bluuebunny/crossref_metadata_2025_split huggingface dataset:
Common analgesics and ovarian cancer survival: the Ovarian cancer Prognosis And Lifestyle (OPAL) Study
Authors: Majidi Azam , Na Renhua , Jordan Susan J , DeFazio Anna , Obermair Andreas , Friedlander Michael , Grant Peter , Webb Penelope M 
Published: February 2023

Abstract

Background
Most women with ovarian cancer (OC) are diagnosed with advanced disease. They often experience recurrence after primary treatment, and their subsequent prognosis is poor. Our goal was to evaluate the association between use of nonsteroidal antiinflammatory drugs (NSAIDs), including regular and low-dose aspirin, and 5-year cancer-specific survival after an OC diagnosis.

Methods
The Ovarian cancer Prognosis And Lifestyle study is a prospective population-based cohort of 958 Australian women with OC. Information was gathered through self-completed questionnaires. We classified NSAID use during the year prediagnosis and postdiagnosis as none or occasional (&lt;1 d/wk), infrequent (1-3 d/wk), and frequent (≥4 d/wk) use. We measured survival from the start of primary treatment: surgery or neoadjuvant chemotherapy for analyses of prediagnosis use, or 12 months after starting treatment (postdiagnosis use) until the earliest of date of death from OC (other deaths were censored) or last follow-up to 5 years. We used Cox proportional hazards regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) and applied inverse-probability of treatment weighting to minimize confounding. We also calculated restricted mean survival times.

Results
Compared with nonusers and infrequent users, we observed better survival associated with frequent NSAID use prediagnosis (HR = 0.73, 95% CI = 0.55 to 0.97) or postdiagnosis (HR = 0.65, 95% CI = 0.45 to 0.94). Estimates were similar for aspirin and nonaspirin NSAIDs, new and continuous users and in weighted models. These differences would translate to a 2.5-month increase in mean survival by 5 years postdiagnosis. There was no association with acetaminophen.

Conclusions
Our findings confirm a previous study suggesting NSAID use might improve OC survival.
Ku–DNA binding inhibitors modulate the DNA damage response in response to DNA double-strand breaks
Authors: Mendoza-Munoz Pamela L , Gavande Navnath S , VanderVere-Carozza Pamela S , Pawelczak Katherine S , Dynlacht Joseph R , Garrett Joy E , Turchi John J 
Published: February 2023

Abstract
The DNA-dependent protein kinase (DNA-PK) plays a critical role in the DNA damage response (DDR) and non-homologous end joining (NHEJ) double-strand break (DSB) repair pathways. Consequently, DNA-PK is a validated therapeutic target for cancer treatment in certain DNA repair-deficient cancers and in combination with ionizing radiation (IR). We have previously reported the discovery and development of a novel class of DNA-PK inhibitors with a unique mechanism of action, blocking the Ku 70/80 heterodimer interaction with DNA. These Ku–DNA binding inhibitors (Ku-DBi's) display nanomolar activity in vitro, inhibit cellular DNA-PK, NHEJ-catalyzed DSB repair and sensitize non-small cell lung cancer (NSCLC) cells to DSB-inducing agents. In this study, we demonstrate that chemical inhibition of the Ku–DNA interaction potentiates the cellular effects of bleomycin and IR via p53 phosphorylation through the activation of the ATM pathway. This response is concomitant with a reduction of DNA-PK catalytic subunit (DNA-PKcs) autophosphorylation at S2056 and a time-dependent increase in H2AX phosphorylation at S139. These results are consistent with Ku-DBi's abrogating DNA-PKcs autophosphorylation to impact DSB repair and DDR signaling through a novel mechanism of action, and thus represent a promising anticancer therapeutic strategy in combination with DNA DSB-inducing agents.
Tumor-suppressive disruption of cancer subtype-associated super enhancer circuits by small molecule treatment
Authors: Koeniger Anke , Polo Pierfrancesco , Brichkina Anna , Finkernagel Florian , Visekruna Alexander , Nist Andrea , Stiewe Thorsten , Daude Michael , Diederich Wibke E , Gress Thomas M , Adhikary Till , Lauth Matthias 
Published: February 2023

Abstract
Transcriptional cancer subtypes which correlate with traits such as tumor growth, drug sensitivity or the chances of relapse and metastasis, have been described for several malignancies. The core regulatory circuits (CRCs) defining these subtypes are established by chromatin super enhancers (SEs) driving key transcription factors (TFs) specific for the particular cell state. In neuroblastoma (NB), one of the most frequent solid pediatric cancer entities, two major SE-directed molecular subtypes have been described: A more lineage-committed adrenergic (ADRN) and a mesenchymal (MES) subtype. Here, we found that a small isoxazole molecule (ISX), a frequently used pro-neural drug, reprogrammed SE activity and switched NB cells from an ADRN subtype towards a growth-retarded MES-like state. The MES-like state shared strong transcriptional overlap with ganglioneuroma (GN), a benign and highly differentiated tumor of the neural crest. Mechanistically, ISX suppressed chromatin binding of N-MYC, a CRC-amplifying transcription factor, resulting in loss of key ADRN subtype-enriched components such as N-MYC itself, PHOX2B and ALK, while concomitently, MES subtype markers were induced. Globally, ISX treatment installed a chromatin accessibility landscape typically associated with low risk NB. In summary, we provide evidence that CRCs and cancer subtype reprogramming might be amenable to future therapeutic targeting.
Antibody-Based Therapeutics for the Treatment of Renal Cell Carcinoma: Challenges and Opportunities
Authors: Mahmoud Ahmed M , Nabavizadeh Reza , Rodrigues Pessoa Rodrigo , Garg Ishita , Orme Jacob , Costello Brian A , Cheville John , Lucien Fabrice 
Published: February 2023

AbstractRenal cell carcinoma (RCC) is among the top 10 most common cancers in both men and women with an estimated 75 000 cases each year in the US. Over the last decade, the therapeutic landscape for patients with metastatic RCC has significantly evolved, with immunotherapy emerging as the new front-line therapy. Despite significant improvement in toxicity profile and survival outcomes, key concerns such as patient selection, treatment sequencing, and intrinsic and acquired resistance remain unresolved. Emerging options such as antibody-based therapeutics (eg, anti-CD70, anti-CA9, and anti-ENPP3) are being explored in clinical trials for patients with cancer resistant or refractory to current immunotherapies. Despite positive results for hematological cancers, breast cancer, and more recently bladder cancer, most antibody-based therapies failed to improve the outcomes in patients with advanced RCC. This underscores the need to understand the underlying causes of failed responses to this treatment class, which will ultimately support the rational design of more effective and tolerable treatments. In this review, we summarize the evolving landscape of RCC therapeutics and describe recent clinical trials with emerging antibody-based therapeutics. We also describe the challenges that need to be overcome for the successful creation of therapeutic antibodies for treating RCC.
SPINDLY mediates O-fucosylation of hundreds of proteins and sugar-dependent growth in Arabidopsis
Authors: Bi Yang , Shrestha Ruben , Zhang Zhenzhen , Hsu Chuan-Chih , Reyes Andres V , Karunadasa Sumudu , Baker Peter R , Maynard Jason C , Liu Yang , Hakimi Amirmansoor , Lopez-Ferrer Daniel , Hassan Tahmid , Chalkley Robert J , Xu Shou-Ling , Wang Zhi-Yong 
Published: February 2023

Abstract
The recent discovery of SPINDLY (SPY)-catalyzed protein O-fucosylation revealed a novel mechanism for regulating nucleocytoplasmic protein functions in plants. Genetic evidence indicates the important roles of SPY in diverse developmental and physiological processes. However, the upstream signal controlling SPY activity and the downstream substrate proteins O-fucosylated by SPY remain largely unknown. Here, we demonstrated that SPY mediates sugar-dependent growth in Arabidopsis (Arabidopsis thaliana). We further identified hundreds of O-fucosylated proteins using lectin affinity chromatography followed by mass spectrometry. All the O-fucosylation events quantified in our proteomic analyses were undetectable or dramatically decreased in the spy mutants, and thus likely catalyzed by SPY. The O-fucosylome includes mostly nuclear and cytosolic proteins. Many O-fucosylated proteins function in essential cellular processes, phytohormone signaling, and developmental programs, consistent with the genetic functions of SPY. The O-fucosylome also includes many proteins modified by O-linked N-acetylglucosamine (O-GlcNAc) and by phosphorylation downstream of the target of rapamycin (TOR) kinase, revealing the convergence of these nutrient signaling pathways on key regulatory functions such as post-transcriptional/translational regulation and phytohormone responses. Our study identified numerous targets of SPY/O-fucosylation and potential nodes of crosstalk among sugar/nutrient signaling pathways, enabling future dissection of the signaling network that mediates sugar regulation of plant growth and development.
A novel biomimetic trabecular bone metal plate for bone repair and osseointegration
Authors: Ma Zhijie , Liu Baoyi , Li Shuqiang , Wang Xiaohu , Li Jingyu , Yang Jiahui , Tian Simiao , Wu Chengjun , Zhao Dewei 
Published: February 2023

Abstract
Fracture is one of the most common traumatic diseases in clinical practice, and metal plates have always been the first choice for fracture treatment because of their high strength. However, the bone plates have high elastic modulus and do not match the biomechanics of human bone, which adversely affects callus formation and fracture healing. Moreover, the complex microenvironment in the human body can induce corrosion of metallic materials and release toxic ions, which reduces the biocompatibility of the bone plate, and may necessitate surgical removal of the implant. In this study, tantalum (Ta) was deposited on porous silicon carbide (SiC) scaffolds by chemical vapor deposition technology to prepare a novel porous tantalum (pTa) trabecular bone metal plate. The function of the novel bone plate was evaluated by implantation in an animal fracture model. The results showed that the novel bone plate was effective in fracture fixation, without breakage. Both X-ray and microcomputed tomography analysis showed indirect healing by both pTa trabecular bone metal plates and titanium (Ti) plates; however, elastic fixation and obvious callus formation were observed after fixation with pTa trabecular bone metal plates, indicating better bone repair. Histology showed that pTa promoted the formation of new bone and integrated well with the host bone. Therefore, this novel pTa trabecular bone metal plate has good prospects for application in treating fractures.
Does Socially Responsible Investing Change Firm Behavior?
Authors: Heath Davidson , Macciocchi Daniele , Michaely Roni , C. Ringgenberg Matthew 
Published: February 2023

Abstract
Using micro-level data, we examine the behavior of socially responsible investment (SRI) funds. SRI funds select firms with lower pollution, more board diversity, higher employee satisfaction, and better workplace safety. Yet, both in the cross-section and using an exogenous shock to SRI capital, we find that SRI funds do not significantly change firm behavior. Moreover, we find little evidence that they try to impact firm behavior using shareholder proposals. Our results suggest that SRI funds are not greenwashing, but they are impact washing; they invest in a portfolio of firms with better environmental and social conduct but do not follow through on their promise of impact.
EPR DOSIMETRIC PROPERTIES OF DI-SODIUM TARTRATE
Authors: Maghraby Ahmed M , Ahmed Monem A , Eissa H M 
Published: February 2023

AbstractA new dosimetry system based on di-sodium tartrate was investigated. Unirradiated and irradiated sample spectra were recorded and described. Effects of the change in microwave power and modulation amplitude values on the signal amplitude and the line width of the two peaks were plotted. Response to the Cs-137 gamma radiation was studied in two ranges: high-dose range (2409.66–41.97) Gy and low-dose range (41.97–1.40) Gy. The first peak of di-sodium tartrate is found to be 1.2 times more sensitive than that of alanine in the dose range (2409.66–41.97) Gy; moreover, in the dose range (41.97–1.40) Gy, it is found to be 1.3 times more than that of alanine. For the second peak of di-sodium tartrate, it is found to be less sensitive than that of alanine in the dose range (2409.66–41.97) Gy by a factor of 0.41, whereas in the dose range (41.97–1.40) Gy, it is found to be 0.44 times less than that of alanine The minimum detectable dose for di-sodium tartrate is about 0.05 Gy for the first peak and 1.4 Gy for the second peak.
How and Why the Circadian Clock Regulates Proliferation of Adult Epithelial Stem Cells
Authors: Andersen Bogi , Duan Junyan , Karri Satya Swaroop 
Published: February 2023

Abstract
First described in the early 20th century, diurnal oscillations in stem cell proliferation exist in multiple internal epithelia, including in the gastrointestinal tract, and in the epidermis. In the mouse epidermis, 3- to 4-fold more stem cells are in S-phase during the night than during the day. More recent work showed that an intact circadian clock intrinsic to keratinocytes is required for these oscillations in epidermal stem cell proliferation. The circadian clock also regulates DNA excision repair and DNA damage in epidermal stem cells in response to ultraviolet B radiation. During skin inflammation, epidermal stem cell proliferation is increased and diurnal oscillations are suspended. Here we discuss possible reasons for the evolution of this stem cell phenomenon. We argue that the circadian clock coordinates intermediary metabolism and the cell cycle in epidermal stem cells to minimize the accumulation of DNA damage from metabolism-generated reactive oxygen species. Circadian disruption, common in modern society, leads to asynchrony between metabolism and the cell cycle, and we speculate this will lead to oxidative DNA damage, dysfunction of epidermal stem cells, and skin aging.
Impact and mitigation of sampling bias to determine viral spread: Evaluating discrete phylogeography through CTMC modeling and structured coalescent model approximations
Authors: Layan Maylis , Müller Nicola F , Dellicour Simon , De Maio Nicola , Bourhy Hervé , Cauchemez Simon , Baele Guy 
Published: February 2023

AbstractBayesian phylogeographic inference is a powerful tool in molecular epidemiological studies, which enables reconstruction of the origin and subsequent geographic spread of pathogens. Such inference is, however, potentially affected by geographic sampling bias. Here, we investigated the impact of sampling bias on the spatiotemporal reconstruction of viral epidemics using Bayesian discrete phylogeographic models and explored different operational strategies to mitigate this impact. We considered the continuous-time Markov chain (CTMC) model and two structured coalescent approximations (Bayesian structured coalescent approximation [BASTA] and marginal approximation of the structured coalescent [MASCOT]). For each approach, we compared the estimated and simulated spatiotemporal histories in biased and unbiased conditions based on the simulated epidemics of rabies virus (RABV) in dogs in Morocco. While the reconstructed spatiotemporal histories were impacted by sampling bias for the three approaches, BASTA and MASCOT reconstructions were also biased when employing unbiased samples. Increasing the number of analyzed genomes led to more robust estimates at low sampling bias for the CTMC model. Alternative sampling strategies that maximize the spatiotemporal coverage greatly improved the inference at intermediate sampling bias for the CTMC model, and to a lesser extent, for BASTA and MASCOT. In contrast, allowing for time-varying population sizes in MASCOT resulted in robust inference. We further applied these approaches to two empirical datasets: a RABV dataset from the Philippines and a SARS-CoV-2 dataset describing its early spread across the world. In conclusion, sampling biases are ubiquitous in phylogeographic analyses but may be accommodated by increasing the sample size, balancing spatial and temporal composition in the samples, and informing structured coalescent models with reliable case count data.
Predicting axial length in patients with Marfan syndrome and ectopia lentis after modified capsular tension ring and intraocular lens implantation
Authors: Chen Ze-Xu , Jia Wan-Nan , Ma Yong , Chen Tian-Hui , Hong Jia-Hao , Sun Yang , Liu Yan , Song Ling-Hao , Jiang Yong-Xiang 
Published: February 2023

Purpose:
To predict the growth of axial length (AL) in patients with Marfan syndrome (MFS) and ectopia lentis (EL).

Setting:
Eye and ENT Hospital of Fudan University, Shanghai, China.

Design:
Consecutive retrospective case series.

Methods:
Eyes were evaluated that had modified capsular tension ring and intraocular lens (IOL) implantation. The rate of AL growth (RALG) was calculated using AL divided by log10-transformed age. A multivariate linear regression model of RALG was developed after validation.

Results:
128 patients with MFS and EL were enrolled with a median follow-up duration of about 3 years. RALG was independent of age between 3 years and 15 years old (P = .799) and decreased to 0 thereafter (P = .878). Preoperative AL was associated with RALG in patients under 15 years old (P = .003). Beta values for the final model of RALG were as below: intercept (−9.794) and preoperative AL (0.664). The postoperative AL was predicted as: postAL = preAL + RALG × log10 ([postAge + 0.6]/[preAge + 0.6]). The mean prediction error was −0.003 (95% CI, −0.386 to 0.3791) mm and the mean absolute percentage error was 1.93% (95% CI, 0.73% to 3.14%). A Python-based calculator was developed to use the predicted AL in selecting IOL power and setting undercorrection.

Conclusions:
The AL growth of patients with MFS followed a logarithmic pattern and ceased at about age 15. A prediction model of postoperative AL was established for individual MFS patients between 3 and 15 years old, which could potentially optimize the IOL power selection.
Anterior vitreous detachment and retrolental material during cataract surgery: incidence and risk factors, with pathological evidence
Authors: Lin Wenli , Luo Jiawei , Li Pengfei , Ji Min , Guan Huaijin 
Published: February 2023

Purpose:
To determine the incidence of anterior vitreous detachment (AVD) and retrolental material occurrence in cataract surgery, determine the influence of surgical factors on it, and confirm the source of the material.

Setting:
Affiliated Hospital of Nantong University, Jiangsu Province, China.

Design:
Prospective single-center study.

Methods:
Age, sex, ocular complication, nuclear sclerosis grade, ultrasonic time, mean longitudinal power, cumulative dissipated energy (CDE), total aspiration time, and estimated fluid usage were recorded for each patient. Retrolental anatomy was observed before and during surgery using real-time optical coherence tomography integrated into a microscope. The eyes with AVD were carefully observed and recorded during illumination with an optical fiber. Retrolental material was stained using immunohistochemistry.

Results:
205 eyes from 205 patients were included in this study. Spontaneous AVD was found in 5 cases. Intraoperatively, AVD was identified in 115 eyes (56.1%). Retrolental material presence was observed in 75 eyes (36.6%). A logistic regression model showed that CDE and aspiration time had a statistically significant effect on AVD (P < .05, 95% CI, 1.011-1.558; P < .05, 95% CI, 1.026-1.051), and CDE was positively correlated with retrolental material occurrence (P < .05, 95% CI, 1.052-1.534). Samples from 5 cases expressed large amounts of αA- and βA-crystallins.

Conclusions:
Spontaneous AVD is rare in phakic eyes. There was a marked increase in AVD during surgery, with retrolental material occurring in more than a third of cases. Higher CDE and longer total aspiration time were risk factors for AVD. Immunohistochemistry revealed that most of the retrolental materials were lens fragments.
Challenges, Job Satisfiers, and Self-Care among Perinatal Nurses in the United States during the COVID-19 Pandemic
Authors: Iobst Stacey E. , Breman Rachel Blankstein , Walker Mark , Wysong Grace , Best Natasha , Edmonds Joyce K. 
Published: February 2023

Abstract

Purpose:
To explore the perceived challenges, job satisfiers, and self-care of perinatal nurses in the United States during the COVID-19 pandemic.

Study Design and Methods:
In May of 2021, a cross-sectional survey was distributed online to members of the Association of Women's Health, Obstetric, and Neonatal Nurses and the National Association of Neonatal Nurses. We calculated descriptive statistics on respondent characteristics and applied conventional content analysis to free-text comments.

Results:
Perinatal nurses (N = 297) responded to three open-ended questions on their perceived challenges, job satisfiers, and self-care. Frequently reported challenges included changing guidelines and policies (n = 101, 34%), personal protective equipment as a barrier (n = 73, 24.6%), and visitor restrictions (n = 64, 21.5%). Frequently reported job satisfiers were provision of high-quality care (n = 137, 46.1%) and visitor restrictions (n = 77, 25.9%). Respondents reported using mental (n = 152, 51.2%) and physical (n = 145, 48.8%) self-care strategies and 12.8% (n = 38) reported using no self-care strategies.

Clinical Implications:
The ability to provide high-quality care was reported as a leading job satisfier. Poor communication of consistent, evidence-based guidelines, lack of personal protective equipment, and inadequate unit staffing were leading challenges. Visitor restrictions were a challenge and a job satisfier, suggesting opportunities to better include visitors as support people. Most respondents reported engaging in one or more types of self-care outside of the hospital setting. Future research is needed to examine strategies for self-care among perinatal nurses when at work in the hospital setting.
Deeper habitats and cooler temperatures moderate a climate-driven seagrass disease
Authors: Graham Olivia J. , Stephens Tiffany , Rappazzo Brendan , Klohmann Corinne , Dayal Sukanya , Adamczyk Emily M. , Olson Angeleen , Hessing-Lewis Margot , Eisenlord Morgan , Yang Bo , Burge Colleen , Gomes Carla P. , Harvell Drew 
Published: February 2023

Eelgrass creates critical coastal habitats worldwide and fulfills essential ecosystem functions as a foundation seagrass. Climate warming and disease threaten eelgrass, causing mass mortalities and cascading ecological impacts. Subtidal meadows are deeper than intertidal and may also provide refuge from the temperature-sensitive seagrass wasting disease. From cross-boundary surveys of 5761 eelgrass leaves from Alaska to Washington and assisted with a machine-language algorithm, we measured outbreak conditions. Across summers 2017 and 2018, disease prevalence was 16% lower for subtidal than intertidal leaves; in both tidal zones, disease risk was lower for plants in cooler conditions. Even in subtidal meadows, which are more environmentally stable and sheltered from temperature and other stressors common for intertidal eelgrass, we observed high disease levels, with half of the sites exceeding 50% prevalence. Models predicted reduced disease prevalence and severity under cooler conditions, confirming a strong interaction between disease and temperature. At both tidal zones, prevalence was lower in more dense eelgrass meadows, suggesting disease is suppressed in healthy, higher density meadows. These results underscore the value of subtidal eelgrass and meadows in cooler locations as refugia, indicate that cooling can suppress disease, and have implications for eelgrass conservation and management under future climate change scenarios.
This article is part of the theme issue ‘Infectious disease ecology and evolution in a changing world’.