the improved scheme shows an equivalent improvement of albedo estimates at both 1- and 5-km grid spacing over the eastern Tibetan Plateau; this is also true for snow-cover estimates.

Significance Statement
Snow albedo schemes in widely used numerical weather prediction models show notable shortcomings in complex mountainous regions, hindering accurate surface energy balance and snow-cover prediction. The purpose of this study is to better understand the role of snow albedo on snow-cover estimates and reveal the application potential of an improved snow albedo scheme across the Tibetan Plateau. This is important because snow albedo influences the timing and rate of snowmelt, and in turn snow-cover estimates, through regulating the surface energy budget. Our results highlight the strong application potential of our improved scheme in reducing snow simulation errors, confirm the importance of snow depth on snow albedo, and provide a new perspective for improving the accuracy of snow forecast over the topographically high Tibetan Plateau.
Optimization of Endoscopic Submucosal Dissection and Endoscopic Mucosal Resection Strategies for Rectal Neuroendocrine Tumors Within 20 mm
Authors: Yu Qianwei , Zhang Yanxi , Su Yuan , Zhao Qian , Xiong Kangwei , Zhang Lijiu , Fang Haiming 
Published: January 2024

Aims No consensus regarding the optimal endoscopic resection approach for rectal neuroendocrine tumors (R-NETs) measuring 10-20 mm, this study aims to investigate this issue. Methods Patients with R-NETs underwent either endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). The primary endpoint was the complete resection rate, and the secondary endpoints were surgery-related complications and long-term outcomes. Results 96 patients met the inclusion criteria, 84 patients completed endoscopic resection, and 5 patients were excluded. 79 patients were enrolled and divided into EMR (n = 21) and ESD groups (n = 58). 100% of ESD excisions reached the primary endpoint, while 90.5% of EMR. Endoscopic submucosal dissection can achieve higher R0 rate and lower positive margin rate than EMR. The mean operative time of ESD and EMR was 35.22 ± 8.96 min and 13.14 ± 3.26 min, respectively. The complication rates of ESD and EMR were 3.4% and 4.8%, respectively. For R-NETs between 10 mm and 20 mm, the R0 rate of ESD was significantly higher than that of EMR (100% vs 71.4%, P = .01) and the margin positive rate of ESD was significant lower than that of EMR (4.8% vs 42.9%, P < .05). Both ESD and EMR obtained 100% R0 resection of less than 10 mm R-NET. The median follow-up was 13 months (3-84 months); 1 patient relapsed 25 months after EMR and was re-treated with ESD. Conclusion For R-NETs with a diameter less than 10 mm, both EMR and ESD were safe and effective and EMR is convenient and fast, with advantages. ESD offers superiority for R-NETs between 10 and 20 mm and can be considered as the preferred method.